TY - JOUR T1 - Plasma homocysteine and risk for congestive heart failure in adults without prior myocardial infarction. AN - 85240102; pmid-12633186 AB - CONTEXT: Elevated plasma homocysteine levels are associated with increased risk of vascular disease. It is unclear whether elevated homocysteine levels are a risk factor for congestive heart failure (CHF). OBJECTIVE: To study prospectively the association between nonfasting plasma homocysteine and incidence of CHF. DESIGN, SETTING, AND PARTICIPANTS: Community-based prospective cohort study of 2491 adults (mean age 72 years, 1547 women) who participated in the Framingham Heart Study during the 1979-1982 and 1986-1990 examinations and were free of CHF or prior myocardial infarction (recognized or unrecognized) at baseline. MAIN OUTCOME MEASURE: Incidence of a first episode of CHF during an 8-year follow-up period. RESULTS: During follow-up, 156 subjects (88 women) developed CHF. In multivariable analyses controlling for established risk factors for CHF including the occurrence of myocardial infarction (recognized or unrecognized) during follow-up, plasma homocysteine levels higher than the sex-specific median value were associated with an adjusted hazards ratio for heart failure of 1.93 in women (95% confidence interval, 1.19-3.14) and 1.84 in men (95% confidence interval, 1.06-3.17). The relation of plasma homocysteine levels to CHF risk was more continuous in women than in men. In analyses restricted to participants without any manifestation of coronary heart disease at baseline, the association of plasma homocysteine levels with risk of CHF was maintained in men and women. CONCLUSIONS: An increased plasma homocysteine level independently predicts risk of the development of CHF in adults without prior myocardial infarction. Additional investigations are warranted to confirm these findings. JF - JAMA AU - Vasan, Ramachandran S AU - Beiser Alexa AU - D'Agostino, Ralph B AU - Levy, Daniel AU - Selhub Jacob AU - Jacques, Paul F AU - Rosenberg, Irwin H AU - Wilson Peter W F AD - National Heart, Lung, and Blood Institute's Framingham Heart Study, 73 Mt Wayte Ave, Site 2, Framingham, MA 01702-5803, USA. PY - 2003 SP - 1251 EP - 1257 VL - 289 IS - 10 SN - 0098-7484, 0098-7484 KW - Support, U.S. Gov't, P.H.S. KW - Human KW - Aged KW - Heart Failure, Congestive KW - Multivariate Analysis KW - Prospective Studies KW - Aged, 80 and over KW - Risk Factors KW - Support, U.S. Gov't, Non-P.H.S. KW - Support, Non-U.S. Gov't KW - Incidence KW - Middle Age KW - Myocardial Infarction KW - Homocysteine KW - Male KW - Female KW - Biological Markers KW - Proportional Hazards Models UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85240102?accountid=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=Plasma+homocysteine+and+risk+for+congestive+heart+failure+in+adults+without+prior+myocardial+infarction.&rft.au=Vasan%2C+Ramachandran+S%3BBeiser+Alexa%3BD%27Agostino%2C+Ralph+B%3BLevy%2C+Daniel%3BSelhub+Jacob%3BJacques%2C+Paul+F%3BRosenberg%2C+Irwin+H%3BWilson+Peter+W+F&rft.aulast=Vasan&rft.aufirst=Ramachandran&rft.date=2003-03-01&rft.volume=289&rft.issue=10&rft.spage=1251&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 - Interactions of cyclic adenosine monophosphate, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor treatment on the survival and growth of postnatal mesencephalic dopamine neurons in vitro. AN - 85235278; pmid-12668147 AB - The survival of rat postnatal mesencephalic dopamine (DA) neurons in dissociated cell cultures was studied by examining the combinatorial effects of dibutyryl cyclic adenosine monophosphate (db-cAMP), glial cell line-derived neurotrophic factor (GDNF), and brain-derived neurotrophic factor (BDNF), as well as selective inhibitors of protein kinase A (PKA), and mitogen-activated protein kinase (MAPK). Postnatal DA neurons were maintained for 14 days in vitro, and were identified by immunohistochemistry using tyrosine hydroxylase antibody. The survival and growth of DA neurons was significantly increased by the inclusion of either >100 microM db-cAMP or 10 microM Forskolin plus 100 microM IBMX in the culture medium. Neither 10-50 ng/ml GDNF nor 50 ng/ml BDNF alone significantly increased DA neuron survival in vitro. However, the combined use of GDNF and BDNF did increase DA neuron survival, and the addition of either db-cAMP or IBMX/Forskolin to media containing these neurotrophins markedly increased DA neuron survival and growth. The cAMP inhibitor Rp-cAMP, the cAMP-dependent protein kinase A inhibitor H89, and the MAP kinase (MAPK) pathway inhibitor PD98059 significantly reduced the survival of DA neurons when applied alone in the absence of added growth factors. Application of GDNF plus BDNF, or db-cAMP significantly protected the DA neurons from the deleterious effects on survival of either 20 microM H89 or 20 microM PD 98059. The results suggest that BDNF, GDNF, and cAMP produce convergent signals to activate PKA and MAPK pathways which are involved in the survival of postnatal mesencephalic DA neurons in vitro. JF - Experimental Neurology AU - Lara, Jesus AU - Kusano Kiyoshi AU - House, Shirley AU - Gainer, Harold AD - Laboratory of Neurochemistry, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-4120, USA. PY - 2003 SP - 32 EP - 45 VL - 180 IS - 1 SN - 0014-4886, 0014-4886 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85235278?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+Neurology&rft.atitle=Interactions+of+cyclic+adenosine+monophosphate%2C+brain-derived+neurotrophic+factor%2C+and+glial+cell+line-derived+neurotrophic+factor+treatment+on+the+survival+and+growth+of+postnatal+mesencephalic+dopamine+neurons+in+vitro.&rft.au=Lara%2C+Jesus%3BKusano+Kiyoshi%3BHouse%2C+Shirley%3BGainer%2C+Harold&rft.aulast=Lara&rft.aufirst=Jesus&rft.date=2003-03-01&rft.volume=180&rft.issue=1&rft.spage=32&rft.isbn=&rft.btitle=&rft.title=Experimental+Neurology&rft.issn=00144886&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - [Mussolini's fight against occupational diseases (1922-1943): Italian leadership in the production of artificial silk]. TT - La lotta di Mussolini contro le malattie professionali (1922-1943). I lavoratori e il primato italiano nella produzione di seta artificiale. AN - 73462704; 12848024 AB - After the end of the World War I Italy's economy was predominantly rural; industrialization had taken place only in the North-Western "Milan-Genoa-Turin triangle". Technological know-how and experience in developing the production cycles were scarce. The early experience in occupational medicine had been abruptly interrupted by the war. The attitudes of the Fascist regime with regard to work protection were ambiguous: work was claimed to be a sacred source of the national wealth worth being safeguarded by the regime, but the workers' potential to antagonize the regime was seen as a constant danger to public order. This scenery is well exemplified by a case study: Viscose-Ray-on Industry developed in synchrony with Mussolini's seizing power, in the early 20s. Thanks to the initiative of some manufacturers, Italy acquired a predominant role in this sector and became the second producer after the United States. Huge factories were created and complex equipment was imported from abroad. No attention was paid to health and safety at work. The major source of risk was carbon disulphide, used as a solvent in the production of xanthogenate starting from cellulose, the raw material; which produces progressive conditions following prolonged exposure. The slowness and the substantial inertia of the Fascist regime in the protection of workers' health contrasted with the reality in the Unit States, Italy's main competitor of Italy in the production of rayon. In order to exploit masses of workers, Fascism, unlike Nazism, needed no inferior "race": social discrimination was equally effective. Modern industrial development in Italy relied on masses of semiliterate farmers originating first from the Venetian region and later (after World War II) from Southern Italy. Shortly after 1945, during the so-called "Reconstruction-period", health protection developed slowly and circumspectly. National agencies supposed to have a proactive role in prevention, such as ENPI, confirmed their role as consultant of the employers for hygiene and prevention matters. Only the workers' fight around 1970 overcame the concept of the Corporative state introduced by the Fascism. JF - Epidemiologia e prevenzione AU - Carnevale, Francesco AU - Baldasseroni, Alberto AD - Azienda sanitaria di Firenze, Unità funzionale prevenzione igiene e sicurezza nei luoghi di lavoro. francesco.carnevale@asf.toscana.it PY - 2003 SP - 114 EP - 120 VL - 27 IS - 2 SN - 1120-9763, 1120-9763 KW - Cellulose KW - 9004-34-6 KW - rayon, purified KW - BX81F82EWG KW - Index Medicus KW - Mussolini KW - History, 20th Century KW - Humans KW - Famous Persons KW - Italy KW - Textile Industry -- history KW - Occupational Health -- history KW - Occupational Diseases -- prevention & control KW - Occupational Diseases -- history KW - Cellulose -- history UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73462704?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epidemiologia+e+prevenzione&rft.atitle=%5BMussolini%27s+fight+against+occupational+diseases+%281922-1943%29%3A+Italian+leadership+in+the+production+of+artificial+silk%5D.&rft.au=Carnevale%2C+Francesco%3BBaldasseroni%2C+Alberto&rft.aulast=Carnevale&rft.aufirst=Francesco&rft.date=2003-03-01&rft.volume=27&rft.issue=2&rft.spage=114&rft.isbn=&rft.btitle=&rft.title=Epidemiologia+e+prevenzione&rft.issn=11209763&rft_id=info:doi/ LA - Italian DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-22 N1 - Date created - 2003-07-09 N1 - Date revised - 2017-01-13 N1 - People - Mussolini N1 - Last updated - 2017-01-18 N1 - SubjectsTermNotLitGenreText - Mussolini ER - TY - JOUR T1 - Bayesian modeling of time-varying and waning exposure effects. AN - 73314600; 12762444 AB - In epidemiologic studies, there is often interest in assessing the association between exposure history and disease incidence. For many diseases, incidence may depend not only on cumulative exposure, but also on the ages at which exposure occurred. This article proposes a flexible Bayesian approach for modeling age-varying and waning exposure effects. The Cox model is generalized to allow the hazard of disease to depend on an integral, across the exposed ages, of a piecewise polynomial function of age, multiplied by an exponential decay term. Linearity properties of the model facilitate posterior computation via a Gibbs sampler, which generalizes previous algorithms for Cox regression with time-dependent covariates. The approach is illustrated by an application to the study of protective effects of breastfeeding on incidence of childhood asthma. JF - Biometrics AU - Dunson, David B AU - Chulada, Patricia AU - Arbes, Samuel J AD - Biostatistics Branch, MD A3-03, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, North Carolina 27709, USA. dunson1@niehs.nih.gov Y1 - 2003/03// PY - 2003 DA - March 2003 SP - 83 EP - 91 VL - 59 IS - 1 SN - 0006-341X, 0006-341X KW - Index Medicus KW - Asthma -- epidemiology KW - Age Factors KW - Breast Feeding KW - Humans KW - Adult KW - Asthma -- prevention & control KW - Algorithms KW - Data Interpretation, Statistical KW - Child KW - Time Factors KW - Proportional Hazards Models KW - Environmental Exposure KW - Bayes Theorem UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73314600?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Bayesian+modeling+of+time-varying+and+waning+exposure+effects.&rft.au=Dunson%2C+David+B%3BChulada%2C+Patricia%3BArbes%2C+Samuel+J&rft.aulast=Dunson&rft.aufirst=David&rft.date=2003-03-01&rft.volume=59&rft.issue=1&rft.spage=83&rft.isbn=&rft.btitle=&rft.title=Biometrics&rft.issn=0006341X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-16 N1 - Date created - 2003-05-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Occupation and the risk of adult glioma in the United States. AN - 73291774; 12749719 AB - Previous studies have observed increased glioma incidence associated with employment in the petroleum and electrical industries, and in farming. Several other occupations have also been associated with increased risk, but with inconsistent results. We evaluated associations between occupational title and glioma incidence in adults. Cases were 489 patients with glioma diagnosed from 1994 to 1998 at three United States hospitals. Controls were 799 patients admitted to the same hospitals for non-malignant conditions. An experienced industrial hygienist grouped occupations that were expected to have similar tasks and exposures. The risk of adult glioma was evaluated for those subjects who ever worked in an occupational group for at least six months, those who worked longer than five years in the occupation, and those with more than ten years latency since starting work in the occupation. Several occupational groups were associated with increased glioma incidence for having ever worked in the occupation, including butchers and meat cutters (odds ratio [OR] = 2.4; 95% confidence limits [CL]: 1.0, 6.0), computer programmers and analysts (OR = 2.0; 95% CL: 1.0, 3.8), electricians (OR = 1.8; 95% CL: 0.8, 4.1), general farmers and farmworkers (OR = 2.5; 95% CL: 1.4, 4.7), inspectors, checkers, examiners, graders, and testers (OR = 1.5; 95% CL: 0.8, 2.7), investigators, examiners, adjustors, and appraisers (OR = 1.7; 95% CL: 0.8, 3.7), physicians and physician assistants (OR = 2.4; 95% CL: 0.8, 7.2), and store managers (OR = 1.6; 95% CL: 0.8, 3.1), whereas occupation as a childcare worker was associated with decreased glioma incidence (OR = 0.4; 95% CL: 0.2, 0.9). These associations generally persisted when the subjects worked longer than five years in the occupation, and for those with more than ten years latency since starting to work in the occupation. This is our first analysis of occupation and will guide future exposure-specific assessments. JF - Cancer causes & control : CCC AU - De Roos, A J AU - Stewart, P A AU - Linet, M S AU - Heineman, E F AU - Dosemeci, M AU - Wilcosky, T AU - Shapiro, W R AU - Selker, R G AU - Fine, H A AU - Black, P M AU - Inskip, P D AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. Y1 - 2003/03// PY - 2003 DA - March 2003 SP - 139 EP - 150 VL - 14 IS - 2 SN - 0957-5243, 0957-5243 KW - Index Medicus KW - Logistic Models KW - Risk Factors KW - Humans KW - Adult KW - Food Industry KW - Case-Control Studies KW - Occupational Exposure -- adverse effects KW - Incidence KW - Aged KW - Middle Aged KW - United States -- epidemiology KW - Male KW - Female KW - Central Nervous System Neoplasms -- etiology KW - Glioma -- etiology KW - Glioma -- epidemiology KW - Occupations KW - Central Nervous System Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73291774?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+causes+%26+control+%3A+CCC&rft.atitle=Occupation+and+the+risk+of+adult+glioma+in+the+United+States.&rft.au=De+Roos%2C+A+J%3BStewart%2C+P+A%3BLinet%2C+M+S%3BHeineman%2C+E+F%3BDosemeci%2C+M%3BWilcosky%2C+T%3BShapiro%2C+W+R%3BSelker%2C+R+G%3BFine%2C+H+A%3BBlack%2C+P+M%3BInskip%2C+P+D&rft.aulast=De+Roos&rft.aufirst=A&rft.date=2003-03-01&rft.volume=14&rft.issue=2&rft.spage=139&rft.isbn=&rft.btitle=&rft.title=Cancer+causes+%26+control+%3A+CCC&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-11 N1 - Date created - 2003-05-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Breast cancers among very young premenopausal women (United States). AN - 73291486; 12749720 AB - To assess risk factors for breast cancer among very young compared to older premenopausal women. Between 1990 and 1992 a population-based case-control study conducted in Atlanta, GA, Seattle/Puget Sound, WA, and central NJ interviewed 3307 premenopausal women aged 20-54 years. Logistic regression models estimated adjusted relative risks (RR) and 95% confidence intervals (CI) for each of three 10-year age groups. Among the youngest age group (<35 years, n = 545), significant predictors of risk included African-American race (RR = 2.66: 95% CI 1.4-4.9) and recent use of oral contraceptives (RR = 2.26; 95% CI 1.4-3.6). Although these relationships were strongest for estrogen receptor-negative (ER-) tumors (RRs of 3.30 for race and 3.56 for recent oral contraceptive use), these associations were also apparent for young women with ER+ tumors. Delayed childbearing was a risk factor for ER+ tumors among the older premenopausal women (Ptrend < 0.01), but not for women <35 years in whom early childbearing was associated with an increased risk, reflecting a short-term increase in risk immediately following a birth. Family history of early-onset breast cancer was more strongly associated with risk among women <35 years (RR = 3.22) than those 45-54 years (RR = 1.51). Risk factors for premenopausal breast cancer not significantly modified by age at diagnosis included early age at menarche, low body mass index, and heavy alcohol consumption. These findings suggest the possibility that women who develop breast cancers at very young ages may be etiologically as well as clinically distinct. JF - Cancer causes & control : CCC AU - Althuis, Michelle D AU - Brogan, Donna D AU - Coates, Ralph J AU - Daling, Janet R AU - Gammon, Marilie D AU - Malone, Kathleen E AU - Schoenberg, Janet B AU - Brinton, Louise A AD - National Cancer Institute, Rockville, MD, USA. althuism@mail.nih.gov Y1 - 2003/03// PY - 2003 DA - March 2003 SP - 151 EP - 160 VL - 14 IS - 2 SN - 0957-5243, 0957-5243 KW - Contraceptives, Oral, Hormonal KW - 0 KW - Index Medicus KW - Age Factors KW - Logistic Models KW - Risk Factors KW - Humans KW - Continental Population Groups KW - Adult KW - Case-Control Studies KW - Alcohol Drinking -- adverse effects KW - Middle Aged KW - Contraceptives, Oral, Hormonal -- adverse effects KW - United States -- epidemiology KW - Female KW - Premenopause KW - Breast Neoplasms -- etiology KW - Carcinoma in Situ -- epidemiology KW - Breast Neoplasms -- epidemiology KW - Carcinoma in Situ -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73291486?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+causes+%26+control+%3A+CCC&rft.atitle=Breast+cancers+among+very+young+premenopausal+women+%28United+States%29.&rft.au=Althuis%2C+Michelle+D%3BBrogan%2C+Donna+D%3BCoates%2C+Ralph+J%3BDaling%2C+Janet+R%3BGammon%2C+Marilie+D%3BMalone%2C+Kathleen+E%3BSchoenberg%2C+Janet+B%3BBrinton%2C+Louise+A&rft.aulast=Althuis&rft.aufirst=Michelle&rft.date=2003-03-01&rft.volume=14&rft.issue=2&rft.spage=151&rft.isbn=&rft.btitle=&rft.title=Cancer+causes+%26+control+%3A+CCC&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-11 N1 - Date created - 2003-05-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - AIDS-related lipodystrophy/insulin resistance syndrome. AN - 73279125; 12734771 AB - The recent development and clinical use of three different types of highly effective anti-HIV-1 drugs, including nucleotide and non-nucleotide reverse transcriptase inhibitors (NRTIs) and non-peptidic viral protease inhibitors (PIs) and their combinations, termed highly active antiretroviral therapy (HAART), have dramatically reduced the infection-related mortality of AIDS patients in developed countries. However, the prolongation of the life expectancy of HIV-1-infected patients and/or long-term use of the above antiviral agents have generated a score of new problems and complications. Among them is the relatively common AIDS-related lipodystrophy/insulin resistance syndrome, which is associated with severe metabolic disturbances such as carbohydrate intolerance/diabetes mellitus and severe dyslipidemia, which influence the quality of life and threaten the life expectancies of HIV-1-infected patients by increasing the risk of atherosclerotic cardiovascular disease. The etiology of this syndrome appears to be multi-factorial; the classes of anti-viral drugs listed above, hypercytokinemia in AIDS patients, and the HIV-1 infection itself could induce the pathologic changes of this syndrome or increase the vulnerability of patients to the adverse effect of the therapeutic compounds. In this article, we review our current understanding of the pathogenesis of this severe AIDS-associated metabolic disorder. JF - Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme AU - Kino, T AU - Mirani, M AU - Alesci, S AU - Chrousos, G P AD - Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. kinot@mail.nih.gov Y1 - 2003/03// PY - 2003 DA - March 2003 SP - 129 EP - 136 VL - 35 IS - 3 SN - 0018-5043, 0018-5043 KW - Cytokines KW - 0 KW - Gene Products, tat KW - Gene Products, vpr KW - Glucocorticoids KW - HIV Protease Inhibitors KW - tat Gene Products, Human Immunodeficiency Virus KW - vpr Gene Products, Human Immunodeficiency Virus KW - 11-beta-Hydroxysteroid Dehydrogenase Type 1 KW - EC 1.1.1.146 KW - Index Medicus KW - Acquired Immunodeficiency Syndrome -- complications KW - Glucocorticoids -- physiology KW - Mitochondrial Diseases -- complications KW - 11-beta-Hydroxysteroid Dehydrogenase Type 1 -- metabolism KW - Humans KW - Acquired Immunodeficiency Syndrome -- drug therapy KW - Gene Products, tat -- physiology KW - Antiretroviral Therapy, Highly Active -- adverse effects KW - Cytokines -- physiology KW - Gene Products, vpr -- physiology KW - HIV Protease Inhibitors -- adverse effects KW - HIV-Associated Lipodystrophy Syndrome -- etiology KW - Metabolic Syndrome X -- therapy KW - Metabolic Syndrome X -- etiology KW - HIV-Associated Lipodystrophy Syndrome -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73279125?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hormone+and+metabolic+research+%3D+Hormon-+und+Stoffwechselforschung+%3D+Hormones+et+metabolisme&rft.atitle=AIDS-related+lipodystrophy%2Finsulin+resistance+syndrome.&rft.au=Kino%2C+T%3BMirani%2C+M%3BAlesci%2C+S%3BChrousos%2C+G+P&rft.aulast=Kino&rft.aufirst=T&rft.date=2003-03-01&rft.volume=35&rft.issue=3&rft.spage=129&rft.isbn=&rft.btitle=&rft.title=Hormone+and+metabolic+research+%3D+Hormon-+und+Stoffwechselforschung+%3D+Hormones+et+metabolisme&rft.issn=00185043&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-19 N1 - Date created - 2003-05-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Epidemiologic considerations to assess altered DNA methylation from environmental exposures in cancer. AN - 73271270; 12724223 AB - Epidemiologic studies in human populations have identified a broad spectrum of risk factors for cancer. Gene-damaging agents have been a primary focus of cancer epidemiology; however, all xenobiotics do not interact with DNA directly. Some exogenous agents induce epigenetic changes. In view of this, markers that measure changes to the epigenome must also be incorporated into molecular epidemiologic studies. We review the current understanding of the impact of exogenous agents including: micronutrients, chemotherapeutic agents, metals, and others, on DNA methylation. Two categories of genes are described: (1) genes that can alter susceptibility to aberrant DNA methylation and (2) genes that increase susceptibility to cancer when they are silenced through DNA methylation. Methods for incorporating markers of DNA methylation status into etiologic investigations of the impact of environmental exposures on disease (e.g., cancer) are discussed. JF - Annals of the New York Academy of Sciences AU - Moore, Lee E AU - Huang, Wen-Yi AU - Chung, Joyce AU - Hayes, Richard B AD - Occupational Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA. moorele@mail.nih.gov Y1 - 2003/03// PY - 2003 DA - March 2003 SP - 181 EP - 196 VL - 983 SN - 0077-8923, 0077-8923 KW - Biomarkers, Tumor KW - 0 KW - Index Medicus KW - Polymorphism, Genetic KW - Humans KW - Neoplasms -- epidemiology KW - Genetic Predisposition to Disease KW - Neoplasms -- genetics KW - Neoplasms -- etiology KW - DNA Methylation KW - Environmental Exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73271270?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Epidemiologic+considerations+to+assess+altered+DNA+methylation+from+environmental+exposures+in+cancer.&rft.au=Moore%2C+Lee+E%3BHuang%2C+Wen-Yi%3BChung%2C+Joyce%3BHayes%2C+Richard+B&rft.aulast=Moore&rft.aufirst=Lee&rft.date=2003-03-01&rft.volume=983&rft.issue=&rft.spage=181&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 - 2003-05-14 N1 - Date created - 2003-05-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hypomethylation: one side of a larger picture. AN - 73255201; 12724210 AB - Hypomethylation signifies one end of a spectrum of DNA methylation states. In most cases hypomethylation refers to a relative state that represents a change from the "normal" methylation level. Hypomethylation, when approached from a topographical perspective, has been used to describe either overall decreases in the methylation status of the entire genome (global hypomethylation) or more localized relative demethylation of specific subsets of the genome, such as the promoter regions of protooncogenes or normally highly methylated repetitive sequences. Global hypomethylation accompanied by gene-specific hypermethylation is observed in at least two important settings: cancer and aging. Global hypomethylation is generally reflective of decreased methylation in CpGs dispersed throughout repetitive sequences as well as the bodies of genes. Hypomethylation of repetitive and parasitic DNA sequences correlates with a number of adverse outcomes. For example, decreased methylation of repetitive sequences in the satellite DNA of the pericentric region of chromosomes is associated with increased chromosomal rearrangements, a hallmark of cancer. Decreased methylation of proviral sequences can lead to reactivation and increased infectivity. However, hypomethylation in cancer can also affect the CpGs in the promoters of specific genes-namely, protooncogenes-leading to their overexpression and resulting in the functional outcome of increased cell proliferation. Thus, hypomethylation, in a variety of settings in which it represents a deviation from "normal," appears to correlate with progression to cancer and offers potential mechanisms to explain the carcinogenic process. JF - Annals of the New York Academy of Sciences AU - Dunn, Barbara K AD - Basic Prevention Sciences Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland 20892, USA. dunnb@mail.nih.gov Y1 - 2003/03// PY - 2003 DA - March 2003 SP - 28 EP - 42 VL - 983 SN - 0077-8923, 0077-8923 KW - Index Medicus KW - Humans KW - Genome KW - Male KW - Female KW - DNA Methylation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73255201?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Hypomethylation%3A+one+side+of+a+larger+picture.&rft.au=Dunn%2C+Barbara+K&rft.aulast=Dunn&rft.aufirst=Barbara&rft.date=2003-03-01&rft.volume=983&rft.issue=&rft.spage=28&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 - 2003-05-14 N1 - Date created - 2003-05-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Viral genes and methylation. AN - 73247452; 12724222 AB - Epigenetics represents a new frontier in cancer research. Methylation is the best studied of the epigenetic mechanisms that regulate gene expression. Regulation of gene expression by means of methylation has been reported for tumor suppressor genes, oncogenes, viral promoters, and age-related genes. In this review, the regulation of viral gene expression by methylation is discussed, with particular emphasis on: (1) the virus-specific factors that bind to promoter regions; (2) the implications of this knowledge for designing viral vectors that can be used to deliver genes for the purpose of gene therapy; and (3) the use of this knowledge for the early detection and prevention of cancer. Since methylation can be reversed by a variety of exogenous agents, great potential exists to develop interventions that target cancer-associated aberrant methylation in an effort to reverse or prevent carcinogenesis. JF - Annals of the New York Academy of Sciences AU - Verma, Mukesh AD - Cancer Biomarkers Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20852-7362, USA. mv66j@nih.gov Y1 - 2003/03// PY - 2003 DA - March 2003 SP - 170 EP - 180 VL - 983 SN - 0077-8923, 0077-8923 KW - Index Medicus KW - Animals KW - Neoplasms -- diagnosis KW - Humans KW - Neoplasms -- prevention & control KW - Neoplasms -- microbiology KW - Neoplasms -- genetics KW - DNA Methylation KW - Genes, Viral KW - Gene Expression Regulation, Viral -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73247452?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Viral+genes+and+methylation.&rft.au=Verma%2C+Mukesh&rft.aulast=Verma&rft.aufirst=Mukesh&rft.date=2003-03-01&rft.volume=983&rft.issue=&rft.spage=170&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 - 2003-05-14 N1 - Date created - 2003-05-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Early detection and risk assessment: proceedings and recommendations from the Workshop on Epigenetics in Cancer Prevention. AN - 73244408; 12724234 AB - Recent advances in molecular biology that have provided a greater understanding of multistage carcinogenesis include the use of biomarkers of early detection and risk assessment. Prominent among such biomarkers are epigenetic changes. The field of epigenetics has seen a recent surge of interest among cancer researchers since alterations in DNA methylation have emerged as one of the most consistent molecular alterations in multiple neoplasms. Chromatin condensation, histone deacetylation, and promoter methylation are major steps in the epigenetic regulation of gene expression. Epigenetic changes may occur due to environmental factors, aging, and genomic imprinting. An important distinction between genetic and epigenetic alterations in cancer prevention is that the latter might be more easily reversed using therapeutic interventions. In the workshop the following areas of research were recognized for emphasis in future work: (1) basic epigenetic mechanisms in cancer need further investigation; (2) technology development in the area of epigenetics, such as high-throughput quantitative assays and increased sensitivity/specificity, is essential for the early detection and risk assessment of cancer; (3) the clinical application of epigenetic changes to cancer prevention and risk assessment needs further investigation. Further research will lead to the identification of new targets for cancer prevention. JF - Annals of the New York Academy of Sciences AU - Verma, Mukesh AU - Dunn, Barbara K AU - Ross, Sharon AU - Jain, Pawan AU - Wang, Wendy AU - Hayes, Richard AU - Umar, Asad Y1 - 2003/03// PY - 2003 DA - March 2003 SP - 298 EP - 319 VL - 983 KW - Chromatin KW - 0 KW - Histones KW - Index Medicus KW - Chromatin -- metabolism KW - DNA Methylation KW - Humans KW - Histones -- metabolism KW - Aging -- genetics KW - Risk Assessment KW - Genomic Imprinting KW - Neoplasms -- diagnosis KW - Neoplasms -- prevention & control KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73244408?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Early+detection+and+risk+assessment%3A+proceedings+and+recommendations+from+the+Workshop+on+Epigenetics+in+Cancer+Prevention.&rft.au=Verma%2C+Mukesh%3BDunn%2C+Barbara+K%3BRoss%2C+Sharon%3BJain%2C+Pawan%3BWang%2C+Wendy%3BHayes%2C+Richard%3BUmar%2C+Asad&rft.aulast=Verma&rft.aufirst=Mukesh&rft.date=2003-03-01&rft.volume=983&rft.issue=&rft.spage=298&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 - 2003-05-14 N1 - Date created - 2003-05-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Environmental exposure, DNA methylation, and gene regulation: lessons from diethylstilbesterol-induced cancers. AN - 73242786; 12724221 AB - DNA methylation is an epigenetic mechanism that regulates chromosomal stability and gene expression. Abnormal DNA methylation patterns have been observed in many types of human tumors, including those of the breast, prostate, colon, thyroid, stomach, uterus, and cervix. We and others have shown that exposure to a wide variety of xenobiotics during critical periods of mammalian development can persistently alter the pattern of DNA methylation, resulting in potentially adverse biological effects such as aberrant gene expression. Thus, this epigenetic mechanism may underlie the observed increased risk in adulthood of several chronic diseases, including cancer, in response to xenobiotic exposures early in life. We present here the lessons learned from studies on the effects of perinatal diethylstilbesterol (DES) exposure on the methylation pattern of the promoters of several estrogen-responsive genes associated with the development of reproductive organs. Perinatal DES exposure, which induces epithelial tumors of the uterus in mice and is associated with several reproductive tract abnormalities and increased vaginal and cervical cancer risk in women, provides a clear example of how estrogenic xenobiotic exposure during a critical period of development can abnormally demethylate DNA sequences during organ development and possibly increase cancer risk later in life. In addition, nutritional factors and stress may also alter DNA methylation during early life and modulate the risk of cancer and other chronic diseases in adulthood. We suggest that DNA methylation status may be influenced by environmental exposures in early life, leading to increased risk of cancer in adulthood. JF - Annals of the New York Academy of Sciences AU - Li, Shuanfang AU - Hursting, Stephen D AU - Davis, Barbara J AU - McLachlan, John A AU - Barrett, J Carl AD - Laboratory of Biosystems and Cancer, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2003/03// PY - 2003 DA - March 2003 SP - 161 EP - 169 VL - 983 SN - 0077-8923, 0077-8923 KW - Diethylstilbestrol KW - 731DCA35BT KW - Index Medicus KW - Animals KW - Cocarcinogenesis KW - Humans KW - Male KW - Female KW - Gene Expression Regulation, Neoplastic KW - Diethylstilbestrol -- adverse effects KW - Neoplasms -- chemically induced KW - Environmental Exposure KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73242786?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=WY14%2C643%2C+a+peroxisome+proliferator-activated+receptor+alpha+%28PPARalpha+%29+agonist%2C+improves+hepatic+and+muscle+steatosis+and+reverses+insulin+resistance+in+lipoatrophic+A-ZIP%2FF-1+mice.&rft.au=Chou%2C+Chieh+J%3BHaluzik%2C+Martin%3BGregory%2C+Charmaine%3BDietz%2C+Kelly+R%3BVinson%2C+Charles%3BGavrilova%2C+Oksana%3BReitman%2C+Marc+L&rft.aulast=Chou&rft.aufirst=Chieh&rft.date=2002-07-05&rft.volume=277&rft.issue=27&rft.spage=24484&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 - 2003-05-14 N1 - Date created - 2003-05-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antisense DNAs as targeted genetic medicine to treat cancer. AN - 73236181; 12723929 AB - Nucleic acid therapies represent a direct genetic approach for cancer treatment. Such an approach takes advantage of mechanisms that activate genes known to confer a growth advantage to neoplastic cells. The ability to block the expression of these genes allows exploration of normal growth regulation. Progress in antisense technology has been rapid, and the traditional antisense inhibition of gene expression is now viewed on a genomic scale. This global view has led to a new vision in antisense technology, the elimination of nonspecific and undesirable side effects, and ultimately, the generation of more effective and less toxic nucleic acid medicines. Several antisense oligonucleotides are in clinical trials, are well tolerated, and are potentially active therapeutically. Antisense oligonucleotides are promising molecular medicines for treating human cancer in the near future. JF - Archives of pharmacal research AU - Cho-Chung, Yoon S AD - Cellular Biochemistry Section, Basic Research Laboratory, National Cancer Institute, NIH, Bethesda, MD 20892-1750, USA. chochung@helix.nih.gov Y1 - 2003/03// PY - 2003 DA - March 2003 SP - 183 EP - 191 VL - 26 IS - 3 SN - 0253-6269, 0253-6269 KW - DNA, Antisense KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Neoplasms -- drug therapy KW - Genetic Therapy -- methods KW - Drug Delivery Systems -- methods KW - DNA, Antisense -- genetics KW - Neoplasms -- genetics KW - DNA, Antisense -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73236181?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pharmacal+research&rft.atitle=Antisense+DNAs+as+targeted+genetic+medicine+to+treat+cancer.&rft.au=Cho-Chung%2C+Yoon+S&rft.aulast=Cho-Chung&rft.aufirst=Yoon&rft.date=2003-03-01&rft.volume=26&rft.issue=3&rft.spage=183&rft.isbn=&rft.btitle=&rft.title=Archives+of+pharmacal+research&rft.issn=02536269&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-01 N1 - Date created - 2003-05-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Colorectal carcinoma in black and white race. AN - 73228733; 12716038 AB - Worldwide, colorectal carcinoma (CRC) varies by race-ethnicity. The highest incidence occurs in whites of European descent. Rates in blacks of South Africa are much lower, but rise with migration to westernized countries, i.e. African Americans (blacks) in the US. In the US, CRC age-specific incidence rates increased dramatically with biologic aging for black and white men and women. For all ages, rates were slightly higher for black than for whites. Among whites, overall annual rates peaked in the 1980s then declined. Stage- and subsite-specific rate shifts suggested earlier detection of cancers through screening, particularly in the distal colon. Blacks have not experienced the same stage- and subsite temporal shifts, which were observed in whites. CRC racial differences have been attributed to biologic and/or non-biologic factors as well as to routine screening patterns. Racial variations demonstrate the need for a more comprehensive understanding of colorectal carcinogenesis, epidemiology, and colorectal screening patterns for low- and high-risk populations. JF - Cancer metastasis reviews AU - Anderson, William F AU - Umar, Asad AU - Brawley, Otis W AD - National Cancer Institute/Division of Cancer Prevention/Gastrointestinal Cancer and Other Cancers Research Group, Bethesda, Maryland, USA. Y1 - 2003/03// PY - 2003 DA - March 2003 SP - 67 EP - 82 VL - 22 IS - 1 SN - 0167-7659, 0167-7659 KW - Index Medicus KW - Survival Rate KW - Humans KW - Incidence KW - Male KW - Female KW - Colorectal Neoplasms -- mortality KW - European Continental Ancestry Group KW - Colorectal Neoplasms -- ethnology KW - African Continental Ancestry Group UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73228733?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+metastasis+reviews&rft.atitle=Colorectal+carcinoma+in+black+and+white+race.&rft.au=Anderson%2C+William+F%3BUmar%2C+Asad%3BBrawley%2C+Otis+W&rft.aulast=Anderson&rft.aufirst=William&rft.date=2003-03-01&rft.volume=22&rft.issue=1&rft.spage=67&rft.isbn=&rft.btitle=&rft.title=Cancer+metastasis+reviews&rft.issn=01677659&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-12 N1 - Date created - 2003-04-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prevention and early detection clinical trials: opportunities for primary care providers and their patients. AN - 73209247; 12691266 AB - Enrollment into cancer prevention and early detection clinical trials represents a unique challenge compared with a diagnostic or treatment trial because it involves subjects without a diagnosis of cancer. This paper examines some of the barriers to participation in prevention and early detection trials and provides detailed information about two ongoing prevention and two ongoing early detection clinical trials open to enrollment as well as brief summaries of seven additional trials now open to enrollment. JF - CA: a cancer journal for clinicians AU - Ford, Leslie G AU - Minasian, Lori M AU - McCaskill-Stevens, Worta AU - Pisano, Etta D AU - Sullivan, Dan AU - Smith, Robert A AD - Division of Cancer Prevention, National Cancer Institute, Bethesda, MD, USA. PY - 2003 SP - 82 EP - 101 VL - 53 IS - 2 SN - 0007-9235, 0007-9235 KW - Anticarcinogenic Agents KW - 0 KW - Antioxidants KW - Tamoxifen KW - 094ZI81Y45 KW - Vitamin E KW - 1406-18-4 KW - Raloxifene Hydrochloride KW - 4F86W47BR6 KW - Selenium KW - H6241UJ22B KW - Abridged Index Medicus KW - Index Medicus KW - Anticarcinogenic Agents -- therapeutic use KW - Breast Neoplasms -- diagnosis KW - Tamoxifen -- therapeutic use KW - Humans KW - Raloxifene Hydrochloride -- therapeutic use KW - Vitamin E -- therapeutic use KW - Prostatic Neoplasms -- prevention & control KW - Patient Selection KW - Selenium -- therapeutic use KW - Antioxidants -- therapeutic use KW - Tamoxifen -- adverse effects KW - Breast Neoplasms -- prevention & control KW - Anticarcinogenic Agents -- adverse effects KW - Raloxifene Hydrochloride -- adverse effects KW - Female KW - Male KW - Neoplasms -- diagnosis KW - Lung Neoplasms -- diagnosis KW - Clinical Trials as Topic KW - Primary Health Care KW - Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73209247?accountid=14244 L2 - http://onlinelibrary.wiley.com/doi/10.3322/canjclin.53.2.82/full LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-24 N1 - Date created - 2003-04-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: CA Cancer J Clin. 2003 Mar-Apr;53(2):69-72 [12691264] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The interplay of genetic and environmental factors in craniofacial morphogenesis: holoprosencephaly and the role of cholesterol. AN - 73200683; 12692399 AB - Cyclopia, the paradigmatic "face [that] predicts the brain" in severe holoprosencephaly (HPE) (DeMyer et al., 1964), has been recognized since ancient times. Descriptive embryologists and pathologists have noted the continuum of defective separation of the forebrain and loss of central nervous system (CNS) midline structures for more than a century. It has been recognized more recently that inhibitors of cholesterol biosynthesis, whether consumed in native plants by range sheep, or experimentally applied to early embryos, could phenocopy the natural malformation, as could a variety of other teratogens (maternal diabetes, alcohol). Yet it has been less than a decade that the genomic knowledge base and powerful analytic methods have brought the sciences of descriptive, molecular, and genetic embryology within range of each other. In this review, we discuss the clinical presentations and pathogenesis of HPE. We will outline various genetic and teratogenic mechanisms leading to HPE. Lastly, we will attempt to examine the pivotal role of cholesterol and the Sonic Hedgehog (Shh) pathway in this disorder and in normal embryonic forebrain development. JF - Congenital anomalies AU - Edison, Robin AU - Muenke, Maximilian AD - Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA. Y1 - 2003/03// PY - 2003 DA - March 2003 SP - 1 EP - 21 VL - 43 IS - 1 SN - 0914-3505, 0914-3505 KW - Hedgehog Proteins KW - 0 KW - SHH protein, human KW - Trans-Activators KW - Cholesterol KW - 97C5T2UQ7J KW - Index Medicus KW - Environment KW - Animals KW - Age Factors KW - Facies KW - Sheep KW - Mothers KW - Humans KW - Morphogenesis KW - Infant, Newborn KW - Models, Biological KW - Maternal Exposure KW - Infant KW - Trans-Activators -- genetics KW - Central Nervous System -- abnormalities KW - Chromosome Aberrations KW - Prosencephalon -- abnormalities KW - Models, Chemical KW - Time Factors KW - Prosencephalon -- embryology KW - Male KW - Female KW - Cytogenetics KW - Cholesterol -- physiology KW - Holoprosencephaly -- diagnosis KW - Cholesterol -- metabolism KW - Holoprosencephaly -- etiology KW - Holoprosencephaly -- genetics KW - Holoprosencephaly -- embryology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73200683?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Congenital+anomalies&rft.atitle=The+interplay+of+genetic+and+environmental+factors+in+craniofacial+morphogenesis%3A+holoprosencephaly+and+the+role+of+cholesterol.&rft.au=Edison%2C+Robin%3BMuenke%2C+Maximilian&rft.aulast=Edison&rft.aufirst=Robin&rft.date=2003-03-01&rft.volume=43&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Congenital+anomalies&rft.issn=09143505&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-05 N1 - Date created - 2003-04-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunobiological treatments of hairy-cell leukaemia. AN - 73151127; 12670470 AB - Hairy cell leukaemia (HCL) is extremely responsive to purine analogue theropy developed during the early 1990s, but some patients have emerged with resistance to purine analogues. For these patients, as well as for those with primarily refractory HCL, new treatments are necessary. Several new therapeutic options have been developed for the salvage treatment of HCL. These include recombinant immunotoxins and unlabelled monoclonal antibodies (mAbs). Recombinant immunotoxins are chimeric proteins in which the Fv portion of a mAb is fused to a 38 kDa fragment of Pseudomonas exotoxin A. Two recombinant immunotoxins, BL22 and LMB-2, targeting CD22 and CD25, respectively, have demonstrated efficacy in patients with HCL resistant to purine analogues. BL22 was reported to induce complete remissions (CRs) in the majority of patients with cladribine-resistant HCL; its clinical efficacy and safety profile are currently being further defined. The unlabelled mAb rituximab has also been reported to induce responses in the majority of HCL patients treated, and several CRs have been observed. JF - Best practice & research. Clinical haematology AU - Kreitman, Robert J AU - Pastan, Ira AD - Laboratory of Molecular Biology, Centers for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 37, Room 5106, Bethesda, MD 20892-4255, USA. kreitmar@mail.nih.gov Y1 - 2003/03// PY - 2003 DA - March 2003 SP - 117 EP - 133 VL - 16 IS - 1 SN - 1521-6926, 1521-6926 KW - Antibodies, Monoclonal KW - 0 KW - Antineoplastic Agents KW - B3(Fv)-PE38KDEL recombinant immunotoxin KW - Exotoxins KW - Immunotoxins KW - Cladribine KW - 47M74X9YT5 KW - Index Medicus KW - Dose-Response Relationship, Drug KW - Humans KW - Cladribine -- therapeutic use KW - Remission Induction -- methods KW - Drug Resistance, Neoplasm KW - Exotoxins -- therapeutic use KW - Time Factors KW - Models, Biological KW - Exotoxins -- pharmacokinetics KW - Immunotoxins -- pharmacokinetics KW - Leukemia, Hairy Cell -- metabolism KW - Antineoplastic Agents -- pharmacokinetics KW - Leukemia, Hairy Cell -- drug therapy KW - Immunotoxins -- therapeutic use KW - Antineoplastic Agents -- therapeutic use KW - Leukemia, Hairy Cell -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73151127?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mechanisms+underlying+the+cytotoxic+effects+of+Tachpyr--a+novel+metal+chelator.&rft.au=Samuni%2C+Ayelet+M%3BKrishna%2C+Murali+C%3BDeGraff%2C+William%3BRusso%2C+Angelo%3BPlanalp%2C+Roy+P%3BBrechbiel%2C+Martin+W%3BMitchell%2C+James+B&rft.aulast=Samuni&rft.aufirst=Ayelet&rft.date=2002-07-03&rft.volume=1571&rft.issue=3&rft.spage=211&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 - 2003-12-02 N1 - Date created - 2003-04-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - G x E: a NIAAA workshop on gene-environment interactions. AN - 73145547; 12658122 AB - The National Institute on Alcohol Abuse and Alcoholism (NIAAA) sponsored a May 2002 workshop on gene-environment interaction (G x E) research to identify potential roadblocks to further research and to propose solutions to those roadblocks, to optimize investigative opportunities and multidisciplinary or multi-institution collaborations, and to explore ways that NIAAA can facilitate G x E studies. Sessions included panels on animal models; phenotypes; genetic findings in humans; study designs and analytical methods; and assessment of environmental risk. Key among the identified challenges to progress in G x E research were issues of study design and sampling strategies; logistic and methodological costs and constraints; availability and understanding of data analysis techniques; potential stigmatization of study populations; and organizational/bureaucratic structures that are inadequate to address the unique needs of large-scale, multicenter, longitudinal projects. Participants proposed a series of recommendations to address these issues. Session coordinators included: Gayle Boyd, Kendall Bryant, Page Chiapella, Vivian Faden, David Goldman, and Antonio Noronha. Session participants included: Laura Almasy, Henri Begleiter, Raul Caetano, Bruce Dudek, Mary Dufour, Cindy Ehlers, Mary-Anne Enoch, Joel Gelernter, David Goldman, Bridget Grant, Lorraine Gunzerath, Deborah Hasin, Andrew Heath, Victor Hesselbrock, J. Dee Higley, Shirley Hill, Kerry Jang, Raynard S. Kington, Rick Kittles, George Koob, Kenneth Leonard, Ting-Kai Li, Jeffrey Long, William McBride, Matthew McGue, Kathleen Merikangas, Tamara Phillips, Bernice Porjesz, Carol Prescott, Theodore Reich, John Rice, Richard Rose, Charmaine Royal, Arnold Sameroff, Marc Schuckit, Kenneth Sher, Renee Sieving, Robert Taylor, Michael Windle, and Robert Zucker. JF - Alcoholism, clinical and experimental research AU - Gunzerath, Lorraine AU - Goldman, David Y1 - 2003/03// PY - 2003 DA - March 2003 SP - 540 EP - 562 VL - 27 IS - 3 KW - Index Medicus KW - United States KW - Genotype KW - Animals KW - Humans KW - Environment KW - National Institutes of Health (U.S.) KW - Alcoholism -- genetics KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73145547?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Urban+Studies&rft.atitle=Bridging+the+Divide%3F+Complementary+Perspectives+on+Property&rft.au=Guy%2C+Simon%3BHenneberry%2C+John&rft.aulast=Guy&rft.aufirst=Simon&rft.date=2002-07-01&rft.volume=39&rft.issue=8&rft.spage=1471&rft.isbn=&rft.btitle=&rft.title=Urban+Studies&rft.issn=00420980&rft_id=info:doi/10.1080%2F00420980220142736 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-24 N1 - Date created - 2003-03-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gene expression profiling of preneoplastic liver disease and liver cancer: a new era for improved early detection and treatment of these deadly diseases? AN - 73129415; 12663493 AB - Hepatocellular carcinoma (HCC) is a multi-step process associated with changes in gene expression. Currently, several technologies enable global gene expression profiling. The number of studies to probe global gene expression profiles of HCC or preneoplastic chronic liver diseases has increased exponentially in recent years. These studies have quickly provided rich information and some additional clues to the genesis of liver cancer. The application of gene expression profiling to preneoplastic liver diseases and HCC is growing in importance and practicality. In this commentary, we review the recent advances in the utilization of global gene expression profiling to liver cancer, which have provided new insight into the molecular mechanisms underlying the development of HCC. We have also discussed the problems related to these new technologies, as well as their contributions and implications. By recognizing the shortcomings, we can reassess our current approaches, which allow us to better design and analyze global gene expression-based experiments. These new approaches will undoubtedly contribute to a better understanding of hepatocarcinogenesis. JF - Carcinogenesis AU - Kim, Jin Woo AU - Wang, Xin Wei AD - Building 37, Room 2C25, Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892-4255, USA. Y1 - 2003/03// PY - 2003 DA - March 2003 SP - 363 EP - 369 VL - 24 IS - 3 SN - 0143-3334, 0143-3334 KW - Index Medicus KW - Humans KW - Gene Expression Profiling KW - Precancerous Conditions -- genetics KW - Precancerous Conditions -- therapy KW - Liver Neoplasms -- therapy KW - Precancerous Conditions -- diagnosis KW - Liver Neoplasms -- diagnosis KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73129415?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Gene+expression+profiling+of+preneoplastic+liver+disease+and+liver+cancer%3A+a+new+era+for+improved+early+detection+and+treatment+of+these+deadly+diseases%3F&rft.au=Kim%2C+Jin+Woo%3BWang%2C+Xin+Wei&rft.aulast=Kim&rft.aufirst=Jin&rft.date=2003-03-01&rft.volume=24&rft.issue=3&rft.spage=363&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-30 N1 - Date created - 2003-03-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Establishment of early donor engraftment after reduced-intensity allogeneic hematopoietic stem cell transplantation to potentiate the graft-versus-lymphoma effect against refractory lymphomas. AN - 73127186; 12652466 AB - Reduced-intensity allogeneic hematopoietic stem cell transplantation (alloHSCT), which typically results in mixed chimerism initially after transplantation, has had limited efficacy in chemotherapy-refractory lymphomas. We hypothesized that the rapid establishment of complete donor chimerism would potentiate a graft-versus-lymphoma effect. Fifteen patients with chemotherapy-refractory lymphoma initially received induction with a conventional chemotherapy regimen (etoposide, prednisone, vincristine, cyclophosphamide, adriamycin, fludarabine [EPOCH-F]) to deplete host T cells and provide disease control prior to alloHSCT. Patients then received conditioning with fludarabine and cyclophosphamide followed by alloHSCT from HLA-matched siblings. Graft-versus-host disease prophylaxis consisted of cyclosporine alone. EPOCH-F resulted in 73% of patients having partial responses or stable disease. EPOCH-F depleted host CD4(+) T cells from a median of 235 cells/microL to 56 cells/microL. Fourteen patients underwent alloHSCT, and all had >95% donor engraftment by day 14 after transplantation. The incidence of Grade II to III acute graft-versus-host disease was 71%. There were two therapy-related deaths. There were 8 partial responses and 3 complete responses (CRs) at day 28. Five additional CRs were observed at day 100 without withdrawal of cyclosporine or donor lymphocyte infusion. The rate of CRs for all 15 patients was 60%. The 1-year progression-free survival rate from time of study entry is 67% with only 1 relapse among 9 CRs. At a median potential follow-up of 28 months, the overall survival rate is 53%. These data demonstrate that a potent and durable graft-versus-lymphoma effect can occur against chemotherapy-refractory lymphomas and suggest that this effect may be associated with rapid, complete donor chimerism after reduced-intensity alloHSCT. Copyright 2003 American Society for Blood and Marrow Transplantation JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation AU - Bishop, Michael R AU - Hou, Jeannie Whit-Shan AU - Wilson, Wyndham H AU - Steinberg, Seth M AU - Odom, Jeanne AU - Castro, Kathleen AU - Kasten-Sportes, Claude AU - Gea-Banacloche, Juan AU - Marchigiani, Donna AU - Gress, Ronald AU - Fowler, Daniel H AD - Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. mbishop@mail.nih.gov Y1 - 2003/03// PY - 2003 DA - March 2003 SP - 162 EP - 169 VL - 9 IS - 3 SN - 1083-8791, 1083-8791 KW - Index Medicus KW - Drug Administration Schedule KW - Humans KW - Transplantation Chimera KW - Salvage Therapy KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Transplantation, Homologous KW - Graft vs Host Disease -- prevention & control KW - Antineoplastic Combined Chemotherapy Protocols -- toxicity KW - Hematopoiesis KW - Transplantation Conditioning -- methods KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Remission Induction -- methods KW - Time Factors KW - Female KW - Male KW - Survival Analysis KW - Lymphoma -- mortality KW - Lymphoma -- therapy KW - Hematopoietic Stem Cell Transplantation -- mortality KW - Graft vs Tumor Effect KW - Graft Survival KW - Lymphoma -- complications KW - Hematopoietic Stem Cell Transplantation -- methods KW - Hematopoietic Stem Cell Transplantation -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73127186?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biology+of+blood+and+marrow+transplantation+%3A+journal+of+the+American+Society+for+Blood+and+Marrow+Transplantation&rft.atitle=Establishment+of+early+donor+engraftment+after+reduced-intensity+allogeneic+hematopoietic+stem+cell+transplantation+to+potentiate+the+graft-versus-lymphoma+effect+against+refractory+lymphomas.&rft.au=Bishop%2C+Michael+R%3BHou%2C+Jeannie+Whit-Shan%3BWilson%2C+Wyndham+H%3BSteinberg%2C+Seth+M%3BOdom%2C+Jeanne%3BCastro%2C+Kathleen%3BKasten-Sportes%2C+Claude%3BGea-Banacloche%2C+Juan%3BMarchigiani%2C+Donna%3BGress%2C+Ronald%3BFowler%2C+Daniel+H&rft.aulast=Bishop&rft.aufirst=Michael&rft.date=2003-03-01&rft.volume=9&rft.issue=3&rft.spage=162&rft.isbn=&rft.btitle=&rft.title=Biology+of+blood+and+marrow+transplantation+%3A+journal+of+the+American+Society+for+Blood+and+Marrow+Transplantation&rft.issn=10838791&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-05 N1 - Date created - 2003-03-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carcinogenesis of the food mutagen PhIP in mice is independent of CYP1A2. AN - 73124598; 12663521 AB - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant of the heterocyclic amines found in cooked meat. Based on in vitro studies with rats and humans, CYP1A2 is believed to be the primary enzyme responsible for N(2)-hydroxylation, the initial step in the metabolic activation of PhIP. To determine whether CYP1A2 is the primary P450 responsible for metabolic activation of PhIP in mice that leads to tumor formation, neonatal Cyp1a2-null and wild-type mice were treated with approximately 11 (low dose) and approximately 22 (high dose) mg/kg PhIP at days 8 and 15, corresponding cumulatively to 600 and 1200 nmol PhIP, and analyzed at 19-21 months of age. Three major induced tumors were found; lymphomas and tumors in lung and liver. The incidence of lymphoma was higher in Cyp1a2-null females than wild-type females treated with low dose (600 nmol) PhIP whereas no significant differences were observed in other treatment groups of mice. Overall differences in incidences of lung adenoma/adenocarcinoma were in general not consistent among sexes, genotypes and PhIP doses used, although reduced incidences of lung tumors were found in Cyp1a2-null males with low dose (600 nmol) and null females with high dose (1200 nmol) PhIP. Higher incidences of hepatocellular adenoma were observed in Cyp1a2-null female and male mice as compared with wild-type mice. In vitro studies using Cyp1a2-null and wild-type mouse liver microsomes revealed that CYP1A2 is the major enzyme required for PhIP N2-hydroxylation in mouse, the initial metabolic activation of PhIP that is thought to lead to tumor formation. These in vivo and in vitro results suggest that although the metabolic activation of PhIP is carried out primarily by CYP1A2, an unknown pathway unrelated to CYP1A2 appears to be responsible for PhIP carcinogenesis in mouse when examined in the neonatal bioassay. In fact, CYP1A2 may even be protective against all transformation, especially in females. JF - Carcinogenesis AU - Kimura, Shioko AU - Kawabe, Mayumi AU - Yu, Aiming AU - Morishima, Hideki AU - Fernandez-Salguero, Pedro AU - Hammons, George J AU - Ward, Jerrold M AU - Kadlubar, Fred F AU - Gonzalez, Frank J AD - Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2003/03// PY - 2003 DA - March 2003 SP - 583 EP - 587 VL - 24 IS - 3 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - Imidazoles KW - Mutagens KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - Cytochrome P-450 CYP1A2 KW - EC 1.14.14.1 KW - Index Medicus KW - Mass Spectrometry KW - Animals KW - Dose-Response Relationship, Drug KW - Chromatography, Liquid KW - Carcinogenicity Tests KW - Mice KW - Male KW - Female KW - Mice, Knockout KW - Imidazoles -- toxicity KW - Cytochrome P-450 CYP1A2 -- genetics KW - Food KW - Cytochrome P-450 CYP1A2 -- metabolism KW - Carcinogens -- toxicity KW - Mutagens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73124598?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Carcinogenesis+of+the+food+mutagen+PhIP+in+mice+is+independent+of+CYP1A2.&rft.au=Kimura%2C+Shioko%3BKawabe%2C+Mayumi%3BYu%2C+Aiming%3BMorishima%2C+Hideki%3BFernandez-Salguero%2C+Pedro%3BHammons%2C+George+J%3BWard%2C+Jerrold+M%3BKadlubar%2C+Fred+F%3BGonzalez%2C+Frank+J&rft.aulast=Kimura&rft.aufirst=Shioko&rft.date=2003-03-01&rft.volume=24&rft.issue=3&rft.spage=583&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-30 N1 - Date created - 2003-03-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - From mouse to man: redefining the role of insulin-like growth factor-I in the acquisition of bone mass. AN - 73094849; 12626768 AB - The insulin-like growth factor system (IGF) has been linked to the process of bone acquisition through epidemiologic analyses of large cohorts and in vitro studies of bone cells. But the exact relationship between expression of IGF-I in bone and skeletal homeostasis or pathologic conditions, such as osteoporosis, remains poorly defined. Recent advances in genomic engineering have resulted in the development of better in vivo models to test the role of IGF-I during development and maintenance of the adult skeleton. It is now established that skeletal expression of IGF-I is critical for differentiative bone cell function. It may also be essential for the full anabolic effects of parathyroid hormone on trabecular bone and for some component of biomineralization. Evidence from conditional mutagenesis studies suggests that serum IGF-I may represent more than a storage depot or permissive factor during the final phase of skeletal acquisition. This work re-examines the original tenets of the "somatomedin hypothesis" in light of these newer mouse models and their remarkable skeletal phenotypes. The implications are far reaching and suggest that newer approaches for manipulating the IGF regulatory system may one day be useful as therapeutic adjuncts for the treatment of osteoporosis. JF - Experimental biology and medicine (Maywood, N.J.) AU - Yakar, Shoshana AU - Rosen, Clifford J AD - The National Institutes of Health and The Jackson Laboratory and St Joseph Hospital, Bangor, Maine 04401, USA. Y1 - 2003/03// PY - 2003 DA - March 2003 SP - 245 EP - 252 VL - 228 IS - 3 SN - 1535-3702, 1535-3702 KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Index Medicus KW - Animals KW - Humans KW - Mice KW - Insulin-Like Growth Factor I -- physiology KW - Bone Remodeling -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73094849?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+biology+and+medicine+%28Maywood%2C+N.J.%29&rft.atitle=From+mouse+to+man%3A+redefining+the+role+of+insulin-like+growth+factor-I+in+the+acquisition+of+bone+mass.&rft.au=Yakar%2C+Shoshana%3BRosen%2C+Clifford+J&rft.aulast=Yakar&rft.aufirst=Shoshana&rft.date=2003-03-01&rft.volume=228&rft.issue=3&rft.spage=245&rft.isbn=&rft.btitle=&rft.title=Experimental+biology+and+medicine+%28Maywood%2C+N.J.%29&rft.issn=15353702&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-18 N1 - Date created - 2003-03-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A highly efficient recombineering-based method for generating conditional knockout mutations. AN - 73082486; 12618378 AB - Phage-based Escherichia coli homologous recombination systems have recently been developed that now make it possible to subclone or modify DNA cloned into plasmids, BACs, or PACs without the need for restriction enzymes or DNA ligases. This new form of chromosome engineering, termed recombineering, has many different uses for functional genomic studies. Here we describe a new recombineering-based method for generating conditional mouse knockout (cko) mutations. This method uses homologous recombination mediated by the lambda phage Red proteins, to subclone DNA from BACs into high-copy plasmids by gap repair, and together with Cre or Flpe recombinases, to introduce loxP or FRT sites into the subcloned DNA. Unlike other methods that use short 45-55-bp regions of homology for recombineering, our method uses much longer regions of homology. We also make use of several new E. coli strains, in which the proteins required for recombination are expressed from a defective temperature-sensitive lambda prophage, and the Cre or Flpe recombinases from an arabinose-inducible promoter. We also describe two new Neo selection cassettes that work well in both E. coli and mouse ES cells. Our method is fast, efficient, and reliable and makes it possible to generate cko-targeting vectors in less than 2 wk. This method should also facilitate the generation of knock-in mutations and transgene constructs, as well as expedite the analysis of regulatory elements and functional domains in or near genes. JF - Genome research AU - Liu, Pentao AU - Jenkins, Nancy A AU - Copeland, Neal G AD - Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, USA. Y1 - 2003/03// PY - 2003 DA - March 2003 SP - 476 EP - 484 VL - 13 IS - 3 SN - 1088-9051, 1088-9051 KW - Bcl11a protein, mouse KW - 0 KW - Carrier Proteins KW - DNA, Recombinant KW - Nuclear Proteins KW - Index Medicus KW - Animals KW - Stem Cells -- chemistry KW - Nuclear Proteins -- genetics KW - Plasmids -- genetics KW - Carrier Proteins -- genetics KW - Cloning, Molecular -- methods KW - Escherichia coli -- genetics KW - Mice KW - Stem Cells -- metabolism KW - Attachment Sites, Microbiological -- genetics KW - DNA Damage -- genetics KW - Mice, Knockout KW - DNA Repair -- genetics KW - Exons -- genetics KW - Mice, Inbred Strains KW - Organ Specificity -- genetics KW - DNA, Recombinant -- genetics KW - Cell Line KW - Recombination, Genetic -- genetics KW - Mutagenesis, Site-Directed -- genetics KW - Mutation -- genetics KW - Genetic Engineering -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73082486?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genome+research&rft.atitle=A+highly+efficient+recombineering-based+method+for+generating+conditional+knockout+mutations.&rft.au=Liu%2C+Pentao%3BJenkins%2C+Nancy+A%3BCopeland%2C+Neal+G&rft.aulast=Liu&rft.aufirst=Pentao&rft.date=2003-03-01&rft.volume=13&rft.issue=3&rft.spage=476&rft.isbn=&rft.btitle=&rft.title=Genome+research&rft.issn=10889051&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-11 N1 - Date created - 2003-03-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Gen Genet. 1999 Oct;262(3):543-51 [10589843] Nucleic Acids Res. 2001 Dec 15;29(24):5156-62 [11812849] Mol Cell Biol. 2000 May;20(9):3178-86 [10757802] Gene. 2000 Apr 4;246(1-2):321-30 [10767554] Proc Natl Acad Sci U S A. 2000 May 23;97(11):5978-83 [10811905] Nat Genet. 2000 Jun;25(2):139-40 [10835623] Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6640-5 [10829079] Nat Biotechnol. 2000 Dec;18(12):1314-7 [11101815] Genesis. 2001 Jan;29(1):14-21 [11135458] Trends Biochem Sci. 2001 May;26(5):325-31 [11343926] Genomics. 2001 Apr 1;73(1):56-65 [11352566] FEMS Microbiol Lett. 2001 Jul 10;201(1):9-14 [11445160] Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11450-5 [11553794] Nat Rev Genet. 2001 Oct;2(10):769-79 [11584293] Blood. 2001 Dec 1;98(12):3413-20 [11719382] Nat Genet. 2002 Jan;30(1):31-9 [11753384] Dev Biol. 2002 Apr 15;244(2):305-18 [11944939] Gene. 1982 Feb;17(2):123-30 [6211394] Nucleic Acids Res. 1993 Jul 11;21(14):3329-30 [8341614] Yeast. 1996 Mar 15;12(3):259-65 [8904338] Science. 1997 Oct 3;278(5335):120-3 [9311916] Nat Biotechnol. 1998 Jul;16(7):657-62 [9661200] Nat Genet. 1998 Oct;20(2):123-8 [9771703] Gene. 1998 Nov 26;223(1-2):95-102 [9858698] Nucleic Acids Res. 1999 Mar 15;27(6):1555-7 [10037821] Genesis. 2000 Feb;26(2):99-109 [10686599] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tamoxifen and the farnesyl transferase inhibitor FTI-277 synergize to inhibit growth in estrogen receptor-positive breast tumor cell lines. AN - 73070109; 12611458 AB - Farnesyl transferase inhibitors (FTIs) serve to specifically inhibit farnesyl isoprenoid lipid modification of proteins. Although originally developed as anti-Ras oncoprotein drugs, it now appears that these compounds function independently of Ras. FTIs have been shown to inhibit transformation by a variety of mechanisms, including apoptosis involving cytochrome c release from mitochondria. Tamoxifen exhibits both anti-estrogenic and estrogenic properties and is widely used as an estrogen antagonist for the treatment of estrogen receptor (ER) positive human breast tumors. Tamoxifen can induce ER-dependent apoptosis in human breast tumor cells by a mechanism involving the Bcl2/mitochondrial arm of the apoptotic machinery. Since tamoxifen and FTIs may stimulate distinct components of the mitochondrial-based apoptotic machinery, we reasoned that their effects might be synergistic. Here we show that anti-estrogens and an FTI (FTI-277) synergize to inhibit cell growth and enhance cell death in ER positive, human breast tumor cell lines. However, the drugs exhibited only additive effects on an ER negative cell line. Analysis of treated ER positive T-47D cells demonstrated that a synergistic increase in apoptosis was induced, as measured by increased caspase 3 activity. Thus, tamoxifen and FTIs may synergize to promote apoptotic cell death in ER positive human breast tumor cells. JF - Breast cancer research and treatment AU - Ellis, Chad A AU - Vos, Michele D AU - Wickline, Meredith AU - Riley, Christine AU - Vallecorsa, Teresa AU - Telford, William G AU - Zujewskil, JoAnne AU - Clark, Geoffrey J AD - NCI, Department of Cell and Cancer Biology, Rockville, MD 20850-3300, USA. Y1 - 2003/03// PY - 2003 DA - March 2003 SP - 59 EP - 67 VL - 78 IS - 1 SN - 0167-6806, 0167-6806 KW - Antineoplastic Agents KW - 0 KW - Enzyme Inhibitors KW - FTI 277 KW - Receptors, Estrogen KW - Tamoxifen KW - 094ZI81Y45 KW - Methionine KW - AE28F7PNPL KW - Index Medicus KW - Tumor Cells, Cultured KW - Humans KW - Drug Synergism KW - Female KW - Breast Neoplasms -- drug therapy KW - Enzyme Inhibitors -- therapeutic use KW - Methionine -- therapeutic use KW - Breast Neoplasms -- physiopathology KW - Tamoxifen -- therapeutic use KW - Breast Neoplasms -- metabolism KW - Methionine -- analogs & derivatives KW - Receptors, Estrogen -- metabolism KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73070109?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Tamoxifen+and+the+farnesyl+transferase+inhibitor+FTI-277+synergize+to+inhibit+growth+in+estrogen+receptor-positive+breast+tumor+cell+lines.&rft.au=Ellis%2C+Chad+A%3BVos%2C+Michele+D%3BWickline%2C+Meredith%3BRiley%2C+Christine%3BVallecorsa%2C+Teresa%3BTelford%2C+William+G%3BZujewskil%2C+JoAnne%3BClark%2C+Geoffrey+J&rft.aulast=Ellis&rft.aufirst=Chad&rft.date=2003-03-01&rft.volume=78&rft.issue=1&rft.spage=59&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 - 2003-09-16 N1 - Date created - 2003-03-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic susceptibility to benzene-induced toxicity: role of NADPH: quinone oxidoreductase-1. AN - 73063253; 12615705 AB - Enzymes that activate and detoxify benzene are likely genetic determinants of benzene-induced toxicity.NAD(P)H: quinone oxidoreductase-1 (NQO1) detoxifies benzoquinones, proposed toxic metabolites of benzene. NQO1 deficiency in humans is associated with an increased risk of leukemia, specifically acute myelogenous leukemia, and benzene poisoning. We examined the importance of NQO1 in benzene-induced toxicity by hypothesizing that NQO1-deficient (NQO1-/-) mice are more sensitive to benzene than mice with wild-type NQO1 (NQO1+/+; 129/Sv background strain). Male and female NQO1-/- and NQO1+/+ mice were exposed to inhaled benzene (0, 10, 50, or 100 ppm) for 2 weeks, 6 h/day, 5 days/week. Micronucleated peripheral blood cells were counted to assess genotoxicity. Peripheral blood counts and bone marrow histology were used to assess hematotoxicity and myelotoxicity. p21 mRNA levels in bone marrow cells were used as determinants of DNA damage response. Female NQO1-/- mice were more sensitive (6-fold) to benzene-induced genotoxicity than the female NQO1+/+ mice. Female NQO1-/- mice had a 9-fold increase (100 versus 0 ppm) in micronucleated reticulocytes compared with a 3-fold increase in the female NQO1+/+ mice. However, the induced genotoxic response in male mice was similar between the two genotypes (> or = 10-fold increase at 100 ppm versus 0 ppm). Male and female NQO1-/- mice exhibited greater hematotoxicity than NQO1+/+ mice. p21 mRNA levels were induced significantly in male mice (>10-fold) from both strains and female NQO1-/- mice (> 8-fold), which indicates an activated DNA damage response. These results indicate that NQO1 deficiency results in substantially greater benzene-induced toxicity. However, the specific patterns of toxicity differed between the male and female mice. JF - Cancer research AU - Bauer, Alison K AU - Faiola, Brenda AU - Abernethy, Diane J AU - Marchan, Rosemarie AU - Pluta, Linda J AU - Wong, Vicki A AU - Roberts, Kay AU - Jaiswal, Anil K AU - Gonzalez, Frank J AU - Butterworth, Byron E AU - Borghoff, Susan AU - Parkinson, Horace AU - Everitt, Jeffrey AU - Recio, Leslie AD - CIIT Centers for Health Research, Research Triangle Park, North Carolina 27709, USA. bauer1@niehs.nih.gov Y1 - 2003/03/01/ PY - 2003 DA - 2003 Mar 01 SP - 929 EP - 935 VL - 63 IS - 5 SN - 0008-5472, 0008-5472 KW - DNA KW - 9007-49-2 KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - NAD(P)H Dehydrogenase (Quinone) KW - EC 1.6.5.2 KW - NQO1 protein, human KW - Benzene KW - J64922108F KW - Index Medicus KW - Bone Marrow Cells -- drug effects KW - Animals KW - DNA Damage KW - Mice KW - Cytochrome P-450 CYP2E1 -- metabolism KW - DNA -- drug effects KW - Hematologic Diseases -- chemically induced KW - Microsomes, Liver -- enzymology KW - Bone Marrow Cells -- pathology KW - Genetic Predisposition to Disease KW - Hematologic Diseases -- pathology KW - Inactivation, Metabolic -- genetics KW - Female KW - Male KW - NAD(P)H Dehydrogenase (Quinone) -- genetics KW - NAD(P)H Dehydrogenase (Quinone) -- deficiency KW - Benzene -- pharmacokinetics KW - Benzene -- toxicity KW - NAD(P)H Dehydrogenase (Quinone) -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73063253?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Genetic+susceptibility+to+benzene-induced+toxicity%3A+role+of+NADPH%3A+quinone+oxidoreductase-1.&rft.au=Bauer%2C+Alison+K%3BFaiola%2C+Brenda%3BAbernethy%2C+Diane+J%3BMarchan%2C+Rosemarie%3BPluta%2C+Linda+J%3BWong%2C+Vicki+A%3BRoberts%2C+Kay%3BJaiswal%2C+Anil+K%3BGonzalez%2C+Frank+J%3BButterworth%2C+Byron+E%3BBorghoff%2C+Susan%3BParkinson%2C+Horace%3BEveritt%2C+Jeffrey%3BRecio%2C+Leslie&rft.aulast=Bauer&rft.aufirst=Alison&rft.date=2003-03-01&rft.volume=63&rft.issue=5&rft.spage=929&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 - 2003-04-01 N1 - Date created - 2003-03-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Apoptotic susceptibility of cancer cells selected for camptothecin resistance: gene expression profiling, functional analysis, and molecular interaction mapping. AN - 73062988; 12615715 AB - To study the molecular mechanisms by which drug resistance develops, we compared DU145 humanprostate cancer cells with a subline selected for resistance to camptothecin. Differences in gene expression level were assessed by hybridizing the two cell types against each other using quadruplicate "Oncochip" cDNA microarrays that included 1648 cancer-related genes. Expression levels differing by a factor of >1.5 were detected for 181 of the genes. These differences were judged statistically reliable on the basis of a stratum-adjusted Kruskal-Wallis test, after taking into account a dye-dependent variable. The 181 expression-altered genes included a larger than expected number of the "apoptosis-related" genes (P = 0.04). To assess whether this observation reflected a generalized resistance of RCO.1 to apoptosis, we exposed the cells to a range of stresses (cisplatin, staurosporine, UV, ionizing radiation, and serum starvation) and found greatly reduced apoptotic responses for RC0.1 (relative to DU145) using flow cytometric Annexin V and terminal deoxynucleotidyl transferase-mediated nick end labeling assays. We next examined the apoptosis-related genes in the context of a molecular interaction map and found expression differences in the direction "expected" on the basis of the apoptosis-resistance of RC0.1 for BAD, caspase-6, and genes that signal via the Akt pathway. Exposure of the cells to wortmannin, an inhibitor of the Akt effector phosphatidylinositol 3-kinase, provided functional support for involvement of the Akt pathway. However, closer examination of the molecular interaction map revealed a paradox: many of the expression differences observed for apoptosis-related genes were in the direction "contrary" to that expected given the resistance of RC0.1. The map indicated that most of these unexpected expression differences were associated with genes involved in the nuclear factor kappa B and transforming growth factor beta pathways. Overall, the patterns that emerged suggested a two-step model for the selection process that led to resistance in RC0.1 cells. The first hypothesized step would involve a decrease in apoptotic susceptibility through changes in the apoptosis-control machinery associated with the Bcl-2 and caspase gene families, and also in antiapoptotic pathways operating through Akt/PKB. The second step would involve changes in multifunctional upstream genes (including some genes in the nuclear factor kappa B and transforming growth factor beta pathways) that can facilitate apoptosis but that would also tend to contribute to cell proliferation in the presence of drug. Thus, we propose that a downstream blockade of apoptosis was "permissive" for the selection of upstream pathway changes that would otherwise have induced apoptosis. This model is analogous to one suggested previously for the relationship between oncogene function and apoptosis in carcinogenesis. JF - Cancer research AU - Reinhold, William C AU - Kouros-Mehr, Hosein AU - Kohn, Kurt W AU - Maunakea, Alika K AU - Lababidi, Samir AU - Roschke, Anna AU - Stover, Kristen AU - Alexander, Jes AU - Pantazis, Panayotis AU - Miller, Lance AU - Liu, Edison AU - Kirsch, Ilan R AU - Urasaki, Yoshimasa AU - Pommier, Yves AU - Weinstein, John N AD - Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. wcr@mail.nih.gov Y1 - 2003/03/01/ PY - 2003 DA - 2003 Mar 01 SP - 1000 EP - 1011 VL - 63 IS - 5 SN - 0008-5472, 0008-5472 KW - Androstadienes KW - 0 KW - Antineoplastic Agents, Phytogenic KW - Enzyme Inhibitors KW - RNA, Messenger KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Camptothecin KW - XT3Z54Z28A KW - wortmannin KW - XVA4O219QW KW - Index Medicus KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - Androstadienes -- pharmacology KW - Drug Resistance, Neoplasm KW - Reverse Transcriptase Polymerase Chain Reaction KW - RNA, Messenger -- genetics KW - Gene Expression Regulation, Neoplastic -- drug effects KW - RNA, Messenger -- biosynthesis KW - Gene Expression Profiling KW - Tumor Cells, Cultured KW - Enzyme Inhibitors -- pharmacology KW - Flow Cytometry KW - Drug Synergism KW - Male KW - Phosphatidylinositol 3-Kinases -- antagonists & inhibitors KW - Prostatic Neoplasms -- metabolism KW - Prostatic Neoplasms -- pathology KW - Apoptosis -- genetics KW - Camptothecin -- pharmacology KW - Apoptosis -- drug effects KW - Antineoplastic Agents, Phytogenic -- pharmacology KW - Prostatic Neoplasms -- genetics KW - Prostatic Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73062988?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Apoptotic+susceptibility+of+cancer+cells+selected+for+camptothecin+resistance%3A+gene+expression+profiling%2C+functional+analysis%2C+and+molecular+interaction+mapping.&rft.au=Reinhold%2C+William+C%3BKouros-Mehr%2C+Hosein%3BKohn%2C+Kurt+W%3BMaunakea%2C+Alika+K%3BLababidi%2C+Samir%3BRoschke%2C+Anna%3BStover%2C+Kristen%3BAlexander%2C+Jes%3BPantazis%2C+Panayotis%3BMiller%2C+Lance%3BLiu%2C+Edison%3BKirsch%2C+Ilan+R%3BUrasaki%2C+Yoshimasa%3BPommier%2C+Yves%3BWeinstein%2C+John+N&rft.aulast=Reinhold&rft.aufirst=William&rft.date=2003-03-01&rft.volume=63&rft.issue=5&rft.spage=1000&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 - 2003-04-01 N1 - Date created - 2003-03-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Short peptide amyloid organization: stabilities and conformations of the islet amyloid peptide NFGAIL. AN - 73062584; 12609890 AB - Experimentally, short peptides have been shown to form amyloids similar to those of their parent proteins. Consequently, they present useful systems for studies of amyloid conformation. Here we simulate extensively the NFGAIL peptide, derived from the human islet amyloid polypeptide (residues 22-27). We simulate different possible strand/sheet organizations, from dimers to nonamers. Our simulations indicate that the most stable conformation is an antiparallel strand orientation within the sheets and parallel between sheets. Consistent with the alanine mutagenesis, we find that the driving force is the hydrophobic effect. Whereas the NFGAIL forms stable oligomers, the NAGAIL oligomer is unstable, and disintegrates very quickly after the beginning of the simulation. The simulations further identify a minimal seed size. Combined with our previous simulations of the prion-derived AGAAAAGA peptide, AAAAAAAA, and the Alzheimer Abeta fragments 16-22, 24-36, 16-35, and 10-35, and the solid-state NMR data for Abeta fragments 16-22, 10-35, and 1-40, some insight into the length and the sequence matching effects may be obtained. JF - Biophysical journal AU - Zanuy, David AU - Ma, Buyong AU - Nussinov, Ruth AD - Laboratory of Experimental and Computational Biology, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA. Y1 - 2003/03// PY - 2003 DA - March 2003 SP - 1884 EP - 1894 VL - 84 IS - 3 SN - 0006-3495, 0006-3495 KW - Amyloid KW - 0 KW - Islet Amyloid Polypeptide KW - Macromolecular Substances KW - Oligopeptides KW - Protein Subunits KW - amylin (22-27) KW - Index Medicus KW - Sensitivity and Specificity KW - Hydrophobic and Hydrophilic Interactions KW - Drug Stability KW - Protein Structure, Secondary KW - Computer Simulation KW - Reproducibility of Results KW - Humans KW - Protein Folding KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Protein Subunits -- chemistry KW - Protein Conformation KW - Models, Molecular KW - Oligopeptides -- chemistry KW - Amyloid -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73062584?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Short+peptide+amyloid+organization%3A+stabilities+and+conformations+of+the+islet+amyloid+peptide+NFGAIL.&rft.au=Zanuy%2C+David%3BMa%2C+Buyong%3BNussinov%2C+Ruth&rft.aulast=Zanuy&rft.aufirst=David&rft.date=2003-03-01&rft.volume=84&rft.issue=3&rft.spage=1884&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 - 2003-11-04 N1 - Date created - 2003-02-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13407-12 [9811813] Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14126-31 [12391326] J Mol Biol. 1999 Dec 17;294(5):1375-85 [10600392] Proc Natl Acad Sci U S A. 1990 Jul;87(13):5036-40 [2195544] Biochem Biophys Res Commun. 1996 May 6;222(1):78-82 [8630078] Biochemistry. 1996 Dec 17;35(50):16094-104 [8973180] Q Rev Biophys. 1998 Feb;31(1):1-39 [9717197] J Mol Biol. 2000 Jan 28;295(4):1055-71 [10656810] Curr Opin Struct Biol. 2000 Feb;10(1):60-8 [10679462] Diabetologia. 2000 Jun;43(6):687-95 [10907112] J Struct Biol. 2000 Jun;130(2-3):99-108 [10940218] J Struct Biol. 2000 Jun;130(2-3):153-73 [10940223] Biochemistry. 2000 Nov 14;39(45):13748-59 [11076514] Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13045-50 [11069287] Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2375-80 [11226247] J Mol Biol. 2001 May 4;308(3):515-25 [11327784] J Mol Biol. 2001 May 11;308(4):783-94 [11350174] Prog Biophys Mol Biol. 2001;76(1-2):1-102 [11389934] J Biol Chem. 2001 Sep 7;276(36):34156-61 [11445568] J Mol Biol. 2001 Oct 5;312(5):1103-19 [11580253] Biochim Biophys Acta. 2001 Nov 29;1537(3):179-203 [11731221] FASEB J. 2002 Jan;16(1):77-83 [11772939] J Mol Biol. 2002 Jan 18;315(3):339-50 [11786016] Nat Struct Biol. 2002 Feb;9(2):137-43 [11799398] Nature. 2002 Apr 4;416(6880):507-11 [11932737] Science. 2002 Jul 19;297(5580):353-6 [12130773] Protein Sci. 2002 Oct;11(10):2335-50 [12237456] Biochemistry. 1999 Feb 9;38(6):1811-8 [10026261] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - TP53 and liver carcinogenesis. AN - 73062415; 12619106 AB - Primary hepatocellular carcinoma (HCC) is one of the most common malignancies and has the fourth highest mortality rate worldwide. The major risk factors, including chronic infections with the hepatitis B or C virus, are exposure to dietary aflatoxin B1(AFB1), vinyl chloride, or alcohol consumption. Southern China and sub-Saharan Africa have the highest dietary AFB1 exposure, making it and hepatitis B virus (HBV) the major causes of cancer mortality in these geographic areas. Recent studies have discovered genetic and epigenetic changes involved in the molecular pathogenesis of HCC, including somatic mutations in the p53 tumor suppressor gene (TP53). AFB1 induces typical G:C to T:A transversions at the third base in codon 249 of p53. Chronic active hepatitis B and C (HCV) infection, and further inflammatory and oxyradical disorders including Wilson disease (WD) or hemochromatosis, generate reactive oxygen/nitrogen species that can damage DNA and mutate the p53 gene. The X gene of HBV (HBx) is the most common open reading frame integrated into the host genome in HCC. The integrated HBx is frequently mutated and has a diminished ability to function as a transcriptional cotransactivator and to activate the NF-kappa B pathway. However, the mutant HBx proteins still retain their ability to bind to and abrogate p53-mediated apoptosis. In summary, both viruses and chemicals are implicated in the etiology and molecular pathogenesis of HCC. The resultant molecular changes in the ras and Wnt signal-transduction pathways, and the p53 and Rb tumor suppressor pathways significantly contribute to liver carcinogenesis Published 2003 Wiley-Liss, Inc. JF - Human mutation AU - Staib, Frank AU - Hussain, S Perwez AU - Hofseth, Lorne J AU - Wang, Xin W AU - Harris, Curtis C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 2003/03// PY - 2003 DA - March 2003 SP - 201 EP - 216 VL - 21 IS - 3 KW - Tumor Suppressor Protein p53 KW - 0 KW - Index Medicus KW - Gene Expression Regulation, Neoplastic KW - DNA Repair KW - Humans KW - Cell Cycle -- physiology KW - Apoptosis -- physiology KW - Mutation KW - Tumor Suppressor Protein p53 -- physiology KW - Carcinoma, Hepatocellular -- genetics KW - Tumor Suppressor Protein p53 -- genetics KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73062415?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=TP53+and+liver+carcinogenesis.&rft.au=Staib%2C+Frank%3BHussain%2C+S+Perwez%3BHofseth%2C+Lorne+J%3BWang%2C+Xin+W%3BHarris%2C+Curtis+C&rft.aulast=Staib&rft.aufirst=Frank&rft.date=2003-03-01&rft.volume=21&rft.issue=3&rft.spage=201&rft.isbn=&rft.btitle=&rft.title=Human+mutation&rft.issn=1098-1004&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-24 N1 - Date created - 2003-03-05 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 191170; OMIM N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Heterocyclic amines, meat intake, and association with colon cancer in a population-based study. AN - 73056854; 12615608 AB - The authors examined the association between colon cancer and meat intake categorized by level of doneness, cooking method, and estimated levels of heterocyclic amines (HCAs), benzo[a]pyrene, and mutagenicity. Data were collected as part of a population-based, case-control study of colon cancer in North Carolina between 1996 and 2000 that included 701 African-American (274 cases, 427 controls) and 957 White (346 cases, 611 controls) participants. Odds ratios were calculated by using unconditional logistic regression, comparing the fifth to the first quintile levels of intake or exposure. Intake of red meat was positively associated with colon cancer (odds ratio (OR) = 2.0, 95% confidence interval (CI): 1.3, 3.2). Associations with meat intake by cooking method were strongest for pan-fried red meat (OR = 2.0, 95% CI: 1.4, 3.0). Associations with meat intake by doneness were strongest for well-/very well done red meat (OR = 1.7, 95% CI: 1.2, 2.5). The strongest association for individual HCAs was reported for 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) across all levels of exposure, with odds ratios of 1.8-2.0. Overall, sophisticated exposure measures were used to report modest, positive associations between red meat intake and colon cancer consistent with the hypothesis that HCAs may be among the etiologically relevant compounds in red meat. JF - American journal of epidemiology AU - Butler, L M AU - Sinha, R AU - Millikan, R C AU - Martin, C F AU - Newman, B AU - Gammon, M D AU - Ammerman, A S AU - Sandler, R S AD - Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. butler3@niehs.nih.gov Y1 - 2003/03/01/ PY - 2003 DA - 2003 Mar 01 SP - 434 EP - 445 VL - 157 IS - 5 SN - 0002-9262, 0002-9262 KW - Amines KW - 0 KW - Heterocyclic Compounds KW - Index Medicus KW - Humans KW - African Americans -- statistics & numerical data KW - Aged KW - European Continental Ancestry Group -- statistics & numerical data KW - North Carolina -- epidemiology KW - Aged, 80 and over KW - Logistic Models KW - Adult KW - Cooking KW - Surveys and Questionnaires KW - Case-Control Studies KW - Middle Aged KW - Female KW - Male KW - Eating KW - Colonic Neoplasms -- epidemiology KW - Meat -- adverse effects KW - Colonic Neoplasms -- etiology KW - Heterocyclic Compounds -- adverse effects KW - Amines -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73056854?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Heterocyclic+amines%2C+meat+intake%2C+and+association+with+colon+cancer+in+a+population-based+study.&rft.au=Butler%2C+L+M%3BSinha%2C+R%3BMillikan%2C+R+C%3BMartin%2C+C+F%3BNewman%2C+B%3BGammon%2C+M+D%3BAmmerman%2C+A+S%3BSandler%2C+R+S&rft.aulast=Butler&rft.aufirst=L&rft.date=2003-03-01&rft.volume=157&rft.issue=5&rft.spage=434&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 - 2003-03-27 N1 - Date created - 2003-03-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nitrate in public water supplies and risk of bladder cancer. AN - 73054173; 12606884 AB - Nitrate is a precursor compound in the formation of N-nitroso compounds, most of which are potent animal carcinogens. N-nitroso compounds and their precursors have not been extensively evaluated as bladder cancer risk factors. We conducted a population-based case-control study of bladder cancer in Iowa. Cases were men and women newly diagnosed with bladder cancer in 1986-1989. Nitrate data for Iowa public water supplies were sparse before the 1960s. To reduce misclassification by unknown nitrate levels, we included only those who used public supplies with nitrate data for 70% or more of their person-years since 1960 (808 cases, 1259 controls). Among controls, the median average nitrate level for their Iowa residences with public water supplies was 1.3 mg/liter nitrate-nitrogen (interquartile range = 0.6-3.0). After adjustment for confounders, we found no increased risk of bladder cancer with increasing average nitrate levels in drinking water; the highest quartile odds ratio for women was 0.8 (95% confidence interval = 0.4-0.8), and for men 0.5 (0.4-0.8). We observed no association among those with high water nitrate exposure (>median) and low (3-fold higher as compared with mGSTA2-2. The crystal structure of mGSTA1-1 in complex with the GSH conjugate of (+)-anti-7,8-dihydroxy-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (GSBpd) reveals that R216 and I221 in the last helix play important roles in catalysis [Gu, Y., Singh, S. V., and Ji, X. (2000) Biochemistry 39, 12552-12557]. The crystal structure of mGSTA2-2 in complex with GSBpd has been determined, which reveals a different binding mode of GSBpd. Comparison of the two structures suggests that residues 207 and 221 are responsible for the different binding mode of GSBpd and therefore contribute to the distinct catalytic efficiency of the two isozymes. JF - Biochemistry AU - Gu, Yijun AU - Xiao, Bing AU - Wargo, Heather L AU - Bucher, Matthew H AU - Singh, Shivendra V AU - Ji, Xinhua AD - Macromolecular Crystallographic Laboratory, National Cancer Institute, Frederick, Maryland 21702, USA. Y1 - 2003/02/04/ PY - 2003 DA - 2003 Feb 04 SP - 917 EP - 921 VL - 42 IS - 4 SN - 0006-2960, 0006-2960 KW - Amino Acids KW - 0 KW - Benzopyrenes KW - DNA Adducts KW - Isoenzymes KW - Protein Subunits KW - anti-benzo(a)pyrene-dA adduct KW - glutathione-BPDE conjugate KW - Isoleucine KW - 04Y7590D77 KW - Phenylalanine KW - 47E5O17Y3R KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide KW - 55097-80-8 KW - Arginine KW - 94ZLA3W45F KW - Methionine KW - AE28F7PNPL KW - Glutathione Transferase KW - EC 2.5.1.18 KW - glutathione S-transferase alpha KW - Glutathione KW - GAN16C9B8O KW - Leucine KW - GMW67QNF9C KW - Alanine KW - OF5P57N2ZX KW - Index Medicus KW - Animals KW - Arginine -- chemistry KW - Glutathione -- metabolism KW - Alanine -- chemistry KW - Leucine -- chemistry KW - Mice KW - Binding Sites KW - Static Electricity KW - Phenylalanine -- chemistry KW - Glutathione -- chemistry KW - Crystallography, X-Ray KW - Substrate Specificity KW - Methionine -- chemistry KW - Catalysis KW - Isoleucine -- chemistry KW - Isoenzymes -- chemistry KW - Benzopyrenes -- chemistry KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- metabolism KW - DNA Adducts -- chemistry KW - Amino Acids -- chemistry KW - Glutathione Transferase -- metabolism KW - Glutathione Transferase -- chemistry KW - Benzopyrenes -- metabolism KW - Protein Subunits -- metabolism KW - Protein Subunits -- chemistry KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- chemistry KW - Isoenzymes -- metabolism KW - DNA Adducts -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72987999?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Residues+207%2C+216%2C+and+221+and+the+catalytic+activity+of+mGSTA1-1+and+mGSTA2-2+toward+benzo%5Ba%5Dpyrene-%287R%2C8S%29-diol-%289S%2C10R%29-epoxide.&rft.au=Gu%2C+Yijun%3BXiao%2C+Bing%3BWargo%2C+Heather+L%3BBucher%2C+Matthew+H%3BSingh%2C+Shivendra+V%3BJi%2C+Xinhua&rft.aulast=Gu&rft.aufirst=Yijun&rft.date=2003-02-04&rft.volume=42&rft.issue=4&rft.spage=917&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-27 N1 - Date created - 2003-01-28 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 1ML6; PDB N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ru2 and Ru encode mouse orthologs of the genes mutated in human Hermansky-Pudlak syndrome types 5 and 6 AN - 877592298; 13746554 AB - Hermansky-Pudlak syndrome (HPS) is a genetically heterogeneous disease involving abnormalities of melanosomes, platelet dense granules and lysosomes. Here we have used positional candidate and transgenic rescue approaches to identify the genes mutated in ruby-eye 2 and ruby-eye mice (ru2 and ru, respectively), two 'mimic' mouse models of HPS. We also show that these genes are orthologs of the genes mutated in individuals with HPS types 5 and 6, respectively, and that their protein products directly interact. Both genes are previously unknown and are found only in higher eukaryotes, and together represent a new class of genes that have evolved in higher organisms to govern the synthesis of highly specialized lysosome-related organelles. JF - Nature Genetics AU - Zhang, Qing AU - Zhao, Baohui AU - Li, Wei AU - Oiso, Naoki AU - Novak, Edward K AU - Rusiniak, Michael E AU - Gautam, Rashi AU - Chintala, Sreenivasulu AU - O'Brien, Edward P AU - Zhang, Yuke AU - Roe, Bruce A AU - Elliott, Rosemary W AU - Eicher, Eva M AU - Liang, Ping AU - Kratz, Christian AU - Legius, Eric AU - Spritz, Richard A AU - O'Sullivan, TNorene AU - Copeland, Neal G AU - Jenkins, Nancy A AU - Swank, Richard T AD - Mouse Cancer Genetics Program, National Cancer Institute, Frederick, Maryland, USA. Y1 - 2003/02// PY - 2003 DA - February 2003 SP - 145 EP - 153 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 33 IS - 2 SN - 1061-4036, 1061-4036 KW - Genetics Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Toxicology Abstracts KW - Granules KW - Animal models KW - Hermansky-Pudlak syndrome KW - Platelets KW - Melanosomes KW - Organelles KW - Lysosomes KW - N 14845:Miscellaneous KW - X 24300:Methods KW - G 07780:Fungi UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/877592298?accountid=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=Nature+Genetics&rft.atitle=Ru2+and+Ru+encode+mouse+orthologs+of+the+genes+mutated+in+human+Hermansky-Pudlak+syndrome+types+5+and+6&rft.au=Zhang%2C+Qing%3BZhao%2C+Baohui%3BLi%2C+Wei%3BOiso%2C+Naoki%3BNovak%2C+Edward+K%3BRusiniak%2C+Michael+E%3BGautam%2C+Rashi%3BChintala%2C+Sreenivasulu%3BO%27Brien%2C+Edward+P%3BZhang%2C+Yuke%3BRoe%2C+Bruce+A%3BElliott%2C+Rosemary+W%3BEicher%2C+Eva+M%3BLiang%2C+Ping%3BKratz%2C+Christian%3BLegius%2C+Eric%3BSpritz%2C+Richard+A%3BO%27Sullivan%2C+TNorene%3BCopeland%2C+Neal+G%3BJenkins%2C+Nancy+A%3BSwank%2C+Richard+T&rft.aulast=Zhang&rft.aufirst=Qing&rft.date=2003-02-01&rft.volume=33&rft.issue=2&rft.spage=145&rft.isbn=&rft.btitle=&rft.title=Nature+Genetics&rft.issn=10614036&rft_id=info:doi/10.1038%2Fng1087 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-10-01 N1 - Last updated - 2016-02-04 N1 - SubjectsTermNotLitGenreText - Granules; Platelets; Hermansky-Pudlak syndrome; Animal models; Melanosomes; Organelles; Lysosomes DO - http://dx.doi.org/10.1038/ng1087 ER - TY - JOUR T1 - Category-specific representations of social and nonsocial knowledge in the human prefrontal cortex. AN - 85269456; pmid-12676061 AB - Complex social behavior and the relatively large size of the prefrontal cortex are arguably two of the characteristics that distinguish humans from other animals. Grafman presented a framework concerning how the prefrontal cortex (PFC) controls complex behavior using stored structured event complexes (SECs). We report behavioral and imaging data from a modified go/no-go paradigm in which subjects had to classify words (semantic) and phrases (SEC) according to category. In experimental trials, subjects classified items according to social or nonsocial activity; in control trials, they classified items according to font. Subjects were faster to classify social than nonsocial semantic items, with the reverse pattern evident for the social and nonsocial SEC items. In addition, the conditions were associated with different patterns of PFC activation. These results suggest that there are different psychological and neural substrates for social and nonsocial semantic and SEC representations. JF - Journal of Cognitive Neuroscience AU - Wood, J N AU - Romero, S G AU - Makale, M AU - Grafman, J AD - National Institutes of Health, Bethesda, MD 20892-1440, USA. PY - 2003 SP - 236 EP - 248 VL - 15 IS - 2 SN - 0898-929X, 0898-929X KW - Magnetic Resonance Imaging KW - Statistics KW - Human KW - Social Behavior KW - Activities of Daily Living KW - Mental Recall KW - Prefrontal Cortex KW - Decision Making KW - Comparative Study KW - Classification KW - Terminology KW - Mental Processes KW - Adult KW - Psychomotor Performance KW - Male KW - Female KW - Reaction Time KW - Brain Mapping KW - Interpersonal Relations UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85269456?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Cognitive+Neuroscience&rft.atitle=Category-specific+representations+of+social+and+nonsocial+knowledge+in+the+human+prefrontal+cortex.&rft.au=Wood%2C+J+N%3BRomero%2C+S+G%3BMakale%2C+M%3BGrafman%2C+J&rft.aulast=Wood&rft.aufirst=J&rft.date=2003-02-01&rft.volume=15&rft.issue=2&rft.spage=236&rft.isbn=&rft.btitle=&rft.title=Journal+of+Cognitive+Neuroscience&rft.issn=0898929X&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Reliability and validity of a Japanese version of the Eating Disorder Inventory. AN - 85265456; pmid-12674271 AB - The rapid increase of patients with eating disorders in Japan has male necessary the reliable and valid measurement of psychological factors in eating disorders. The purpose of this study was to examine the reliability and validity of the Japanese version of the Eating Disorder Inventory. 766 females without eating disorders and 139 female patients with eating disorders responded to the Eating Attitude Test and the Eating Disorder Inventory. Principal factor extraction with promax rotation isolated 9 interpretable factors with satisfactory internal consistency (Cronbach alpha range=.74-.90). Compared with controls, patients scored significantly higher on all factors after minimizing the influence of Body Mass Index. There were strong correlations among factor scores and scores on the Eating Attitudes Test, particularly among patients. These results indicate the Eating Disorder Inventory as showing psychometrically sound internal consistency and concurrent validity. JF - Psychological Reports AU - Shimura Midori AU - Horie Harumi AU - Kumano Hiroaki AU - Sakano Yuji AU - Suematsu Hiroyuki AD - National Institute of Mental Health, National Center of Neurology and Psychiatry, Ichikawa, Chiba, Japan. PY - 2003 SP - 131 EP - 140 VL - 92 IS - 1 SN - 0033-2941, 0033-2941 KW - Reproducibility of Results KW - Psychotherapy KW - Human KW - Adult KW - Child KW - Body Mass Index KW - Adolescent KW - Psychometrics KW - Diagnostic and Statistical Manual of Mental Disorders KW - Eating Disorders KW - Questionnaires KW - Language UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85265456?accountid=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=Psychological+Reports&rft.atitle=Reliability+and+validity+of+a+Japanese+version+of+the+Eating+Disorder+Inventory.&rft.au=Shimura+Midori%3BHorie+Harumi%3BKumano+Hiroaki%3BSakano+Yuji%3BSuematsu+Hiroyuki&rft.aulast=Shimura+Midori&rft.aufirst=&rft.date=2003-02-01&rft.volume=92&rft.issue=1&rft.spage=131&rft.isbn=&rft.btitle=&rft.title=Psychological+Reports&rft.issn=00332941&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Limiting frequency of the cochlear amplifier based on electromotility of outer hair cells. AN - 85249411; pmid-12547758 AB - Outer hair cells are the critical element for the sensitivity and sharpness of frequency selectivity of the ear. It is believed that fast motility (electromotility) of these cells is essential for this function. Indeed, force produced by outer hair cells follows their membrane potential very closely at least up to 60 kHz. However, it has been pointed out that the cell's receptor potential is attenuated by a low-pass RC circuit inherent to these cells, with the RC roll-off frequencies significantly lower than their operating frequencies. This would render electromotility ineffective in producing force. To address this issue, we assume that multiple degrees of freedom and vibrational modes due to the complex structure of the organ of Corti provide optimal phases for outer hair cells' force to cancel viscous drag. Our derived frequency limit depends on the drag-capacitance product, not directly on the RC time constant. With a reasonable assumption for the viscous drag, the estimated limit is 10-13 kHz, exceeding the RC corner frequency. Our analysis shows that a fast-activating potassium current can substantially extend the frequency limit by counteracting the capacitive current. JF - Biophysical Journal AU - Ospeck, Mark AU - Xiao-Xia, Dong AU - Iwasa, Kuni H AD - Biophysics Section, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892-8027.; National Institute on Deafness and Other Communication Disorders PY - 2003 SP - 739 EP - 749 VL - 84 IS - 2 SN - 0006-3495, 0006-3495 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85249411?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biophysical+Journal&rft.atitle=Limiting+frequency+of+the+cochlear+amplifier+based+on+electromotility+of+outer+hair+cells.&rft.au=Ospeck%2C+Mark%3BXiao-Xia%2C+Dong%3BIwasa%2C+Kuni+H&rft.aulast=Ospeck&rft.aufirst=Mark&rft.date=2003-02-01&rft.volume=84&rft.issue=2&rft.spage=739&rft.isbn=&rft.btitle=&rft.title=Biophysical+Journal&rft.issn=00063495&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Functional properties of brain areas associated with motor execution and imagery. AN - 85231504; pmid-12574475 AB - Imagining motor acts is a cognitive task that engages parts of the executive motor system. While motor imagery has been intensively studied using neuroimaging techniques, most studies lack behavioral observations. Here, we used functional MRI to compare the functional neuroanatomy of motor execution and imagery using a task that objectively assesses imagery performance. With surface electromyographic monitoring within a scanner, 10 healthy subjects performed sequential finger-tapping movements according to visually presented number stimuli in either a movement or an imagery mode of performance. We also examined effects of varied and fixed stimulus types that differ in stimulus dependency of the task. Statistical parametric mapping revealed movement-predominant activity, imagery-predominant activity, and activity common to both movement and imagery modes of performance (movement-and-imagery activity). The movement-predominant activity included the primary sensory and motor areas, parietal operculum, and anterior cerebellum that had little imagery-related activity (-0.1 ~ 0.1%), and the caudal premotor areas and area 5 that had mild-to-moderate imagery-related activity (0.2 ~ 0.7%). Many frontoparietal areas and posterior cerebellum demonstrated movement-and-imagery activity. Imagery-predominant areas included the precentral sulcus at the level of middle frontal gyrus and the posterior superior parietal cortex/precuneus. Moreover, activity of the superior precentral sulcus and intraparietal sulcus areas, predominantly on the left, was associated with accuracy of the imagery task performance. Activity of the inferior precentral sulcus (area 6/44) showed stimulus-type effect particularly for the imagery mode. A time-course analysis of activity suggested a functional gradient, which was characterized by a more "executive" or more "imaginative" property in many areas related to movement and/or imagery. The results from the present study provide new insights into the functional neuroanatomy of motor imagery, including the effects of imagery performance and stimulus-dependency on brain activity. JF - Journal of Neurophysiology AU - Hanakawa Takashi AU - Immisch Ilka AU - Toma Keiichiro AU - Dimyan, Michael A AU - Van Gelderen Peter AU - Hallett, Mark AD - Human Motor Control Section, Medical Neurology Branch, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 2003 SP - 989 EP - 1002 VL - 89 IS - 2 SN - 0022-3077, 0022-3077 KW - Support, U.S. Gov't, P.H.S. KW - Human KW - Cerebellum KW - Motor Skills KW - Movement KW - Parietal Lobe KW - Motor Cortex KW - Fingers KW - Brain Mapping KW - Imagination KW - Adult KW - Support, Non-U.S. Gov't KW - Male KW - Female KW - Magnetic Resonance Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85231504?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Neurophysiology&rft.atitle=Functional+properties+of+brain+areas+associated+with+motor+execution+and+imagery.&rft.au=Hanakawa+Takashi%3BImmisch+Ilka%3BToma+Keiichiro%3BDimyan%2C+Michael+A%3BVan+Gelderen+Peter%3BHallett%2C+Mark&rft.aulast=Hanakawa+Takashi&rft.aufirst=&rft.date=2003-02-01&rft.volume=89&rft.issue=2&rft.spage=989&rft.isbn=&rft.btitle=&rft.title=Journal+of+Neurophysiology&rft.issn=00223077&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Total cerebral volume is reduced in patients with localization-related epilepsy and a history of complex febrile seizures. AN - 85222420; pmid-12580711 AB - CONTEXT: Febrile seizures may lead to later epilepsy. They have been associated with hippocampal atrophy but their effect on total cerebral volume is unknown. OBJECTIVE: To compare total cerebral volume in patients with mesial temporal lobe epilepsy with and without a history of complex febrile seizures (CFS). DESIGN: Survey. SETTING: Epilepsy monitoring center. SUBJECTS: Forty patients with localization-related epilepsy and temporal lobe onset determined by video electroencephalogram and 20 controls. INTERVENTION: Magnetic resonance imaging measurement of cerebral volume. MAIN OUTCOME MEASURE: Total cerebral volume. RESULTS: Patients with a history of CFS had significantly reduced total cerebral volume compared with patients without CFS. In addition, male patients with CFS had significantly lower total cerebral volume than male normal controls. There was no significant difference between patients without CFS, or all patients, and controls. CONCLUSION: Complex febrile seizures may have a global effect on brain development. JF - Archives of Neurology AU - Theodore, William H AU - DeCarli, Charles AU - Gaillard, William D AD - Clinical Epilepsy Section, National Institutes of Health, Bldg 10, Room 5N-250, Bethesda, MD 20892, USA. PY - 2003 SP - 250 EP - 252 VL - 60 IS - 2 SN - 0003-9942, 0003-9942 KW - Magnetic Resonance Imaging KW - Support, U.S. Gov't, P.H.S. KW - Human KW - Risk Factors KW - Adult KW - Brain KW - Seizures, Febrile KW - Middle Age KW - Epilepsy, Temporal Lobe KW - Female KW - Male UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85222420?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+Neurology&rft.atitle=Total+cerebral+volume+is+reduced+in+patients+with+localization-related+epilepsy+and+a+history+of+complex+febrile+seizures.&rft.au=Theodore%2C+William+H%3BDeCarli%2C+Charles%3BGaillard%2C+William+D&rft.aulast=Theodore&rft.aufirst=William&rft.date=2003-02-01&rft.volume=60&rft.issue=2&rft.spage=250&rft.isbn=&rft.btitle=&rft.title=Archives+of+Neurology&rft.issn=00039942&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - HIV-associated nephropathy in African Americans. AN - 73479201; 12864874 AB - Human immunodeficiency virus-1 (HIV-1) infection is associated with several glomerular syndromes, the most prevalent of which is HIV-associated focal segmental glomerulosclerosis (FSGS). At present, HIV-associated FSGS may account for up to 30% of patients in the United States entering end-stage renal disease (ESRD) as a consequence of FSGS. The mechanisms responsible for HIV-associated FSGS are not well defined, but evidence has been presented in favor of direct infection of renal parenchymal cells and toxicity of HIV-1 accessory proteins. HIV-associated FSGS has a striking predilection for patients of African descent. This likely has a genetic basis, although the gene or genes responsible have not yet been identified. One approach is to examine candidate genes for polymorphisms that are associated with disease. Another approach uses a genome-wide scan, relying upon linkage disequilibrium between DNA markers and the disease gene, to identify the causal gene or genes. African Americans are an admixed population, with genetic contributions from African, European, and Native American populations. In admixed populations, linkage disequilibrium between disease genes and marker genes can be exploited to identify disease genes, using an approach termed mapping by admixture linkage disequilibrium (MALD). JF - Kidney international. Supplement AU - Kopp, Jeffrey B AU - Winkler, Cheryl AD - Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA. jbkopp@nih.gov Y1 - 2003/02// PY - 2003 DA - February 2003 SP - S43 EP - S49 IS - 83 SN - 0098-6577, 0098-6577 KW - Index Medicus KW - Humans KW - United States -- epidemiology KW - Prevalence KW - AIDS-Associated Nephropathy -- ethnology KW - AIDS-Associated Nephropathy -- genetics KW - African Americans -- statistics & numerical data KW - Linkage Disequilibrium UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73479201?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Kidney+international.+Supplement&rft.atitle=HIV-associated+nephropathy+in+African+Americans.&rft.au=Kopp%2C+Jeffrey+B%3BWinkler%2C+Cheryl&rft.aulast=Kopp&rft.aufirst=Jeffrey&rft.date=2003-02-01&rft.volume=&rft.issue=83&rft.spage=S43&rft.isbn=&rft.btitle=&rft.title=Kidney+international.+Supplement&rft.issn=00986577&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-26 N1 - Date created - 2003-07-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Appendix: The National Institutes of Health Consensus Development Conference Management of Hepatitis C 2002. AN - 73173846; 12691470 AB - The incidence of newly acquired hepatitis C infection has diminished in the United States. This decline is largely because of a decrease in cases among IDUs for reasons that are unclear and, to a lesser extent, to testing of blood donors for HCV. The virus is transmitted by blood, and such transmission now occurs primarily through injection drug use, sex with an infected partner or multiple partners, and occupational exposure. Most infections become chronic, and therefore the prevalence of HCV infections is high, with about 3 million Americans estimated, to be chronically infected. HCV is a leading cause of cirrhosis, a common cause of HCC and the leading cause of liter transplantation in the United States. The disease spectrum associated with HCV infection varies greatly. Various studies have suggested that 3% to 10% of chronically infected patients will develop cirrhosis over a 20-year period, and these patients are at risk for HCC. Persons who are older at the time of infection, patients with continuous exposure to alcohol, and those coinfected with HIV or HBV demonstrate accelerated progression to more advanced liver disease. Conversely, individuals infected at a younger age have little or no disease progression over several decades. The diagnosis of chronic hepatitis C infection often is suggested by abnormalities in ALT levels and is established by EIA followed by confirmatory determination of HCV RNA. Several sensitive and specific assays are automated partly for the purposes of detecting HCV RNA and quantifying the viral level. Although there is little correlation between viral level and disease manifestations, these assays have proven useful in identifying those patients who are more likely to benefit from treatment and, particularly, in demonstrating successful response to treatment as defined by an SVR. Liver biopsy is useful in defining baseline abnormalities of liver disease and in enabling patients and healthcare providers to reach a decision regarding antiviral therapy. Noninvasive tests do not provide the information that can be obtained through liver biopsy. Information on the genotype of the virus is important to guide treatment decisions. Genotype 1, most commonly found in the United States, is less amenable to treatment than genotypes 2 or 3. Therefore, clinical trials of antiviral therapies require genotyping information for appropriate stratification of subjects. Recent therapeutic trials in defined, selected populations have shown clearly that combinations of interferons and ribavirin are more effective than monotherapy. Moreover, trials using pegylated interferons have yielded improved SVR rates with similar toxicity profiles. Results continue to show, however, that the SVR rate is less common in patients with genotype 1 infections, higher HCV RNA levels, or more advanced stages of fibrosis. Genotype 1 infections require therapy for 48 weeks, whereas shorter treatment is feasible in genotype 2 and 3 infections. In genotype 1, the lack of an early virologic response (< 2 log decrease in HCV RNA) is associated with failure to achieve an SVR. The SVR is lower in patients with advanced liver disease than in patients without cirrhosis. Ongoing trials are exploring the usefulness of combination therapy in various populations. Preliminary experience in IDUs, individuals coinfected with HIV, children, and other special groups suggests similar responses are achievable in these populations. Patients with acute hepatitis C may be treated, but specific recommendations for antiviral treatment must await further evaluation of the rate of spontaneous clearance of the virus and determination of the optimal time to initiate treatment. Preventive measures beyond blood-banking practices include prompt identification of infected individuals, awareness of the potential for perinatal transmission, implementation of safe injection practices, linkage of drug users to drug treatment programs. and implementation of community-based education and support programs to modify risk behavior. Some of these measures have been implemented successfully in the control of HIV infections, and it stands to reason that they would be valuable for reducing HCV transmission. Future advances in the diagnosis and management of hepatitis C require continued vigilance concerning the transmission of this infection, extending treatment to populations not evaluated previously in treatment trials, and the introduction of more effective therapies. JF - Clinics in liver disease AU - Seeff, Leonard B AU - Hoofnagle, Jay H AD - National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Health, 31A Center Drive, Room 9A27, Building 37, Bethesda, MD 20892, USA. seeffL@extra.niddk.nih.gov Y1 - 2003/02// PY - 2003 DA - February 2003 SP - 261 EP - 287 VL - 7 IS - 1 SN - 1089-3261, 1089-3261 KW - Antiviral Agents KW - 0 KW - Index Medicus KW - Substance Abuse, Intravenous -- virology KW - Blood Transfusion -- adverse effects KW - Humans KW - Consensus Development Conferences, NIH as Topic KW - United States -- epidemiology KW - Antiviral Agents -- therapeutic use KW - Hepatitis C -- drug therapy KW - Hepatitis C -- etiology KW - Hepatitis C -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73173846?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Clinics+in+liver+disease&rft.atitle=Appendix%3A+The+National+Institutes+of+Health+Consensus+Development+Conference+Management+of+Hepatitis+C+2002.&rft.au=Seeff%2C+Leonard+B%3BHoofnagle%2C+Jay+H&rft.aulast=Seeff&rft.aufirst=Leonard&rft.date=2003-02-01&rft.volume=7&rft.issue=1&rft.spage=261&rft.isbn=&rft.btitle=&rft.title=Clinics+in+liver+disease&rft.issn=10893261&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-15 N1 - Date created - 2003-04-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Plasma and cerebrospinal fluid pharmacokinetics of intravenous temozolomide in non-human primates. AN - 73169049; 12675312 AB - Temozolomide is a prodrug that undergoes spontaneous chemical degradation at physiologic pH to form the highly reactive alkylating agent, methyl-triazenyl imidazole carboxamide (MTIC). In clinical trials, temozolomide has activity in gliomas and is approved for recurrent anaplastic astrocytoma. We, therefore, studied the penetration of temozolomide into the cerebrospinal fluid (CSF) as a surrogate for blood-brain barrier penetration in a non-human primate model. Three Rhesus monkeys with indwelling Ommaya reservoirs received 7.5 mg/kg (150 mg/m2) of temozolomide as a 1 h intravenous infusion. Frequent blood and CSF samples were obtained over 24 h, plasma was immediately separated by centrifugation at 4 degrees C, and plasma and CSF samples were acidified with HCl. Temozolomide concentration in plasma and CSF was measured by reverse-phase high-pressure liquid chromatography. Plasma temozolomide concentration peaked 0.5 h after the end of the infusion and was 104 +/- 3 microM. The mean peak CSF temozolomide concentration was 26 +/- 4 microM at 2.5 h. The mean areas under the temozolomide concentration-time curves in plasma and CSF were 392 +/- 18 and 126 +/- 18 microM h, respectively, and the CSF: plasma ratio was 0.33 +/- 0.06. Clearance of temozolomide was 0.116 +/- 0.004 l/kg/h, and the volume of distribution at steady state was 0.254 +/- 0.033 l/kg. In this non-human primate model, temozolomide penetrated readily across the blood-brain barrier. These findings are consistent with the activity of temozolomide in brain tumors. JF - Journal of neuro-oncology AU - Patel, Mahendra AU - McCully, Cynthia AU - Godwin, Karen AU - Balis, Frank M AD - Pediatric Oncology Branch, National Cancer Institute, National Institute of Health, Bethesda, MD 20892-1920, USA. Y1 - 2003/02// PY - 2003 DA - February 2003 SP - 203 EP - 207 VL - 61 IS - 3 SN - 0167-594X, 0167-594X KW - Antineoplastic Agents, Alkylating KW - 0 KW - Dacarbazine KW - 7GR28W0FJI KW - temozolomide KW - YF1K15M17Y KW - Index Medicus KW - Animals KW - Infusions, Intravenous KW - Half-Life KW - Area Under Curve KW - Blood-Brain Barrier -- physiology KW - Macaca mulatta KW - Male KW - Dacarbazine -- blood KW - Dacarbazine -- analogs & derivatives KW - Antineoplastic Agents, Alkylating -- cerebrospinal fluid KW - Dacarbazine -- administration & dosage KW - Antineoplastic Agents, Alkylating -- blood KW - Antineoplastic Agents, Alkylating -- administration & dosage KW - Dacarbazine -- cerebrospinal fluid UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73169049?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neuro-oncology&rft.atitle=Plasma+and+cerebrospinal+fluid+pharmacokinetics+of+intravenous+temozolomide+in+non-human+primates.&rft.au=Patel%2C+Mahendra%3BMcCully%2C+Cynthia%3BGodwin%2C+Karen%3BBalis%2C+Frank+M&rft.aulast=Patel&rft.aufirst=Mahendra&rft.date=2003-02-01&rft.volume=61&rft.issue=3&rft.spage=203&rft.isbn=&rft.btitle=&rft.title=Journal+of+neuro-oncology&rft.issn=0167594X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-30 N1 - Date created - 2003-04-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombinant toxins for the treatment of cancer. AN - 73168568; 12669470 AB - Recombinant toxins are proteins made by genetic engineering consisting of a toxin fused to a ligand which binds selectively to a target cell. Recombinant toxins used for cancer treatment generally contain either a growth factor or a recombinant fragment of a monoclonal antibody fused to a truncated bacterial toxin, derived either from Pseudomonas exotoxin or from diphtheria toxin. One recombinant toxin containing human interleukin (IL)-2 and truncated diphtheria toxin (DAB389-IL-2, denileukin diftitox or Ontak; Seragen Inc) is approved for clinical use in advanced stage cutaneous T-cell lymphoma. Recombinant toxins containing truncated Pseudomonas exotoxin and fragments of anti-CD22 and anti-CD25 monoclonal antibodies have induced remissions in chemotherapy-resistant hematological malignancies, particularly hairy cell leukemia, and are currently undergoing experimental testing. The number of approved recombinant toxins for the treatment of cancer is expected to increase in the coming years. JF - Current opinion in molecular therapeutics AU - Kreitman, Robert J AD - Division of Cancer Biology, National Institutes of Health, 9000 Rockville, Bethesda, MD 20892, USA. kreitmar@mail.nih.gov Y1 - 2003/02// PY - 2003 DA - February 2003 SP - 44 EP - 51 VL - 5 IS - 1 SN - 1464-8431, 1464-8431 KW - Antibodies, Monoclonal KW - 0 KW - Diphtheria Toxin KW - Immunotoxins KW - Interleukin-2 KW - Recombinant Proteins KW - Index Medicus KW - Animals KW - Diphtheria Toxin -- chemistry KW - Interleukin-2 -- therapeutic use KW - Humans KW - Clinical Trials as Topic KW - Diphtheria Toxin -- therapeutic use KW - Leukemia, Hairy Cell -- therapy KW - Antibodies, Monoclonal -- therapeutic use KW - Immunotoxins -- immunology KW - Recombinant Proteins -- immunology KW - Immunotoxins -- therapeutic use KW - Recombinant Proteins -- chemistry KW - Neoplasms -- therapy KW - Recombinant Proteins -- therapeutic use KW - Neoplasms -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73168568?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+molecular+therapeutics&rft.atitle=Recombinant+toxins+for+the+treatment+of+cancer.&rft.au=Kreitman%2C+Robert+J&rft.aulast=Kreitman&rft.aufirst=Robert&rft.date=2003-02-01&rft.volume=5&rft.issue=1&rft.spage=44&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+molecular+therapeutics&rft.issn=14648431&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-28 N1 - Date created - 2003-04-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A serine/threonine phosphorylation site in the ectodomain of a T cell receptor beta chain is required for activation by superantigen. AN - 73157569; 12680588 AB - The presence of consensus phosphorylation sites in the ectodomains of cell surface proteins suggests that such post-translational modification may be important in regulation of surface receptor activity. To date, the only cell surface receptor for which such ectodomain phosphorylation has been conclusively demonstrated is the clonally expressed T cell antigen receptor (TCR). Attempts to conclusively identify individual phosphorylated residues in TCR alpha and beta chains and determine their functional significance by biochemical approaches failed due to insufficient quantities of purified molecules. Here we present the results of an alternative approach where survey of phosphorylation sites in the TCR alpha and beta chains was accomplished using site-directed mutagenesis and retroviral vector expression, as well as in vitro phosphorylation of synthetic peptide substrates. All mutants studied directed the cell surface expression of normal amounts of TCR, and all transfectants could be stimulated to produce IL-2 in response to substrate-immobilized antibody to TCR. However, mutation of serine-88 in the protein kinase A phosphorylation site of the TCR beta chain resulted in a complete lack of response to the superantigen staphylococcal enterotoxin B (SEB). In addition, this mutation abolished TCR-associated tyrosine phosphorylation, consistent with the impairment of cell signaling. Reversion of the serine-88/alanine mutation with phosphorylatable threonine completely restored the SEB recognition by TCR. These results, interpreted in the context of the known three-dimensional structure of the complex of SEB and TCR, are consistent with the view that serine-88 is important for the contact of the TCR beta chain with SEB. JF - Journal of receptor and signal transduction research AU - Lukashev, Dmitriy E AU - Caldwell, Charles C AU - Chen, Pearl AU - Apasov, Sergey G AU - Margulies, David H AU - Sitkovsky, Michail V AD - Biochemistry and Immunopharmacology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/02// PY - 2003 DA - February 2003 SP - 33 EP - 52 VL - 23 IS - 1 SN - 1079-9893, 1079-9893 KW - Antigens, CD3 KW - 0 KW - DNA, Complementary KW - Enterotoxins KW - Interleukin-2 KW - Receptors, Antigen, T-Cell, alpha-beta KW - Superantigens KW - Threonine KW - 2ZD004190S KW - enterotoxin B, staphylococcal KW - 39424-53-8 KW - Serine KW - 452VLY9402 KW - Index Medicus KW - Animals KW - Antigens, CD3 -- chemistry KW - DNA, Complementary -- genetics KW - Hybridomas KW - Antigens, CD3 -- metabolism KW - Models, Molecular KW - Protein Processing, Post-Translational KW - Interleukin-2 -- biosynthesis KW - Mice KW - Amino Acid Sequence KW - Serine -- chemistry KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Threonine -- chemistry KW - Phosphorylation KW - In Vitro Techniques KW - Enterotoxins -- pharmacology KW - Binding Sites -- genetics KW - Protein Structure, Tertiary KW - T-Lymphocytes -- immunology KW - Amino Acid Substitution KW - Cell Line KW - Receptors, Antigen, T-Cell, alpha-beta -- metabolism KW - Superantigens -- pharmacology KW - Receptors, Antigen, T-Cell, alpha-beta -- chemistry KW - Receptors, Antigen, T-Cell, alpha-beta -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73157569?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+receptor+and+signal+transduction+research&rft.atitle=A+serine%2Fthreonine+phosphorylation+site+in+the+ectodomain+of+a+T+cell+receptor+beta+chain+is+required+for+activation+by+superantigen.&rft.au=Lukashev%2C+Dmitriy+E%3BCaldwell%2C+Charles+C%3BChen%2C+Pearl%3BApasov%2C+Sergey+G%3BMargulies%2C+David+H%3BSitkovsky%2C+Michail+V&rft.aulast=Lukashev&rft.aufirst=Dmitriy&rft.date=2003-02-01&rft.volume=23&rft.issue=1&rft.spage=33&rft.isbn=&rft.btitle=&rft.title=Journal+of+receptor+and+signal+transduction+research&rft.issn=10799893&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-28 N1 - Date created - 2003-04-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemoprevention of skin cancer. AN - 73121233; 12638382 AB - To discuss the principles, science, and roles of nurses related to skin cancer chemoprevention. Journal articles and federal government reports. The skin is a model organ for investigating cancer prevention processes that may be relevant to other organs as well. Agents that selectively target molecular hallmarks of skin carcinogenesis are under intense clinical and preclinical investigation. Nurses play key roles in coordinating clinical trials, stimulating public awareness, and ensuring access to and acceptance of new agents. Nurses play a role in translational research by bridging the gap between technologic development and patient care. JF - Seminars in oncology nursing AU - Richmond, Ellen AU - Viner, Jaye L AD - Gastrointestinal & Other Cancers Research Group, National Cancer Institute, Division of Cancer Prevention, Suite 2141, 6130 Executive Blvd, Bethesda, MD 20892-7317, USA. Y1 - 2003/02// PY - 2003 DA - February 2003 SP - 62 EP - 69 VL - 19 IS - 1 SN - 0749-2081, 0749-2081 KW - Anticarcinogenic Agents KW - 0 KW - Index Medicus KW - Nursing KW - Cocarcinogenesis KW - Anticarcinogenic Agents -- therapeutic use KW - Risk Factors KW - Humans KW - Precancerous Conditions -- prevention & control KW - Clinical Trials as Topic KW - Nurse's Role KW - Oncology Nursing -- methods KW - Health Education -- methods KW - Skin Neoplasms -- etiology KW - Chemoprevention -- methods KW - Skin Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73121233?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Seminars+in+oncology+nursing&rft.atitle=Chemoprevention+of+skin+cancer.&rft.au=Richmond%2C+Ellen%3BViner%2C+Jaye+L&rft.aulast=Richmond&rft.aufirst=Ellen&rft.date=2003-02-01&rft.volume=19&rft.issue=1&rft.spage=62&rft.isbn=&rft.btitle=&rft.title=Seminars+in+oncology+nursing&rft.issn=07492081&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-04 N1 - Date created - 2003-03-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Anticlastogenic, antigenotoxic and apoptotic activity of epigallocatechin gallate: a green tea polyphenol. AN - 73084453; 12628501 AB - Modulation of events characteristic of carcinogenesis or of cancer cells is being emphasized as a rational strategy to control cancer. Green tea polyphenol epigallocatechin gallate (EGCG) has been shown to be highly active as a cancer chemopreventive agent. Certain cellular and molecular events relevant to carcinogenesis are also modified by EGCG. The present investigation was carried out to examine the effects of EGCG on the cytogenetic change and DNA damage induced by toxicant H(2)O(2) and carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in Chinese hamster V-79 cells in culture. Cytogenetic change as evident by the formation of micronuclei and DNA damage in the form of comet tail length during single cell gel electrophoresis was found to be significantly suppressed by EGCG in a dose dependent manner. Cells preincubated with EGCG were protected from subsequent damage by the genotoxic agents. Apoptosis, a highly organized physiological mechanism to eliminate injured or abnormal cells, is also implicated in multistage carcinogenesis. Initiated cells, cells at promotional stage or fully transformed cells can be eliminated through apoptosis. It was observed that EGCG suppressed growth and proliferation of K-562 cells derived from human chronic myelogenic leukemia. Morphological features of treated cells and characteristic DNA fragmentation revealed that the cytotoxicity was due to induction of apoptosis. This was mediated by activation of caspase 3 and caspase 8. Results show that EGCG not only protects normal cells against genotoxic hazard but also eliminate cancer cells through induction of apoptosis. Copyright 2002 Elsevier Science B.V. JF - Mutation research AU - Roy, Madhumita AU - Chakrabarty, Sutapa AU - Sinha, Dona AU - Bhattacharya, Rathin Kumar AU - Siddiqi, Maqsood AD - Department of Environmental Carcinogenesis and Toxicology, Chittaranjan National Cancer Institute, 37 SP Mukherjee Road, Kolkata 700 026, India. PY - 2003 SP - 33 EP - 41 VL - 523-524 SN - 0027-5107, 0027-5107 KW - Anticarcinogenic Agents KW - 0 KW - Antimutagenic Agents KW - Tea KW - Catechin KW - 8R1V1STN48 KW - Hydrogen Peroxide KW - BBX060AN9V KW - epigallocatechin gallate KW - BQM438CTEL KW - Caspases KW - EC 3.4.22.- KW - Index Medicus KW - Comet Assay KW - Animals KW - Micronucleus Tests KW - Cricetulus KW - Dose-Response Relationship, Drug KW - Humans KW - Hydrogen Peroxide -- pharmacology KW - K562 Cells KW - Cell Line KW - Caspases -- metabolism KW - Cricetinae KW - Antimutagenic Agents -- pharmacology KW - Cell Survival -- drug effects KW - Catechin -- analogs & derivatives KW - Apoptosis -- drug effects KW - Anticarcinogenic Agents -- pharmacology KW - Cell Division -- drug effects KW - Catechin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73084453?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Anticlastogenic%2C+antigenotoxic+and+apoptotic+activity+of+epigallocatechin+gallate%3A+a+green+tea+polyphenol.&rft.au=Roy%2C+Madhumita%3BChakrabarty%2C+Sutapa%3BSinha%2C+Dona%3BBhattacharya%2C+Rathin+Kumar%3BSiddiqi%2C+Maqsood&rft.aulast=Roy&rft.aufirst=Madhumita&rft.date=2003-02-01&rft.volume=523-524&rft.issue=&rft.spage=33&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 - 2003-04-24 N1 - Date created - 2003-03-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Up-regulation of inducible nitric oxide synthase in the substantia nigra by lipopolysaccharide causes microglial activation and neurodegeneration. AN - 73073251; 12609487 AB - The present study was designed to examine whether expression of iNOS was involved in LPS-induced neurodegeneration in rat substantia nigra (SN) and to study the role of NO in the loss of the SN dopaminergic neurons. In Western blot analysis, iNOS was induced in the SN after injection of LPS in a time- and dose-dependent manner. Immunofluorescence and immunohistochemical analyses revealed that the iNOS is located in a fully activated microglia with the characteristic amoeboid morphology. Furthermore, LPS-induced loss of dopaminergic neurons was significantly inhibited by the administration of L-N(G)-nitroarginine, a selective inhibitor of NOS, and the glucocorticoid dexamethasone. These inhibiting agents for iNOS reduced LPS-induced microglial activation, suggesting that NO has a role in inflammatory-mediated microglial activation. These results demonstrate that LPS induces the expression of iNOS in activated microglia in the SN, and that NO and/or its metabolites may play a crucial role in inflammation-mediated degeneration of dopaminergic neurons. JF - Neurobiology of disease AU - Arimoto, Toyoko AU - Bing, Guoying AD - Department of Anatomy and Neurobiology, Medical Center, University of Kentucky, 800 Rose Street, Room MN 225, Lexington, KY 40536-5276, USA. arimoto@niehs.nih.gov Y1 - 2003/02// PY - 2003 DA - February 2003 SP - 35 EP - 45 VL - 12 IS - 1 SN - 0969-9961, 0969-9961 KW - Antigens, CD KW - 0 KW - Antigens, Neoplasm KW - Antigens, Surface KW - Avian Proteins KW - Blood Proteins KW - Bsg protein, Gallus gallus KW - Bsg protein, rat KW - Enzyme Inhibitors KW - Lipopolysaccharides KW - Membrane Glycoproteins KW - Antigens, CD147 KW - 136894-56-9 KW - Nitric Oxide KW - 31C4KY9ESH KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Lipopolysaccharides -- pharmacology KW - Neurons -- drug effects KW - Substantia Nigra -- drug effects KW - Disease Models, Animal KW - Dopamine -- metabolism KW - Substantia Nigra -- enzymology KW - Neurons -- pathology KW - Rats KW - Rats, Sprague-Dawley KW - Substantia Nigra -- pathology KW - Enzyme Inhibitors -- pharmacology KW - Neurons -- enzymology KW - Immunohistochemistry KW - Male KW - Membrane Glycoproteins -- metabolism KW - Gliosis -- physiopathology KW - Encephalitis -- enzymology KW - Encephalitis -- physiopathology KW - Nerve Degeneration -- physiopathology KW - Nerve Degeneration -- chemically induced KW - Parkinson Disease -- physiopathology KW - Nitric Oxide -- biosynthesis KW - Gliosis -- enzymology KW - Up-Regulation -- physiology KW - Up-Regulation -- drug effects KW - Nerve Degeneration -- enzymology KW - Encephalitis -- chemically induced KW - Gliosis -- chemically induced KW - Parkinson Disease -- enzymology KW - Nitric Oxide Synthase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73073251?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=DDT+metabolite+and+androgens+in+African-American+farmers.&rft.au=Martin%2C+Stephen+A%3BHarlow%2C+Siob%C3%A1n+D%3BSowers%2C+Mary+Fran%3BLongnecker%2C+Matthew+P%3BGarabrant%2C+David%3BShore%2C+David+L%3BSandler%2C+Dale+P&rft.aulast=Martin&rft.aufirst=Stephen&rft.date=2002-07-01&rft.volume=13&rft.issue=4&rft.spage=454&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 - 2003-05-09 N1 - Date created - 2003-02-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phosphatidylinositol 3-kinase and mek1/2 are necessary for insulin-like growth factor-I-induced vascular endothelial growth factor synthesis in prostate epithelial cells: a role for hypoxia-inducible factor-1? AN - 73061202; 12612059 AB - Due to the importance of vascular endothelial growth factor (VEGF) in the neovascularization of solid tumors, a clear understanding of how VEGF is regulated in normal and tumor cells is warranted. We investigated insulin-like growth factor (IGF)-I-stimulated signaling pathways that increase the rate of VEGF synthesis in primary cultures of normal prostate epithelial cells (PrEC). IGF-I increased the secretion of VEGF(165) into PrEC growth medium and stimulated transcription of a reporter gene driven by a 1.5-kb region of the VEGF promoter. Inhibition of either phosphatidylinositol 3-kinase (PI3-K) or Mek1/2 signaling pathways completely abrogated the IGF-I-induced increase in VEGF secretion and promoter activity, indicating a dependence on coordinate signaling from both pathways to produce this effect. Levels of the transcription factors hypoxia-inducible factor (HIF)-1 and Fos were elevated in response to IGF-I in a PI3-K-dependent and Mek1/2-dependent manner, respectively. The expression of an activator protein (AP)-1 dominant negative in an immortalized prostate epithelial cell line PZ-HPV-7 suppressed the IGF-I-induced increase in VEGF promoter activity. Mutation of the hypoxia response element (HRE), which mediates hypoxic stimulation of VEGF transcription, did not inhibit the effect of IGF-I on the VEGF promoter, despite the fact that this mutation inhibited PI3-K-stimulated VEGF promoter activity in prostate cancer cells. These data indicate that PI3-K signaling does not increase VEGF transcription through transactivation by HIF-1 at the HRE in normal PrEC. This work also suggests that an additional signal, not stimulated by IGF-I in PrEC, is needed for HIF-1 to stimulate transcription from the VEGF HRE. JF - Molecular cancer research : MCR AU - Burroughs, Kevin D AU - Oh, Jennifer AU - Barrett, J Carl AU - DiAugustine, Richard P AD - Hormones and Cancer Group, Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 2003/02// PY - 2003 DA - February 2003 SP - 312 EP - 322 VL - 1 IS - 4 SN - 1541-7786, 1541-7786 KW - DNA-Binding Proteins KW - 0 KW - HIF1A protein, human KW - Hypoxia-Inducible Factor 1 KW - Hypoxia-Inducible Factor 1, alpha Subunit KW - Intercellular Signaling Peptides and Proteins KW - Nuclear Proteins KW - Transcription Factors KW - Vascular Endothelial Growth Factor A KW - myotrophin KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Index Medicus KW - MAP Kinase Signaling System -- drug effects KW - Transcription, Genetic -- drug effects KW - Humans KW - Gene Expression Regulation -- drug effects KW - Time Factors KW - Prostate -- cytology KW - Male KW - Cell Line KW - Epithelial Cells -- metabolism KW - Vascular Endothelial Growth Factor A -- biosynthesis KW - Epithelial Cells -- enzymology KW - Epithelial Cells -- drug effects KW - Phosphatidylinositol 3-Kinases -- metabolism KW - Nuclear Proteins -- metabolism KW - Intercellular Signaling Peptides and Proteins -- pharmacology KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73061202?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cancer+research+%3A+MCR&rft.atitle=Phosphatidylinositol+3-kinase+and+mek1%2F2+are+necessary+for+insulin-like+growth+factor-I-induced+vascular+endothelial+growth+factor+synthesis+in+prostate+epithelial+cells%3A+a+role+for+hypoxia-inducible+factor-1%3F&rft.au=Burroughs%2C+Kevin+D%3BOh%2C+Jennifer%3BBarrett%2C+J+Carl%3BDiAugustine%2C+Richard+P&rft.aulast=Burroughs&rft.aufirst=Kevin&rft.date=2003-02-01&rft.volume=1&rft.issue=4&rft.spage=312&rft.isbn=&rft.btitle=&rft.title=Molecular+cancer+research+%3A+MCR&rft.issn=15417786&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-17 N1 - Date created - 2003-03-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Services integration and cost-effectiveness. AN - 73048950; 12605076 AB - Alcohol treatment services are increasingly combined with other health and social services to address the needs of multiple-problem clients. Hence, it has been of growing policy interest to find the most effective and the most cost-effective ways of linking these services. This symposium presents some recent studies in this area. The small but growing body of studies in this area has great potential to inform public policy debates. JF - Alcoholism, clinical and experimental research AU - Hilton, Michael E AU - Fleming, Michael AU - Glick, Henry AU - Gutman, Marjorie A AU - Lu, Yun AU - McKay, James AU - McLellan, A Thomas AU - Manning, Willard AU - Meadows, Julie AU - Mertens, Jennifer R AU - Moore, Charles AU - Mullahy, John AU - Mundt, Marlon AU - Parthasarathy, Sujaya AU - Polsky, Daniel AU - Ray, G Thomas AU - Sterling, Stacy AU - Weisner, Constance AD - Division of Clinical and Prevention Research, NIAAA, Bethesda, Maryland 20892-7003, USA. mhilton@niaaa.nih.gov Y1 - 2003/02// PY - 2003 DA - February 2003 SP - 271 EP - 280 VL - 27 IS - 2 SN - 0145-6008, 0145-6008 KW - Index Medicus KW - United States KW - Case Management -- economics KW - Social Work -- economics KW - Humans KW - Cost-Benefit Analysis KW - Managed Care Programs -- economics KW - Health Services Research KW - Treatment Outcome KW - Behavior Therapy -- economics KW - Comorbidity KW - Alcoholism -- rehabilitation KW - Alcoholism -- epidemiology KW - Delivery of Health Care, Integrated -- economics KW - Alcoholism -- economics KW - Patient Care Team -- economics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73048950?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Services+integration+and+cost-effectiveness.&rft.au=Preston%2C+Kenzie+L%3BUmbricht%2C+Annie%3BEpstein%2C+David+H&rft.aulast=Preston&rft.aufirst=Kenzie&rft.date=2002-07-01&rft.volume=67&rft.issue=2&rft.spage=125&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 - 2003-12-02 N1 - Date created - 2003-02-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Genetics of alcoholism using intermediate phenotypes. AN - 73044401; 12605066 AB - This article represents the proceedings of a symposium at the 2002 meeting of the Research Society on Alcoholism in San Francisco, CA. It was organized by Mary-Anne Enoch and David Goldman and chaired by David Goldman. The presentations were (1) Two functional polymorphisms and their intermediate phenotypes in complex behaviors: COMT/executive cognition and anxiety and HTT/anxiety, by David Goldman; (2) Role of the EEG in determining genetic risk for alcoholism and anxiety disorders, by Mary-Anne Enoch; (3) The response to alcohol as an intermediate phenotype for alcoholism, by Marc A. Schuckit; and (4) Pharmacogenomic approaches to alcoholism treatment: toward a hypothesis, by Bankole A. Johnson. JF - Alcoholism, clinical and experimental research AU - Enoch, Mary-Anne AU - Schuckit, Marc A AU - Johnson, Bankole A AU - Goldman, David Y1 - 2003/02// PY - 2003 DA - February 2003 SP - 169 EP - 176 VL - 27 IS - 2 KW - Carrier Proteins KW - 0 KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - SLC6A4 protein, human KW - Serotonin Plasma Membrane Transport Proteins KW - Slc6a4 protein, mouse KW - Catechol O-Methyltransferase KW - EC 2.1.1.6 KW - Index Medicus KW - Anxiety Disorders -- genetics KW - Animals KW - Catechol O-Methyltransferase -- genetics KW - Polymorphism, Genetic -- genetics KW - Carrier Proteins -- genetics KW - Humans KW - Mice KW - Anxiety Disorders -- physiopathology KW - Chromosome Mapping KW - Mice, Knockout KW - Gene Expression Regulation -- physiology KW - Promoter Regions, Genetic -- genetics KW - Alcohol Drinking -- genetics KW - Membrane Glycoproteins -- genetics KW - Phenotype KW - Alcoholism -- physiopathology KW - Alcoholism -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73044401?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=Genetics+of+alcoholism+using+intermediate+phenotypes.&rft.au=Enoch%2C+Mary-Anne%3BSchuckit%2C+Marc+A%3BJohnson%2C+Bankole+A%3BGoldman%2C+David&rft.aulast=Enoch&rft.aufirst=Mary-Anne&rft.date=2003-02-01&rft.volume=27&rft.issue=2&rft.spage=169&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 - 2003-12-02 N1 - Date created - 2003-02-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Breast-feeding and the prevalence of asthma and wheeze in children: analyses from the Third National Health and Nutrition Examination Survey, 1988-1994. AN - 73040593; 12589353 AB - Asthma prevalence has increased dramatically in recent years, especially among children. Breast-feeding might protect children against asthma and related conditions (recurrent wheeze), and this protective effect might depend on the duration and exclusivity of the breast-feeding regimen. We sought to determine whether there is an association between breast-feeding and asthma, recurrent wheeze, or both in children up to 72 months of age and whether the duration and exclusivity of breast-feeding affect this association. Data were from the third National Health and Nutrition Examination Survey, a nationally representative cross-sectional survey conducted from 1988 to 1994. We tested for significant associations between breast-feeding and physician-diagnosed asthma and recurrent wheeze (> or =3 episodes in the past 12 months) before and after adjusting for potential confounders. Crude analyses showed that breast-feeding was associated with significantly reduced risks for asthma and recurrent wheeze in children 2 to 71 months of age, but after adjusting for potential confounders, these overall protective associations attenuated and were no longer statistically significant. However, 2 new and important associations were revealed after adjusting for confounders: (1) compared with never breast-fed children, ever breast-fed children had significantly reduced odds of being diagnosed with asthma and of having recurrent wheeze before 24 months of age, and (2) among children 2 to 71 months of age who had been exposed to environmental tobacco smoke, those who had ever been breast-fed had significantly reduced risks of asthma and wheeze compared with those who had never been breast-fed. Breast-feeding might delay the onset of or actively protect children less than 24 months of age against asthma and recurrent wheeze. Breast-feeding might reduce the prevalence of asthma and recurrent wheeze in children exposed to environmental tobacco smoke. JF - The Journal of allergy and clinical immunology AU - Chulada, Patricia C AU - Arbes, Samuel J AU - Dunson, David AU - Zeldin, Darryl C AD - Office of Clinical Research, National Institute of Environmental Health Sciences/NIH, PO Box 12233, Research Triangle Park, NC 27709, USA. Y1 - 2003/02// PY - 2003 DA - February 2003 SP - 328 EP - 336 VL - 111 IS - 2 SN - 0091-6749, 0091-6749 KW - Tobacco Smoke Pollution KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Infant KW - Humans KW - Tobacco Smoke Pollution -- adverse effects KW - Data Collection KW - United States -- epidemiology KW - Male KW - Female KW - Pregnancy KW - Multivariate Analysis KW - Child, Preschool KW - Asthma -- epidemiology KW - Respiratory Sounds -- etiology KW - Breast Feeding KW - Asthma -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73040593?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+allergy+and+clinical+immunology&rft.atitle=Breast-feeding+and+the+prevalence+of+asthma+and+wheeze+in+children%3A+analyses+from+the+Third+National+Health+and+Nutrition+Examination+Survey%2C+1988-1994.&rft.au=Chulada%2C+Patricia+C%3BArbes%2C+Samuel+J%3BDunson%2C+David%3BZeldin%2C+Darryl+C&rft.aulast=Chulada&rft.aufirst=Patricia&rft.date=2003-02-01&rft.volume=111&rft.issue=2&rft.spage=328&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+allergy+and+clinical+immunology&rft.issn=00916749&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-25 N1 - Date created - 2003-02-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Allergy Clin Immunol. 2004 May;113(5):1002; author reply 1002-3 [15148965] J Allergy Clin Immunol. 2003 Oct;112(4):807-8; author reply 808-9 [14564371] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - House dust mite allergen in US beds: results from the First National Survey of Lead and Allergens in Housing. AN - 73033534; 12589364 AB - Although exposure to house dust mite allergen is a major risk factor for allergic sensitization and asthma, nationwide estimates of dust mite allergen levels in US homes have not been reported. The purpose of this study was to estimate the prevalence of dust mite allergen in beds of US homes and to identify predictors of dust mite allergen concentration. Data were obtained from the first National Survey of Lead and Allergens in Housing, a cross-sectional survey of 831 permanently occupied noninstitutional housing units that permitted resident children. Dust mite allergen concentration (Der f 1 plus Der p 1) was determined from a dust sample collected from a bed. The percentages of homes with concentrations at or greater than detection, 2.0 microg/g bed dust, and 10.0 microg/g bed dust were estimated. Independent predictors of allergen concentration were assessed with multivariable linear regression. The percentages of US homes with dust mite allergen concentrations at or greater than detection, 2.0 microg/g, and 10.0 microg/g were 84.2% (SE, 1.73), 46.2% (SE, 2.0), and 24.2% (SE, 2.1), respectively. Independent predictors of higher levels were older homes, non-West census regions, single-family homes, no resident children, lower household income, heating sources other than forced air, musty or mildew odor, and higher bedroom humidity. Most US homes have detectable levels of dust mite allergen in a bed. Levels previously associated with allergic sensitization and asthma are common in US bedrooms. Predictors can be used to identify conditions under which homes are more likely to have increased dust mite allergen levels. JF - The Journal of allergy and clinical immunology AU - Arbes, Samuel J AU - Cohn, Richard D AU - Yin, Ming AU - Muilenberg, Michael L AU - Burge, Harriet A AU - Friedman, Warren AU - Zeldin, Darryl C AD - Division of Intramural Research, National Institute of Environmental Health Sciences/NIH, 111 Alexander Drive, Research Triangle Park, NC 27709, USA. Y1 - 2003/02// PY - 2003 DA - February 2003 SP - 408 EP - 414 VL - 111 IS - 2 SN - 0091-6749, 0091-6749 KW - Allergens KW - 0 KW - Antigens, Dermatophagoides KW - Arthropod Proteins KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Dermatophagoides farinae antigen f 1 KW - Dermatophagoides pteronyssinus antigen p 1 KW - Abridged Index Medicus KW - Index Medicus KW - United States KW - Animals KW - Asthma -- etiology KW - Housing KW - Risk Factors KW - Humans KW - Data Collection KW - Child KW - Bedding and Linens -- parasitology KW - Antigens, Dermatophagoides -- analysis KW - Bedding and Linens -- adverse effects KW - Allergens -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73033534?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+allergy+and+clinical+immunology&rft.atitle=House+dust+mite+allergen+in+US+beds%3A+results+from+the+First+National+Survey+of+Lead+and+Allergens+in+Housing.&rft.au=Arbes%2C+Samuel+J%3BCohn%2C+Richard+D%3BYin%2C+Ming%3BMuilenberg%2C+Michael+L%3BBurge%2C+Harriet+A%3BFriedman%2C+Warren%3BZeldin%2C+Darryl+C&rft.aulast=Arbes&rft.aufirst=Samuel&rft.date=2003-02-01&rft.volume=111&rft.issue=2&rft.spage=408&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+allergy+and+clinical+immunology&rft.issn=00916749&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-25 N1 - Date created - 2003-02-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of imatinib on haematopoietic recovery following idarubicin exposure. AN - 73026687; 12592326 AB - SCF is a potent pro-proliferative cytokine crucial for haematopoiesis, which binds to c-kit and activates its tyrosine kinase activity. Inactivating mutations of either SCF or c-kit have been described in mice and lead to increased sensitivity to treatment with ionising radiation. Imatinib is a tyrosine kinase inhibitor with high affinity for c-Abl, PDGFR and c-kit. In this study we investigated the effect of concomitant administration of imatinib and idarubicin, an anthracycline with haematosuppressive activity, in nu/nu mice and murine bone marrow cells. Double-treated animals showed significantly increased mortality compared to mice that received imatinib or idarubicin alone only when idarubicin and imatinib were given simultaneously. The combined treatment induced a more severe neutropenia with a slower recovery when compared to mice treated with idarubicin alone. The myeloid metaplasia usually observed in the spleen after idarubicin treatment was absent in mice co-treated with imatinib. Bone marrow from double-treated animals also showed decreased numbers of megakaryocytes and myeloid precursor cells. In vitro culture of murine bone marrow cells in the presence of imatinib inhibited SCF-induced proliferation and recovery from treatment with idarubicin. Our results indicate that the simultaneous administration of imatinib enhances idarubicin-induced haematopoietic toxicity in vivo and in vitro. JF - Leukemia AU - Ruchatz, H AU - Puttini, M AU - Cleris, L AU - Pilotti, S AU - Gambacorti-Passerini, C AU - Formelli, F AD - Department of Experimental Oncology, The National Cancer Institute, Milan, Italy. Y1 - 2003/02// PY - 2003 DA - February 2003 SP - 298 EP - 304 VL - 17 IS - 2 SN - 0887-6924, 0887-6924 KW - Antineoplastic Agents KW - 0 KW - Benzamides KW - Piperazines KW - Pyrimidines KW - Imatinib Mesylate KW - 8A1O1M485B KW - Idarubicin KW - ZRP63D75JW KW - Index Medicus KW - Animals KW - Bone Marrow -- pathology KW - Drug Administration Schedule KW - Spleen -- pathology KW - Mice KW - Mice, Nude KW - Weight Loss KW - Body Weight -- drug effects KW - Spleen -- drug effects KW - Bone Marrow -- drug effects KW - Female KW - Hematopoiesis -- physiology KW - Antineoplastic Agents -- administration & dosage KW - Hematopoietic Stem Cells -- cytology KW - Pyrimidines -- pharmacology KW - Idarubicin -- administration & dosage KW - Piperazines -- pharmacology KW - Pyrimidines -- administration & dosage KW - Piperazines -- administration & dosage KW - Piperazines -- toxicity KW - Hematopoietic Stem Cells -- drug effects KW - Hematopoiesis -- drug effects KW - Pyrimidines -- toxicity KW - Antineoplastic Agents -- toxicity KW - Idarubicin -- toxicity KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73026687?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effect+of+imatinib+on+haematopoietic+recovery+following+idarubicin+exposure.&rft.au=Ruchatz%2C+H%3BPuttini%2C+M%3BCleris%2C+L%3BPilotti%2C+S%3BGambacorti-Passerini%2C+C%3BFormelli%2C+F&rft.aulast=Ruchatz&rft.aufirst=H&rft.date=2003-02-01&rft.volume=17&rft.issue=2&rft.spage=298&rft.isbn=&rft.btitle=&rft.title=Leukemia&rft.issn=08876924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-11 N1 - Date created - 2003-02-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Leukemia. 2004 Apr;18(4):886-7; author reply 887-8 [14961027] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bleomycin-induced chromosome breaks as a risk marker for lung cancer: a case-control study with population and hospital controls. AN - 73023876; 12584177 AB - Environmental exposure to carcinogens and individual susceptibility play significant roles in cancer risk. Suboptimal DNA repair capability, measured by quantifying mutagen-induced chromosome breaks, might explain variable host susceptibility to environmental carcinogens. In an ongoing lung cancer case-control study, we compared individual sensitivity to bleomycin-induced chromosome breaks in 152 non-small cell lung cancer patients with 94 population controls and 85 hospital controls with no history of cancer. Mutagen sensitivity was measured by mean number of chromatid breaks per cell in cultured peripheral blood lymphocytes treated with bleomycin. Non-parametric tests and chi(2) tests were used to determine the statistical significance of the crude case-control comparisons, followed by logistic regression to adjust for important covariates. The mean number of bleomycin-induced breaks per cell was 1.01 for the cases compared with 0.86 for hospital controls (P 65 years old and 0.81 for those 0.84 break/cell (the median level in population controls), 67% of the cases were bleomycin sensitive compared with 49% of the hospital controls [adjusted odds ratio (OR) = 2.69, 95% confidence interval (CI) = 1.44, 5.04], and 51% of the population controls (adjusted OR = 2.18, 95% CI = 1.13, 4.21). Our data indicate that the increased number of bleomycin-induced chromosome breaks was significantly associated with an increased risk of lung cancer in the first 331 subjects. JF - Carcinogenesis AU - Zheng, Yun-Ling AU - Loffredo, Christopher A AU - Yu, Zhipeng AU - Jones, Raymond T AU - Krasna, Mark J AU - Alberg, Anthony J AU - Yung, Rex AU - Perlmutter, Donna AU - Enewold, Lindsey AU - Harris, Curtis C AU - Shields, Peter G AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2003/02// PY - 2003 DA - February 2003 SP - 269 EP - 274 VL - 24 IS - 2 SN - 0143-3334, 0143-3334 KW - Antimetabolites, Antineoplastic KW - 0 KW - Mutagens KW - Bleomycin KW - 11056-06-7 KW - Index Medicus KW - Risk Factors KW - Mutagens -- adverse effects KW - Humans KW - Case-Control Studies KW - Aged KW - Middle Aged KW - Maryland -- epidemiology KW - Male KW - Female KW - Lung Neoplasms -- epidemiology KW - Antimetabolites, Antineoplastic -- adverse effects KW - Carcinoma, Non-Small-Cell Lung -- genetics KW - Chromosome Aberrations KW - Lung Neoplasms -- genetics KW - Carcinoma, Non-Small-Cell Lung -- enzymology KW - Population Surveillance KW - Bleomycin -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73023876?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Bleomycin-induced+chromosome+breaks+as+a+risk+marker+for+lung+cancer%3A+a+case-control+study+with+population+and+hospital+controls.&rft.au=Zheng%2C+Yun-Ling%3BLoffredo%2C+Christopher+A%3BYu%2C+Zhipeng%3BJones%2C+Raymond+T%3BKrasna%2C+Mark+J%3BAlberg%2C+Anthony+J%3BYung%2C+Rex%3BPerlmutter%2C+Donna%3BEnewold%2C+Lindsey%3BHarris%2C+Curtis+C%3BShields%2C+Peter+G&rft.aulast=Zheng&rft.aufirst=Yun-Ling&rft.date=2003-02-01&rft.volume=24&rft.issue=2&rft.spage=269&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-31 N1 - Date created - 2003-02-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Carcinogenesis. 2003 Aug;24(8):1425 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 15. Vasculitis. AN - 73023314; 12592306 AB - Vasculitis is histologically defined by the presence of blood vessel inflammation. It can be observed in a wide variety of settings, either occurring secondarily to another process or as the pathologic foundation of a primary vasculitic disease. The primary systemic vasculitides comprise a broad group of disease entities that are uniquely identified by the nature of their clinical, histopathologic, or therapeutic characteristics. Individual diseases often predominantly affect blood vessels of a particular size, the pattern of which influences their clinical manifestations and has been used in their classification. The vasculitides span a wide range of disease severity, extending from illnesses that rarely produce death to those almost universally fatal before the introduction of effective therapy. Immunosuppressive and cytotoxic agents are used to treat many vasculitic diseases. Although such approaches can be effective, long-term treatment may be complicated by chronic sequelae from organ damage, disease relapses, and medication side effects. Recent investigations have focused on understanding the pathophysiology of these diseases, which may lead to more efficacious and less toxic therapeutic options. JF - The Journal of allergy and clinical immunology AU - Langford, Carol A AD - Immunologic Diseases Section, National Institute of Allergy and Infectious Diseases/NIH, Building 10, Room 11B-13, Bethesda, MD 20892, USA. Y1 - 2003/02// PY - 2003 DA - February 2003 SP - S602 EP - S612 VL - 111 IS - 2 Suppl SN - 0091-6749, 0091-6749 KW - Antibodies, Antineutrophil Cytoplasmic KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Antibodies, Antineutrophil Cytoplasmic -- analysis KW - Vasculitis -- physiopathology KW - Vasculitis -- complications KW - Vasculitis -- diagnosis KW - Vasculitis -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73023314?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+allergy+and+clinical+immunology&rft.atitle=15.+Vasculitis.&rft.au=Langford%2C+Carol+A&rft.aulast=Langford&rft.aufirst=Carol&rft.date=2003-02-01&rft.volume=111&rft.issue=2+Suppl&rft.spage=S602&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+allergy+and+clinical+immunology&rft.issn=00916749&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-18 N1 - Date created - 2003-02-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Time-dependent increases in brain-derived neurotrophic factor protein levels within the mesolimbic dopamine system after withdrawal from cocaine: implications for incubation of cocaine craving. AN - 73022165; 12574402 AB - Using a rat model of drug craving, we found that the responsiveness to cocaine cues progressively increases or incubates over the first 60 d of cocaine withdrawal. Here we studied whether alterations in brain-derived neurotrophic factor (BDNF) protein levels within the mesolimbic dopamine system are associated with this incubation phenomenon. BDNF is involved in synaptic plasticity and was found to enhance responding for cues associated with natural rewards. Rats were trained to press a lever to receive intravenous cocaine or oral sucrose for 6 hr/d for 10 d; each earned reward was paired with a tone-light cue. Resumption of lever-pressing behavior was then assessed on days 1, 30, or 90 of reward withdrawal. First, resistance to extinction was assessed during 6 hr in which lever presses were not reinforced and the cue was absent. Second, cue-induced reinstatement was assessed after extinction during 1 hr in which responding led to cue presentations. Other rats were killed without testing on days 1, 30, and 90 of reward withdrawal, and BDNF and nerve growth factor (NGF) protein levels were measured in the ventral tegmental area (VTA), accumbens, and amygdala. Lever pressing during extinction and cue-induced reinstatement tests of cocaine craving progressively increased after cocaine withdrawal. Time-dependent changes also were observed during the tests for sucrose craving, with maximal responding on day 30. BDNF, but not NGF, levels in the VTA, accumbens, and amygdala progressively increased after cocaine, but not sucrose, withdrawal. Time-dependent increases in BDNF levels may lead to synaptic modifications that underlie enhanced responsiveness to cocaine cues after prolonged withdrawal periods. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Grimm, Jeffrey W AU - Lu, Lin AU - Hayashi, Teruo AU - Hope, Bruce T AU - Su, Tsung-Ping AU - Shaham, Yavin AD - Behavioral Neuroscience Branch, Intramural Research Program/National Institute on Drug Abuse/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland 21224, USA. Y1 - 2003/02/01/ PY - 2003 DA - 2003 Feb 01 SP - 742 EP - 747 VL - 23 IS - 3 KW - Brain-Derived Neurotrophic Factor KW - 0 KW - Sucrose KW - 57-50-1 KW - Nerve Growth Factor KW - 9061-61-4 KW - Cocaine KW - I5Y540LHVR KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Rats, Long-Evans KW - Nucleus Accumbens -- drug effects KW - Nerve Growth Factor -- metabolism KW - Disease Models, Animal KW - Cocaine -- administration & dosage KW - Cocaine -- adverse effects KW - Drug Administration Routes KW - Rats KW - Behavior, Animal -- drug effects KW - Amygdala -- metabolism KW - Time KW - Self Administration KW - Reward KW - Cues KW - Nucleus Accumbens -- metabolism KW - Ventral Tegmental Area -- metabolism KW - Acoustic Stimulation KW - Amygdala -- drug effects KW - Extinction, Psychological -- drug effects KW - Ventral Tegmental Area -- drug effects KW - Sucrose -- administration & dosage KW - Cocaine -- pharmacology KW - Male KW - Brain-Derived Neurotrophic Factor -- metabolism KW - Substance Withdrawal Syndrome -- physiopathology KW - Limbic System -- drug effects KW - Limbic System -- metabolism KW - Cocaine-Related Disorders -- physiopathology KW - Dopamine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73022165?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=A+phase+I+pharmacologic+and+pharmacodynamic+study+of+pyrazoloacridine+given+as+a+weekly+24-hour+continuous+intravenous+infusion+in+adult+cancer+patients.&rft.au=Grem%2C+Jean+L%3BHarold%2C+Nancy%3BKeith%2C+Bruce%3BChen%2C+Alice+P%3BKao%2C+Viven%3BTakimoto%2C+Chris+H%3BHamilton%2C+J+Michael%3BPang%2C+Janet%3BPace%2C+Marie%3BJasser%2C+Gada+B%3BQuinn%2C+Mary+G%3BMonahan%2C+Brian+P&rft.aulast=Grem&rft.aufirst=Jean&rft.date=2002-07-01&rft.volume=8&rft.issue=7&rft.spage=2149&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 - 2003-02-21 N1 - Date created - 2003-02-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Flavopiridol-related proinflammatory syndrome is associated with induction of interleukin-6. AN - 73021435; 12576419 AB - Flavopiridol is a flavonoid with antiproliferative effects mediated, in part, by inhibition of cyclin-dependent kinases. Clinical manifestations in a previous Phase I trial in patients with refractory malignancies treated with a 72-h flavopiridol infusion included a proinflammatory syndrome consisting of fever, fatigue, and "local" tumor pain with concomitant alterations in plasma acute-phase reactant proteins. The aim of this study was to determine whether the proinflammatory syndrome observed in this trial was associated with modulation of plasma cytokines. Patients receiving flavopiridol (n = 76) had serial plasma samples drawn preinfusion and during the infusion for evaluation of interleukin (IL)-6, IL-10, IL-12, granulocyte macrophage colony-stimulating factor, basic-fibroblast growth factor, transforming growth factor-beta, and tumor necrosis factor-alpha levels by standard ELISA assays. The Wilcoxon signed rank test was used to test the significance of the difference between the baseline (time 0) plasma cytokine levels compared with the values of each subsequent data collection time points (8, 24, 48, and 72 h). There was a significant and sustained increase in plasma IL-6 levels at all time points when compared with baseline values. Paired values were used in the statistical analysis. Median plasma (interquartile range) values of IL-6 were elevated from 15.5 (9-52) pg/ml at baseline to 23 (4-48) pg/ml (P < 0.01) at 8 h; from 15 (2-48) pg/ml at baseline to 46 (21-105) pg/ml (P < 0.001) at 24 h; from 16 (9-52) pg/ml at baseline to 61 (32-170) pg/ml (P < 0.001) at 48 h; and from 15.5 (6-48) pg/ml to 68 (40-200) pg/ml (P < 0.001) at 72 h. Significance was maintained even when adjusted for multiple comparisons. The relative increase in IL-6 concentration was dose-dependent. Moreover, IL-6 elevation had a direct correlation with flavopiridol peak plasma concentration, flavopiridol area under the curve, and plasma C-Reactive protein levels. A significant decrease in plasma granulocyte macrophage colony-stimulating factor occurred at the 8-h sampling point: 50 pg/ml (interquartile range 10-205 pg/ml, P < 0.01) when compared with baseline plasma levels and 71 pg/ml (interquartile range 5-152 pg/ml, P < 0.01). No changes in the other pro or anti-inflammatory cytokines were observed. Immunohistochemistry studies in bone marrow aspirates from a prospective group of patients in this trial demonstrated approximately 4-fold induction of IL-6 (compared with baseline), mostly in non-T cells. Biochemical analysis of plasma in patients undergoing infusional flavopiridol found a significant dose-dependent induction of IL-6. IL-6 elevation could be a marker for the process leading to the appearance of the proinflammatory syndrome observed in patients treated with infusional flavopiridol. The mechanism(s) underlying IL-6 induction and its significance are still unknown but may influence strategies to modulate flavopiridol's clinical effects. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Messmann, Richard A AU - Ullmann, Claudio Dansky AU - Lahusen, Tyler AU - Kalehua, Audrey AU - Wasfy, Jason AU - Melillo, Giovanni AU - Ding, Ivan AU - Headlee, Donna AU - Figg, William D AU - Sausville, Edward A AU - Senderowicz, Adrian M AD - Developmental Therapeutics Program, Radiation Oncology Branch, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland 20892, USA. Y1 - 2003/02// PY - 2003 DA - February 2003 SP - 562 EP - 570 VL - 9 IS - 2 SN - 1078-0432, 1078-0432 KW - Antineoplastic Agents KW - 0 KW - Enzyme Inhibitors KW - Flavonoids KW - Interleukin-6 KW - Interleukins KW - Piperidines KW - alvocidib KW - 45AD6X575G KW - Cyclin-Dependent Kinases KW - EC 2.7.11.22 KW - Index Medicus KW - Enzyme Inhibitors -- adverse effects KW - Bone Marrow -- pathology KW - Interleukins -- blood KW - Enzyme Inhibitors -- administration & dosage KW - Infusions, Intravenous KW - Humans KW - Cyclin-Dependent Kinases -- antagonists & inhibitors KW - Neoplasms -- drug therapy KW - Interleukin-6 -- blood KW - Antineoplastic Agents -- administration & dosage KW - Neoplasms -- blood KW - Inflammation -- chemically induced KW - Flavonoids -- adverse effects KW - Piperidines -- administration & dosage KW - Piperidines -- adverse effects KW - Neoplasms -- immunology KW - Flavonoids -- administration & dosage KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73021435?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Flavopiridol-related+proinflammatory+syndrome+is+associated+with+induction+of+interleukin-6.&rft.au=Messmann%2C+Richard+A%3BUllmann%2C+Claudio+Dansky%3BLahusen%2C+Tyler%3BKalehua%2C+Audrey%3BWasfy%2C+Jason%3BMelillo%2C+Giovanni%3BDing%2C+Ivan%3BHeadlee%2C+Donna%3BFigg%2C+William+D%3BSausville%2C+Edward+A%3BSenderowicz%2C+Adrian+M&rft.aulast=Messmann&rft.aufirst=Richard&rft.date=2003-02-01&rft.volume=9&rft.issue=2&rft.spage=562&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 - 2003-08-01 N1 - Date created - 2003-02-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increased 99mTc-sestamibi accumulation in normal liver and drug-resistant tumors after the administration of the glycoprotein inhibitor, XR9576. AN - 73015534; 12576431 AB - 99mTc-sestamibi, a substrate of the multidrug transporter P-glycoprotein (Pgp), has been used as a functional imaging agent for the multidrug resistance-1 (MDR1) phenotype. In vitro, retention of (99m)Tc-sestamibi by cells that overexpress Pgp can be enhanced by the addition of Pgp inhibitors. XR9576 (Tariquidar) is a potent and selective noncompetitive inhibitor of Pgp that is active at 25-80 nM. A Phase I trial of XR9576 in combination with vinorelbine (Navelbine) was conducted in 26 patients with metastatic cancers. A (99m)Tc-sestamibi scan was obtained at baseline followed 48-96 h later by a second scan 1-3 h after the administration of XR9576. Time activity curves and areas under the curves (AUCs) were obtained for tumor, liver, lung, and heart, and tissue:heart AUC ratios were calculated. XR9576 enhanced (99m)Tc-sestamibi accumulation and retention in the liver of all but two patients with a mean change of +128%. Furthermore, in 13 of 17 patients with tumor masses visible by (99m)Tc-sestamibi, the tumor:heart (99m)Tc-sestamibi AUC(0-3 h) increased after the administration of XR9576, with increases of 36-263% seen in 8 patients. We conclude that in vivo administration of XR9576 inhibits (99m)Tc-sestamibi efflux in both the normal liver and in drug resistant tumors. This study provides convincing evidence of the existence of XR9576-inhibitable (99m)Tc-sestamibi efflux in a large fraction of drug resistant tumors. One can predict that efflux of Pgp substrates also occurs in these tumors. XR9576 provides an efficient way to inhibit this efflux and offers the potential to increase drug exposure in human cancer. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Agrawal, Manish AU - Abraham, Jame AU - Balis, Frank M AU - Edgerly, Maureen AU - Stein, Wilfred D AU - Bates, Susan AU - Fojo, Tito AU - Chen, Clara C AD - Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2003/02// PY - 2003 DA - February 2003 SP - 650 EP - 656 VL - 9 IS - 2 SN - 1078-0432, 1078-0432 KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Quinolines KW - Radiopharmaceuticals KW - Vinblastine KW - 5V9KLZ54CY KW - Technetium Tc 99m Sestamibi KW - 971Z4W1S09 KW - tariquidar KW - J58862DTVD KW - vinorelbine KW - Q6C979R91Y KW - Index Medicus KW - Area Under Curve KW - Antineoplastic Agents, Phytogenic -- adverse effects KW - Humans KW - Adult KW - Neoplasm Metastasis KW - Aged KW - Middle Aged KW - Drug Resistance, Neoplasm KW - Male KW - Female KW - Radionuclide Imaging KW - Radiopharmaceuticals -- pharmacokinetics KW - Vinblastine -- analogs & derivatives KW - Quinolines -- pharmacology KW - Liver Neoplasms -- pathology KW - Technetium Tc 99m Sestamibi -- pharmacokinetics KW - Liver -- drug effects KW - Liver Neoplasms -- drug therapy KW - Liver Neoplasms -- diagnostic imaging KW - Vinblastine -- adverse effects KW - Liver -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73015534?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Increased+99mTc-sestamibi+accumulation+in+normal+liver+and+drug-resistant+tumors+after+the+administration+of+the+glycoprotein+inhibitor%2C+XR9576.&rft.au=Agrawal%2C+Manish%3BAbraham%2C+Jame%3BBalis%2C+Frank+M%3BEdgerly%2C+Maureen%3BStein%2C+Wilfred+D%3BBates%2C+Susan%3BFojo%2C+Tito%3BChen%2C+Clara+C&rft.aulast=Agrawal&rft.aufirst=Manish&rft.date=2003-02-01&rft.volume=9&rft.issue=2&rft.spage=650&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 - 2003-08-01 N1 - Date created - 2003-02-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Risk of non-Hodgkin's lymphoma and prediagnostic serum organochlorines: beta-hexachlorocyclohexane, chlordane/heptachlor-related compounds, dieldrin, and hexachlorobenzene. AN - 73015530; 12573902 AB - Increases in non-Hodgkin's lymphoma (NHL) incidence and mortality rates during the past few decades remain largely unexplained. Studies suggest that organochlorine pesticides may contribute to an increased risk of NHL. In 1974, serum samples were obtained from 25,802 participants in the Campaign Against Cancer and Stroke in Washington County, Maryland (USA), and cryopreserved for future study. We measured prediagnostic levels of chlordane, lindane (gamma-hexachlorocyclohexane), beta-hexachlorocyclohexane, transnonachlor, heptachlor, heptachlor epoxide, oxychlordane, dieldrin, and hexachlorobenzene in serum samples of 74 cases of NHL and 147 matched controls. Previously, we found an association between NHL and serum levels of total PCBs (polychlorinated biphenyls), but not DDT (dichlorodiphenyltrichloroethane) and related compounds. In this instance, there was no evidence of an association between NHL risk and serum levels of any of the individual lipid- and recovery-corrected organochlorines that we evaluated, nor of the summed chlordane-related compounds (transnonachlor, heptachlor, heptachlor epoxide, oxychlordane). These findings do not support the hypothesis that the organochlorine compounds included in this study are strongly linked to the development of NHL. The possibility of a weak association cannot be excluded by these data. JF - Environmental health perspectives AU - Cantor, Kenneth P AU - Strickland, Paul T AU - Brock, John W AU - Bush, David AU - Helzlsouer, Kathy AU - Needham, Larry L AU - Zahm, Shelia Hoar AU - Comstock, George W AU - Rothman, Nathaniel AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892-7240, USA. cantork@nih.gov Y1 - 2003/02// PY - 2003 DA - February 2003 SP - 179 EP - 183 VL - 111 IS - 2 SN - 0091-6765, 0091-6765 KW - Hydrocarbons, Chlorinated KW - 0 KW - Insecticides KW - Index Medicus KW - Odds Ratio KW - Humans KW - Case-Control Studies KW - Incidence KW - Risk Assessment KW - Lymphoma, Non-Hodgkin -- epidemiology KW - Insecticides -- adverse effects KW - Environmental Exposure KW - Lymphoma, Non-Hodgkin -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73015530?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Risk+of+non-Hodgkin%27s+lymphoma+and+prediagnostic+serum+organochlorines%3A+beta-hexachlorocyclohexane%2C+chlordane%2Fheptachlor-related+compounds%2C+dieldrin%2C+and+hexachlorobenzene.&rft.au=Cantor%2C+Kenneth+P%3BStrickland%2C+Paul+T%3BBrock%2C+John+W%3BBush%2C+David%3BHelzlsouer%2C+Kathy%3BNeedham%2C+Larry+L%3BZahm%2C+Shelia+Hoar%3BComstock%2C+George+W%3BRothman%2C+Nathaniel&rft.aulast=Cantor&rft.aufirst=Kenneth&rft.date=2003-02-01&rft.volume=111&rft.issue=2&rft.spage=179&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 - 2003-05-13 N1 - Date created - 2003-02-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Scand J Work Environ Health. 1981;7 Suppl 4:140-6 [7330625] Cancer. 1999 Mar 15;85(6):1353-60 [10189142] J Natl Cancer Inst. 1987 May;78(5):899-910 [3471999] Arch Environ Contam Toxicol. 1989 Jul-Aug;18(4):495-500 [2505694] Arch Environ Health. 1967 Jul;15(1):97-101 [4143660] J Clin Pathol. 1990 Feb;43(2):98-101 [1690760] Cancer Res. 1990 Oct 15;50(20):6585-91 [2208120] J Occup Med. 1979 Nov;21(11):745-8 [556268] Arch Intern Med. 1990 Nov;150(11):2393-5 [1700687] Epidemiology. 1990 Sep;1(5):349-56 [2078610] Cancer Res. 1992 May 1;52(9):2447-55 [1568215] Scand J Work Environ Health. 1992 Jun;18(3):155-61 [1615289] Cancer Res. 1992 Oct 1;52(19 Suppl):5432s-5440s [1394149] Scand J Work Environ Health. 1992 Aug;18(4):209-15 [1411362] Eur J Pediatr. 1992 Nov;151(11):802-5 [1468452] Oncology (Williston Park). 1994 Aug;8(8):67-73; discussion 73-8 [7947004] Cancer Surv. 1994;19-20:423-53 [7534635] J Occup Environ Med. 1995 Apr;37(4):471-8 [7670904] Arch Environ Health. 1996 Jan-Feb;51(1):22-5 [8629858] J Anal Toxicol. 1996 Nov-Dec;20(7):528-36 [8934301] Environ Mol Mutagen. 1997;29(1):46-52 [9020306] Occup Med. 1997 Apr-Jun;12(2):269-89 [9220486] Lancet. 1997 Jul 26;350(9073):240-4 [9242800] Occup Environ Med. 1997 Oct;54(10):702-7 [9404316] Am J Ind Med. 1998 Jan;33(1):82-7 [9408531] Cancer Causes Control. 1997 May;8(3):420-43 [9498903] Cancer Epidemiol Biomarkers Prev. 1998 Jun;7(6):489-96 [9641493] Cad Saude Publica. 1998;14 Suppl 3:41-66 [9819464] Arch Environ Health. 1999 Mar-Apr;54(2):102-9 [10094287] Int Arch Occup Environ Health. 1985;56(2):75-9 [4055072] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic and environmental contributions to atherosclerosis phenotypes in men and women: heritability of carotid intima-media thickness in the Framingham Heart Study. AN - 73013812; 12574549 AB - Carotid intima-media thickness (IMT) is a quantitative measure of subclinical atherosclerosis that is predictive of subsequent myocardial infarction and stroke. There is controversy regarding the proportion of variability in IMT explained by genetic factors. Thus, it is uncertain whether carotid IMT is a heritable trait that can be used in genetic studies. From 1996 to 1998, we measured carotid IMT in 906 men (mean age, 56.7 years) and 980 women (mean age, 57.4 years) from 586 extended families (1630 sib pairs) in the Framingham Offspring cohort. B-mode carotid ultrasonography was used to define mean and maximum IMT of the common carotid artery (CCA) and internal carotid artery (ICA). Correlation coefficients were calculated in pairs of siblings. Variance component methods were used to estimate heritability with crude, age- and sex-adjusted, and multivariable-adjusted normalized deviates. Multivariable-adjusted correlation coefficients for mean CCA and ICA IMT were 0.16 and 0.16, respectively. Crude, age- and sex-adjusted, and multivariable-adjusted heritabilities were 0.67, 0.44, and 0.38 for the mean CCA IMT (all P<0.001) and 0.43, 0.37, and 0.35 for the mean ICA IMT (all P<0.001). For CCA IMT, 27% of the overall variance was due to measured covariates; 38% was due to heritable factors. These data suggest that a substantial proportion of the variability in carotid IMT is explained by genetic factors. Further studies of genetic linkage and candidate gene association are warranted to identify specific genetic variants predisposing to subclinical atherosclerosis and stroke. JF - Stroke AU - Fox, Caroline S AU - Polak, Joseph F AU - Chazaro, Irmarie AU - Cupples, Adrienne AU - Wolf, Philip A AU - D'Agostino, Ralph A AU - O'Donnell, Christopher J AU - Framingham Heart Study AD - National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, Mass 01702, USA. ; Framingham Heart Study Y1 - 2003/02// PY - 2003 DA - February 2003 SP - 397 EP - 401 VL - 34 IS - 2 KW - Index Medicus KW - Tunica Intima -- diagnostic imaging KW - Genetic Variation KW - Analysis of Variance KW - Humans KW - Ultrasonography KW - Multivariate Analysis KW - Phenotype KW - Quantitative Trait, Heritable KW - Tunica Media -- diagnostic imaging KW - Risk Factors KW - Cohort Studies KW - Middle Aged KW - Sex Distribution KW - Female KW - Male KW - Carotid Artery Diseases -- etiology KW - Carotid Artery Diseases -- epidemiology KW - Genetic Predisposition to Disease KW - Environmental Exposure -- adverse effects KW - Carotid Artery Diseases -- diagnostic imaging KW - Carotid Arteries -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73013812?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Stroke&rft.atitle=Genetic+and+environmental+contributions+to+atherosclerosis+phenotypes+in+men+and+women%3A+heritability+of+carotid+intima-media+thickness+in+the+Framingham+Heart+Study.&rft.au=Fox%2C+Caroline+S%3BPolak%2C+Joseph+F%3BChazaro%2C+Irmarie%3BCupples%2C+Adrienne%3BWolf%2C+Philip+A%3BD%27Agostino%2C+Ralph+A%3BO%27Donnell%2C+Christopher+J%3BFramingham+Heart+Study&rft.aulast=Fox&rft.aufirst=Caroline&rft.date=2003-02-01&rft.volume=34&rft.issue=2&rft.spage=397&rft.isbn=&rft.btitle=&rft.title=Stroke&rft.issn=1524-4628&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-14 N1 - Date created - 2003-02-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical pharmacology and pharmacogenetics of flavopiridol 1-h i.v. infusion in patients with refractory neoplasms. AN - 73010602; 12569299 AB - A phase I trial of flavopiridol administered as a 1-h i.v. infusion schedule was explored. Fifty-five patients were treated with flavopiridol at doses ranging from 12 to 78 mg/m2 daily for 5, 3 and 1 day every 3 weeks. Pharmacokinetic and pharmacodynamic analysis was performed together with analysis of a promoter polymorphism of the UGT1A1 gene. Peak concentrations and areas under the time-concentration curve of flavopiridol were linear within the doses studied. Estimated clearance was 13.8+/-4.9 l/h/m2 (mean+/-SD), volume of distribution at steady-state was 64.9+/-43.4 l/m2 and elimination half-life was 5.2+/-4.9 h. Forty-nine of the 55 patients were genotyped for the promoter polymorphism. We found five (10%) homozygous and 11 (22%) heterozygous patients for UGT1A1*28, which alters the reference sequence (TA)6TAA to the variant (TA)7TAA by an extra TA dinucleotide insertion within the TATA box. One patient was heterozygous for the sequence of five TA repeats, (TA)5TAA. The remaining 32 patients did not have the UGT1A1*28 allele (homozygous for the reference sequence). Associations of the UGT1A1 promoter genotype with either the pharmacokinetic parameters or diarrhea (occurrence and severity) were not observed in this study. The pharmacogenetic analyses did not support that the UGT1A1 promoter polymorphism could affect flavopiridol pharmacokinetics and alter the incidence and severity of diarrhea induced by the drug. Copyright 2003 Lippincott Williams & Wilkins JF - Anti-cancer drugs AU - Zhai, Suoping AU - Sausville, Edward A AU - Senderowicz, Adrian M AU - Ando, Yuichi AU - Headlee, Donna AU - Messmann, Richard A AU - Arbuck, Susan AU - Murgo, Anthony J AU - Melillo, Giovanni AU - Fuse, Eiichi AU - Figg, William D AD - Clinical Pharmacology Research Core, Medical Oncology Clinical Research Unit Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2003/02// PY - 2003 DA - February 2003 SP - 125 EP - 135 VL - 14 IS - 2 SN - 0959-4973, 0959-4973 KW - Antineoplastic Agents KW - 0 KW - Flavonoids KW - Piperidines KW - alvocidib KW - 45AD6X575G KW - UGT1A1 enzyme KW - EC 2.4.1.- KW - Glucuronosyltransferase KW - EC 2.4.1.17 KW - Cyclin-Dependent Kinases KW - EC 2.7.11.22 KW - Index Medicus KW - Area Under Curve KW - Infusions, Intravenous KW - Dose-Response Relationship, Drug KW - Humans KW - Aged KW - Pharmacology, Clinical KW - Pharmacogenetics KW - Biological Availability KW - Genotype KW - Half-Life KW - Adult KW - Treatment Outcome KW - Cyclin-Dependent Kinases -- antagonists & inhibitors KW - Middle Aged KW - Maximum Tolerated Dose KW - Female KW - Male KW - Piperidines -- pharmacology KW - Neoplasms -- drug therapy KW - Glucuronosyltransferase -- genetics KW - Antineoplastic Agents -- administration & dosage KW - Antineoplastic Agents -- pharmacokinetics KW - Piperidines -- pharmacokinetics KW - Piperidines -- administration & dosage KW - Flavonoids -- pharmacology KW - Flavonoids -- pharmacokinetics KW - Antineoplastic Agents -- pharmacology KW - Neoplasms -- metabolism KW - Flavonoids -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73010602?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Clinical+pharmacology+and+pharmacogenetics+of+flavopiridol+1-h+i.v.+infusion+in+patients+with+refractory+neoplasms.&rft.au=Zhai%2C+Suoping%3BSausville%2C+Edward+A%3BSenderowicz%2C+Adrian+M%3BAndo%2C+Yuichi%3BHeadlee%2C+Donna%3BMessmann%2C+Richard+A%3BArbuck%2C+Susan%3BMurgo%2C+Anthony+J%3BMelillo%2C+Giovanni%3BFuse%2C+Eiichi%3BFigg%2C+William+D&rft.aulast=Zhai&rft.aufirst=Suoping&rft.date=2003-02-01&rft.volume=14&rft.issue=2&rft.spage=125&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 - 2003-09-24 N1 - Date created - 2003-02-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of cyclooxygenase-2 expression by the Wnt and ras pathways. AN - 73004842; 12566320 AB - Mutations in the adenomatous polyposis coli (APC) gene and K-ras occur in the majority of human colorectal cancers. Loss of functional APC protein activates the Wnt signal transduction pathway, allowing the nuclear accumulation of beta-catenin, which then binds to T-cell factor-4 (Tcf-4), causing increased transcriptional activation of downstream target genes. We investigated the hypothesis that the activation of the WNT pathway regulates cyclooxygenase-2 (COX-2). COX-2 was down-regulated after the induction of full-length APC in the HT29-APC cell line. We identified a Tcf-4-binding element (TBE) in the COX-2 promoter that specifically bound to Tcf-4 in an electrophoretic mobility shift assay. COX-2 promoter luciferase activity is down-regulated by APC in a promoter reporter construct containing the, TBE but not with mutant TBE. Mutant beta-catenin expression up-regulated the COX-2 promoter activity and the endogenous COX-2 mRNA expression in HuH7, hepatocellular carcinoma cell line, which is partially abrogated by cotransfection with a dominant-negative Tcf-4 expression vector. Although beta-catenin alone did not increase COX-2 protein to detectable levels in HuH7 cells, coexpression of both mutant beta-catenin and mutant K-ras increased COX-2 protein expression, which is consistent with the previous reports that K-ras can stabilize COX-2 mRNA. Taken together, our data support the hypothesis that COX-2 is down-regulated by APC and up-regulated by nuclear beta-catenin accumulation, and additionally implicate the Wnt signal transduction pathway in colon and liver carcinogenesis. JF - Cancer research AU - Araki, Yuzuru AU - Okamura, Shu AU - Hussain, S Perwez AU - Nagashima, Makoto AU - He, Peijun AU - Shiseki, Masayuki AU - Miura, Koh AU - Harris, Curtis C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/02/01/ PY - 2003 DA - 2003 Feb 01 SP - 728 EP - 734 VL - 63 IS - 3 SN - 0008-5472, 0008-5472 KW - Adenomatous Polyposis Coli Protein KW - 0 KW - CTNNB1 protein, human KW - Cytoskeletal Proteins KW - DNA-Binding Proteins KW - Isoenzymes KW - Membrane Proteins KW - Proto-Oncogene Proteins KW - RNA, Messenger KW - Recombinant Fusion Proteins KW - TCF Transcription Factors KW - TCF7L2 protein, human KW - Trans-Activators KW - Transcription Factor 7-Like 2 Protein KW - Transcription Factors KW - Wnt Proteins KW - Zebrafish Proteins KW - beta Catenin KW - Luciferases KW - EC 1.13.12.- KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - PTGS2 protein, human KW - Prostaglandin-Endoperoxide Synthases KW - ras Proteins KW - EC 3.6.5.2 KW - Index Medicus KW - Adenomatous Polyposis Coli Protein -- biosynthesis KW - Transcription Factors -- metabolism KW - Humans KW - Luciferases -- metabolism KW - Transcription, Genetic KW - Adenomatous Polyposis Coli Protein -- physiology KW - RNA, Messenger -- genetics KW - RNA, Messenger -- biosynthesis KW - Recombinant Fusion Proteins -- metabolism KW - Gene Expression Regulation, Neoplastic KW - Signal Transduction -- physiology KW - Promoter Regions, Genetic KW - Down-Regulation KW - Cytoskeletal Proteins -- physiology KW - HT29 Cells KW - Up-Regulation KW - Trans-Activators -- physiology KW - Luciferases -- genetics KW - Adenomatous Polyposis Coli Protein -- genetics KW - DNA-Binding Proteins -- metabolism KW - Isoenzymes -- biosynthesis KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - Isoenzymes -- genetics KW - ras Proteins -- physiology KW - Proto-Oncogene Proteins -- physiology KW - Prostaglandin-Endoperoxide Synthases -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73004842?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Regulation+of+cyclooxygenase-2+expression+by+the+Wnt+and+ras+pathways.&rft.au=Araki%2C+Yuzuru%3BOkamura%2C+Shu%3BHussain%2C+S+Perwez%3BNagashima%2C+Makoto%3BHe%2C+Peijun%3BShiseki%2C+Masayuki%3BMiura%2C+Koh%3BHarris%2C+Curtis+C&rft.aulast=Araki&rft.aufirst=Yuzuru&rft.date=2003-02-01&rft.volume=63&rft.issue=3&rft.spage=728&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 - 2003-03-07 N1 - Date created - 2003-02-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicology and carcinogenesis studies of microencapsulated citral in rats and mice. AN - 72996727; 12563105 AB - Citral, a widely used natural ingredient, is added to foods and cosmetics as a flavoring and fragrance agent. Male and female F344/N rats and B6C3F1 mice were exposed to microencapsulated citral in the feed for 14 weeks or two years. All studies included untreated and vehicle control groups. In the 14-week studies, rats and mice were given diets containing 3,900, 7,800, 15,600, or 31,300 ppm citral. In rats, food consumption was reduced in the two highest dose groups. In mice an apparent increase in food consumption was observed, but was due to mice scattering the feed. Body weights of all treated animals were less than controls. All rats and four male mice were killed moribund in the high dose groups. In rats, forestomach and kidney lesions were observed. At the higher doses, lesions observed in the bone marrow, testes, and thymus in rats and in the ovary in mice were considered related to inanition and resultant moribundity. In the two-year studies, rats were exposed to 1,000, 2,000, or 4,000 ppm citral. Body weights were reduced in the 4,000 ppm rats. Mice were exposed to 500, 1,000, or 2,000 ppm citral. Body weights in the 1,000 and 2,000 ppm groups were reduced. No neoplasms were attributed to citral in rats or mice. Malignant lymphoma occurred with a positive trend and was significantly greater than controls in female mice in the 2,000 ppm group. However, the incidences were within the NTP historical control range and could not be clearly related to citral administration. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Ress, N B AU - Hailey, J R AU - Maronpot, R R AU - Bucher, J R AU - Travlos, G S AU - Haseman, J K AU - Orzech, D P AU - Johnson, J D AU - Hejtmancik, M R AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2003/02// PY - 2003 DA - February 2003 SP - 198 EP - 206 VL - 71 IS - 2 SN - 1096-6080, 1096-6080 KW - Carcinogens KW - 0 KW - Flavoring Agents KW - Monoterpenes KW - citral KW - T7EU0O9VPP KW - Index Medicus KW - Administration, Oral KW - Animals KW - Kidney -- pathology KW - Drug Compounding KW - Dose-Response Relationship, Drug KW - Kidney -- drug effects KW - Mice KW - Stomach -- drug effects KW - Rats KW - Mice, Inbred Strains KW - Stomach -- pathology KW - Rats, Inbred F344 KW - Body Weight -- drug effects KW - Diet KW - Female KW - Male KW - Monoterpenes -- toxicity KW - Flavoring Agents -- toxicity KW - Carcinogens -- administration & dosage KW - Neoplasms, Experimental -- etiology KW - Monoterpenes -- administration & dosage KW - Carcinogens -- toxicity KW - Carcinogenicity Tests KW - Flavoring Agents -- administration & dosage KW - Neoplasms, Experimental -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72996727?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Does+place+of+birth+influence+endogenous+hormone+levels+in+Asian-American+women%3F&rft.au=Falk%2C+R+T%3BFears%2C+T+R%3BHoover%2C+R+N%3BPike%2C+M+C%3BWu%2C+A+H%3BNomura%2C+A+M+Y%3BKolonel%2C+L+N%3BWest%2C+D+W%3BZiegler%2C+R+G&rft.aulast=Falk&rft.aufirst=R&rft.date=2002-07-01&rft.volume=87&rft.issue=1&rft.spage=54&rft.isbn=&rft.btitle=&rft.title=British+Journal+of+Cancer&rft.issn=00070920&rft_id=info:doi/10.1038%2Fsj.bjc.6600339 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-29 N1 - Date created - 2003-02-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High rates of behavioral problems in perinatally HIV-infected children are not linked to HIV disease. AN - 72994586; 12563068 AB - Descriptive studies and clinical reports have suggested that human immunodeficiency virus (HIV)-positive children are at risk for behavioral problems. Inadequate control groups and sample sizes have limited the ability of investigators to consider multiple influences that place HIV-positive children at risk for poor behavioral outcomes. We examined the unique and combined influences of HIV, prenatal drug exposure, and environmental factors on behavior in children who were perinatally exposed to HIV. Participants included 307 children who were born to HIV-positive mothers (96 HIV infected and 211 seroreverters) and enrolled in a natural history, longitudinal study of women to infant HIV transmission. Caregivers completed parent behavioral rating scales, beginning when the children were 3 years old. Data were also collected on prenatal drug exposure; child age, gender, and ethnicity; caregiver relationship to child; and birth complications. Multivariate analyses comparing the HIV-infected children with perinatally exposed but uninfected children from similar backgrounds failed to find an association between either HIV status or prenatal drug exposure and poor behavioral outcomes. The strongest correlates of increased behavioral symptoms were demographic characteristics. This study suggests that although a high prevalence of behavioral problems does exist among HIV-infected children, neither HIV infection nor prenatal drug exposure is the underlying cause. Rather, other biological and environmental factors are likely contributors toward poor behavioral outcomes. JF - Pediatrics AU - Mellins, Claude A AU - Smith, Renee AU - O'Driscoll, Peter AU - Magder, Lawrence S AU - Brouwers, Pim AU - Chase, Cynthia AU - Blasini, Ileana AU - Hittleman, Joan AU - Llorente, Antolin AU - Matzen, Elaine AU - NIH NIAID/NICHD/NIDA-Sponsored Women and Infant Transmission Study Group AD - Columbia College of Physicians and Surgeons, New York, New York, USA. cam14@columbia.edu ; NIH NIAID/NICHD/NIDA-Sponsored Women and Infant Transmission Study Group Y1 - 2003/02// PY - 2003 DA - February 2003 SP - 384 EP - 393 VL - 111 IS - 2 KW - Abridged Index Medicus KW - Index Medicus KW - Infectious Disease Transmission, Vertical -- statistics & numerical data KW - HIV Seropositivity -- psychology KW - Sex Factors KW - Humans KW - Parenting -- psychology KW - Infant, Newborn KW - Pregnancy Complications, Infectious -- epidemiology KW - Pregnancy Complications, Infectious -- ethnology KW - Brief Psychiatric Rating Scale KW - Longitudinal Studies KW - Pregnancy Complications, Infectious -- virology KW - Pregnancy KW - Multivariate Analysis KW - Maternal-Fetal Exchange -- physiology KW - Adult KW - Caregivers -- statistics & numerical data KW - Incidence KW - Pregnancy Complications, Infectious -- psychology KW - Adolescent KW - Male KW - Caregivers -- psychology KW - Female KW - Substance Abuse, Intravenous -- psychology KW - HIV Infections -- transmission KW - HIV Infections -- complications KW - Child Behavior Disorders -- chemically induced KW - Child Behavior Disorders -- psychology KW - Child Behavior Disorders -- genetics KW - HIV Infections -- psychology KW - HIV Infections -- epidemiology KW - Child Behavior Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72994586?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatrics&rft.atitle=High+rates+of+behavioral+problems+in+perinatally+HIV-infected+children+are+not+linked+to+HIV+disease.&rft.au=Mellins%2C+Claude+A%3BSmith%2C+Renee%3BO%27Driscoll%2C+Peter%3BMagder%2C+Lawrence+S%3BBrouwers%2C+Pim%3BChase%2C+Cynthia%3BBlasini%2C+Ileana%3BHittleman%2C+Joan%3BLlorente%2C+Antolin%3BMatzen%2C+Elaine%3BNIH+NIAID%2FNICHD%2FNIDA-Sponsored+Women+and+Infant+Transmission+Study+Group&rft.aulast=Mellins&rft.aufirst=Claude&rft.date=2003-02-01&rft.volume=111&rft.issue=2&rft.spage=384&rft.isbn=&rft.btitle=&rft.title=Pediatrics&rft.issn=1098-4275&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-20 N1 - Date created - 2003-02-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An apoptosis-differentiation program in human polymorphonuclear leukocytes facilitates resolution of inflammation. AN - 72992935; 12554809 AB - Human polymorphonuclear leukocytes (PMNs) are an essential part of innate immunity and contribute significantly to inflammation. Although much is understood about the inflammatory response, the molecular basis for termination of inflammation in humans is largely undefined. We used human oligonucleotide microarrays to identify genes differentially regulated during the onset of apoptosis occurring after PMN phagocytosis. Genes encoding proteins that regulate cell metabolism and vesicle trafficking comprised 198 (98 genes induced, 100 genes repressed) of 867 differentially expressed genes. We discovered that complex cellular pathways involving glutathione and thioredoxin detoxification systems, heme catabolism, ubiquitin-proteasome degradation, purine nucleotide metabolism, and nuclear import were regulated at the level of gene expression during the initial stages of PMN apoptosis. Eleven genes encoding key regulators of glycolysis, the hexose monophosphate shunt, the glycerol-phosphate shuttle, and oxidative phosphorylation were induced. Increased levels of cellular reduced glutathione and gamma-glutamyltransferase and glycolytic activity confirmed that several of these metabolic pathways were up-regulated. In contrast, seven genes encoding critical enzymes involved in fatty acid beta-oxidation, which can generate toxic lipid peroxides, were down-regulated. Our results indicate that energy metabolism and oxidative stress-response pathways are gene-regulated during PMN apoptosis. We propose that changes in PMN gene expression leading to programmed cell death are part of an apoptosis-differentiation program, a final stage of transcriptionally regulated PMN maturation that is accelerated significantly by phagocytosis. These findings provide new insight into the molecular events that contribute to the resolution of inflammation in humans. JF - Journal of leukocyte biology AU - Kobayashi, Scott D AU - Voyich, Jovanka M AU - Somerville, Greg A AU - Braughton, Kevin R AU - Malech, Harry L AU - Musser, James M AU - DeLeo, Frank R AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT 59840, USA. Y1 - 2003/02// PY - 2003 DA - February 2003 SP - 315 EP - 322 VL - 73 IS - 2 SN - 0741-5400, 0741-5400 KW - Index Medicus KW - Oxidation-Reduction KW - Neutrophil Activation KW - Inactivation, Metabolic KW - Humans KW - Phagocytosis KW - Energy Metabolism KW - Glycolysis KW - Gene Expression Profiling KW - Apoptosis KW - Inflammation -- etiology KW - Neutrophils -- physiology KW - Inflammation -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72992935?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=An+apoptosis-differentiation+program+in+human+polymorphonuclear+leukocytes+facilitates+resolution+of+inflammation.&rft.au=Kobayashi%2C+Scott+D%3BVoyich%2C+Jovanka+M%3BSomerville%2C+Greg+A%3BBraughton%2C+Kevin+R%3BMalech%2C+Harry+L%3BMusser%2C+James+M%3BDeLeo%2C+Frank+R&rft.aulast=Kobayashi&rft.aufirst=Scott&rft.date=2003-02-01&rft.volume=73&rft.issue=2&rft.spage=315&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 - 2003-02-20 N1 - Date created - 2003-01-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Leukoc Biol. 2003 Sep;74(3):307-8; author reply: 309-10 [12949233] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lung cancer after treatment for Hodgkin's disease: focus on radiation effects. AN - 72991451; 12537521 AB - Aspects of radiation-induced lung cancer were evaluated in an international study of Hodgkin's disease. The study population consisted of 227 patients with lung cancer and 455 matched controls. Unique features included dose determinations to the specific location in the lung where each cancer developed and quantitative data on both chemotherapy and tobacco use obtained from medical records. The estimated excess relative risk (ERR) per Gy was 0.15 (95% CI: 0.06-0.39), and there was little evidence of departure from linearity even though lung doses for the majority of Hodgkin's disease patients treated with radiotherapy exceeded 30 Gy. The interaction of radiation and chemotherapy that included alkylating agents was almost exactly additive, and a multiplicative relationship could be rejected (P = 0.017). Conversely, the interaction of radiation and smoking was consistent with a multiplicative relationship, but not with an additive relationship (P < 0.001). The ERR/Gy for males was about four times that for females, although the difference was not statistically significant. There was little evidence of modification of the ERR/Gy by time since exposure (after a 5-year minimum latent period), age at exposure, or attained age. Because of the very high radiation doses received by Hodgkin's disease patients and the immunodeficiency inherent to this lymphoma and that associated with chemotherapy, generalizing these findings to other populations receiving considerably lower doses of radiation should be done cautiously. JF - Radiation research AU - Gilbert, E S AU - Stovall, M AU - Gospodarowicz, M AU - Van Leeuwen, F E AU - Andersson, M AU - Glimelius, B AU - Joensuu, T AU - Lynch, C F AU - Curtis, R E AU - Holowaty, E AU - Storm, H AU - Pukkala, E AU - van't Veer, M B AU - Fraumeni, J F AU - Boice, J D AU - Clarke, E A AU - Travis, L B AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda Maryland 20852-7238, USA. gilberte@mail.nih.gov Y1 - 2003/02// PY - 2003 DA - February 2003 SP - 161 EP - 173 VL - 159 IS - 2 SN - 0033-7587, 0033-7587 KW - Antineoplastic Agents, Alkylating KW - 0 KW - Index Medicus KW - Space life sciences KW - Antineoplastic Agents, Alkylating -- therapeutic use KW - Antineoplastic Agents, Alkylating -- pharmacology KW - Sex Characteristics KW - Humans KW - Aged KW - Dose-Response Relationship, Radiation KW - Smoking KW - Radiometry KW - Risk Factors KW - Adult KW - Case-Control Studies KW - Environmental Exposure KW - Middle Aged KW - Time Factors KW - Female KW - Male KW - Lung Neoplasms -- etiology KW - Hodgkin Disease -- radiotherapy KW - Neoplasms, Radiation-Induced -- etiology KW - Hodgkin Disease -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72991451?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Lung+cancer+after+treatment+for+Hodgkin%27s+disease%3A+focus+on+radiation+effects.&rft.au=Gilbert%2C+E+S%3BStovall%2C+M%3BGospodarowicz%2C+M%3BVan+Leeuwen%2C+F+E%3BAndersson%2C+M%3BGlimelius%2C+B%3BJoensuu%2C+T%3BLynch%2C+C+F%3BCurtis%2C+R+E%3BHolowaty%2C+E%3BStorm%2C+H%3BPukkala%2C+E%3Bvan%27t+Veer%2C+M+B%3BFraumeni%2C+J+F%3BBoice%2C+J+D%3BClarke%2C+E+A%3BTravis%2C+L+B&rft.aulast=Gilbert&rft.aufirst=E&rft.date=2003-02-01&rft.volume=159&rft.issue=2&rft.spage=161&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 - 2003-02-26 N1 - Date created - 2003-01-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of c-Jun N-terminal kinase, p38 kinase and AP-1 DNA binding in cultured brain neurons: roles in glutamate excitotoxicity and lithium neuroprotection. AN - 72988080; 12558976 AB - In rat cerebellar granule cells, glutamate induced rapid activation of c-Jun N-terminal kinase (JNK) and p38 kinase to phosphorylate c-Jun (at Ser63) and p53 (at Ser15), respectively, and a subsequent marked increase in activator protein-1 (AP-1) binding that preceded apoptotic death. These glutamate-induced effects and apoptosis could largely be prevented by long-term (7 days) pretreatment with 0.5-2 mm lithium, an antibipolar drug. Glutamate's actions could also be prevented by known blockers of this pathway, MK-801 (an NMDA receptor blocker), SB 203580 (a p38 kinase inhibitor) and curcumin (an AP-1 binding inhibitor). The concentration- and time-dependent suppression of glutamate's effects by lithium and curcumin correlated well with their neuroprotective effects. These results suggest a prominent role of JNK and p38, as well as their downstream AP-1 binding activation and p53 phosphorylation in mediating glutamate excitotoxicity. Moreover, the neuroprotective effects of lithium are mediated, at least in part, by suppressing NMDA receptor-mediated activation of the mitogen-activated protein kinase pathway. JF - Journal of neurochemistry AU - Chen, Ren-Wu AU - Qin, Zheng-Hong AU - Ren, Ming AU - Kanai, Hirohiko AU - Chalecka-Franaszek, Elzbieta AU - Leeds, Peter AU - Chuang, De-Maw AD - Molecular Neurobiology Section, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2003/02// PY - 2003 DA - February 2003 SP - 566 EP - 575 VL - 84 IS - 3 SN - 0022-3042, 0022-3042 KW - Enzyme Inhibitors KW - 0 KW - Excitatory Amino Acid Antagonists KW - Neuroprotective Agents KW - Receptors, N-Methyl-D-Aspartate KW - Transcription Factor AP-1 KW - Tumor Suppressor Protein p53 KW - Glutamic Acid KW - 3KX376GY7L KW - DNA KW - 9007-49-2 KW - Lithium KW - 9FN79X2M3F KW - JNK Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinases KW - p38 Mitogen-Activated Protein Kinases KW - Index Medicus KW - Animals KW - MAP Kinase Signaling System -- drug effects KW - MAP Kinase Signaling System -- physiology KW - Apoptosis -- physiology KW - Receptors, N-Methyl-D-Aspartate -- metabolism KW - Tumor Suppressor Protein p53 -- metabolism KW - Phosphorylation -- drug effects KW - Neuroprotective Agents -- pharmacology KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Rats KW - Protein Binding -- physiology KW - Rats, Sprague-Dawley KW - Cerebellum -- cytology KW - Glutamic Acid -- toxicity KW - Time KW - Cells, Cultured KW - Apoptosis -- drug effects KW - Enzyme Activation -- drug effects KW - Enzyme Inhibitors -- pharmacology KW - Lithium -- pharmacology KW - Neurons -- metabolism KW - Transcription Factor AP-1 -- metabolism KW - Mitogen-Activated Protein Kinases -- metabolism KW - DNA -- metabolism KW - Neurons -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72988080?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Regulation+of+c-Jun+N-terminal+kinase%2C+p38+kinase+and+AP-1+DNA+binding+in+cultured+brain+neurons%3A+roles+in+glutamate+excitotoxicity+and+lithium+neuroprotection.&rft.au=Chen%2C+Ren-Wu%3BQin%2C+Zheng-Hong%3BRen%2C+Ming%3BKanai%2C+Hirohiko%3BChalecka-Franaszek%2C+Elzbieta%3BLeeds%2C+Peter%3BChuang%2C+De-Maw&rft.aulast=Chen&rft.aufirst=Ren-Wu&rft.date=2003-02-01&rft.volume=84&rft.issue=3&rft.spage=566&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 - 2003-02-14 N1 - Date created - 2003-01-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Amplification and overexpression of the EMS 1 oncogene, a possible prognostic marker, in human hepatocellular carcinoma. AN - 72986814; 12552080 AB - DNA amplification in cancer cells frequently involves oncogenes whose increased expression confers a selective advantage on tumor cell growth. In an attempt to identify novel oncogenes involved in hepatocarcinogenesis, representational difference analysis (RDA) was performed using DNA from a primary human hepatocellular carcinoma (HCC) that showed high-level DNA amplifications on chromosomes 1p32 and 11q13 by comparative genomic hybridization. Ten amplification fragments were isolated by RDA, and when used to probe Southern blots of tumor DNA, there was a 5- to 50-fold increase in hybridization intensity relative to normal DNA. The sequence of one amplification product matched that of the EMS1 oncogene, which is located on chromosome 11q13 and is amplified in other cancers. We detected EMS1 amplification in 3 of 17 primary HCC. Overexpression of EMS1 mRNA was observed in 12 of 14 HCC cell lines in the absence of gene amplification or an increased copy-number of the gene. The EMS1 gene encodes cortactin, a cortical actin-associated protein that is a substrate for Src kinase and is involved in cytoskeleton organization. Alterations of the EMS1 gene that lead to overexpression of cortactin may be associated with tumor development in HCC. EMS1 amplification and overexpresion is indicative of unfavorable prognosis in several cancers and may have similar prognostic implications in liver cancer. JF - The Journal of molecular diagnostics : JMD AU - Yuan, Bao-Zhu AU - Zhou, Xiaoling AU - Zimonjic, Drazen B AU - Durkin, Marian E AU - Popescu, Nicholas C AD - Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892-4258, USA. Y1 - 2003/02// PY - 2003 DA - February 2003 SP - 48 EP - 53 VL - 5 IS - 1 SN - 1525-1578, 1525-1578 KW - Biomarkers, Tumor KW - 0 KW - CTTN protein, human KW - Cortactin KW - DNA, Neoplasm KW - Microfilament Proteins KW - Index Medicus KW - Polymerase Chain Reaction KW - Biomarkers, Tumor -- genetics KW - Base Sequence KW - Tumor Cells, Cultured KW - Humans KW - Chromosomes, Human, Pair 11 -- genetics KW - Molecular Diagnostic Techniques KW - Prognosis KW - In Situ Hybridization, Fluorescence KW - Gene Expression KW - DNA, Neoplasm -- genetics KW - Gene Amplification KW - Oncogenes KW - Carcinoma, Hepatocellular -- genetics KW - Microfilament Proteins -- genetics KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72986814?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+molecular+diagnostics+%3A+JMD&rft.atitle=Amplification+and+overexpression+of+the+EMS+1+oncogene%2C+a+possible+prognostic+marker%2C+in+human+hepatocellular+carcinoma.&rft.au=Yuan%2C+Bao-Zhu%3BZhou%2C+Xiaoling%3BZimonjic%2C+Drazen+B%3BDurkin%2C+Marian+E%3BPopescu%2C+Nicholas+C&rft.aulast=Yuan&rft.aufirst=Bao-Zhu&rft.date=2003-02-01&rft.volume=5&rft.issue=1&rft.spage=48&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+molecular+diagnostics+%3A+JMD&rft.issn=15251578&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-31 N1 - Date created - 2003-01-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Oncogene. 2001 Oct 1;20(44):6418-34 [11607842] Cancer Res. 2001 Sep 15;61(18):6906-11 [11559568] Science. 1987 Jan 9;235(4785):177-82 [3798106] Science. 1987 Jan 16;235(4786):305-11 [3541204] EMBO J. 1987 Mar;6(3):605-10 [3034598] Oncogene. 1988 Nov;3(5):537-40 [2856253] Genomics. 1992 May;13(1):21-4 [1315716] Hum Genet. 1993 Feb;90(6):584-9 [8383093] Mol Cell Biol. 1993 May;13(5):2891-98 [8474448] Biochem Biophys Res Commun. 1993 Oct 29;196(2):1010-6 [8240318] Cancer Res. 1994 Jun 15;54(12):3107-10 [8205525] Cancer Genet Cytogenet. 1995 Apr;80(2):100-2 [7736422] Genes Chromosomes Cancer. 1995 Apr;12(4):288-95 [7539284] Gene. 1995 Jun 14;159(1):83-96 [7607576] Int J Cancer. 1996 Nov 15;68(4):485-92 [8945620] J Biol Chem. 1997 Mar 14;272(11):7374-80 [9054437] Cancer Res. 1998 May 15;58(10):2196-9 [9605766] J Clin Oncol. 1998 Aug;16(8):2659-71 [9704716] Cell Adhes Commun. 1998;6(2-3):185-209 [9823470] Hepatology. 1999 Apr;29(4):1208-14 [10094966] Hepatology. 1999 Jun;29(6):1858-62 [10347130] Br J Cancer. 1999 Aug;80(12):2034-9 [10471057] Int J Oncol. 2000 Feb;16(2):221-30 [10639563] Genes Chromosomes Cancer. 2000 Jun;28(2):153-63 [10825000] Gastroenterology. 2000 Aug;119(2):431-40 [10930378] Clin Cancer Res. 2000 Aug;6(8):3177-82 [10955801] Clin Cancer Res. 2000 Oct;6(10):4000-9 [11051249] Genes Chromosomes Cancer. 2001 Mar;30(3):245-53 [11170281] Nat Cell Biol. 2001 Mar;3(3):259-66 [11231575] Adv Cancer Res. 1986;47:235-81 [3022564] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lipopolysaccharide endotoxin potentiates the effect of osmotic stimulation on vasopressin synthesis and secretion in the rat hypothalamus. AN - 72984638; 12535156 AB - Vasopressin secreted by magnocellular neurones of the hypothalamic supraoptic and paraventricular nuclei is essential for water balance. In this study, we examined magnocellular neurone responses to osmotic stimulation in vehicle-injected controls or rats receiving an intraperitoneal (i.p.) injection of 250 microg/100 g of lipopolysaccharide (LPS), 3 h or 6 h earlier. LPS injection had no effect on plasma vasopressin concentrations in control rats but it caused marked and transient potentiation of the responses to a single i.p. injection of hypertonic saline (five- and two-fold, 3 and 6 h after LPS, respectively). The enhancement of plasma vasopressin responses was independent of plasma sodium concentrations or changes in blood pressure. Basal vasopressin mRNA expression in the paraventricular and supraoptic nuclei decreased slightly 6 h after LPS injection, without changes in vasopressin transcription as indicated by vasopressin heteronuclear (hn) RNA levels. Parvocellular neurones showed expected increases in vasopressin hnRNA expression following LPS injection and a further increase after i.p. hypertonic saline injection (due to the painful component). In contrast to magnocellular vasopressin mRNA expression, the effects of LPS and hypertonic saline injections in parvocellular neurones were additive and not synergistic. Light microscopic immunohistochemical examination revealed an increase in size of vasopressin but not oxytocin axonal terminals in the neural lobe 3 h after LPS injection. Osmotic stimulation caused marked depletion of vasopressin immunoreactivity in axonal terminals of the neural lobe in both control and LPS-pretreated rats. The changes in vasopressin axon terminals were accompanied by induction of interleukin (IL)-1 beta and IL-6 in the posterior pituitary. The data show that endotoxemia causes morphological and functional alterations of the hypothalamic neurohypophyseal system, resulting in facilitation rather than inhibition of vasopressin synthesis, and secretion in response to osmotic stimulation. JF - Journal of neuroendocrinology AU - Grinevich, V AU - Ma, X-M AU - Jirikowski, G AU - Verbalis, J AU - Aguilera, G AD - Section on Endocrine Physiology, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20982, USA. Y1 - 2003/02// PY - 2003 DA - February 2003 SP - 141 EP - 149 VL - 15 IS - 2 SN - 0953-8194, 0953-8194 KW - Antibodies KW - 0 KW - Interleukin-1 KW - Interleukin-6 KW - Lipopolysaccharides KW - RNA Precursors KW - RNA, Messenger KW - Saline Solution, Hypertonic KW - Vasopressins KW - 11000-17-2 KW - Oxytocin KW - 50-56-6 KW - Sodium KW - 9NEZ333N27 KW - Index Medicus KW - Gene Expression -- drug effects KW - Animals KW - Transcription, Genetic -- drug effects KW - Oxytocin -- analysis KW - RNA, Messenger -- analysis KW - Oxytocin -- immunology KW - Pituitary Gland, Posterior -- physiology KW - Rats KW - Interleukin-6 -- genetics KW - Pituitary Gland, Posterior -- chemistry KW - Rats, Wistar KW - RNA Precursors -- analysis KW - Interleukin-1 -- genetics KW - Sodium -- blood KW - Blood Pressure -- drug effects KW - Drug Synergism KW - Male KW - Paraventricular Hypothalamic Nucleus -- secretion KW - Hypothalamus, Anterior -- drug effects KW - Vasopressins -- secretion KW - Paraventricular Hypothalamic Nucleus -- metabolism KW - Hypothalamus, Anterior -- secretion KW - Saline Solution, Hypertonic -- pharmacology KW - Vasopressins -- genetics KW - Lipopolysaccharides -- pharmacology KW - Hypothalamus, Anterior -- metabolism KW - Water-Electrolyte Balance -- drug effects KW - Vasopressins -- blood KW - Paraventricular Hypothalamic Nucleus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72984638?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neuroendocrinology&rft.atitle=Lipopolysaccharide+endotoxin+potentiates+the+effect+of+osmotic+stimulation+on+vasopressin+synthesis+and+secretion+in+the+rat+hypothalamus.&rft.au=Grinevich%2C+V%3BMa%2C+X-M%3BJirikowski%2C+G%3BVerbalis%2C+J%3BAguilera%2C+G&rft.aulast=Grinevich&rft.aufirst=V&rft.date=2003-02-01&rft.volume=15&rft.issue=2&rft.spage=141&rft.isbn=&rft.btitle=&rft.title=Journal+of+neuroendocrinology&rft.issn=09538194&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-26 N1 - Date created - 2003-01-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Function of Candida glabrata ABC transporter gene, PDH1. AN - 72983490; 12557277 AB - The rapid increase in azole resistance during treatment of patients infected with Candida glabrata may be due to increased azole efflux mediated by ABC transporters, as occurs with increased expression of PDR5 in Saccharomyces cerevisiae. Two known C. glabrata homologues of PDR5 influencing azole susceptibility are PDH1 (CgCDR2) and CgCDR1. Disruption of PDH1 in a cgcdr1::ura3 strain increased susceptibility to rhodamine 6G, cycloheximide and chloramphenicol, and also increased rhodamine 6G accumulation, all properties of pdr5 null mutants. Overexpression of PDH1 in S. cerevisiae complemented the pdr5 mutation by reversing susceptibility to rhodamine 6G, chloramphenicol and cycloheximide, as well as by decreasing rhodamine 6G intracellular concentration. Expression of PDH1 in a C. glabrata cgcdr1::ura3 pdh1Delta::ura3 mutant using a multicopy plasmid almost completely restored the wild-type phenotype, showing that PDH1 at higher levels of expression can replace CgCDR1. Because PDH1 and CgCDR1 have both been reported to have upstream sequences similar to the Pdr1p- and Pdr3p-binding elements of PDR5, we sought similarities in regulation between the three genes. Abundance of PDH1 and CgCDR1 mRNA in C. glabrata was increased by rhodamine 6G, cycloheximide and oligomycin, properties in common with PDR5. PDH1, CgCDR1 and PDR5 have striking similarities in function and regulation. JF - Yeast (Chichester, England) AU - Izumikawa, Koichi AU - Kakeya, Hiroshi AU - Tsai, Huei-Fung AU - Grimberg, Brian AU - Bennett, John E AD - Clinical Mycology Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA. Y1 - 2003/02// PY - 2003 DA - February 2003 SP - 249 EP - 261 VL - 20 IS - 3 SN - 0749-503X, 0749-503X KW - Antifungal Agents KW - 0 KW - DNA, Fungal KW - Fungal Proteins KW - Membrane Proteins KW - Protein Synthesis Inhibitors KW - RNA, Fungal KW - Rhodamines KW - Saccharomyces cerevisiae Proteins KW - rhodamine 6G KW - 037VRW83CF KW - Chloramphenicol KW - 66974FR9Q1 KW - Cycloheximide KW - 98600C0908 KW - Index Medicus KW - Gene Expression Regulation, Fungal KW - RNA, Fungal -- genetics KW - Blotting, Northern KW - Rhodamines -- pharmacology KW - Immunodiffusion KW - Humans KW - Transformation, Genetic -- physiology KW - Chloramphenicol -- pharmacology KW - Polymerase Chain Reaction KW - Antifungal Agents -- pharmacology KW - Protein Synthesis Inhibitors -- pharmacology KW - Cycloheximide -- pharmacology KW - Drug Resistance, Fungal KW - DNA, Fungal -- genetics KW - DNA, Fungal -- chemistry KW - Mutagenesis, Insertional KW - RNA, Fungal -- chemistry KW - Fungal Proteins -- physiology KW - Candida glabrata -- metabolism KW - Candida glabrata -- genetics KW - Membrane Proteins -- genetics KW - Fungal Proteins -- genetics KW - Membrane Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72983490?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Yeast+%28Chichester%2C+England%29&rft.atitle=Function+of+Candida+glabrata+ABC+transporter+gene%2C+PDH1.&rft.au=Izumikawa%2C+Koichi%3BKakeya%2C+Hiroshi%3BTsai%2C+Huei-Fung%3BGrimberg%2C+Brian%3BBennett%2C+John+E&rft.aulast=Izumikawa&rft.aufirst=Koichi&rft.date=2003-02-01&rft.volume=13&rft.issue=6&rft.spage=545&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 - 2003-04-04 N1 - Date created - 2003-01-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The nitric oxide donor, V-PYRRO/NO, protects against acetaminophen-induced hepatotoxicity in mice. AN - 72981747; 12540782 AB - The liver-selective nitric oxide (NO) donor, O(2)-vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (V-PYRRO/NO), is metabolized by P-450 enzymes to release NO in the liver, and is shown to protect the liver from tumor necrosis factor alpha (TNF-alpha)-induced apoptosis and D-glactosamine/endotoxin-induced hepatotoxicity. This study was undertaken to examine the effects of V-PYRRO/NO on acetaminophen-induced hepatotoxicity in mice. Mice were given V-PYRRO/NO via osmotic pumps (1.8-5.4 mg/mL, 8 microL/h) 4 to 16 hours before a hepatotoxic dose of acetaminophen (600 mg/kg, intraperitoneally [ip]). V-PYRRO/NO administration dramatically reduced acetaminophen-induced hepatotoxicity in a dose- and time-dependent manner, as evidenced by reduced serum alanine aminotransferase (ALT) activity, reduced hepatic congestion, apoptosis, and improved hepatocellular pathology. The protection afforded by V-PYRRO/NO does not appear to be caused by a decrease in the formation of toxic acetaminophen metabolites, which consumes glutathione (GSH), because V-PYRRO/NO did not alter acetaminophen-induced hepatic GSH depletion. Acetaminophen-induced lipid peroxidation, as determined by the concentrations of 4-hydroxyalkenals (4-HNE) and malondialdehyde (MDA), was reduced significantly by V-PYRRO/NO treatment. Although pretreatment was most effective, administration of V-PYRRO/NO simultaneously with acetaminophen also was able to reduce acetaminophen hepatotoxicity. Genomic analysis of the liver samples 10 hours after acetaminophen intoxication showed the enhanced expression of genes associated with stress/oxidative stress, apoptosis/cell death, and DNA damage/repair. Acetaminophen-induced alterations in gene expression were attenuated significantly by V-PYRRO/NO. Real-time reverse-transcription polymerase chain reaction (RT-PCR) and Western-blot analysis confirmed microarray results. In conclusion, V-PYRRO/NO is effective in blocking acetaminophen-induced hepatotoxicity in mice. This protection may involve the reduction of oxidative stress, the inhibition of apoptosis, and possibly the maintenance of hepatic vasculature to prevent congestion. JF - Hepatology (Baltimore, Md.) AU - Liu, Jie AU - Li, Chengxiu AU - Waalkes, Michael P AU - Clark, James AU - Myers, Page AU - Saavedra, Joseph E AU - Keefer, Larry K AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at the National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC 27709, USA. Liu6@niehs.nih.gov Y1 - 2003/02// PY - 2003 DA - February 2003 SP - 324 EP - 333 VL - 37 IS - 2 SN - 0270-9139, 0270-9139 KW - Chelating Agents KW - 0 KW - Nitric Oxide Donors KW - O(2)-vinyl-1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate KW - Pyrrolidines KW - Acetaminophen KW - 362O9ITL9D KW - Index Medicus KW - Gene Expression -- drug effects KW - Mice, Inbred Strains KW - Animals KW - Computer Systems KW - Blotting, Western KW - Oligonucleotide Array Sequence Analysis KW - Chemical and Drug Induced Liver Injury KW - Liver Diseases -- mortality KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - Liver Diseases -- prevention & control KW - Female KW - Nitric Oxide Donors -- pharmacology KW - Liver -- pathology KW - Liver -- drug effects KW - Acetaminophen -- poisoning KW - Cytoprotection KW - Pyrrolidines -- pharmacology KW - Chelating Agents -- poisoning UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72981747?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+nitric+oxide+donor%2C+V-PYRRO%2FNO%2C+protects+against+acetaminophen-induced+hepatotoxicity+in+mice.&rft.au=Liu%2C+Jie%3BLi%2C+Chengxiu%3BWaalkes%2C+Michael+P%3BClark%2C+James%3BMyers%2C+Page%3BSaavedra%2C+Joseph+E%3BKeefer%2C+Larry+K&rft.aulast=Liu&rft.aufirst=Jie&rft.date=2003-02-01&rft.volume=37&rft.issue=2&rft.spage=324&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 - 2003-03-12 N1 - Date created - 2003-01-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clove cigarette smoking: biochemical, physiological, and subjective effects. AN - 72971571; 12543240 AB - Alternative tobacco products such as clove (kreteks) and bidi cigarettes have become increasingly popular among US smokers. The nicotine content of a popular clove cigarette (Djarum Special) filler averaged 7.4 mg; conventional cigarettes contained 13.0 mg. However, smoke yields from standardized machine-smoking analysis indicated it delivered more nicotine, carbon monoxide (CO), and tar than conventional cigarettes. In a clinical study, nicotine delivery, physiologic, and subjective effects of the clove cigarette were compared to their own brand of cigarette in 10 adult smokers (7 males). Average time to smoke the clove cigarette (549 s) and number of puffs (15.1) were significantly greater than own brand (314 s and 9.4 puffs). Increases in venous plasma nicotine and exhaled CO after smoking the clove cigarette (17.4 ng/ml; 6 ppm) were similar to those after own brand (17.6 ng/ml; 4.5 ppm). Maximal changes in heart rate (HR), systolic, and diastolic blood pressures (BP) did not differ significantly between the clove and own brand of cigarette. Compared to their own brand of cigarette, the clove cigarette was rated as better tasting and being distinctly different. Our findings indicate that clove cigarettes deliver significant quantities of nicotine, CO, and presumably other toxic components of tobacco smoke. Taste satisfaction, aromatic odor, and novelty may contribute to their appeal to young smokers. JF - Pharmacology, biochemistry, and behavior AU - Malson, Jennifer L AU - Lee, Eun M AU - Murty, Ram AU - Moolchan, Eric T AU - Pickworth, Wallace B AD - National Institute on Drug Abuse, Intramural Research Program, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2003/02// PY - 2003 DA - February 2003 SP - 739 EP - 745 VL - 74 IS - 3 SN - 0091-3057, 0091-3057 KW - Nicotine KW - 6M3C89ZY6R KW - Index Medicus KW - Analysis of Variance KW - Nicotine -- pharmacology KW - Humans KW - Adult KW - Nicotine -- blood KW - Middle Aged KW - Male KW - Female KW - Heart Rate -- drug effects KW - Smoking -- blood KW - Affect -- drug effects KW - Affect -- physiology KW - Heart Rate -- physiology KW - Smoking -- psychology KW - Syzygium UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72971571?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Clove+cigarette+smoking%3A+biochemical%2C+physiological%2C+and+subjective+effects.&rft.au=Malson%2C+Jennifer+L%3BLee%2C+Eun+M%3BMurty%2C+Ram%3BMoolchan%2C+Eric+T%3BPickworth%2C+Wallace+B&rft.aulast=Malson&rft.aufirst=Jennifer&rft.date=2003-02-01&rft.volume=74&rft.issue=3&rft.spage=739&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 - 2003-08-04 N1 - Date created - 2003-01-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Critical role of c-Jun N-terminal protein kinase activation in troglitazone-induced apoptosis of human HepG2 hepatoma cells. AN - 72965073; 12527812 AB - The peroxisome proliferator-activated receptor agonist troglitazone (TRO) was used for treatment of non-insulin-dependent diabetes until its removal from the market because of its severe hepatotoxicity. However, the mechanism for its hepatotoxicity is still poorly understood. In this study, we investigated whether TRO caused cell death by altering signaling pathways associated with cell damage and survival in human hepatoma cells. Our data reveal that TRO caused time- and concentration-dependent apoptosis of HepG2 and Chang liver human hepatoma cells, as evidenced by DNA fragmentation and staining with Hoechst 33342. In contrast, 50 or 100 microM rosiglitazone, a structural analog of TRO, did not cause apoptosis in these hepatoma cells. TRO activated both c-Jun N-terminal protein kinase (JNK) and p38 kinase about 5-fold between 0.5 and 8 h before they returned to control levels at 16 h in HepG2 cells. In contrast, TRO failed to activate the extracellular signal-regulated kinase. Furthermore, TRO increased the levels of proapoptotic proteins, Bad, Bax, release of cytochrome c, and cleavage of Bid in a time-dependent manner. The antiapoptotic Bcl-2 protein level decreased in hepatoma cells treated with TRO. Pretreatment of hepatoma cells with a selective JNK inhibitor, anthra[1,9-cd]pyrazol-6(2H)-one (SP600125), significantly reduced the rate of TRO-induced cell death, whereas 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole (SB203580), an inhibitor of p38 kinase, had little effect on apoptosis. Pretreatment with SP600125 also prevented JNK activation and c-Jun phosphorylation. In addition, rosiglitazone, which is not as toxic to hepatoma cells as TRO, did not stimulate JNK activity. Transfection of cDNA for the dominant-negative mutant JNK-KR (Lys-->Arg) or SEK1-KR (Lys-->Arg), an immediate upstream kinase of JNK, significantly reduced TRO-induced JNK activation and cell death rate. Furthermore, SP600125 pretreatment effectively prevented the TRO-mediated changes in Bad, Bax, Bid cleavage, and cytochrome c release. These data strongly suggest that hepatotoxic TRO causes apoptosis by activating the JNK-dependent cell death pathway accompanied by increased Bid cleavage and elevation of proapoptotic proteins. JF - Molecular pharmacology AU - Bae, Myung-Ae AU - Song, Byoung J AD - Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland 20852, USA. Y1 - 2003/02// PY - 2003 DA - February 2003 SP - 401 EP - 408 VL - 63 IS - 2 SN - 0026-895X, 0026-895X KW - Anthracenes KW - 0 KW - Antineoplastic Agents KW - BH3 Interacting Domain Death Agonist Protein KW - BID protein, human KW - Carrier Proteins KW - Chromans KW - Thiazoles KW - Thiazolidinediones KW - pyrazolanthrone KW - 1TW30Y2766 KW - Cycloheximide KW - 98600C0908 KW - JNK Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinases KW - p38 Mitogen-Activated Protein Kinases KW - troglitazone KW - I66ZZ0ZN0E KW - Index Medicus KW - Drug Interactions KW - Anthracenes -- pharmacology KW - Carrier Proteins -- metabolism KW - Dose-Response Relationship, Drug KW - Enzyme Activation KW - Humans KW - Tumor Cells, Cultured KW - Cycloheximide -- pharmacology KW - Signal Transduction -- drug effects KW - Carcinoma, Hepatocellular -- pathology KW - Time Factors KW - Thiazoles -- pharmacology KW - Chromans -- pharmacology KW - Mitogen-Activated Protein Kinases -- metabolism KW - Apoptosis -- physiology KW - Mitogen-Activated Protein Kinases -- physiology KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72965073?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Body+Composition+in+Studies+of+Aging%3A+New+Opportunities+to+Better+Understand+Health+Risks+Associated+with+Weight&rft.au=Harris%2C+T+B&rft.aulast=Harris&rft.aufirst=T&rft.date=2002-07-01&rft.volume=156&rft.issue=2&rft.spage=122&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 - 2003-02-21 N1 - Date created - 2003-01-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of plasma membrane lipid microdomains in respiratory syncytial virus filament formation. AN - 72962850; 12525608 AB - The fusion protein (F) of respiratory syncytial virus (RSV) is the envelope glycoprotein responsible for the characteristic cytopathology of syncytium formation. RSV has been shown to bud from selective areas of the plasma membrane as pleomorphic virions, including both filamentous and round particles. With immunofluorescent microscopy, we demonstrated evidence of RSV filaments incorporating the fusion protein F and colocalizing with a lipid microdomain-specific fluorescent dye, 1,1-dihexadecyl-3,3,3,3-tetramethylindocarbocyanine perchlorate. Western blot analysis of Triton X-100 cold-extracted membrane fractions confirmed the presence of RSV proteins within the lipid microdomains. RSV proteins also colocalized with cellular proteins associated with lipid microdomains, caveolin-1, and CD44, as well as with RhoA, a small GTPase. ADP-ribosylation of RhoA by Clostridium botulinum exotoxin inactivated RhoA signaling and resulted in the absence of RSV-induced syncytia despite no significant change in viral titer. We demonstrated an overall decrease in both the number and length of the viral filaments and a shift in the localization of F to nonlipid microdomain regions of the membrane in the presence of C3 toxin. This suggests that the selective incorporation of RSV proteins into lipid microdomains during virus assembly may lead to critical interactions of F with cellular proteins, resulting in microvillus projections necessary for the formation of filamentous virus particles and syncytium formation. Thus, manipulation of membrane lipid microdomains may lead to alterations in the production of viral filaments and RSV pathogenesis and provide a new pharmacologic target for RSV therapy. JF - Journal of virology AU - McCurdy, Lewis H AU - Graham, Barney S AD - Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-3017, USA. bgraham@nih.gov Y1 - 2003/02// PY - 2003 DA - February 2003 SP - 1747 EP - 1756 VL - 77 IS - 3 SN - 0022-538X, 0022-538X KW - Antigens, CD44 KW - 0 KW - CAV1 protein, human KW - Caveolin 1 KW - Caveolins KW - Cyclodextrins KW - Viral Fusion Proteins KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - exoenzyme C3, Clostridium botulinum KW - Botulinum Toxins KW - EC 3.4.24.69 KW - rhoA GTP-Binding Protein KW - EC 3.6.5.2 KW - Index Medicus KW - Cyclodextrins -- pharmacology KW - Humans KW - Botulinum Toxins -- pharmacology KW - Antigens, CD44 -- analysis KW - Caveolins -- analysis KW - ADP Ribose Transferases -- pharmacology KW - rhoA GTP-Binding Protein -- analysis KW - Cell Line KW - Virus Assembly KW - Respiratory Syncytial Viruses -- physiology KW - Viral Fusion Proteins -- physiology KW - Membrane Microdomains -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72962850?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Alcohol+%28Fayetteville%2C+N.Y.%29&rft.atitle=Role+of+S-adenosyl-L-methionine+in+the+treatment+of+alcoholic+liver+disease%3A+introduction+and+summary+of+the+symposium.&rft.au=Purohit%2C+Vishnudutt%3BRusso%2C+Denise&rft.aulast=Purohit&rft.aufirst=Vishnudutt&rft.date=2002-07-01&rft.volume=27&rft.issue=3&rft.spage=151&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 - 2003-02-11 N1 - Date created - 2003-01-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Gen Virol. 1987 Sep;68 ( Pt 9):2521-4 [3655746] Anal Biochem. 1984 Apr;138(1):141-3 [6731838] J Med Virol. 1988 Oct;26(2):153-62 [3183639] Biochim Biophys Acta. 1990 Mar 30;1023(1):25-33 [2317494] J Infect Dis. 1990 Aug;162(2):568-9 [2197348] Cell. 1992 Feb 7;68(3):533-44 [1531449] J Infect Dis. 1992 Jun;165(6):987-93 [1583345] Cell. 1992 Aug 7;70(3):389-99 [1643657] J Biol Chem. 1992 Oct 5;267(28):20033-8 [1400319] Virology. 1995 Jan 10;206(1):485-94 [7831804] J Virol. 1995 Apr;69(4):2667-73 [7884920] J Heart Lung Transplant. 1995 May-Jun;14(3):479-85 [7654733] J Biochem. 1996 Aug;120(2):215-28 [8889802] Nature. 1997 Jun 5;387(6633):569-72 [9177342] Arch Virol. 1997;142(6):1247-54 [9229012] Science. 1998 Jan 23;279(5350):509-14 [9438836] J Cell Biol. 1998 Feb 23;140(4):885-95 [9472040] Chest. 1998 Apr;113(4):944-50 [9554629] J Infect Dis. 1999 Jan;179(1):25-30 [9841818] J Biol Chem. 1998 Dec 25;273(52):34663-6 [9856983] J Biol Chem. 1999 Jan 22;274(4):2038-44 [9890962] Annu Rev Cell Dev Biol. 1998;14:111-36 [9891780] Virology. 1999 Feb 1;254(1):81-91 [9927576] J Virol. 1999 Aug;73(8):6610-7 [10400758] J Virol. 1999 Sep;73(9):7262-70 [10438814] JAMA. 1999 Oct 20;282(15):1440-6 [10535434] Exp Cell Res. 1999 Nov 25;253(1):166-79 [10579921] J Virol. 2000 Jan;74(1):305-11 [10590118] Nat Med. 2000 Jan;6(1):35-40 [10613821] J Cell Biol. 1999 Aug 23;146(4):843-54 [10459018] J Virol. 2000 Apr;74(7):3264-72 [10708443] J Virol. 2000 May;74(10):4634-44 [10775599] Biol Cell. 2000 Aug;92(5):305-16 [11071040] Antimicrob Agents Chemother. 2001 Apr;45(4):1231-7 [11257039] EMBO Rep. 2000 Aug;1(2):190-6 [11265761] Virology. 2001 May 10;283(2):188-96 [11336544] J Virol. 2001 Aug;75(15):6825-34 [11435561] AIDS Res Hum Retroviruses. 2001 Jul 20;17(11):1009-19 [11485618] Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13925-30 [11717449] J Gen Virol. 2002 Mar;83(Pt 3):611-21 [11842256] J Exp Med. 2002 Mar 4;195(5):593-602 [11877482] J Gen Virol. 2002 Aug;83(Pt 8):1841-50 [12124448] J Virol. 1976 Nov;20(2):487-500 [62058] J Virol. 1983 Jul;47(1):171-7 [6345804] J Cell Biol. 1988 Nov;107(5):1689-95 [3182934] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The carboxy terminus of Prospero regulates its subcellular localization. AN - 72959829; 12529405 AB - Subcellular localization of the transcription factor Prospero is dynamic. For example, the protein is cytoplasmic in neuroblasts, nuclear in sheath cells, and degraded in newly formed neurons. The carboxy terminus of Prospero, including the homeodomain and Prospero domain, plays roles in regulating these changes. The homeodomain has two distinct subdomains, which exclude proteins from the nucleus, while the intact homeo/Prospero domain masks this effect. One subdomain is an Exportin-dependent nuclear export signal requiring three conserved hydrophobic residues, which models onto helix 1. Another, including helices 2 and 3, requires proteasome activity to degrade nuclear protein. Finally, the Prospero domain is missing in pros(I13) embryos, thus unmasking nuclear exclusion, resulting in constitutively cytoplasmic protein. Multiple processes direct Prospero regulation of cell fate in embryonic nervous system development. JF - Molecular and cellular biology AU - Bi, Xiaolin AU - Kajava, Andrey V AU - Jones, Tamara AU - Demidenko, Zoya N AU - Mortin, Mark A AD - Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/02// PY - 2003 DA - February 2003 SP - 1014 EP - 1024 VL - 23 IS - 3 SN - 0270-7306, 0270-7306 KW - Drosophila Proteins KW - 0 KW - Homeodomain Proteins KW - Nerve Tissue Proteins KW - Nuclear Localization Signals KW - Nuclear Proteins KW - Recombinant Fusion Proteins KW - Transcription Factors KW - pros protein, Drosophila KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Transcription Factors -- metabolism KW - Animals, Genetically Modified KW - Homeodomain Proteins -- chemistry KW - Drosophila -- embryology KW - Recombinant Fusion Proteins -- chemistry KW - Mutagenesis, Site-Directed KW - Recombinant Fusion Proteins -- metabolism KW - Homeodomain Proteins -- genetics KW - Transcription Factors -- chemistry KW - Homeodomain Proteins -- metabolism KW - Molecular Sequence Data KW - Recombinant Fusion Proteins -- genetics KW - Nervous System -- embryology KW - Nervous System -- metabolism KW - Drosophila -- genetics KW - Active Transport, Cell Nucleus KW - Models, Molecular KW - Drosophila -- metabolism KW - Amino Acid Sequence KW - Transcription Factors -- genetics KW - Base Sequence KW - DNA -- genetics KW - Subcellular Fractions -- metabolism KW - Protein Structure, Tertiary KW - Cell Line KW - Drosophila Proteins -- chemistry KW - Nuclear Proteins -- genetics KW - Nerve Tissue Proteins -- metabolism KW - Nuclear Proteins -- chemistry KW - Drosophila Proteins -- genetics KW - Nuclear Proteins -- metabolism KW - Nerve Tissue Proteins -- genetics KW - Nerve Tissue Proteins -- chemistry KW - Drosophila Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72959829?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+carboxy+terminus+of+Prospero+regulates+its+subcellular+localization.&rft.au=Bi%2C+Xiaolin%3BKajava%2C+Andrey+V%3BJones%2C+Tamara%3BDemidenko%2C+Zoya+N%3BMortin%2C+Mark+A&rft.aulast=Bi&rft.aufirst=Xiaolin&rft.date=2003-02-01&rft.volume=23&rft.issue=3&rft.spage=1014&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 - 2003-02-25 N1 - Date created - 2003-01-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Genes Dev. 2000 Jan 15;14(2):147-51 [10652268] Nature. 1997 Nov 20;390(6657):308-11 [9384386] In Silico Biol. 1999;1(3):163-73 [11471237] Annu Rev Genet. 2001;35:341-64 [11700287] Proc Natl Acad Sci U S A. 1990 Jun;87(12):4864-8 [2352953] Nature. 1997 Dec 11;390(6660):625-9 [9403694] Exp Cell Res. 1998 Aug 1;242(2):540-7 [9683540] Mech Dev. 1998 Aug;76(1-2):175-8 [9767161] Dev Biol. 1998 Dec 15;204(2):478-87 [9882484] Development. 1999 May;126(10):2063-71 [10207132] Development. 1999 May;126(10):2083-92 [10207134] Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9112-7 [10430904] Cell. 1990 Nov 2;63(3):579-90 [1977522] Cell. 1991 May 3;65(3):451-64 [1673362] Cell. 1991 Nov 1;67(3):517-28 [1682054] Cell. 1991 Nov 29;67(5):941-53 [1720353] Biochem Biophys Res Commun. 1992 Feb 14;182(3):1326-32 [1540176] Development. 1991;Suppl 2:79-85 [1842358] Development. 1993 Apr;117(4):1211-22 [8404526] Mech Dev. 1993 Nov;44(1):3-16 [7908825] Trends Biochem Sci. 1994 Feb;19(2):70-1 [7909177] J Mol Biol. 1994 Nov 18;244(1):13-22 [7966318] Annu Rev Biochem. 1994;63:487-526 [7979246] Science. 1995 May 5;268(5211):726-31 [7732382] Development. 1995 Oct;121(10):3187-95 [7588053] Nature. 1995 Oct 19;377(6550):627-30 [7566173] J Biol Chem. 1996 Mar 29;271(13):7273-6 [8631740] Methods Enzymol. 1996;266:383-402 [8743695] Genomics. 1996 Aug 1;35(3):517-22 [8812486] Dev Dyn. 1996 Aug;206(4):354-67 [8853985] Comput Chem. 1996 Mar;20(1):3-23 [8867839] Cell. 1997 Aug 8;90(3):449-58 [9267025] Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10991-6 [9380747] J Biol Chem. 1997 Nov 21;272(47):29742-51 [9368044] Development. 2001 Apr;128(8):1359-67 [11262236] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Placental mammal diversification and the Cretaceous-Tertiary boundary AN - 50253391; 2008-061839 AB - Competing hypotheses for the timing of the placental mammal radiation focus on whether extant placental orders originated and diversified before or after the Cretaceous-Tertiary (K/T) boundary. Molecular studies that have addressed this issue suffer from single calibration points, unwarranted assumptions about the molecular clock, and/or taxon sampling that lacks representatives of all placental orders. We investigated this problem using the largest available molecular data set for placental mammals, which includes segments of 19 nuclear and three mitochondrial genes for representatives of all extant placental orders. We used the Thorne/Kishino method, which permits simultaneous constraints from the fossil record and allows rates of molecular evolution to vary on different branches of a phylogenetic tree. Analyses that used different sets of fossil constraints, different priors for the base of Placentalia, and different data partitions all support interordinal divergences in the Cretaceous followed by intraordinal diversification mostly after the K/T boundary. Four placental orders show intraordinal diversification that predates the K/T boundary, but only by an average of 10 million years. In contrast to some molecular studies that date the rat-mouse split as old as 46 million years, our results show improved agreement with the fossil record and place this split at 16-23 million years. To test the hypothesis that molecular estimates of Cretaceous divergence times are an artifact of increased body size subsequent to the K/T boundary, we also performed analyses with a "K/T body size" taxon set. In these analyses, interordinal splits remained in the Cretaceous. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Springer, Mark S AU - Murphy, William J AU - Eizirik, Eduardo AU - O'Brien, Stephen J Y1 - 2003/02// PY - 2003 DA - February 2003 SP - 1056 EP - 1061 PB - National Academy of Sciences, Washington, DC VL - 100 IS - 3 SN - 0027-8424, 0027-8424 KW - lower Paleocene KW - Cretaceous KW - Bayesian analysis KW - DIVTIME5B KW - molecular clocks KW - Upper Cretaceous KW - Cenozoic KW - Theria KW - explosive model KW - Paleocene KW - Eutheria KW - Chordata KW - biodiversity KW - phylogeny KW - Monte Carlo analysis KW - global KW - statistical analysis KW - short fuse model KW - Mammalia KW - long fuse model KW - biologic evolution KW - Paleogene KW - Mesozoic KW - size KW - time scales KW - models KW - Tertiary KW - K-T boundary KW - stratigraphic boundary KW - Vertebrata KW - fossil record KW - Tetrapoda KW - 11:Vertebrate paleontology KW - 12:Stratigraphy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/50253391?accountid=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=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Placental+mammal+diversification+and+the+Cretaceous-Tertiary+boundary&rft.au=Springer%2C+Mark+S%3BMurphy%2C+William+J%3BEizirik%2C+Eduardo%3BO%27Brien%2C+Stephen+J&rft.aulast=Springer&rft.aufirst=Mark&rft.date=2003-02-01&rft.volume=100&rft.issue=3&rft.spage=1056&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/10.1073%2Fpnas.0334222100 L2 - http://www.pnas.org/ LA - English DB - GeoRef N1 - Copyright - GeoRef, Copyright 2012, American Geosciences Institute. N1 - Date revised - 2008-01-01 N1 - Number of references - 48 N1 - PubXState - DC N1 - Document feature - illus. incl. 2 tables N1 - SuppNotes - Supplemental information/data is available in the online version of this article N1 - Last updated - 2012-06-07 N1 - CODEN - PNASA6 N1 - SubjectsTermNotLitGenreText - Bayesian analysis; biodiversity; biologic evolution; Cenozoic; Chordata; Cretaceous; DIVTIME5B; Eutheria; explosive model; fossil record; global; K-T boundary; long fuse model; lower Paleocene; Mammalia; Mesozoic; models; molecular clocks; Monte Carlo analysis; Paleocene; Paleogene; phylogeny; short fuse model; size; statistical analysis; stratigraphic boundary; Tertiary; Tetrapoda; Theria; time scales; Upper Cretaceous; Vertebrata DO - http://dx.doi.org/10.1073/pnas.0334222100 ER - TY - JOUR T1 - Pharmacology, toxicology, and radiation dosimetry evaluation of [123I]5-I-A-85380, a radioligand for in vivo imaging of cerebral neuronal nicotinic acetylcholine receptors in humans AN - 20416871; 7761669 AB - [123I]5-I-A-85380, which selectively binds to 42 nicotinic acetylcholine receptors, may be a suitable single photon emission computed tomography (SPECT) ligand for imaging nicotinic receptors in the human brain. In a mutagenicity study, 5-I-A-85380 produced positive effects in one of five bacterial strains in the bacterial reverse mutation assay only with metabolic activation. The ED50 for 5-I-A-85380 to elicit tonic-clonic convulsions in mice, 7.1 µmol/kg, i.v., was five times that of nicotine (ED50=1.4 µmol/kg, i.v.). A 2-day acute toxicity study (0.03-150 nmol/kg, i.v.) and a 14-day chronic toxicity study (0.3-30 nmol/kg, s.c.) in mice revealed no evidence of gross pathology or histopathological changes. Biodistribution and dosimetry studies revealed that the urinary bladder wall and the thyroid gland were the critical organs with respect to radiation exposure. In unanesthetized rats, 5-I-A-85380 (5.2-174 nmol/kg, i.v.) and nicotine (20-400 nmol/kg, i.v.) produced similar increases in systolic and diastolic blood pressure, heart rate, and locomotor activity. Doses of 5-I-A-85380 that elevated blood pressure and heart rate by 10% ranged from 5-10 nmol/kg, i.v. The highest doses tested, which produced near maximal increases in blood pressure and heart rate, did not affect the PR, QRS, or QTc intervals of the electrocardiogram. Based on these preclinical data, initial SPECT imaging studies in humans (Fujita et al. [2002] Eur J Nucl Med 29:183-190) used a mass dose of 8.6 pmol/kg [123I]5-I-A-8380, estimated to be 1/580th of the dose that elevates blood pressure and heart rate by 10%. Importantly, no clinical pharmacological effects were observed. JF - Drug Development Research AU - Vaupel, D Bruce AU - Tella, Srihari R AU - Huso, David L AU - Mukhin, Alexey G AU - Baum, Ira AU - Wagner III, Valentine O AU - Horti, Andrew G AU - London, Edythe D AU - Koren, Andrei O AU - Kimes, Alane S AD - Intramural Research Program, Neuroimaging Research Branch, National Institute on Drug Abuse, Baltimore, Maryland, bvaupel@irp.nida.nih.gov Y1 - 2003/02// PY - 2003 DA - Feb 2003 SP - 149 EP - 168 PB - John Wiley & Sons, 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 58 IS - 2 SN - 0272-4391, 0272-4391 KW - Toxicology Abstracts; Microbiology Abstracts B: Bacteriology; CSA Neurosciences Abstracts KW - Neuroimaging KW - Mutagenicity KW - Data processing KW - Urinary bladder KW - Pharmacology KW - Dosimetry KW - Heart rate KW - Thyroid KW - Brain KW - Drug development KW - Acute toxicity KW - EKG KW - Acetylcholine receptors (nicotinic) KW - Blood pressure KW - Single photon emission computed tomography KW - Radiation KW - Nicotine KW - Locomotor activity KW - Convulsions KW - Chronic toxicity KW - Radioisotopes KW - Metabolic activation KW - Mutation KW - J 02410:Animal Diseases KW - X 24380:Social Poisons & Drug Abuse KW - N3 11028:Neuropharmacology & toxicology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20416871?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aabiglobal&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Accounting+Review&rft.atitle=Experience+and+Error+Frequency+Knowledge+as+Potential+Determinants+of+Audit+Expertise&rft.au=Ashton%2C+Alison+Hubbard&rft.aulast=Ashton&rft.aufirst=Alison&rft.date=1991-04-01&rft.volume=66&rft.issue=2&rft.spage=218&rft.isbn=&rft.btitle=&rft.title=The+Accounting+Review&rft.issn=00014826&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-01-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Mutagenicity; Neuroimaging; Data processing; Pharmacology; Urinary bladder; Heart rate; Dosimetry; Brain; Thyroid; Drug development; Acute toxicity; Blood pressure; Acetylcholine receptors (nicotinic); EKG; Single photon emission computed tomography; Radiation; Nicotine; Chronic toxicity; Convulsions; Locomotor activity; Radioisotopes; Metabolic activation; Mutation DO - http://dx.doi.org/10.1002/ddr.10152 ER - TY - JOUR T1 - Temporal regulation of outer surface proteins of the Lyme-disease spirochaete Borrelia burgdorferi AN - 19352432; 7094347 AB - In the 20 years since the first agent of Lyme disease was discovered, much interest has focused on the possible biological roles of a few outer surface proteins (Osps) in the alternating life cycle that includes ticks and vertebrate hosts. Two major proteins, OspA and OspC, are differentially regulated by the spirochaete Borrelia burgdorferi during the several days when ticks feed. The reciprocal decrease in OspA with the rapid up-regulation of OspC by the spirochaetes when ticks are feeding suggests that OspA aids in spirochaete attachment while OspC assists in the dissemination of spirochaetes from tick to vertebrate. Future experiments in ticks with mutant spirochaetes that lack these proteins should clarify the speculative functions currently given to these proteins. JF - Biochemical Society Transactions AU - Schwan, T G AD - Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT 59840, USA, tom_schwan@nih.gov Y1 - 2003/02// PY - 2003 DA - Feb 2003 SP - 108 EP - 112 VL - 31 IS - 1 SN - 0300-5127, 0300-5127 KW - Ticks KW - Microbiology Abstracts B: Bacteriology KW - Feeding KW - Borrelia burgdorferi KW - outer surface proteins KW - Ixodidae KW - Life cycle KW - OspA protein KW - Lyme disease KW - J 02870:Invertebrate bacteriology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19352432?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+Society+Transactions&rft.atitle=Temporal+regulation+of+outer+surface+proteins+of+the+Lyme-disease+spirochaete+Borrelia+burgdorferi&rft.au=Schwan%2C+T+G&rft.aulast=Schwan&rft.aufirst=T&rft.date=2003-02-01&rft.volume=31&rft.issue=1&rft.spage=108&rft.isbn=&rft.btitle=&rft.title=Biochemical+Society+Transactions&rft.issn=03005127&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-12-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Feeding; outer surface proteins; Life cycle; OspA protein; Lyme disease; Borrelia burgdorferi; Ixodidae ER - TY - JOUR T1 - VIRTUAL2D: A web-accessible predictive database for proteomics analysis AN - 18918383; 5607307 AB - The available archive of sequence databases compiled from whole genome projects and budding proteomics efforts have enabled us to develop VIRTUAL2D, an interactive system for the assembly of virtual protein expression maps computed on the basis of theoretical isoelectric focusing point, molecular weight, tissue specificity and relative abundance for any set of proteins currently catalogued. This tool will assist in the preliminary, albeit putative, prediction of the identity and location of unknown and/or low abundance proteins in experimentally derived two-dimensional polyacrylamide gel electrophoresis maps. JF - Proteomics AU - Medjahed, D AU - Smythers, G W AU - Powell, DA AU - Stephens, R M AU - Lemkin, P F AU - Munroe, D J AD - National Cancer Institute at Frederick, P.O. Box B, Frederick, Maryland 21702-1201, USA, medjahed@ncifcrf.gov Y1 - 2003/02// PY - 2003 DA - Feb 2003 SP - 129 EP - 138 VL - 3 IS - 2 SN - 1615-9853, 1615-9853 KW - polyacrylamide KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Computer programs KW - Databases KW - Gel electrophoresis KW - W3 33080:Bioinformatics and computer applications KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18918383?accountid=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=Proteomics&rft.atitle=VIRTUAL2D%3A+A+web-accessible+predictive+database+for+proteomics+analysis&rft.au=Medjahed%2C+D%3BSmythers%2C+G+W%3BPowell%2C+DA%3BStephens%2C+R+M%3BLemkin%2C+P+F%3BMunroe%2C+D+J&rft.aulast=Medjahed&rft.aufirst=D&rft.date=2003-02-01&rft.volume=3&rft.issue=2&rft.spage=129&rft.isbn=&rft.btitle=&rft.title=Proteomics&rft.issn=16159853&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 - Gel electrophoresis; Databases; Computer programs ER - TY - JOUR T1 - Mechanisms of Phthalate Ester Toxicity in the Female Reproductive System AN - 18820764; 5707906 AB - Phthalates are high-production-volume synthetic chemicals with ubiquitous human exposures because of their use in plastics and other common consumer products. Recent epidemiologic evidence suggests that women have a unique exposure profile to phthalates, which raises concern about the potential health hazards posed by such exposures. Research in our laboratory examines how phthalates interact with the female reproductive system in animal models to provide insights into the potential health effects of these chemicals in women. Here we review our work and the work of others studying these mechanisms and propose a model for the ovarian action of di-(2ethylhexyl) phthalate (DEHP). In vivo, DEHP (2 g/kg) causes decreased serum estradiol levels, prolonged estrous cycles, and no ovulations in adult, cycling rats. In vitro, monoethylhexyl phthalate (MEHP; the active metabolite of DEHP) decreases granulosa cell aromatase RNA message and protein levels in a dose-dependent manner. MEHP is unique among the phthalates in its suppression of aromatase and in its ability to activate peroxisome proliferator-activated receptors (PPARs). We hypothesize that MEHP activates the PPARs to suppress aromatase in the granulosa cell. MEHP-, PPAR alpha -, and PPAR gamma -specific ligands all similarly decreased estradiol production and RNA message levels of aromatase in vitro. Our model shows that MEHP acts on the granulosa cell by decreasing cAMP stimulated by follicle stimulating hormone and by activating the PPARs, which leads to decreased aromatase transcription. Thus, the environmental contaminant DEHP, through its metabolite MEHP, acts through a receptor-mediated signaling pathway to suppress estradiol production in the ovary, leading to anovulation. JF - Environmental Health Perspectives AU - Lovekamp-Swan, T AU - Davis, B J AD - Laboratory of Women's Health, MD A2-01, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709 USA, davis1@niehs.nih.gov Y1 - 2003/02// PY - 2003 DA - Feb 2003 SP - 139 EP - 145 PB - NIH, Government Printing Office VL - 111 IS - 2 SN - 0091-6765, 0091-6765 KW - females KW - Toxicology Abstracts KW - X 24152:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18820764?accountid=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=Mechanisms+of+Phthalate+Ester+Toxicity+in+the+Female+Reproductive+System&rft.au=Lovekamp-Swan%2C+T%3BDavis%2C+B+J&rft.aulast=Lovekamp-Swan&rft.aufirst=T&rft.date=2003-02-01&rft.volume=111&rft.issue=2&rft.spage=139&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 ER - TY - JOUR T1 - Mortality from Diseases of the Circulatory System in Radiologic Technologists in the United States AN - 18757832; 5628769 AB - Although increased mortality from diseases of the circulatory system has been observed in patients treated with radiotherapy, the effects of chronic low-dose radiation exposure are not clear. Among 90,284 US radiologic technologists who responded to a mailed questionnaire during 1983-1989, the authors evaluated mortality from circulatory system diseases through 1997 in relation to job history and work procedures as surrogates for radiation exposure. They used Poisson regression models stratified for sex, race, age, and calendar year and adjusted for smoking, body mass index, alcohol intake, marital status, parity, menopausal status, and history of myocardial infarction. A total of 1,107,100 person-years accrued, and 1,070 subjects died from circulatory system diseases. Relative risks for first employment during 1950-1959, 1940-1949, or before 1940, compared with 1960 and later, were 1.01 (95% confidence interval (CI): 0.78, 1.30), 1.14 (95% CI: 0.86, 1.50), and 1.42 (95% CI: 1.04, 1.94), respectively (trend p < 0.001). For the subset of deaths from cerebrovascular disease (n = 174), the respective relative risks were 0.90 (95% CI: 0.45, 1.78), 1.54 (95% CI: 0.74, 3.23), and 2.40 (95% CI: 1.09, 5.31) (trend p = 0.004), and for deaths from ischemic heart disease (n = 633), the relative risks were 0.98 (95% CI: 0.71, 1.35), 1.00 (95% CI: 0.71, 1.42), and 1.22 (95% CI: 0.81, 1.82) (trend p = 0.026). The relative risks for mortality from circulatory system diseases and the subset of cerebrovascular disease increased significantly with the number of years worked before 1950 (trend p = 0.007 and < 0.001, respectively). The data suggest increased mortality from diseases of the circulatory system with occupational radiation exposure before 1950 when radiation doses were likely high. JF - American Journal of Epidemiology AU - Hauptmann, M AU - Mohan, A K AU - Doody, M M AU - Linet AU - Mabuchi, K AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA Y1 - 2003/02/01/ PY - 2003 DA - 2003 Feb 01 SP - 239 EP - 248 PB - Johns Hopkins University, School of Hygiene and Public Health VL - 157 IS - 3 SN - 0002-9262, 0002-9262 KW - circulatory system KW - Health & Safety Science Abstracts; Risk Abstracts KW - R2 23020:Technological risks KW - H 8000:Radiation Safety/Electrical Safety UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18757832?accountid=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=Mortality+from+Diseases+of+the+Circulatory+System+in+Radiologic+Technologists+in+the+United+States&rft.au=Hauptmann%2C+M%3BMohan%2C+A+K%3BDoody%2C+M+M%3BLinet%3BMabuchi%2C+K&rft.aulast=Hauptmann&rft.aufirst=M&rft.date=2003-02-01&rft.volume=157&rft.issue=3&rft.spage=239&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Epidemiology&rft.issn=00029262&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Reducing risks of surgery AN - 18755704; 5627126 AB - The risk of postoperative infection is present in all surgical procedures, but can be particularly serious in certain operations, for example, joint replacement. The National Institutes of Health (NIH), Office of Research Services, Division of Engineering Services, has conducted an extensive study on the issue of operating room ventilation systems and their effect on the protection of the surgical site. JF - ASHRAE Journal AU - Memarzadeh, F AU - Manning, A AD - Office of Research Services, Division of Engineering Services at the National Institutes of Health, Bethesda, MD, USA Y1 - 2003/02// PY - 2003 DA - Feb 2003 SP - 28 EP - 29 VL - 45 IS - 2 SN - 0001-2491, 0001-2491 KW - postoperative infection KW - risk reduction KW - surgery KW - Risk Abstracts KW - R2 23020:Technological risks UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18755704?accountid=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=ASHRAE+Journal&rft.atitle=Reducing+risks+of+surgery&rft.au=Memarzadeh%2C+F%3BManning%2C+A&rft.aulast=Memarzadeh&rft.aufirst=F&rft.date=2003-02-01&rft.volume=45&rft.issue=2&rft.spage=28&rft.isbn=&rft.btitle=&rft.title=ASHRAE+Journal&rft.issn=00012491&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 Thermodynamic Contribution of the 5-Methyl Group of Thymine in the Two- and Three-Stranded Complexes Formed by Poly(dU) and Poly(dT) with Poly(dA) AN - 18743255; 5616235 AB - To assess the thermodynamic contribution of the 5-methyl group of thymine, we have studied the two-stranded helical complexes poly(dA) times poly(dU) and poly(dA) times poly(dT) and the three-stranded complexes--poly(dA) times 2poly(dU), poly(dA) times poly(dT) times poly(dU) and poly(dA) times 2poly(dT)--by differential scanning calorimetry, and uv optical melting experiments. The thermodynamic quantities associated with the 3 arrow right 2, 2 arrow right 1, and 3 arrow right 1 melting transitions are found to vary with salt concentration and temperature in a more complex manner than commonly believed. The transition temperatures, T sub(m), are generally not linear in the logarithm of concentration or activity of NaCl. The change in enthalpy and in entropy upon melting varies with salt concentration and temperature, and a change in heat capacity accompanies each transition. The poly(dA) times 2poly(dU) triple helix is markedly different from poly(dA) times 2poly(dT) in both its CD spectrum and thermodynamic behavior, while the poly(dA) times poly(dT) times poly(dU) triple helix resembles poly(dA) times 2poly(dT) in these properties. In comparing poly(dA) times 2poly(dT) with either the poly(dA) times poly(dT) times poly(dU) or the poly(dA) times 2poly(dU) triplexes, the substitution of thymine for uracil in the third strand results in an enhancement of stability against the 3 arrow right 2 dissociation of Delta Delta G degree = -135 plus or minus 85 cal (mol A) super(-1) at 37 degree C. This represents a doubling of the absolute stability toward dissociation compared to the triplexes with poly(dU) as the third strand. The poly (dA) times poly (dT) duplex is more stable than poly(dA) times poly(dU) by Delta Delta G degree = -350 plus or minus 60 cal (mol base pair) super(-1) at 37 degree C. Poly(dA) times poly(dT) has 50% greater stability than poly(dA) times poly(dU) as a result of the dT for dU substitution in the duplex. JF - Biopolymers AU - Ross, P D AU - Howard, F B AD - Laboratory of Molecular Biology, NIDDK, NIH, Bethesda, MD 20892, USA, philipr@intra.niddk.nih.gov Y1 - 2003/02// PY - 2003 DA - Feb 2003 SP - 210 EP - 222 VL - 68 IS - 2 SN - 0006-3525, 0006-3525 KW - poly(dA) times poly(dT) KW - poly(dA) times poly(dU) KW - thymine KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - N 14110:Structure, synthesis & chemical properties KW - W4 330:Biopolymers & Food Biotechnology KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18743255?accountid=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=Biopolymers&rft.atitle=The+Thermodynamic+Contribution+of+the+5-Methyl+Group+of+Thymine+in+the+Two-+and+Three-Stranded+Complexes+Formed+by+Poly%28dU%29+and+Poly%28dT%29+with+Poly%28dA%29&rft.au=Ross%2C+P+D%3BHoward%2C+F+B&rft.aulast=Ross&rft.aufirst=P&rft.date=2003-02-01&rft.volume=68&rft.issue=2&rft.spage=210&rft.isbn=&rft.btitle=&rft.title=Biopolymers&rft.issn=00063525&rft_id=info:doi/10.1002%2Fbip.10306 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1002/bip.10306 ER - TY - JOUR T1 - Uptake and cellular actions of mycolactone, a virulence determinant for Mycobacterium ulcerans AN - 18728959; 5613973 AB - Mycolactone is a macrolide secreted by Mycobacterium ulcerans. Experimental evidence suggests that mycolactone plays a prominent role in the pathogenesis of Buruli ulcer by causing both tissue destruction and immunosuppression. To understand the cell biology of mycolactone activity, we have synthesized the fluorescent mycolactone derivativebodipymycolactone. Although derivatization resulted in a modest decrease in cytopathic activity, the derivatized and native molecules produce identical phenotypes in cultured cells. Confocal microscopy of bodipymycolactone added to cultured fibroblasts, shows that it is localized to the cytosol. Bodipymycolactone fails to bind to the cell membrane and is excluded from the nucleus. Uptake is both nonsaturable and noncompetitive with excess mycolactone, consistent with passive diffusion of this toxin through the cell membrane. These facts, combined with the inability of signal transduction inhibitors to inhibit mycolactone cytopathicity point towards the presence of an cytosolic target for mycolactone. A dose dependent increase in intracellular calcium levels at occurs upon mycolactone exposure, but chelation of intracellular calcium alters neither the cytopathicity nor the caspase induction profile of treated cells. Mitochondrial polarization is maintained in treated cells for up to 3 days arguing that the rise in intracellular calcium levels may be a result of cytoskeletal remodeling. JF - Microbial Pathogenesis AU - Snyder, D S AU - Small, PLC AD - Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA, psmall@tennessee.edu Y1 - 2003/02// PY - 2003 DA - Feb 2003 SP - 91 EP - 101 PB - Elsevier Science VL - 34 IS - 2 SN - 0882-4010, 0882-4010 KW - mycolactone KW - Microbiology Abstracts B: Bacteriology KW - J 02862:Infection UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18728959?accountid=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+Pathogenesis&rft.atitle=Uptake+and+cellular+actions+of+mycolactone%2C+a+virulence+determinant+for+Mycobacterium+ulcerans&rft.au=Snyder%2C+D+S%3BSmall%2C+PLC&rft.aulast=Snyder&rft.aufirst=D&rft.date=2003-02-01&rft.volume=34&rft.issue=2&rft.spage=91&rft.isbn=&rft.btitle=&rft.title=Microbial+Pathogenesis&rft.issn=08824010&rft_id=info:doi/10.1016%2FS0882-4010%2802%2900210-3 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0882-4010(02)00210-3 ER - TY - JOUR T1 - The prevalence and correlates of hazardous drinking in industrial workers: A study from Goa, India AN - 18718309; 5607140 AB - Aims: This study aimed to describe the prevalence and associations of hazardous drinking in a male industrial worker population in India. Methods: A total of 984 subjects from a randomly selected sample of 1013 workers from four industries in Goa, India, were recruited. Interviews included the 10-item Alcohol Use Disorders Identification Test (AUDIT) as an indicator of hazardous drinking and the 12-item General Health Questionnaire (GHQ12) as a measure of common mental disorders (CMDs). Results: The prevalence of hazardous drinking, defined as an AUDIT score of more than 8 was 21%. There was a significant association with CMD (OR 2, P = 0.003). Hazardous drinking was significantly associated with severe health problems, such as head injuries and hospitalization, whereas CMD was found to be a confounder in its association with adverse economic outcomes. Conclusions: Hazardous drinking is common among male industrial workers in Goa. Interventions in the workplace must target both drinking problems and CMDs, since they often co-exist and are associated with different types of adverse outcomes. JF - Alcohol and Alcoholism AU - Silva, M C AU - Gaunekar, G AU - Patel, V AU - Kukalekar, D S AU - Fernandes, J AD - Room No 19, Men's Hostel, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India 560029 Y1 - 2003/02// PY - 2003 DA - Feb 2003 SP - 79 EP - 83 VL - 38 IS - 1 SN - 0735-0414, 0735-0414 KW - substance abuse KW - Health & Safety Science Abstracts KW - H 4000:Food and Drugs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18718309?accountid=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=Alcohol+and+Alcoholism&rft.atitle=The+prevalence+and+correlates+of+hazardous+drinking+in+industrial+workers%3A+A+study+from+Goa%2C+India&rft.au=Silva%2C+M+C%3BGaunekar%2C+G%3BPatel%2C+V%3BKukalekar%2C+D+S%3BFernandes%2C+J&rft.aulast=Silva&rft.aufirst=M&rft.date=2003-02-01&rft.volume=38&rft.issue=1&rft.spage=79&rft.isbn=&rft.btitle=&rft.title=Alcohol+and+Alcoholism&rft.issn=07350414&rft_id=info:doi/10.1093%2Falcalc%2Fagg016 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1093/alcalc/agg016 ER - TY - JOUR T1 - Hidden Markov models and optimized sequence alignments AN - 18715594; 5600978 AB - We present a formulation of the Needleman-Wunsch type algorithm for sequence alignment in which the mutation matrix is allowed to vary under the control of a hidden Markov process. The fully trainable model is applied to two problems in bioinformatics: the recognition of related gene/protein names and the alignment and scoring of homologous proteins. JF - Computational Biology and Chemistry AU - Smith, L AU - Yeganova, L AU - Wilbur, W J AD - Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, Rm. 614D, Bldg. 38A, 8600 Rockville Pike, Bethesda, MD 20894, USA, lsmith@ncbi.nlm.nih.gov Y1 - 2003/02// PY - 2003 DA - Feb 2003 SP - 77 EP - 84 VL - 27 IS - 1 SN - 1476-9271, 1476-9271 KW - hidden Markov models KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18715594?accountid=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=Computational+Biology+and+Chemistry&rft.atitle=Hidden+Markov+models+and+optimized+sequence+alignments&rft.au=Smith%2C+L%3BYeganova%2C+L%3BWilbur%2C+W+J&rft.aulast=Smith&rft.aufirst=L&rft.date=2003-02-01&rft.volume=27&rft.issue=1&rft.spage=77&rft.isbn=&rft.btitle=&rft.title=Computational+Biology+and+Chemistry&rft.issn=14769271&rft_id=info:doi/10.1016%2FS1476-9271%2802%2900096-8 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S1476-9271(02)00096-8 ER - TY - JOUR T1 - Photochemical and Photobiological Studies of Tirapazamine (SR 4233) and Related Quinoxaline 1,4-Di-N-oxide Analogues AN - 18713252; 5594870 AB - Tirapazamine, 3-amino-1,2,4-benzotriazine 1,4-di-N-oxide (TPZ; SR 4233), is currently undergoing phase II and III clinical trials as an antitumor agent. We have studied the photochemical properties of TPZ, and the related analogues 3-amino-2-quinoxalinecarbonitrile 1,4-di-N-oxide (TPZCN) and quinoxaline-1,4-di-N-oxide (quindoxin) with respect to their potential to photodamage DNA both oxidatively and reductively. We have found that TPZ, TPZCN, and quindoxin photosensitized the generation of singlet oxygen with quantum yields of 0.007, 0.19, and 0.02, respectively, in acetonitrile. Irradiation ( lambda > 300 nm) of TPZ at pH 9.4 in the presence of a reducing agent, NADH, generated the corresponding nitroxide radical. At pH 7.4, photoirradiation of either TPZ or TPZCN in the presence of NADH in air saturated buffer gave the superoxide radical, which was trapped by 5,5-dimethyl-1-pyrroline N-oxide (DMPO). In the absence of a reducing agent, singlet oxygen generated from TPZCN oxidized DMPO to 5,5-dimethyl-2-oxopyrrolin-1-oxyl (DMPOX). No spin adducts were detected during photoirradiation of TPZ, NADH, and DMPO in nitrogen-saturated buffer. However, when DMSO was also present, the DMPO/* CH sub(3) adduct was observed, indicating the generation of the free hydroxyl radical. Both TPZ and TPZCN photooxidized reduced glutathione and azide to the glutathiyl and azidyl radicals, respectively. Under anaerobic conditions, NADH increased photoinduced strand breaks in pBR322 plasmid DNA caused by TPZ or TPZCN. For TPZ, the reactive species is probably the aforementioned nitroxide radical or the hydroxyl radical generated from its decomposition. In contrast, DNA damage by quindoxin was not affected by NADH, suggesting a different mechanism, possibly involving a photogenerated oxaziridine intermediate. These studies show that the photochemistry of TPZ, TPZCN, and quindoxin is complex and depends on the redox environment and whether oxygen is present. JF - Chemical Research in Toxicology AU - Inbaraj, J J AU - Motten, A G AU - Chignell, C F AD - Laboratory of Pharmacology & Chemistry, NIEHS, Research Triangle Park, North Carolina 27709, USA Y1 - 2003/02// PY - 2003 DA - February 2003 SP - 164 EP - 170 PB - American Chemical Society, P.O. Box 182426 Columbus OH 43218-2426 USA, [mailto:service@acs.org] VL - 16 IS - 2 SN - 0893-228X, 0893-228X KW - 3-amino-2-quinoxalinecarbonitrile-1,4-di-n-oxide KW - quinoxaline-1,4-di-n-oxide KW - tirapazamine KW - Toxicology Abstracts KW - DNA damage KW - Antineoplastic drugs KW - X 24117:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18713252?accountid=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=Photochemical+and+Photobiological+Studies+of+Tirapazamine+%28SR+4233%29+and+Related+Quinoxaline+1%2C4-Di-N-oxide+Analogues&rft.au=Inbaraj%2C+J+J%3BMotten%2C+A+G%3BChignell%2C+C+F&rft.aulast=Inbaraj&rft.aufirst=J&rft.date=2003-02-01&rft.volume=16&rft.issue=2&rft.spage=164&rft.isbn=&rft.btitle=&rft.title=Chemical+Research+in+Toxicology&rft.issn=0893228X&rft_id=info:doi/10.1021%2Ftx0256073 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2016-05-27 N1 - SubjectsTermNotLitGenreText - DNA damage; Antineoplastic drugs DO - http://dx.doi.org/10.1021/tx0256073 ER - TY - JOUR T1 - Exploring Vaccinia Virus as a Tool for Large-Scale Recombinant Protein Expression AN - 18694101; 5591134 AB - A recombinant vaccinia virus was engineered to express enhanced green fluorescent protein (EGFP) under control of the T7 promoter using the VOTE expression system in HeLa cells. Infection of HeLa cells with this virus and induction with IPTG demonstrated the utility of this construct for easily measuring protein expression. This construct was used to evaluate several production parameters, specifically, multiplicity of infection (MOI), volume during infection, and serum concentration during the infection phase. In static culture, increasing multiplicity of infection was found to increase expression of EGFP up to a plateau around MOI of 1.0. Expression was also shown to increase with decreasing volume during the infection phase. Serum concentration during the infection phase was only marginally significant from 0 to 7.5%. Cytodex 3 microcarriers were found to have the best characteristics for HeLa cell growth. These cells were grown and infected in microcarrier spinner flask culture, and the maximum expression was 2.2 mu g EGFP/(million cells at the time of infection), demonstrating the ability of this system to successfully express recombinant proteins at larger scale. JF - Biotechnology Progress AU - Bleckwenn, NA AU - Bentley, W E AU - Shiloach, J AD - Biotechnology Unit, LCDB, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA, yossi@nih.gov Y1 - 2003/02// PY - 2003 DA - Feb 2003 SP - 130 EP - 136 VL - 19 IS - 1 SN - 8756-7938, 8756-7938 KW - green fluorescent protein KW - growth KW - infection KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Bioengineering Abstracts KW - W3 33340:Other proteins, peptides, amino acids KW - W 30965:Miscellaneous, Reviews KW - W4 320:Cell Culture & Batch Fermentation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18694101?accountid=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+Progress&rft.atitle=Exploring+Vaccinia+Virus+as+a+Tool+for+Large-Scale+Recombinant+Protein+Expression&rft.au=Bleckwenn%2C+NA%3BBentley%2C+W+E%3BShiloach%2C+J&rft.aulast=Bleckwenn&rft.aufirst=NA&rft.date=2003-02-01&rft.volume=19&rft.issue=1&rft.spage=130&rft.isbn=&rft.btitle=&rft.title=Biotechnology+Progress&rft.issn=87567938&rft_id=info:doi/10.1021%2Fbp0255762 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Special Issue: Cell Culture Engineering VIII. N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1021/bp0255762 ER - TY - JOUR T1 - Development of an Ad7 cosmid system and generation of an Ad7 Delta E1 Delta E3HIV sub(MN) env/rev recombinant virus AN - 18686269; 5580168 AB - A strategy to circumvent immune responses to adenovirus (Ad) resulting from natural infection or repeated vector administrations involves sequential use of vectors from different Ad serotypes. To further develop an Ad-HIV recombinant AIDS vaccine approach, a replication-defective recombinant Ad from a non-subgroup C virus was required. Using a cosmid system, we generated an Ad7 Delta E1 Delta E3HIV sub(MN)env/rev recombinant virus and compared expression of the inserted HIV genes with a similarly constructed replication-competent Ad7 Delta E3HIV sub(MN)env/rev recombinant. Ad7 Delta E1 Delta E3HIV sub(MN)env/rev expressed both HIV env and rev gene products. The envelope protein was correctly processed and functional, mediating syncytia formation of Ad7 Delta E1 Delta E3HIV sub(MN)env/rev-infected cells and CD4 super(+) T lymphocytes. Ad7 Delta E1 Delta E3HIV sub(MN)env/rev could be amplified on 293-ORF6 cells, containing the E4 ORF6 gene, shown earlier to support production of an Ad7 vector lacking the E1a gene. The utility of this cell line is now extended to the production of replication-defective Ad7 recombinants lacking E1a, E1b, and protein IX genes. Sequential immunizations with Ad-HIV recombinants based in different Ad serotypes have been shown to effectively elicit both humoral and cellular HIV-specific immune responses. The recombinant Ad7 Delta E1 Delta E3HIV sub(MN)env/rev will be useful in such AIDS vaccine strategies. Further, these studies have created new cosmid vectors that can be applied to generation of single- or double-deleted Ad7 recombinants with foreign genes inserted into the E1 and/or E3 regions. JF - Gene Therapy AU - Nan, X AU - Peng, B AU - Hahn, T-W AU - Richardson, E AU - Lizonova, A AU - Kovesdi, I AU - Robert-Guroff, M AD - National Cancer Institute, 41 Library Drive MSC 5055, Building 41 Room D804, Bethesda, MD 20892-5055, USA Y1 - 2003/02// PY - 2003 DA - Feb 2003 SP - 326 EP - 336 VL - 10 IS - 4 SN - 0969-7128, 0969-7128 KW - HIV KW - env gene KW - rev gene KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Virology & AIDS Abstracts KW - N 14682:Cloning vectors KW - W3 33181:Gene therapy vectors KW - V 22003:AIDS: Immunological aspects KW - W 30965:Miscellaneous, Reviews KW - W4 120:Genetic Engineering in Medicine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18686269?accountid=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=Development+of+an+Ad7+cosmid+system+and+generation+of+an+Ad7+Delta+E1+Delta+E3HIV+sub%28MN%29+env%2Frev+recombinant+virus&rft.au=Nan%2C+X%3BPeng%2C+B%3BHahn%2C+T-W%3BRichardson%2C+E%3BLizonova%2C+A%3BKovesdi%2C+I%3BRobert-Guroff%2C+M&rft.aulast=Nan&rft.aufirst=X&rft.date=2003-02-01&rft.volume=10&rft.issue=4&rft.spage=326&rft.isbn=&rft.btitle=&rft.title=Gene+Therapy&rft.issn=09697128&rft_id=info:doi/10.1038%2Fsj.gt.3301903 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1038/sj.gt.3301903 ER - TY - JOUR T1 - Cloning of human centromeres by transformation-associated recombination in yeast and generation of functional human artificial chromosomes AN - 18678041; 5572555 AB - Human centromeres remain poorly characterized regions of the human genome despite their importance for the maintenance of chromosomes. In part this is due to the difficulty of cloning of highly repetitive DNA fragments and distinguishing chromosome-specific clones in a genomic library. In this work we report the highly selective isolation of human centromeric DNA using transformation-associated recombination (TAR) cloning. A TAR vector with alphoid DNA monomers as targeting sequences was used to isolate large centromeric regions of human chromosomes 2, 5, 8, 11, 15, 19, 21 and 22 from human cells as well as monochromosomal hybrid cells. The alphoid DNA array was also isolated from the 12 Mb human mini-chromosome [Delta]Yq74 that contained the minimum amount of alphoid DNA required for proper chromosome segregation. Preliminary results of the structural analyses of different centromeres are reported in this paper. The ability of the cloned human centromeric regions to support human artificial chromosome (HAC) formation was assessed by transfection into human HT1080 cells. Centromeric clones from [Delta]Yq74 did not support the formation of HACs, indicating that the requirements for the existence of a functional centromere on an endogenous chromosome and those for forming a de novo centromere may be distinct. A construct with an alphoid DNA array from chromosome 22 with no detectable CENP-B motifs formed mitotically stable HACs in the absence of drug selection without detectable acquisition of host DNAs. In summary, our results demonstrated that TAR cloning is a useful tool for investigating human centromere organization and the structural requirements for formation of HAC vectors that might have a potential for therapeutic applications. JF - Nucleic Acids Research AU - Kouprina, N AU - Ebersole, T AU - Koriabine, M AU - Pak, E AU - Rogozin, IB AU - Katoh, M AU - Oshimura, M AU - Ogi, K AU - Peredelchuk, M AU - Solomon, G AU - Brown, W AU - Barrett, J C AU - Larionov, V AD - Laboratory of Biosystems and Cancer, Center for Cancer Research, National Cancer Institute (NCI, NIH), Building 37, Room 5032, Bethesda, MD 20892, USA, kouprinn@mail.nih.gov Y1 - 2003/02// PY - 2003 DA - Feb 2003 SP - 922 EP - 934 VL - 31 IS - 3 SN - 0305-1048, 0305-1048 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - N 14682:Cloning vectors KW - W3 33058:Cloning vectors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18678041?accountid=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=Cloning+of+human+centromeres+by+transformation-associated+recombination+in+yeast+and+generation+of+functional+human+artificial+chromosomes&rft.au=Kouprina%2C+N%3BEbersole%2C+T%3BKoriabine%2C+M%3BPak%2C+E%3BRogozin%2C+IB%3BKatoh%2C+M%3BOshimura%2C+M%3BOgi%2C+K%3BPeredelchuk%2C+M%3BSolomon%2C+G%3BBrown%2C+W%3BBarrett%2C+J+C%3BLarionov%2C+V&rft.aulast=Kouprina&rft.aufirst=N&rft.date=2003-02-01&rft.volume=31&rft.issue=3&rft.spage=922&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Carcinogenic potential of o-nitrotoluene and p-nitrotoluene AN - 18675431; 5572466 AB - The potential of o-nitrotoluene and p-nitrotoluene to cause cancer in mammalian species was studied in male and female F344/N rats and B6C3F1 mice. These chemicals are on the EPA list of high production chemicals and there is potential for human exposure (High Production Volume Chemical List (2000) http://oaspub.cpa.gov/opptintr/chemrtk/volchall.htm.). o-Nitrotoluene, administered in the feed for up to 2 years, caused clear evidence for cancer at multiple sites in rats and mice. Male rats, receiving o-nitrotoluene in the feed (~0, 25, 50, or 90 mg/kg per day), developed treatment-related mesotheliomas, subcutaneous skin neoplasms, mammary gland fibroadenomas, and liver neoplasms. By 2 years, mesotheliomas, skin, liver, mammary gland and liver tumors also occurred in 'stop-study' male rats that received o-nitrotoluene at 125 or 315 mg/kg per day for only the first 3 months of study. These 'stop- studies' showed that the critical events leading to tumor formation occurred after 3 months of dosing, and these events were irreversible and eventually led to cancer at multiple sites. o-Nitrotoluene given in the feed to female rats (~0, 30, 60, or 100 mg/kg per day) and to male and female mice (~0, 150, 320, or 700 mg/kg per day) also caused a carcinogenic response. In female rats, treatment-related subcutaneous skin neoplasms and mammary gland fibroadenomas occurred. Hemangiosarcomas and carcinomas of the large intestine (cecum) were seen in treated male and female mice. In contrast to o-nitrotoluene, p- nitrotoluene given in the feed over approximately the same exposure levels caused only equivocal evidence of carcinogenic activity in male rats (subcutaneous skin neoplasms); some evidence of carcinogenic activity in female rats (clitoral gland neoplasms); equivocal evidence of carcinogenic activity in male mice (lung neoplasms); and no evidence of carcinogenic activity in female mice. Differences in the o-nitrotoluene and p-nitrotoluene carcinogenic activity may be due to differences in the metabolism of the parent compound to carcinogenic metabolites. JF - Toxicology AU - Dunnick, J K AU - Burka, L T AU - Mahler, J AU - Sills, R AD - National Institute of Environmental Health Sciences, National Institutes of Health, 111 T.W. Alexander Drive, P.O. Box 12233, Research Triangle Park, NC 27709, USA, dunnickj@niehs.nih.gov Y1 - 2003/02/01/ PY - 2003 DA - 2003 Feb 01 SP - 221 EP - 234 VL - 183 IS - 1-3 SN - 0300-483X, 0300-483X KW - mice KW - o-Nitrotoluene KW - p-Nitrotoluene KW - rats KW - Toxicology Abstracts KW - X 24152:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18675431?accountid=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=Carcinogenic+potential+of+o-nitrotoluene+and+p-nitrotoluene&rft.au=Dunnick%2C+J+K%3BBurka%2C+L+T%3BMahler%2C+J%3BSills%2C+R&rft.aulast=Dunnick&rft.aufirst=J&rft.date=2003-02-01&rft.volume=183&rft.issue=1-3&rft.spage=221&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/10.1016%2FS0300-483X%2802%2900543-7 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0300-483X(02)00543-7 ER - TY - JOUR T1 - Cancer treatment by telomerase inhibitors: predictions by a kinetic model AN - 18672700; 5572403 AB - The inhibition of telomerase activity in actively dividing cells leads to shortening of their telomeres and suppression of cell growth when the telomere lengths become smaller than a certain threshold value (typically about 1-2 kb of DNA). We evaluated the time (efficacy delay) required to reach the threshold telomeric DNA size after initiation of treatment, which is of critical importance for the efficacy of telomerase inhibitors. A model based on the solution of a system of differential equations was developed to analyze the efficacy delay and dynamics of tumor growth. The efficacy delay was strongly dependent on the size distribution of telomere lengths at the treatment initiation. An increase in the heterogeneity of telomere size resulted in shortening of the delay. However, the long-term dynamics of tumors with homogeneous populations of telomeres were more significantly affected by telomerase inhibitors compared to tumors with heterogeneous size distribution of telomeres. Size distribution of telomeres and tumor doubling times are of critical importance for the dynamics of tumor growth in presence of telomerase inhibitors. JF - Mathematical Biosciences AU - Sidorov, IA AU - Hirsch, K S AU - Harley, C B AU - Dimitrov, D S AD - National Cancer Institute, NCI-Frederick, NIH, P.O. Box B, Frederick, MD 21702-1201, USA, sidorovi@ncifcrf.gov Y1 - 2003/02// PY - 2003 DA - Feb 2003 SP - 209 EP - 221 VL - 181 IS - 2 SN - 0025-5564, 0025-5564 KW - telomerase inhibitors KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W4 140:Bioinformatics & Computers in Health & Medicine KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18672700?accountid=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=Mathematical+Biosciences&rft.atitle=Cancer+treatment+by+telomerase+inhibitors%3A+predictions+by+a+kinetic+model&rft.au=Sidorov%2C+IA%3BHirsch%2C+K+S%3BHarley%2C+C+B%3BDimitrov%2C+D+S&rft.aulast=Sidorov&rft.aufirst=IA&rft.date=2003-02-01&rft.volume=181&rft.issue=3&rft.spage=153&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+Applied+Pharmacology&rft.issn=0041008X&rft_id=info:doi/10.1006%2Ftaap.2002.9410 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0025-5564(02)00132-3 ER - TY - JOUR T1 - Glycerol-3-Phosphate Acquisition in Spirochetes: Distribution and Biological Activity of Glycerophosphodiester Phosphodiesterase (GlpQ) among Borrelia Species AN - 18670554; 5562985 AB - Relapsing-fever spirochetes achieve high cell densities (>10/ml) in their host's blood, while Lyme disease spirochetes do not (<10/ml). This striking contrast in pathogenicity of these two groups of bacteria suggests a fundamental difference in their ability to either exploit or survive in blood. Borrelia hermsii, a tick-borne relapsing-fever spirochete, contains orthologs to glpQ and glpT, genes that encode glycerophosphodiester phosphodiesterase (GlpQ) and glycerol-3-phosphate transporter (GlpT), respectively. In other bacteria, GlpQ hydrolyzes deacylated phospholipids to glycerol-3-phosphate (G3P) while GlpT transports G3P into the cytoplasm. Enzyme assays on 17 isolates of borreliae demonstrated GlpQ activity in relapsing-fever spirochetes but not in Lyme disease spirochetes. Southern blots demonstrated glpQ and glpT in all relapsing-fever spirochetes but not in the Lyme disease group. A Lyme disease spirochete, Borrelia burgdorferi, that was transformed with a shuttle vector containing glpTQ from B. hermsii produced active enzyme, which demonstrated the association of glpQ with the hydrolysis of phospholipids. Sequence analysis of B. hermsii identified glpF, glpK, and glpA, which encode the glycerol facilitator, glycerol kinase, and glycerol-3-phosphate dehydrogenase, respectively, all of which are present in B. burgdorferi. All spirochetes examined had gpsA, which encodes the enzyme that reduces dihydroxyacetone phosphate (DHAP) to G3P. Consequently, three pathways for the acquisition of G3P exist among borreliae: (i) hydrolysis of deacylated phospholipids, (ii) reduction of DHAP, and (iii) uptake and phosphorylation of glycerol. The unique ability of relapsing-fever spirochetes to hydrolyze phospholipids may contribute to their higher cell densities in blood than those of Lyme disease spirochetes. JF - Journal of Bacteriology AU - Schwan, T G AU - Battisti, J M AU - Porcella, S F AU - Raffel, S J AU - Schrumpf, ME AU - Fischer, E R AU - Carroll, JA AU - Stewart, P E AU - Rosa, P AU - Somerville, G A AD - Rocky Mountain Laboratories, 903 S. Fourth St., Hamilton, MT 59840, tom_schwan@nih.gov Y1 - 2003/02// PY - 2003 DA - Feb 2003 SP - 1346 EP - 1356 VL - 185 IS - 4 SN - 0021-9193, 0021-9193 KW - GlpQ protein KW - GlpT protein KW - alpha -glycerophosphoric acid KW - glpF gene KW - glpK gene KW - glycerol 3-phosphate KW - glycerophosphodiester phosphodiesterase KW - gpsA gene KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - G 07320:Bacterial genetics KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18670554?accountid=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=Glycerol-3-Phosphate+Acquisition+in+Spirochetes%3A+Distribution+and+Biological+Activity+of+Glycerophosphodiester+Phosphodiesterase+%28GlpQ%29+among+Borrelia+Species&rft.au=Schwan%2C+T+G%3BBattisti%2C+J+M%3BPorcella%2C+S+F%3BRaffel%2C+S+J%3BSchrumpf%2C+ME%3BFischer%2C+E+R%3BCarroll%2C+JA%3BStewart%2C+P+E%3BRosa%2C+P%3BSomerville%2C+G+A&rft.aulast=Schwan&rft.aufirst=T&rft.date=2003-02-01&rft.volume=185&rft.issue=4&rft.spage=1346&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.185.4.1346-1356.2003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/JB.185.4.1346-1356.2003 ER - TY - JOUR T1 - Repair of Radiation-Induced DNA Double-Strand Breaks is Dependent upon Radiation Quality and the Structural Complexity of Double-Strand Breaks AN - 18668737; 5560939 AB - Mammalian cells primarily repair DSBs by nonhomologous end joining (NHEJ). To assess the ability of human cells to mediate end joining of complex DSBs such as those produced by chemicals, oxidative events, or high- and low-LET radiation, we employed an in vitro double-strand break repair assay using plasmid DNA linearized by these various agents. We found that human HeLa cell extracts support end joining of complex DSBs and form multimeric plasmid products from substrates produced by the radiomimetic drug bleomycin, 60Co gamma rays, and the effects of 125I decay in DNA. End joining was found to be dependent on the type of DSB-damaging agent, and it decreased as the cytotoxicity of the DSB-inducing agent increased. In addition to the inhibitory effects of DSB end-group structures on repair, NHEJ was found to be strongly inhibited by lesions proximal to DSB ends. The initial repair rate for complex non-ligatable bleomycin-induced DSBs was sixfold less than that of similarly configured (blunt-ended) but less complex (ligatable) restriction enzyme-induced DSBs. Repair of DSBs produced by gamma rays was 15-fold less efficient than repair of restriction enzyme-induced DSBs. Repair of the DSBs produced by 125I was near the lower limit of detection in our assay and was at least twofold lower than that of gamma -ray-induced DSBs. In addition, DSB ends produced by 125I were shown to be blocked by 3'-nucleotide fragments: the removal of these by E. coli endonuclease IV permitted ligation. JF - Radiation Research AU - Pastwa , E AU - Neumann, R D AU - Mezhevaya , K AU - Winters, T A AD - Nuclear Medicine Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, twinters@mail.cc.nih.gov Y1 - 2003/02// PY - 2003 DA - Feb 2003 SP - 251 EP - 261 PB - The Radiation Research Society VL - 159 IS - 2 SN - 0033-7587, 0033-7587 KW - double-strand break repair KW - Toxicology Abstracts KW - X 24210:Radiation & radioactive materials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18668737?accountid=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=Radiation+Research&rft.atitle=Repair+of+Radiation-Induced+DNA+Double-Strand+Breaks+is+Dependent+upon+Radiation+Quality+and+the+Structural+Complexity+of+Double-Strand+Breaks&rft.au=Pastwa+%2C+E%3BNeumann%2C+R+D%3BMezhevaya+%2C+K%3BWinters%2C+T+A&rft.aulast=Pastwa+&rft.aufirst=E&rft.date=2003-02-01&rft.volume=159&rft.issue=2&rft.spage=251&rft.isbn=&rft.btitle=&rft.title=Radiation+Research&rft.issn=00337587&rft_id=info:doi/10.1043%2F0033-7587%282003%29159%280251%3ARORIDD%292.0.CO%3B2 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1043/0033-7587(2003)159(0251:RORIDD)2.0.CO;2 ER - TY - JOUR T1 - Maintenance of stable heterochromatin domains by dynamic HP1 binding. AN - 72995197; 12560555 AB - One function of heterochromatin is the epigenetic silencing by sequestration of genes into transcriptionally repressed nuclear neighborhoods. Heterochromatin protein 1 (HP1) is a major component of heterochromatin and thus is a candidate for establishing and maintaining the transcriptionally repressive heterochromatin structure. Here we demonstrate that maintenance of stable heterochromatin domains in living cells involves the transient binding and dynamic exchange of HP1 from chromatin. HP1 exchange kinetics correlate with the condensation level of chromatin and are dependent on the histone methyltransferase Suv39h. The chromodomain and the chromoshadow domain of HP1 are both required for binding to native chromatin in vivo, but they contribute differentially to binding in euchromatin and heterochromatin. These data argue against HP1 repression of transcription by formation of static, higher order oligomeric networks but support a dynamic competition model, and they demonstrate that heterochromatin is accessible to regulatory factors. JF - Science (New York, N.Y.) AU - Cheutin, Thierry AU - McNairn, Adrian J AU - Jenuwein, Thomas AU - Gilbert, David M AU - Singh, Prim B AU - Misteli, Tom AD - National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/01/31/ PY - 2003 DA - 2003 Jan 31 SP - 721 EP - 725 VL - 299 IS - 5607 KW - Amanitins KW - 0 KW - Chromosomal Proteins, Non-Histone KW - Euchromatin KW - Heterochromatin KW - Histones KW - Hydroxamic Acids KW - Recombinant Fusion Proteins KW - heterochromatin-specific nonhistone chromosomal protein HP-1 KW - 107283-02-3 KW - trichostatin A KW - 3X2S926L3Z KW - Methyltransferases KW - EC 2.1.1.- KW - Index Medicus KW - Animals KW - Cell Nucleus -- metabolism KW - Euchromatin -- metabolism KW - HeLa Cells KW - Humans KW - Dimerization KW - Mice KW - Mice, Knockout KW - Binding Sites KW - Recombinant Fusion Proteins -- metabolism KW - Transfection KW - Amanitins -- pharmacology KW - Cells, Cultured KW - Fluorescence Recovery After Photobleaching KW - Kinetics KW - Histones -- metabolism KW - CHO Cells KW - Methyltransferases -- metabolism KW - Protein Structure, Tertiary KW - Hydroxamic Acids -- pharmacology KW - Cricetinae KW - Chromosomal Proteins, Non-Histone -- genetics KW - Heterochromatin -- chemistry KW - Heterochromatin -- metabolism KW - Chromosomal Proteins, Non-Histone -- metabolism KW - Chromosomal Proteins, Non-Histone -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72995197?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Maintenance+of+stable+heterochromatin+domains+by+dynamic+HP1+binding.&rft.au=Cheutin%2C+Thierry%3BMcNairn%2C+Adrian+J%3BJenuwein%2C+Thomas%3BGilbert%2C+David+M%3BSingh%2C+Prim+B%3BMisteli%2C+Tom&rft.aulast=Cheutin&rft.aufirst=Thierry&rft.date=2003-01-31&rft.volume=299&rft.issue=5607&rft.spage=721&rft.isbn=&rft.btitle=&rft.title=Science+%28New+York%2C+N.Y.%29&rft.issn=1095-9203&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-21 N1 - Date created - 2003-01-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dependence of gonadotropin-releasing hormone-induced neuronal MAPK signaling on epidermal growth factor receptor transactivation. AN - 72987975; 12446705 AB - The hypothalamic decapeptide, gonadotropin-releasing hormone (GnRH), utilizes multiple signaling pathways to activate extracellularly regulated mitogen-activated protein kinases (ERK1/2) in normal and immortalized pituitary gonadotrophs and transfected cells expressing the GnRH receptor. In immortalized hypothalamic GnRH neurons (GT1-7 cells), which also express GnRH receptors, GnRH, epidermal growth factor (EGF), and phorbol 12-myristate 13-acetate (PMA) caused marked phosphorylation of ERK1/2. This action of GnRH and PMA, but not that of EGF, was primarily dependent on activation of protein kinase C (PKC), and the ERK1/2 responses to all three agents were abolished by the selective EGF receptor kinase inhibitor, AG1478. Consistent with this, both GnRH and EGF increased tyrosine phosphorylation of the EGF receptor. GnRH and PMA, but not EGF, caused rapid phosphorylation of the proline-rich tyrosine kinase, Pyk2, at Tyr(402). This was reduced by Ca(2+) chelation and inhibition of PKC, but not by AG1478. GnRH stimulation caused translocation of PKC alpha and -epsilon to the cell membrane and enhanced the association of Src with PKC alpha and PKC epsilon, Pyk2, and the EGF receptor. The Src inhibitor, PP2, the C-terminal Src kinase (Csk), and dominant-negative Pyk2 attenuated ERK1/2 activation by GnRH and PMA but not by EGF. These findings indicate that Src and Pyk2 act upstream of the EGF receptor to mediate its transactivation, which is essential for GnRH-induced ERK1/2 phosphorylation in hypothalamic GnRH neurons. JF - The Journal of biological chemistry AU - Shah, Bukhtiar H AU - Soh, Jae-Won AU - Catt, Kevin J AD - Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/01/31/ PY - 2003 DA - 2003 Jan 31 SP - 2866 EP - 2875 VL - 278 IS - 5 SN - 0021-9258, 0021-9258 KW - Culture Media, Serum-Free KW - 0 KW - Gonadotropin-Releasing Hormone KW - 33515-09-2 KW - Epidermal Growth Factor KW - 62229-50-9 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Protein Kinase C-alpha KW - Mitogen-Activated Protein Kinase 1 KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinase 3 KW - Mitogen-Activated Protein Kinases KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Enzyme Activation KW - Mitogen-Activated Protein Kinases -- metabolism KW - Epidermal Growth Factor -- pharmacology KW - Transcriptional Activation KW - Protein Kinase C -- metabolism KW - Phosphorylation KW - Kinetics KW - Mitogen-Activated Protein Kinase 1 -- metabolism KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Line KW - MAP Kinase Signaling System -- drug effects KW - MAP Kinase Signaling System -- physiology KW - Receptor, Epidermal Growth Factor -- genetics KW - Neurons -- physiology KW - Gonadotropin-Releasing Hormone -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72987975?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Dependence+of+gonadotropin-releasing+hormone-induced+neuronal+MAPK+signaling+on+epidermal+growth+factor+receptor+transactivation.&rft.au=Shah%2C+Bukhtiar+H%3BSoh%2C+Jae-Won%3BCatt%2C+Kevin+J&rft.aulast=Shah&rft.aufirst=Bukhtiar&rft.date=2003-01-31&rft.volume=278&rft.issue=5&rft.spage=2866&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 - 2003-04-03 N1 - Date created - 2003-01-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Current mechanistic approaches to the chemoprevention of cancer. AN - 72986903; 12542978 AB - The prevention of cancer is one of the most important public health and medical practices of the 21st century. We have made much progress in this new emerging field, but so much remains to be accomplished before widespread use and practice become common place. Cancer chemoprevention encompasses the concepts of inhibition, reversal, and retardation of the cancer process. This process, called carcinogenesis, requires 20-40 years to reach the endpoint called invasive cancer. It typically follows multiple, diverse and complex pathways in a stochastic process of clonal evolution. These pathways appear amenable to inhibition, reversal or retardation at various points. We must therefore identify key pathways in the evolution of the cancer cell that can be exploited to prevent this carcinogenesis process. Basic research is identifying many genetic lesions and epigenetic processes associated with the progression of precancer to invasive disease. Many of these early precancerous lesions favor cell division over quiescence and protect cells against apoptosis when signals are present. Many oncogenes are active during early development and are reactivated in adulthood by aberrant gene promoting errors. Normal regulatory genes are mutated, making them insensitive to normal regulatory signals. Tumor suppressor genes are deleted or mutated rendering them inactive. Thus there is a wide range of defects in cellular machinery which can lead to evolution of the cancer phenotype. Mistakes may not have to appear in a certain order for cells to progress along the cancer pathway. To conquer this diverse disease, we must attack multiple key pathways at once for a predetermined period of time. Thus, agent combination prevention strategies are essential to decrease cancer morbidity. Furthermore, each cancer type may require custom combination of prevention strategies to be successful. JF - Journal of biochemistry and molecular biology AU - Steele, Vernon E AD - Chemoprevention Agent Development Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. vsly@nih.gov Y1 - 2003/01/31/ PY - 2003 DA - 2003 Jan 31 SP - 78 EP - 81 VL - 36 IS - 1 SN - 1225-8687, 1225-8687 KW - Antioxidants KW - 0 KW - Cyclooxygenase Inhibitors KW - Enzyme Inhibitors KW - Selective Estrogen Receptor Modulators KW - Topoisomerase I Inhibitors KW - Prostaglandin-Endoperoxide Synthases KW - EC 1.14.99.1 KW - Index Medicus KW - Gene Expression Regulation, Neoplastic KW - Animals KW - Oncogenes KW - Prostaglandin-Endoperoxide Synthases -- metabolism KW - Humans KW - DNA Methylation -- drug effects KW - Cell Division -- physiology KW - Enzyme Inhibitors -- pharmacology KW - Inflammation -- metabolism KW - Chemoprevention KW - Antioxidants -- pharmacology KW - Selective Estrogen Receptor Modulators -- pharmacology KW - Neoplasms -- prevention & control KW - Neoplasms -- genetics KW - Neoplasms -- metabolism KW - Cyclooxygenase Inhibitors -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72986903?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+biochemistry+and+molecular+biology&rft.atitle=Current+mechanistic+approaches+to+the+chemoprevention+of+cancer.&rft.au=Steele%2C+Vernon+E&rft.aulast=Steele&rft.aufirst=Vernon&rft.date=2003-01-31&rft.volume=36&rft.issue=1&rft.spage=78&rft.isbn=&rft.btitle=&rft.title=Journal+of+biochemistry+and+molecular+biology&rft.issn=12258687&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-20 N1 - Date created - 2003-01-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemoprevention of Helicobacter pylori-associated gastric carcinogenesis in a mouse model: is it possible? AN - 72977998; 12542979 AB - Although debates still exist whether Helicobacter pylori infection is really class I carcinogen or not, H. pylori has been known to provoke precancerous lesions like gastric adenoma and chronic atrophic gastritis with intestinal metaplasia as well as gastric cancer. Chronic persistent, uncontrolled gastric inflammations are possible basis for ensuing gastric carcinogenesis and H. pylori infection increased COX-2 expressions, which might be the one of the mechanisms leading to gastric cancer. To know the implication of long-term treatment of antiinflammatory drugs, rebamipide or nimesulide, on H. pylori-associated gastric carcinogenesis, we infected C57BL/6 mice with H. pylori, especially after MNU administration to promote carcinogenesis and the effects of the long-term administration of rebamipide or nimesulide were evaluated. C57BL/6 mice were sacrificed 50 weeks after H. pylori infection. Colonization rates of H. pylori, degree of gastric inflammation and other pathological changes including atrophic gastritis and metaplasia, serum levels and mRNA transcripts of various mouse cytokines and chemokines, and NF-kappaB binding activities, and finally the presence of gastric adenocarcinoma were compared between H. pylori infected group (HP), and H. pylori infected group administered with long-term rebamipide containing pellet diets (HPR) or nimesulide mixed pellets (HPN). Gastric mucosal expressions of ICAM-1, HCAM, MMP, and transcriptional regulations of NF-kappaB binding were all significantly decreased in HPR group than in HP group. Multi-probe RNase protection assay showed the significantly decreased mRNA levels of apoptosis related genes and various cytokines genes like IFN-gamma, RANTES, TNF-alpha, TNFR p75, IL-1beta in HPR group. In the experiment designed to provoke gastric cancer through MNU treatment with H. pylori infection, the incidence of gastric carcinoma was not changed between HP and HPR group, but significantly decreased in HPN group, suggesting the chemoprevention of H. pylori-associated gastric carcinogenesis by COX-2 inhibition. Long-term administration of antiinflammatory drugs should be considered in the treatment of H. pylori since they showed the molecular and biologic advantages with possible chemopreventive effect against H. pylori-associated gastric carcinogenesis. If the final concrete proof showing the causal relationship between H. pylori infection and gastric carcinogenesis could be obtained, that will shed new light on chemoprevention of gastric cancer, that is, that gastric cancer could be prevented through either the eradication of H. pylori or lessening the inflammation provoked by H. pylori infection in high risk group. JF - Journal of biochemistry and molecular biology AU - Hahm, Ki Baik AU - Song, Young Joon AU - Oh, Tae Young AU - Lee, Jeong Sang AU - Surh, Young-Joon AU - Kim, Young Bae AU - Yoo, Byung Moo AU - Kim, Jin Hong AU - Han, Sang Uk AU - Nahm, Ki Taik AU - Kim, Myung-Wook AU - Kim, Dae Yong AU - Cho, Sung Won AD - Chemoprevention Agent Development Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/01/31/ PY - 2003 DA - 2003 Jan 31 SP - 82 EP - 94 VL - 36 IS - 1 SN - 1225-8687, 1225-8687 KW - Anti-Inflammatory Agents KW - 0 KW - Anti-Inflammatory Agents, Non-Steroidal KW - Cytokines KW - NF-kappa B KW - Quinolones KW - Sulfonamides KW - Methylnitrosourea KW - 684-93-5 KW - rebamipide KW - LR583V32ZR KW - Alanine KW - OF5P57N2ZX KW - nimesulide KW - V4TKW1454M KW - Index Medicus KW - Animals KW - Helicobacter pylori KW - Cytokines -- drug effects KW - Cytokines -- genetics KW - Humans KW - Disease Models, Animal KW - Mice KW - NF-kappa B -- drug effects KW - Methylnitrosourea -- adverse effects KW - Apoptosis -- genetics KW - Sulfonamides -- pharmacology KW - Apoptosis -- drug effects KW - Quinolones -- pharmacology KW - NF-kappa B -- metabolism KW - Anti-Inflammatory Agents -- pharmacology KW - Anti-Inflammatory Agents, Non-Steroidal -- pharmacology KW - Stomach Neoplasms -- microbiology KW - Alanine -- analogs & derivatives KW - Stomach Neoplasms -- chemically induced KW - Helicobacter Infections -- drug therapy KW - Helicobacter Infections -- complications KW - Stomach Neoplasms -- prevention & control KW - Helicobacter Infections -- pathology KW - Alanine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72977998?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+biochemistry+and+molecular+biology&rft.atitle=Chemoprevention+of+Helicobacter+pylori-associated+gastric+carcinogenesis+in+a+mouse+model%3A+is+it+possible%3F&rft.au=Hahm%2C+Ki+Baik%3BSong%2C+Young+Joon%3BOh%2C+Tae+Young%3BLee%2C+Jeong+Sang%3BSurh%2C+Young-Joon%3BKim%2C+Young+Bae%3BYoo%2C+Byung+Moo%3BKim%2C+Jin+Hong%3BHan%2C+Sang+Uk%3BNahm%2C+Ki+Taik%3BKim%2C+Myung-Wook%3BKim%2C+Dae+Yong%3BCho%2C+Sung+Won&rft.aulast=Hahm&rft.aufirst=Ki&rft.date=2003-01-31&rft.volume=36&rft.issue=1&rft.spage=82&rft.isbn=&rft.btitle=&rft.title=Journal+of+biochemistry+and+molecular+biology&rft.issn=12258687&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-20 N1 - Date created - 2003-01-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of Regions within the Bacteriophage T4 AsiA Protein Involved in its Binding to the sigma super(70) Subunit of E.coli RNA Polymerase and its Role as a Transcriptional Inhibitor and Co-activator AN - 18651553; 5553534 AB - Bacteriophage T4 AsiA, a protein of 90 amino acid residues, binds to the sigma super(70) subunit of Escherichia coli RNA polymerase and inhibits host or T4 early transcription or, together with the T4 MotA protein, activates T4 middle transcription. To investigate which regions within AsiA are involved in forming a complex with sigma super(70) and in providing transcriptional functions we generated random mutations throughout AsiA and targeted mutations within the C-terminal region. We tested mutant proteins for their ability to complement the growth of T4 asiA am phage under non-suppressing conditions, to inhibit E.coli growth, to interact with sigma super(70) region 4 in a two-hybrid assay, to bind to sigma super(70) in a native protein gel, and to inhibit or activate transcription in vitro using a T4 middle promoter that is active with RNA polymerase alone, is inhibited by AsiA, and is activated by MotA/AsiA. We find that substitutions within the N-terminal half of AsiA, at amino acid residues V14, L18, and I40, rendered the protein defective for binding to sigma super(70). These residues reside at the monomer-monomer interface in recent NMR structures of the AsiA dimer. In contrast, AsiA missing the C-terminal 44 amino acid residues interacted well with sigma super(70) region 4 in the two-hybrid assay, and AsiA missing the C-terminal 17 amino acid residues ( Delta 74-90) bound to sigma super(70) and was fully competent in standard in vitro transcription assays. However, the presence of the C-terminal region delayed formation of transcriptionally competent species when the AsiA /polymerase complex was pre-incubated with the promoter in the absence of MotA. Our results suggest that amino acid residues within the N-terminal half of AsiA are involved in forming or maintaining the AsiA/ sigma super(70) complex. The C-terminal region of AsiA, while not absolutely required for inhibition or co-activation, aids inhibition by slowing the formation of transcription complexes between a promoter and the AsiA/polymerase complex. JF - Journal of Molecular Biology AU - Pal, D AU - Vuthoori, M AU - Pande, S AU - Wheeler, D AU - Hinton, D M AD - Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA, dhinton@helix.nih.gov Y1 - 2003/01/31/ PY - 2003 DA - 2003 Jan 31 SP - 827 EP - 841 PB - Elsevier Science Ltd VL - 325 IS - 5 SN - 0022-2836, 0022-2836 KW - AsiA protein KW - MotA protein KW - sigma 70 Factor KW - sigma 70 protein KW - Virology & AIDS Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - N 14721:RNA polymerases KW - J 02750:Phage-host interactions KW - V 22070:Phage-host interactions including lysogeny & transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18651553?accountid=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=Analysis+of+Regions+within+the+Bacteriophage+T4+AsiA+Protein+Involved+in+its+Binding+to+the+sigma+super%2870%29+Subunit+of+E.coli+RNA+Polymerase+and+its+Role+as+a+Transcriptional+Inhibitor+and+Co-activator&rft.au=Pal%2C+D%3BVuthoori%2C+M%3BPande%2C+S%3BWheeler%2C+D%3BHinton%2C+D+M&rft.aulast=Pal&rft.aufirst=D&rft.date=2003-01-31&rft.volume=325&rft.issue=5&rft.spage=827&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - How well do parents manage young driver crash risks? AN - 18643518; 5549722 AB - Motor vehicle crashes are extremely high among young drivers during at least the first year of licensure. Crash risks decline with increased experience, but the more newly licensed teenagers drive, the greater their risk exposure. Hence, the dilemma facing policy makers and parents is how to provide young drivers with driving experience without unduly increasing their crash risk. Graduated driver licensing policies serve to delay licensure and then limit exposure to the highest risk conditions after licensure, allowing young drivers to gain experience only under less risky driving conditions. A similar strategy is needed to guide parents. Parents do not appear to appreciate just how risky driving is for novice drivers and tend to exert less control over their teenage children's driving than might be expected. Recent research has demonstrated that simple motivational strategies can persuade parents to adopt driving agreements and impose greater restrictions on early teen driving. JF - Journal of Safety Research AU - Simons-Morton, B G AU - Hartos, J L AD - Prevention Research Branch, Division of Epidemiology, Statistics, and Prevention Research, National Institute of Child Health and Human Development, 6100 Executive Boulevard, 7B05, Bethesda, MD 20892-7510, USA, mortonb@mail.nih.gov Y1 - 2003/01/30/ PY - 2003 DA - 2003 Jan 30 SP - 91 EP - 97 VL - 34 IS - 1 SN - 0022-4375, 0022-4375 KW - driving ability KW - graduated licensing KW - traffic safety KW - Risk Abstracts; Health & Safety Science Abstracts KW - R2 23020:Technological risks KW - H 2000:Transportation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18643518?accountid=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+Safety+Research&rft.atitle=How+well+do+parents+manage+young+driver+crash+risks%3F&rft.au=Simons-Morton%2C+B+G%3BHartos%2C+J+L&rft.aulast=Simons-Morton&rft.aufirst=B&rft.date=2003-01-30&rft.volume=34&rft.issue=1&rft.spage=91&rft.isbn=&rft.btitle=&rft.title=Journal+of+Safety+Research&rft.issn=00224375&rft_id=info:doi/10.1016%2FS0022-4375%2802%2900085-3 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0022-4375(02)00085-3 ER - TY - JOUR T1 - Practice parameter: treatment of the child with a first unprovoked seizure: Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. AN - 72986536; 12552027 AB - The Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society develop practice parameters as strategies for patient management based on analysis of evidence regarding risks and benefits. This parameter reviews published literature relevant to the decision to begin treatment after a child or adolescent experiences a first unprovoked seizure and presents evidence-based practice recommendations. Reasons why treatment may be considered are discussed. Evidence is reviewed concerning risk of recurrence as well as effect of treatment on prevention of recurrence and development of chronic epilepsy. Studies of side effects of anticonvulsants commonly used to treat seizures in children are also reviewed. Relevant articles are classified according to the Quality Standards Subcommittee classification scheme. Treatment after a first unprovoked seizure appears to decrease the risk of a second seizure, but there are few data from studies involving only children. There appears to be no benefit of treatment with regard to the prognosis for long-term seizure remission. Antiepileptic drugs (AED) carry risks of side effects that are particularly important in children. The decision as to whether or not to treat children and adolescents who have experienced a first unprovoked seizure must be based on a risk-benefit assessment that weighs the risk of having another seizure against the risk of chronic AED therapy. The decision should be individualized and take into account both medical issues and patient and family preference. JF - Neurology AU - Hirtz, D AU - Berg, A AU - Bettis, D AU - Camfield, C AU - Camfield, P AU - Crumrine, P AU - Gaillard, W D AU - Schneider, S AU - Shinnar, S AU - Quality Standards Subcommittee of the American Academy of Neurology AU - Practice Committee of the Child Neurology Society AD - National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA. ; Quality Standards Subcommittee of the American Academy of Neurology ; Practice Committee of the Child Neurology Society Y1 - 2003/01/28/ PY - 2003 DA - 2003 Jan 28 SP - 166 EP - 175 VL - 60 IS - 2 KW - Anticonvulsants KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - United States KW - Humans KW - Prognosis KW - Child KW - Risk Assessment KW - Child, Preschool KW - Clinical Trials as Topic -- statistics & numerical data KW - Behavior -- drug effects KW - Cognition -- drug effects KW - Drug Eruptions KW - Adult KW - Cohort Studies KW - Treatment Outcome KW - Follow-Up Studies KW - Sleep Stages -- drug effects KW - Adolescent KW - Secondary Prevention KW - Remission Induction KW - Seizures -- classification KW - Seizures -- diagnosis KW - Anticonvulsants -- adverse effects KW - Seizures -- drug therapy KW - Anticonvulsants -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72986536?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurology&rft.atitle=Practice+parameter%3A+treatment+of+the+child+with+a+first+unprovoked+seizure%3A+Report+of+the+Quality+Standards+Subcommittee+of+the+American+Academy+of+Neurology+and+the+Practice+Committee+of+the+Child+Neurology+Society.&rft.au=Hirtz%2C+D%3BBerg%2C+A%3BBettis%2C+D%3BCamfield%2C+C%3BCamfield%2C+P%3BCrumrine%2C+P%3BGaillard%2C+W+D%3BSchneider%2C+S%3BShinnar%2C+S%3BQuality+Standards+Subcommittee+of+the+American+Academy+of+Neurology%3BPractice+Committee+of+the+Child+Neurology+Society&rft.aulast=Porter&rft.aufirst=Dale&rft.date=2002-06-14&rft.volume=175&rft.issue=1-3&rft.spage=63&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-05 N1 - Date created - 2003-01-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bcl-2 reduces mutant rates in a transgenic lacZ reporter gene in mouse pre-B lymphocytes. AN - 72949884; 12517419 AB - To assess mutagenesis during early B-lymphocyte development in vitro, progenitor B cells (pre-B cells) were obtained from fetal livers of BALB/c mice and DBA/2N mice that harbored the transgenic shuttle vector, pUR288, with a lacZ reporter gene for the determination of mutant frequencies (MFs). Differentiation-arrested pre-B cells demonstrated a marked dose-dependent increase in lacZ mutant levels after exposure to gamma-irradiation with a peak MF of 250 x 10(-5) at 2.5 Gy. Without genotoxic treatment, pre-B cells undergoing spontaneous differentiation into surface IgM expressing immature B cells exhibited lacZ mutant levels of up to 95 x 10(-5). The mutational pattern was dominated in both experiments by illegitimate recombination mutations of lacZ, not point mutations. Likewise, in both experiments, the enforced expression of Bcl-2 resulted in a striking reduction of lacZ mutations. These findings indicated that mouse pre-B cells are prone to accumulate induced and self-inflicted mutations, particularly recombinations. Additionally, our studies revealed a heretofore unknown role of Bcl-2 in inhibiting mutagenesis during early B-cell development in mice. Copyright 2002 Elsevier Science B.V. JF - Mutation research AU - Felix, Klaus AU - Rolink, Antonius AU - Melchers, Fritz AU - Janz, Siegfried AD - Laboratory of Genetics, Center for Cancer Research, National Cancer Institute, Room 2B10, Building 37, NIH, Bethesda, MD 20892-4255, USA. Y1 - 2003/01/28/ PY - 2003 DA - 2003 Jan 28 SP - 135 EP - 144 VL - 522 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Proto-Oncogene Proteins c-bcl-2 KW - 0 KW - Index Medicus KW - Fetus KW - Animals KW - Gamma Rays KW - Transfection KW - Genetic Vectors KW - Mice, Inbred C57BL KW - Mice KW - Retroviridae -- genetics KW - Mice, Inbred BALB C KW - Lac Operon KW - Radiation, Ionizing KW - Mice, Inbred DBA KW - Cell Differentiation -- radiation effects KW - Mutagenesis -- radiation effects KW - Proto-Oncogene Proteins c-bcl-2 -- metabolism KW - B-Lymphocytes -- radiation effects KW - Genes, Reporter KW - B-Lymphocytes -- metabolism KW - Proto-Oncogene Proteins c-bcl-2 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72949884?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Bcl-2+reduces+mutant+rates+in+a+transgenic+lacZ+reporter+gene+in+mouse+pre-B+lymphocytes.&rft.au=Felix%2C+Klaus%3BRolink%2C+Antonius%3BMelchers%2C+Fritz%3BJanz%2C+Siegfried&rft.aulast=Felix&rft.aufirst=Klaus&rft.date=2003-01-28&rft.volume=522&rft.issue=1-2&rft.spage=135&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 - 2003-03-03 N1 - Date created - 2003-01-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A novel PHD-finger motif protein, p47ING3, modulates p53-mediated transcription, cell cycle control, and apoptosis. AN - 72977337; 12545155 AB - A candidate tumor suppressor gene, p33ING1, was previously identified by using the genetic suppressor element methodology. p33ING1 cooperates with p53 and plays a significant role in p53-mediated cellular processes. Recently, we have identified p33ING2, which shows a sequence homology similar to p33ING1 and modulates p53 function. In the present study, we identified and characterized another 'ING family' gene. The estimated molecular weight of the encoded protein is 46.8 kDa, thus, we named it p47ING3. The p47ING3 gene is located at chromosome 7q31.3 and consists of 12 exons that encode 418 amino acids. A computational domain search revealed a C-terminal PHD-finger motif. Such motifs are common in proteins involved in chromatin remodeling. p47ING3 is highly expressed in some normal human tissues or organs, including the spleen, testis, skeletal muscle, and heart. p47ING3 expression levels varied among cancer cell lines. p47ING3 overexpression resulted in a decreased population of cells in S phase, a diminished colony-forming efficiency, and induced apoptosis in RKO cells, but not in RKO-E6 cells with inactivated p53. p47ING3 activates p53-transactivated promoters, including promoters of p21/waf1 and bax. Thus, we have isolated a novel ING family gene, p47ING3, which modulates p53-mediated transcription, cell cycle control, and apoptosis. JF - Oncogene AU - Nagashima, Makoto AU - Shiseki, Masayuki AU - Pedeux, Remy M AU - Okamura, Shu AU - Kitahama-Shiseki, Mariko AU - Miura, Koh AU - Yokota, Jun AU - Harris, Curtis C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD 20892-4255, USA. Y1 - 2003/01/23/ PY - 2003 DA - 2003 Jan 23 SP - 343 EP - 350 VL - 22 IS - 3 SN - 0950-9232, 0950-9232 KW - Homeodomain Proteins KW - 0 KW - ING2 protein, human KW - ING3 protein, human KW - Receptors, Cytoplasmic and Nuclear KW - Trans-Activators KW - Tumor Suppressor Protein p53 KW - Tumor Suppressor Proteins KW - Index Medicus KW - Reference Values KW - Testis -- metabolism KW - Spleen -- metabolism KW - Exons KW - Genes, Tumor Suppressor KW - Humans KW - Protein Processing, Post-Translational KW - Lymphocytes -- metabolism KW - Transcription, Genetic KW - Amino Acid Sequence KW - Chromosomes, Human, Pair 7 KW - Myocardium -- metabolism KW - Promoter Regions, Genetic KW - Amino Acid Motifs KW - Cells, Cultured KW - Sequence Analysis KW - Lymphocytes -- radiation effects KW - Molecular Sequence Data KW - Zinc Fingers KW - Sequence Homology, Amino Acid KW - Lymphocytes -- drug effects KW - Male KW - Trans-Activators -- metabolism KW - Homeodomain Proteins -- genetics KW - Trans-Activators -- genetics KW - Cell Cycle -- physiology KW - Apoptosis -- physiology KW - Tumor Suppressor Proteins -- metabolism KW - Tumor Suppressor Proteins -- genetics KW - Homeodomain Proteins -- metabolism KW - Tumor Suppressor Protein p53 -- genetics KW - Tumor Suppressor Protein p53 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72977337?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=A+novel+PHD-finger+motif+protein%2C+p47ING3%2C+modulates+p53-mediated+transcription%2C+cell+cycle+control%2C+and+apoptosis.&rft.au=Nagashima%2C+Makoto%3BShiseki%2C+Masayuki%3BPedeux%2C+Remy+M%3BOkamura%2C+Shu%3BKitahama-Shiseki%2C+Mariko%3BMiura%2C+Koh%3BYokota%2C+Jun%3BHarris%2C+Curtis+C&rft.aulast=Nagashima&rft.aufirst=Makoto&rft.date=2003-01-23&rft.volume=22&rft.issue=3&rft.spage=343&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-12 N1 - Date created - 2003-01-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DLC-1 gene inhibits human breast cancer cell growth and in vivo tumorigenicity. AN - 72972620; 12545165 AB - The human DLC-1 (deleted in liver cancer 1) gene was cloned from a primary human hepatocellular carcinoma (HCC) and mapped to the chromosome 8p21-22 region frequently deleted in common human cancers and suspected to harbor tumor suppressor genes. DLC-1 was found to be deleted or downregulated in a significant number of HCCs. We expanded our investigations to other cancers with recurrent deletions of 8p22, and in this study examined alterations of DLC-1 in primary human breast tumors, human breast, colon, and prostate tumor cell lines. Genomic deletion of DLC-1 was observed in 40% of primary breast tumors, whereas reduced or undetectable levels of DLC-1 mRNA were seen in 70% of breast, 70% of colon, and 50% of prostate tumor cell lines To see whether DLC-1 expression affects cell growth and tumorigenicity, two breast carcinoma cell lines lacking the expression of endogenous gene were transfected with the DLC-1 cDNA. In both cell lines, DLC-1 transfection caused significant growth inhibition and reduction of colony formation. Furthermore, introduction of the DLC-1 cDNA abolished the in vivo tumorigenicity in nude mice, suggesting that the DLC-1 gene plays a role in breast cancer by acting as a bona fide tumor suppressor gene. JF - Oncogene AU - Yuan, Bao-Zhu AU - Zhou, Xiaoling AU - Durkin, Marian E AU - Zimonjic, Drazen B AU - Gumundsdottir, Katrin AU - Eyfjord, Jorunn E AU - Thorgeirsson, Snorri S AU - Popescu, Nicholas C AD - Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2003/01/23/ PY - 2003 DA - 2003 Jan 23 SP - 445 EP - 450 VL - 22 IS - 3 SN - 0950-9232, 0950-9232 KW - DLC1 protein, human KW - 0 KW - GTPase-Activating Proteins KW - Tumor Suppressor Proteins KW - Index Medicus KW - Animals KW - Reference Values KW - Colonic Neoplasms -- genetics KW - Humans KW - Prostatic Neoplasms -- genetics KW - Mammary Neoplasms, Experimental -- genetics KW - Mice KW - Adenocarcinoma -- genetics KW - Mice, Inbred BALB C KW - Gene Deletion KW - Gene Expression Regulation, Neoplastic KW - Prostatic Neoplasms -- pathology KW - Tumor Cells, Cultured KW - Transfection KW - Carcinogenicity Tests -- methods KW - Colonic Neoplasms -- pathology KW - Cell Division -- genetics KW - Female KW - Male KW - Breast Neoplasms -- genetics KW - Breast Neoplasms -- pathology KW - Tumor Suppressor Proteins -- metabolism KW - Tumor Suppressor Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72972620?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Acute+ethanol+administration+downregulates+human+immunodeficiency+virus-1+glycoprotein+120-induced+KC+and+RANTES+production+by+murine+Kupffer+cells+and+splenocytes.&rft.au=Bautista%2C+Abraham+P%3BWang%2C+Enze&rft.aulast=Bautista&rft.aufirst=Abraham&rft.date=2002-06-14&rft.volume=71&rft.issue=4&rft.spage=371&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 - 2003-02-12 N1 - Date created - 2003-01-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intranasal immunization with a lipooligosaccharide-based conjugate vaccine from nontypeable Haemophilus influenzae enhances bacterial clearance in mouse nasopharynx AN - 18691403; 5576628 AB - Nontypeable Haemophilus influenzae (NTHi) is a major cause of otitis media in children. We investigated whether intranasal immunization with a detoxified lipooligosaccharide-tetanus toxoid (dLOS-TT) conjugate vaccine would generate protective immunity against NTHi in a mouse model of nasopharyngeal clearance. The results demonstrated that intranasal immunization with dLOS-TT plus adjuvant cholera toxin (CT) significantly induced LOS-specific IgA antibodies in mouse external secretions, especially in nasal wash (90-fold), bronchoalveolar lavage fluid (25-fold), saliva (13-fold) and fecal extract (three-fold). LOS-specific IgA antibody-forming cells were also found in mucosal and lymphoid tissues with their highest numbers in the nasal passage (528 per 10 super(6) cells). In addition, the intranasal immunization elicited a significant rise in LOS-specific IgG (32-fold) and IgA (13-fold) in serum. For the immunized mice which had been challenged through the nose with 10 super(7) live NTHi strain 9274 cells, the vaccine group showed a significant reduction (74-77%) of NTHi, compared to that of control groups with CT alone or dLOS plus CT (P0.05). Negative correlations were found between bacterial counts and the levels of nasal wash IgA or IgG, saliva IgA and serum IgG. The clearance of five heterologous strains was investigated and revealed a significant clearance of strains 3198, 5657 and 7502 but not of strains 1479 and 2019. These data suggest that intranasal immunization with dLOS-TT vaccine elicits both mucosal and systemic immunity against NTHi and enhances bacterial clearance from nasopharynx in mice. Such a vaccine and vaccination regime may be applicable to humans with an appropriate formulation. JF - FEMS Immunology and Medical Microbiology AU - Hirano, T AU - Hou, Y AU - Jiao, X AU - Gu, X AD - National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 5 Research Court, Rockville, MD 20850, USA, guxx@nidcd.nih.gov Y1 - 2003/01/21/ PY - 2003 DA - 2003 Jan 21 SP - 1 EP - 10 PB - Federation of European Microbiological Societies VL - 35 IS - 1 SN - 0928-8244, 0928-8244 KW - cholera toxin KW - clearance KW - conjugate vaccines KW - intranasal immunization KW - lipooligosaccharides KW - mice KW - tetanus toxin KW - tetanus toxoid KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - J 02834:Vaccination and immunization KW - F 06807:Active immunization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18691403?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FEMS+Immunology+and+Medical+Microbiology&rft.atitle=Intranasal+immunization+with+a+lipooligosaccharide-based+conjugate+vaccine+from+nontypeable+Haemophilus+influenzae+enhances+bacterial+clearance+in+mouse+nasopharynx&rft.au=Hirano%2C+T%3BHou%2C+Y%3BJiao%2C+X%3BGu%2C+X&rft.aulast=Hirano&rft.aufirst=T&rft.date=2003-01-21&rft.volume=35&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=FEMS+Immunology+and+Medical+Microbiology&rft.issn=09288244&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Microarrays: the use of oligonucleotides and cDNA for the analysis of gene expression AN - 18689261; 5577791 AB - Completion of the human genome sequence has made it possible to study the expression of the entire human gene complement (>30,000 estimated genes). Aiding in this remarkable feat, DNA microarrays have become the main technological workhorse for gene expression studies. To date, detection platforms for most microarrays have relied on short (25 base) oligonucleotides synthesized in situ, or longer, highly variable length DNAs from PCR amplification of cDNA libraries. A third choice, long (50-80 base) oligonucleotide arrays, is now available and might eventually eliminate the use of cDNA arrays. The technology has advanced to such a point that researchers now demand microarrays that are cost-effective and have flexibility and quality assurance. Short- and long-oligonucleotide technologies offer such advantages, and could possibly become the major competing platform in the near future. JF - Drug Discovery Today AU - Barrett, J C AU - Kawasaki, E S AD - Center for Cancer Research, National Cancer Institute, 31 Center Drive, MSC-2440, Bethesda, MD 20892, USA Y1 - 2003/01/21/ PY - 2003 DA - 2003 Jan 21 SP - 134 EP - 141 PB - Elsevier Science Ltd VL - 8 IS - 3 SN - 1359-6446, 1359-6446 KW - DNA microarrays KW - cDNA KW - man KW - oligonucleotides KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33243:Molecular methods KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18689261?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+Discovery+Today&rft.atitle=Microarrays%3A+the+use+of+oligonucleotides+and+cDNA+for+the+analysis+of+gene+expression&rft.au=Barrett%2C+J+C%3BKawasaki%2C+E+S&rft.aulast=Barrett&rft.aufirst=J&rft.date=2003-01-21&rft.volume=8&rft.issue=3&rft.spage=134&rft.isbn=&rft.btitle=&rft.title=Drug+Discovery+Today&rft.issn=13596446&rft_id=info:doi/10.1016%2FS1359-6446%2802%2902578-3 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S1359-6446(02)02578-3 ER - TY - JOUR T1 - Potent antitumor activity of a urokinase-activated engineered anthrax toxin AN - 18654631; 5551857 AB - The acquisition of cell-surface urokinase plasminogen activator activity is a hallmark of malignancy. We generated an engineered anthrax toxin that is activated by cell-surface urokinase in vivo and displays limited toxicity to normal tissue but broad and potent tumoricidal activity. Native anthrax toxin protective antigen, when administered with a chimeric anthrax toxin lethal factor, Pseudomonas exotoxin fusion protein, was extremely toxic to mice, causing rapid and fatal organ damage. Replacing the furin activation sequence in anthrax toxin protective antigen with an artificial peptide sequence efficiently activated by urokinase greatly attenuated toxicity to mice. In addition, the mutation conferred cell-surface urokinase-dependent toxin activation in vivo, as determined by using a panel of plasminogen, plasminogen activator, plasminogen activator receptor, and plasminogen activator inhibitor-deficient mice. Surprisingly, toxin activation critically depended on both urokinase plasminogen activator receptor and plasminogen in vivo, showing that both proteins are essential cofactors for the generation of cell-surface urokinase. The engineered toxin displayed potent tumor cell cytotoxicity to a spectrum of transplanted tumors of diverse origin and could eradicate established solid tumors. This tumoricidal activity depended strictly on tumor cell-surface plasminogen activation. The data show that a simple change of protease activation specificity converts anthrax toxin from a highly lethal to a potent tumoricidal agent. JF - Proceedings of the National Academy of Sciences, USA AU - Liu, S AU - Aaronson, H AU - Mitola, D J AU - Leppla, SH AU - Bugge, TH AD - Oral Infection and Immunity Branch and Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, Leppla@nih.gov Y1 - 2003/01/21/ PY - 2003 DA - 2003 Jan 21 SP - 657 EP - 662 VL - 100 IS - 2 SN - 0027-8424, 0027-8424 KW - mice KW - u-plasminogen activator receptors KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Bioengineering Abstracts KW - W4 130:General Biomedical Engineering: Tools & Techniques KW - W3 33374:Antitumor agents KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18654631?accountid=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=Potent+antitumor+activity+of+a+urokinase-activated+engineered+anthrax+toxin&rft.au=Liu%2C+S%3BAaronson%2C+H%3BMitola%2C+D+J%3BLeppla%2C+SH%3BBugge%2C+TH&rft.aulast=Liu&rft.aufirst=S&rft.date=2003-01-21&rft.volume=41&rft.issue=23&rft.spage=7407&rft.isbn=&rft.btitle=&rft.title=Biochemistry&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 DO - http://dx.doi.org/10.1073/pnas.0236849100 ER - TY - JOUR T1 - CSF monoamine metabolites and MRI brain volumes in alcohol dependence. AN - 73020422; 12589880 AB - Correlations between cerebrospinal fluid (CSF) concentrations of monoamine metabolites (MAM) and brain structure have been described in schizophrenia, but not in alcoholism. To investigate the relationship between monoaminergic transmission and brain structure in alcoholism, the metabolites of dopamine (homovanillic acid, HVA), norepinephrenine (3-methoxy-4-hydroxyphenylethyleneglycol, MHPG) and serotonin (5-hydroxyindoleacetic acid, 5-HIAA) were measured in lumbar CSF in 54 alcohol-dependent patients and 20 healthy subjects. The volumes of the cerebrum, total grey and white matter, total and ventricular CSF, left and right hippocampus, and corpus callosum area were measured with MRI. MHPG and age were positively correlated in alcoholic women. The MAM concentrations were not significantly correlated with the MRI volumes in the subject categories. There were no differences in MAM across subjects defined by diagnosis and gender, age of onset of alcoholism or comorbidity of psychiatric disorders. Total CSF, cerebrum, and white and grey matter tissue volumes differed between patients and healthy subjects. The greatest difference was the white matter reduction in alcoholic women. In alcoholic women and men, monoaminergic neurotransmission measured by the CSF MAM HVA, MHPG, and 5-HIAA is not significantly correlated with the size of different brain structures. Copyright 2002 Elsevier Science Ireland Ltd. JF - Psychiatry research AU - Agartz, Ingrid AU - Shoaf, Susan AU - Rawlings, Robert R AU - Momenan, Reza AU - Hommer, Daniel W AD - Section on Electrophysiology and Brain Imaging, Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892-1256, USA. ingrid.agartz@cns.ki.se Y1 - 2003/01/20/ PY - 2003 DA - 2003 Jan 20 SP - 21 EP - 35 VL - 122 IS - 1 SN - 0165-1781, 0165-1781 KW - Biogenic Monoamines KW - 0 KW - Serotonin KW - 333DO1RDJY KW - Methoxyhydroxyphenylglycol KW - 534-82-7 KW - Norepinephrine KW - X4W3ENH1CV KW - Homovanillic Acid KW - X77S6GMS36 KW - Index Medicus KW - Homovanillic Acid -- cerebrospinal fluid KW - Methoxyhydroxyphenylglycol -- cerebrospinal fluid KW - Serotonin -- cerebrospinal fluid KW - Humans KW - Adult KW - Middle Aged KW - Norepinephrine -- cerebrospinal fluid KW - Male KW - Female KW - Magnetic Resonance Imaging KW - Biogenic Monoamines -- cerebrospinal fluid KW - Brain -- anatomy & histology KW - Alcoholism -- metabolism KW - Brain -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73020422?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=CSF+monoamine+metabolites+and+MRI+brain+volumes+in+alcohol+dependence.&rft.au=Agartz%2C+Ingrid%3BShoaf%2C+Susan%3BRawlings%2C+Robert+R%3BMomenan%2C+Reza%3BHommer%2C+Daniel+W&rft.aulast=Agartz&rft.aufirst=Ingrid&rft.date=2003-01-20&rft.volume=122&rft.issue=1&rft.spage=21&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 - 2003-06-18 N1 - Date created - 2003-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of methylenetetrahydrofolate reductase 677C-->T polymorphism on toxicity and homocysteine plasma level after chronic methotrexate treatment of ovarian cancer patients. AN - 72886817; 12471611 AB - MTHFR is a critical enzyme that regulates the metabolism of folate and methionine, both of which are important factors in DNA methylation and synthesis. Subjects with the 677C-->T variant have impaired remethylation of Hcy to methionine that could determine hyperhomocysteinemia. Remethylation of Hcy into methionine and DNA methylation are also affected by MTX treatment. Thus, a combined effect between MTX and reduced activity of the MTHFR 677C-->T polymorphism could occur, leading to toxicity. In a clinical trial, 43 ovarian cancer patients were treated with low doses of MTX. During MTX therapy, 12 patients (27.9%) developed G3/4 WHO toxicity. In these 12 patients, we observed 6 G3/4 thrombocytopenias, 1 G3 neutropenia, 1 G3 anemia, 9 G3 mucositis cases and 1 G4 mucositis case. A significant association was observed between toxicity and TT MTHFR 677 genotype (p < 0.0001). G3/4 toxicity occurred in 10 of 13 (77%), 1 of 17 (6%) and 1 of 13 (8%) patients with the TT, CT and CC MTHFR genotypes, respectively. According to the logistic regression model, patients with the TT genotype had a relative risk of 42.0 (95% CI 4.2-418.6) of developing G3/4 toxicity compared to patients with the CC and CT genotypes. Patients with the TT genotype had Hcy plasma levels after MTX therapy significantly (p = 0.0001) higher than basal levels (mean +/- SD = 16.71 +/- 4.72 vs. 12.48 +/- 3.57 micromol/l); moreover, they also had higher Hcy plasma levels after MTX than patients with other MTHFR 677 genotypes (CC mean +/- SD = 9.87 +/- 3.61 micromol/l and CT mean +/- SD = 11.48 +/- 3.13 micromol/l). Finally, significant associations were observed between G3/4 WHO toxicity and higher Hcy plasma levels after MTX treatment (p = 0.0004). In conclusion, our data suggest that the TT MTHFR 677 genotype is associated with marked MTX-induced hyperhomocysteinemia and could represent a pharmacogenetic marker for toxicity after chronic treatment with low doses of MTX. Copyright 2002 Wiley-Liss, Inc. JF - International journal of cancer AU - Toffoli, Giuseppe AU - Russo, Antonio AU - Innocenti, Federico AU - Corona, Giuseppe AU - Tumolo, Salvatore AU - Sartor, Franca AU - Mini, Enrico AU - Boiocchi, Mauro AD - Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy. gtoffoli@cro.it Y1 - 2003/01/20/ PY - 2003 DA - 2003 Jan 20 SP - 294 EP - 299 VL - 103 IS - 3 SN - 0020-7136, 0020-7136 KW - Antimetabolites, Antineoplastic KW - 0 KW - DNA Primers KW - Homocysteine KW - 0LVT1QZ0BA KW - Oxidoreductases Acting on CH-NH Group Donors KW - EC 1.5.- KW - Methylenetetrahydrofolate Reductase (NADPH2) KW - EC 1.5.1.20 KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Neoplasm Staging KW - Humans KW - Aged KW - Hyperhomocysteinemia -- chemically induced KW - Genotype KW - Polymerase Chain Reaction KW - Hematologic Diseases -- chemically induced KW - Adult KW - Middle Aged KW - Hyperhomocysteinemia -- etiology KW - Female KW - Platelet Count KW - DNA Primers -- chemistry KW - Homocysteine -- blood KW - Ovarian Neoplasms -- genetics KW - Polymorphism, Genetic -- genetics KW - Oxidoreductases Acting on CH-NH Group Donors -- genetics KW - Homocysteine -- deficiency KW - Methotrexate -- therapeutic use KW - Antimetabolites, Antineoplastic -- therapeutic use KW - Ovarian Neoplasms -- drug therapy KW - Oxidoreductases Acting on CH-NH Group Donors -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72886817?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effect+of+methylenetetrahydrofolate+reductase+677C--%26gt%3BT+polymorphism+on+toxicity+and+homocysteine+plasma+level+after+chronic+methotrexate+treatment+of+ovarian+cancer+patients.&rft.au=Toffoli%2C+Giuseppe%3BRusso%2C+Antonio%3BInnocenti%2C+Federico%3BCorona%2C+Giuseppe%3BTumolo%2C+Salvatore%3BSartor%2C+Franca%3BMini%2C+Enrico%3BBoiocchi%2C+Mauro&rft.aulast=Toffoli&rft.aufirst=Giuseppe&rft.date=2003-01-20&rft.volume=103&rft.issue=3&rft.spage=294&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 - 2003-01-21 N1 - Date created - 2002-12-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High Cloning Capacity of In Vitro Packaged SV40 Vectors with No SV40 Virus Sequences AN - 18682654; 5580673 AB - In vitro packaging of plasmid DNA using recombinant SV40 capsid proteins is a potentially useful procedure that overcomes some restrictions of the other SV40 systems such as the requirement for SV40 sequences and the limitation in size of DNA that can be packaged. The in vitro packaging system uses the four SV40 proteins (VP1, VP2, VP3, and agno) or VP1 only. The ability to confer drug resistance by three ABC transporter genes (MDR1, MRP1, or MXR) was determined using the surrogate fluorescent substrates rhodamine-123 or calcein AM and their specific inhibitors, or by using specific antibodies to the transporters to detect cell surface expression by fluorescence-activated cell sorter analysis (FACS). A green fluorescent protein plasmid (EGFP-C1) was also used to monitor gene transfer. The packaged plasmids ranged in size from 4.2 to 17.6 kb, and only slightly affected particle size as determined by electron microscopy. When 9.5 kb and larger plasmids were packaged using all SV40 proteins, MDR1 expression was decreased compared to VP1 alone. The size of the 15.2 kb DNA after packaging was the same as the original DNA. Packaging with SV40 capsid proteins in vitro does not require any SV40 sequences. Using either the MDR1 or the GFP gene we could demonstrate enhanced expression when cells were pretreated with phorbol 12-myristate 13-acetate (PMA) at low concentrations. Interferon- gamma did not alter expression. We conclude that in vitro packaging is more flexible then previously realized, permitting packaging of at least 17 kb plasmid DNA without the requirement for any viral sequences. This system combines efficient gene delivery of the SV40 viral vector with the presumed safety of nonviral vectors. JF - Human Gene Therapy AU - Kimchi-Sarfaty, C AU - Arora, M AU - Sandalon, Z AU - Oppenheim, A AU - Gottesman, M M AD - Laboratory of Cell Biology, Building 37, Room 1A09, National Cancer Institute, National Institutes of Health, 37 Convent Drive, MSC 4254, Bethesda, MD 20892-4254, USA, mgottesman@nih.gov Y1 - 2003/01/20/ PY - 2003 DA - 2003 Jan 20 SP - 167 EP - 177 VL - 14 IS - 2 SN - 1043-0342, 1043-0342 KW - MDR1 gene KW - MRP1 gene KW - MXR gene KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Bioengineering Abstracts KW - W3 33181:Gene therapy vectors KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews KW - W4 120:Genetic Engineering in Medicine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18682654?accountid=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+Cloning+Capacity+of+In+Vitro+Packaged+SV40+Vectors+with+No+SV40+Virus+Sequences&rft.au=Kimchi-Sarfaty%2C+C%3BArora%2C+M%3BSandalon%2C+Z%3BOppenheim%2C+A%3BGottesman%2C+M+M&rft.aulast=Kimchi-Sarfaty&rft.aufirst=C&rft.date=2003-01-20&rft.volume=14&rft.issue=2&rft.spage=167&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Identification of Dss1 as a 12-O-tetradecanoylphorbol-13-acetate-responsive gene expressed in keratinocyte progenitor cells, with possible involvement in early skin tumorigenesis. AN - 72947126; 12419822 AB - This study identifies genes expressed early in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin carcinogenesis in genetically initiated Tg.AC v-Ha-ras transgenic mice. Keratinocyte progenitor cells from TPA-treated Tg.AC mice were isolated with fluorescence-activated cell sorting and expression was analyzed using cDNA microarray technology. Eleven genes were identified whose expression changed significantly in response to carcinogen treatment. Deleted in split hand/split foot 1 (Dss1) is a gene associated with a heterogeneous limb developmental disorder called split hand/split foot malformation. cDNA microarray expression analysis showed that the mouse homologue of Dss1 is induced by TPA. Dss1 overexpression was detected by Northern blot analysis in early TPA-treated hyperplastic skins and in JB6 Cl 41-5a epidermal cells. Interestingly, Dss1 expression was also shown to be elevated in skin papillomas relative to normal skins, and further increased in squamous cell malignancies. Functional studies by ectopically constitutive expression of Dss1 in JB6 Cl 41-5a preneoplastic cells strongly increased focus formation and proliferation of these cells and enhanced efficiency of neoplastic transformation of the cells in soft agar. These results strongly suggest that Dss1 is a TPA-inducible gene that may play an important role in the early stages of skin carcinogenesis. JF - The Journal of biological chemistry AU - Wei, Sung-Jen AU - Trempus, Carol S AU - Cannon, Ronald E AU - Bortner, Carl D AU - Tennant, Raymond W AD - National Center for Toxicogenomics and the Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. wei2@niehs.nih.gov Y1 - 2003/01/17/ PY - 2003 DA - 2003 Jan 17 SP - 1758 EP - 1768 VL - 278 IS - 3 SN - 0021-9258, 0021-9258 KW - DNA Primers KW - 0 KW - Proteins KW - Shfdg1 protein, mouse KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Gene Expression Profiling KW - Animals KW - In Situ Hybridization KW - Base Sequence KW - Mice KW - Subcellular Fractions -- metabolism KW - Reverse Transcriptase Polymerase Chain Reaction KW - Male KW - Cell Transformation, Neoplastic KW - Cell Division KW - Skin Neoplasms -- genetics KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Skin Neoplasms -- pathology KW - Keratinocytes -- metabolism KW - Gene Expression Regulation -- drug effects KW - Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72947126?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+Dss1+as+a+12-O-tetradecanoylphorbol-13-acetate-responsive+gene+expressed+in+keratinocyte+progenitor+cells%2C+with+possible+involvement+in+early+skin+tumorigenesis.&rft.au=Wei%2C+Sung-Jen%3BTrempus%2C+Carol+S%3BCannon%2C+Ronald+E%3BBortner%2C+Carl+D%3BTennant%2C+Raymond+W&rft.aulast=Wei&rft.aufirst=Sung-Jen&rft.date=2003-01-17&rft.volume=278&rft.issue=3&rft.spage=1758&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 - 2003-02-14 N1 - Date created - 2003-01-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selective neurodegeneration of hippocampus and entorhinal cortex correlates with spatial learning impairments in rats with bilateral ibotenate lesions of ventral subiculum. AN - 72946713; 12505652 AB - Rats with bilateral ibotenic acid lesions of ventral subiculum were tested in an eight-arm radial maze task for spatial learning and memory functions. The performance of the lesioned rats was severely impaired relative to control rats in both acquisition and retention of the spatial task. Following subicular lesions, profound neurodegeneration of the CA1 and CA3 sub sectors of hippocampus and entorhinocortical layers I, II, III, V and VI was observed. These results support the concept that neurons in the ventral subiculum are a part of the neural network along with the above neurons, which could be involved in the processing of spatial information. JF - Brain research AU - Devi, Latha AU - Diwakar, Latha AU - Raju, T R AU - Kutty, Bindu M AD - Department of Neurophysiology, National Institute of Mental Health and NeuroSciences (NIMHANS), Bangalore 560 029, India. Y1 - 2003/01/17/ PY - 2003 DA - 2003 Jan 17 SP - 9 EP - 15 VL - 960 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Excitatory Amino Acid Agonists KW - 0 KW - Ibotenic Acid KW - 2552-55-8 KW - Index Medicus KW - Rats KW - Animals KW - Cell Count KW - Rats, Wistar KW - Memory -- physiology KW - Female KW - Cell Survival KW - Entorhinal Cortex -- pathology KW - Maze Learning -- physiology KW - Nerve Degeneration -- pathology KW - Nerve Degeneration -- psychology KW - Learning Disorders -- psychology KW - Hippocampus -- pathology KW - Ibotenic Acid -- toxicity KW - Excitatory Amino Acid Agonists -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72946713?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Selective+neurodegeneration+of+hippocampus+and+entorhinal+cortex+correlates+with+spatial+learning+impairments+in+rats+with+bilateral+ibotenate+lesions+of+ventral+subiculum.&rft.au=Devi%2C+Latha%3BDiwakar%2C+Latha%3BRaju%2C+T+R%3BKutty%2C+Bindu+M&rft.aulast=Devi&rft.aufirst=Latha&rft.date=2003-01-17&rft.volume=960&rft.issue=1-2&rft.spage=9&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 - 2003-03-28 N1 - Date created - 2002-12-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification and characterization of a gene encoding a putative mouse Rho GTPase activating protein gene 8, Arhgap8. AN - 72989491; 12559566 AB - Rho GTPase activating proteins promote the intrinsic GTP hydrolysis activity of Rho family proteins. We isolated a putative mouse ortholog of the human Rho GTPase activating protein 8, ARHGAP8. The open reading frame encodes a peptide of 387 amino acids with high homology to human ARHGAP8 in its N-terminal domain. Both radiation hybrid mapping and fluorescent in situ hybridization localized the gene to mouse chromosome 15E. The 23 kb genomic Arhgap8 sequence consists of eight exons and seven introns. Northern blot and RT-PCR analyses showed that a transcript of approximately 1.9 kb is ubiquitously expressed in various adult mouse tissues with particularly strong expression in kidney. JF - Gene AU - Shan, Zhihong AU - Haaf, Thomas AU - Popescu, Nicholas C AD - Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/01/16/ PY - 2003 DA - 2003 Jan 16 SP - 55 EP - 61 VL - 303 SN - 0378-1119, 0378-1119 KW - Arhgap8 protein, mouse KW - 0 KW - DNA, Complementary KW - GTPase-Activating Proteins KW - RNA, Messenger KW - rho GTPase-activating protein KW - Index Medicus KW - Animals KW - Blotting, Northern KW - DNA, Complementary -- genetics KW - Radiation Hybrid Mapping KW - Exons KW - Gene Expression KW - In Situ Hybridization, Fluorescence KW - Mice KW - Amino Acid Sequence KW - Sequence Analysis, DNA KW - RNA, Messenger -- genetics KW - Chromosome Mapping KW - Genes -- genetics KW - Cloning, Molecular KW - Base Sequence KW - Sequence Alignment KW - RNA, Messenger -- metabolism KW - Molecular Sequence Data KW - Introns KW - DNA, Complementary -- chemistry KW - Sequence Homology, Amino Acid KW - Male KW - GTPase-Activating Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72989491?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Identification+and+characterization+of+a+gene+encoding+a+putative+mouse+Rho+GTPase+activating+protein+gene+8%2C+Arhgap8.&rft.au=Shan%2C+Zhihong%3BHaaf%2C+Thomas%3BPopescu%2C+Nicholas+C&rft.aulast=Shan&rft.aufirst=Zhihong&rft.date=2003-01-16&rft.volume=303&rft.issue=&rft.spage=55&rft.isbn=&rft.btitle=&rft.title=Gene&rft.issn=03781119&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-24 N1 - Date created - 2003-01-31 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF482997; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer in Fanconi anemia, 1927-2001. AN - 72956519; 12518367 AB - Fanconi anemia (FA) is an autosomal recessive disease associated with an abnormal response to DNA damage. Although FA is well known for the association of aplastic anemia and characteristic birth defects, leukemia and solid tumors also occur at a high rate in this group of patients. A review of all reported cases is informative with regard to the specific types of cancer, the ages at which they occur, and the cumulative probability of their development. Medline and bibliographies of publications were searched for articles containing "Fanconi's anemia" or "aplastic anemia" and all cases of FA from 1927 through 2001 were included in the database. Cancer cases were identified within these reports. Descriptive statistical analyses were performed using Stata7 software. One thousand three hundred cases of FA were identified. Nine percent had leukemia (primarily acute myeloid leukemia), 7% had myelodysplastic syndrome, 5% had solid tumors, and 3% had liver tumors. Patients with cancer were older than the cancer-free patients at the time of diagnosis of FA. The median age for cancer (including leukemia) was 16, compared with 68 in the general population. The most frequent solid tumors were aerodigestive and gynecological carcinomas. In approximately 25% of patients with cancer, the malignancy preceded the diagnosis of FA. If the competing risks of aplastic anemia and leukemia could be removed, the estimated cumulative probability of development of a solid tumor in FA patients is 76% by the age of 45 years. Carcinogenic pathways and cancer prevention, surveillance, and treatment can be studied to advantage in this genetic model of human cancer. JF - Cancer AU - Alter, Blanche P AD - Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892-7231, USA. alterb@mail.nih.gov Y1 - 2003/01/15/ PY - 2003 DA - 2003 Jan 15 SP - 425 EP - 440 VL - 97 IS - 2 SN - 0008-543X, 0008-543X KW - Abridged Index Medicus KW - Index Medicus KW - Probability KW - Age of Onset KW - Humans KW - Infant, Newborn KW - Leukemia -- complications KW - Liver Neoplasms -- epidemiology KW - Child KW - Myelodysplastic Syndromes -- genetics KW - Child, Preschool KW - Leukemia -- genetics KW - Infant KW - Liver Neoplasms -- complications KW - Myelodysplastic Syndromes -- complications KW - Leukemia -- epidemiology KW - Adult KW - Myelodysplastic Syndromes -- epidemiology KW - Middle Aged KW - Adolescent KW - Male KW - Female KW - Survival Analysis KW - Liver Neoplasms -- genetics KW - Fanconi Anemia -- complications KW - Neoplasms -- complications KW - Fanconi Anemia -- epidemiology KW - Neoplasms -- epidemiology KW - Fanconi Anemia -- genetics KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72956519?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cancer+in+Fanconi+anemia%2C+1927-2001.&rft.au=Alter%2C+Blanche+P&rft.aulast=Alter&rft.aufirst=Blanche&rft.date=2003-01-15&rft.volume=97&rft.issue=2&rft.spage=425&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-31 N1 - Date created - 2003-01-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Blood. 2003 Mar 1;101(5):2072 [12584146] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The GTP-binding domain of class II transactivator regulates its nuclear export. AN - 72956055; 12517958 AB - The transcriptional coactivator class II transactivator (CIITA), although predominantly localized in the nucleus, is also present in the cytoplasm. The subcellular distribution of CIITA is actively regulated by the opposing actions of nuclear export and import. In this study, we show that nuclear export is negatively regulated by the GTP-binding domain (GBD; aa 421-561) of CIITA: mutation or deletion of the GBD markedly increased export of CIITA from the nucleus. Remarkably, a CIITA GBD mutant binds CRM1/exportin significantly better than does wild-type CIITA, leading to the conclusion that GTP is a negative regulator of CIITA nuclear export. We also report that, in addition to the previously characterized N- and C-terminal nuclear localization signal elements, there is an additional N-terminal nuclear localization activity, present between aa 209 and 222, which overlaps the proline/serine/threonine-rich domain of CIITA. Thus, fine-tuning of the nucleocytoplasmic distribution of coactivator proteins involved in transcription is an active and dynamic process that defines a novel mechanism for controlling gene regulation. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Raval, Aparna AU - Weissman, Jocelyn D AU - Howcroft, T Kevin AU - Singer, Dinah S AD - Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/01/15/ PY - 2003 DA - 2003 Jan 15 SP - 922 EP - 930 VL - 170 IS - 2 SN - 0022-1767, 0022-1767 KW - Karyopherins KW - 0 KW - MHC class II transactivator protein KW - Nuclear Localization Signals KW - Nuclear Proteins KW - Peptide Fragments KW - Receptors, Cytoplasmic and Nuclear KW - Trans-Activators KW - exportin 1 protein KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Humans KW - Nuclear Localization Signals -- metabolism KW - Peptide Fragments -- physiology KW - Mutagenesis, Site-Directed KW - Protein Binding -- physiology KW - Protein Structure, Tertiary -- genetics KW - Transcriptional Activation -- immunology KW - Models, Immunological KW - Cytoplasm -- genetics KW - Cytoplasm -- metabolism KW - Nuclear Localization Signals -- physiology KW - Protein Structure, Tertiary -- physiology KW - Nuclear Localization Signals -- genetics KW - Peptide Fragments -- metabolism KW - Karyopherins -- metabolism KW - Peptide Fragments -- genetics KW - HeLa Cells KW - Genetic Vectors -- metabolism KW - Active Transport, Cell Nucleus -- immunology KW - Transfection KW - Active Transport, Cell Nucleus -- genetics KW - Protein Binding -- genetics KW - Subcellular Fractions -- metabolism KW - Cell Line KW - Cricetinae KW - Trans-Activators -- metabolism KW - Trans-Activators -- genetics KW - Cell Nucleus -- metabolism KW - GTP-Binding Proteins -- metabolism KW - GTP-Binding Proteins -- physiology KW - Trans-Activators -- physiology KW - GTP-Binding Proteins -- genetics KW - Cell Nucleus -- genetics KW - Genes, MHC Class II UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72956055?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=The+GTP-binding+domain+of+class+II+transactivator+regulates+its+nuclear+export.&rft.au=Raval%2C+Aparna%3BWeissman%2C+Jocelyn+D%3BHowcroft%2C+T+Kevin%3BSinger%2C+Dinah+S&rft.aulast=Raval&rft.aufirst=Aparna&rft.date=2003-01-15&rft.volume=170&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 - 2003-03-04 N1 - Date created - 2003-01-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Redox imbalance and mutagenesis in spleens of mice harboring a hypomorphic allele of Gpdx(a) encoding glucose 6-phosphate dehydrogenase. AN - 72949472; 12521604 AB - Mice harboring the activity-attenuated Gpdx(a-m2Neu) allele and also harboring a chromosomally integrated lacZ reporter gene to study mutagenesis (pUR288) were used to demonstrate that moderate glucose 6-phosphate dehydrogenase (G6PD) deficiency causes elevated mutagenesis and endogenous oxidative stress in the spleen. G6PD-deficient spleens with a residual enzyme activity of 22% exhibited a dramatic shift in the mutational pattern of lacZ (4.6-fold increase in the prevalence of recombination mutations of lacZ) together with a 1.8-fold increase in mutant frequencies in lacZ. A concomitant 3-fold reduction in catalase activity (dependent upon NADPH) indicated that the in vivo supply of G6PD-generated NADPH was insufficient. An additional 3-fold increase in oxidized glutathione suggested that redox control was disturbed in G6PD-deficient spleens. These findings indicate that G6PD is required for limiting oxidative mutagenesis in the mouse spleen. Gpdx(a-m2Neu) is the first hypomorphic allele of a mouse housekeeping gene associated with elevated somatic mutagenesis in vivo. JF - Free radical biology & medicine AU - Felix, Klaus AU - Rockwood, Lynne D AU - Pretsch, Walter AU - Bornkamm, Georg Wilhelm AU - Janz, Siegfried AD - Laboratory of Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/01/15/ PY - 2003 DA - 2003 Jan 15 SP - 226 EP - 232 VL - 34 IS - 2 SN - 0891-5849, 0891-5849 KW - Glucosephosphate Dehydrogenase KW - EC 1.1.1.49 KW - Index Medicus KW - Oxidation-Reduction KW - Lac Operon -- genetics KW - Animals KW - Base Sequence KW - Recombination, Genetic -- genetics KW - Sequence Deletion -- genetics KW - Oxidative Stress KW - Mice KW - Alleles KW - Spleen -- metabolism KW - Glucosephosphate Dehydrogenase -- metabolism KW - Spleen -- enzymology KW - Glucosephosphate Dehydrogenase -- genetics KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72949472?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Redox+imbalance+and+mutagenesis+in+spleens+of+mice+harboring+a+hypomorphic+allele+of+Gpdx%28a%29+encoding+glucose+6-phosphate+dehydrogenase.&rft.au=Felix%2C+Klaus%3BRockwood%2C+Lynne+D%3BPretsch%2C+Walter%3BBornkamm%2C+Georg+Wilhelm%3BJanz%2C+Siegfried&rft.aulast=Felix&rft.aufirst=Klaus&rft.date=2003-01-15&rft.volume=34&rft.issue=2&rft.spage=226&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 - 2004-01-23 N1 - Date created - 2003-01-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Levels of phospho-Smad2/3 are sensors of the interplay between effects of TGF-beta and retinoic acid on monocytic and granulocytic differentiation of HL-60 cells. AN - 72936803; 12393416 AB - We have investigated the role of Smad family proteins, known to be important cytoplasmic mediators of signals from the transforming growth factor-beta (TGF-beta) receptor serine/threonine kinases, in TGF-beta-dependent differentiation of hematopoietic cells, using as a model the human promyelocytic leukemia cell line, HL-60. TGF-beta-dependent differentiation of these cells to monocytes, but not retinoic acid-dependent differentiation to granulocytes, was accompanied by rapid phosphorylation and nuclear translocation of Smad2 and Smad3. Vitamin D(3) also induced phosphorylation of Smad2/3 and monocytic differentiation; however the effects were indirect, dependent on its ability to induce expression of TGF-beta1. Simultaneous treatment of these cells with TGF-beta1 and all-trans-retinoic acid (ATRA), which leads to almost equal numbers of granulocytes and monocytes, significantly reduced the level of phospho-Smad2/3 and its nuclear accumulation, compared with that in cells treated with TGF-beta1 alone. TGF-beta1 and ATRA activate P42/44 mitogen-activated protein (MAP) kinase with nearly identical kinetics, ruling out its involvement in these effects on Smad phosphorylation. Addition of the inhibitor-of-protein serine/threonine phosphatases, okadaic acid, blocks the ATRA-mediated reduction in TGF-beta-induced phospho-Smad2 and shifts the differentiation toward monocytic end points. In HL-60R mutant cells, which harbor a defective retinoic acid receptor-alpha (RAR-alpha), ATRA is unable to reduce levels of TGF-beta-induced phospho-Smad2/3, coincident with its inability to differentiate these cells along granulocytic pathways. Together, these data suggest a new level of cross-talk between ATRA and TGF-beta, whereby a putative RAR-alpha-dependent phosphatase activity limits the levels of phospho-Smad2/3 induced by TGF-beta, ultimately reducing the levels of nuclear Smad complexes mediating the TGF-beta-dependent differentiation of the cells to monocytic end points. JF - Blood AU - Cao, Zhouhong AU - Flanders, Kathleen C AU - Bertolette, Daniel AU - Lyakh, Lyudmila A AU - Wurthner, Jens U AU - Parks, W Tony AU - Letterio, John J AU - Ruscetti, Francis W AU - Roberts, Anita B AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2003/01/15/ PY - 2003 DA - 2003 Jan 15 SP - 498 EP - 507 VL - 101 IS - 2 SN - 0006-4971, 0006-4971 KW - DNA-Binding Proteins KW - 0 KW - SMAD2 protein, human KW - SMAD3 protein, human KW - Smad2 Protein KW - Smad3 Protein KW - TGFB1 protein, human KW - Trans-Activators KW - Transforming Growth Factor beta KW - Transforming Growth Factor beta1 KW - Cholecalciferol KW - 1C6V77QF41 KW - Tretinoin KW - 5688UTC01R KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Abridged Index Medicus KW - Index Medicus KW - Drug Interactions KW - Cholecalciferol -- pharmacology KW - Mitogen-Activated Protein Kinases -- metabolism KW - HL-60 Cells KW - Humans KW - Cell Differentiation -- drug effects KW - Signal Transduction KW - Phosphorylation -- drug effects KW - Tretinoin -- pharmacology KW - Transforming Growth Factor beta -- pharmacology KW - Trans-Activators -- metabolism KW - Monocytes -- cytology KW - Monocytes -- drug effects KW - Granulocytes -- drug effects KW - DNA-Binding Proteins -- physiology KW - Trans-Activators -- physiology KW - Granulocytes -- cytology KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72936803?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Levels+of+phospho-Smad2%2F3+are+sensors+of+the+interplay+between+effects+of+TGF-beta+and+retinoic+acid+on+monocytic+and+granulocytic+differentiation+of+HL-60+cells.&rft.au=Cao%2C+Zhouhong%3BFlanders%2C+Kathleen+C%3BBertolette%2C+Daniel%3BLyakh%2C+Lyudmila+A%3BWurthner%2C+Jens+U%3BParks%2C+W+Tony%3BLetterio%2C+John+J%3BRuscetti%2C+Francis+W%3BRoberts%2C+Anita+B&rft.aulast=Cao&rft.aufirst=Zhouhong&rft.date=2003-01-15&rft.volume=101&rft.issue=2&rft.spage=498&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-08 N1 - Date created - 2003-01-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immobilized nicotinic receptor stationary phases: going with the flow in high-throughput screening and pharmacological studies AN - 20793029; 5555555 AB - The nicotinic acetylcholine receptor (nAChR) subtypes [alpha]3[beta]4-nAChR and [alpha]4[beta]2-nAChR have been immobilized and the resulting stationary phases used to determine binding affinities. The [alpha]3[beta]4-nAChR column was coupled to a C sub(18) column and a mixture of 18 compounds was sorted into ligands and non-ligands for the [alpha]3[beta]4-nAChR. The results demonstrate that the nAChR stationary phases can be used for on-line high-throughput screening (HTS). JF - Journal of Pharmaceutical and Biomedical Analysis AU - Moaddel, R AU - Wainer, I W AD - Gerontology Research Center, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224-6825, USA, wainerir@grc.nia.nih.gov Y1 - 2003/01/15/ PY - 2003 DA - 2003 Jan 15 SP - 1715 EP - 1724 VL - 30 IS - 6 SN - 0731-7085, 0731-7085 KW - Biotechnology and Bioengineering Abstracts KW - stationary phase KW - high-throughput screening KW - Acetylcholine receptors (nicotinic) KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20793029?accountid=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+Pharmaceutical+and+Biomedical+Analysis&rft.atitle=Immobilized+nicotinic+receptor+stationary+phases%3A+going+with+the+flow+in+high-throughput+screening+and+pharmacological+studies&rft.au=Moaddel%2C+R%3BWainer%2C+I+W&rft.aulast=Moaddel&rft.aufirst=R&rft.date=2003-01-15&rft.volume=30&rft.issue=6&rft.spage=1715&rft.isbn=&rft.btitle=&rft.title=Journal+of+Pharmaceutical+and+Biomedical+Analysis&rft.issn=07317085&rft_id=info:doi/10.1016%2FS0731-7085%2802%2900513-7 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-08-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Acetylcholine receptors (nicotinic); stationary phase; high-throughput screening DO - http://dx.doi.org/10.1016/S0731-7085(02)00513-7 ER - TY - JOUR T1 - Finding weak similarities between proteins by sequence profile comparison AN - 18669070; 5564610 AB - To improve the recognition of weak similarities between proteins a method of aligning two sequence profiles is proposed. It is shown that exploring the sequence space in the vicinity of the sequence with unknown properties significantly improves the performance of sequence alignment methods. Consistent with the previous observations the recognition sensitivity and alignment accuracy obtained by a profile-profile alignment method can be as much as 30% higher compared to the sequence-profile alignment method. It is demonstrated that the choice of score function and the diversity of the test profile are very important factors for achieving the maximum performance of the method, whereas the optimum range of these parameters depends on the level of similarity to be recognized. JF - Nucleic Acids Research AU - Panchenko, A R AD - Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Building 38A, Room 8N805, 8600 Rockville Pike, Bethesda, MD 20894, USA, panch@ncbi.nlm.nih.gov Y1 - 2003/01/15/ PY - 2003 DA - 2003 Jan 15 SP - 683 EP - 689 VL - 31 IS - 2 SN - 0305-1048, 0305-1048 KW - alignments KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - N 14400:General KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18669070?accountid=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=Finding+weak+similarities+between+proteins+by+sequence+profile+comparison&rft.au=Panchenko%2C+A+R&rft.aulast=Panchenko&rft.aufirst=A&rft.date=2003-01-15&rft.volume=31&rft.issue=2&rft.spage=683&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Hexamerization of p97-VCP is promoted by ATP binding to the D1 domain and required for ATPase and biological activities. AN - 72944467; 12504076 AB - The 97-kDa valosin-containing protein (p97-VCP or VCP), a hexameric AAA ATPase, plays an important role in diverse cell activities, including ubiquitin-proteasome mediated protein degradation. In this report, we studied dissociation-reassembly kinetics to analyze the structure-function relationship in VCP. Urea-dissociated VCP can reassemble by itself, but addition of ATP, ADP, or ATP-gamma S accelerates the reassembly. Mutation in the ATP-binding site of D1, but not D2, domain abolishes the ATP acceleration effect and further delays the reassembly. Using hybrid hexamers of the wild type and ATP-binding site mutant, we show that hexameric structure and proper communication among the subunits are required for the ATPase activity and ubiquitin-proteasome mediated degradation. Thus, ATP-binding site in D1 plays a major role in VCP hexamerization, of which proper inter-subunit interaction is essential for the activities. JF - Biochemical and biophysical research communications AU - Wang, Qing AU - Song, Changcheng AU - Li, Chou-Chi H AD - Basic Research Laboratory, National Cancer Institute at Frederick, National Institutes of Health, Frederick, MD 21702, USA. Y1 - 2003/01/10/ PY - 2003 DA - 2003 Jan 10 SP - 253 EP - 260 VL - 300 IS - 2 SN - 0006-291X, 0006-291X KW - Cell Cycle Proteins KW - 0 KW - Multienzyme Complexes KW - Protein Subunits KW - Ubiquitin KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Urea KW - 8W8T17847W KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - CDC48 protein KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Multienzyme Complexes -- metabolism KW - Animals KW - Ubiquitin -- metabolism KW - Kinetics KW - Cysteine Endopeptidases -- metabolism KW - Protein Denaturation KW - Protein Structure, Tertiary KW - Urea -- pharmacology KW - Structure-Activity Relationship KW - Binding Sites KW - Cell Cycle Proteins -- physiology KW - Cell Cycle Proteins -- chemistry KW - Adenosine Triphosphatases -- physiology KW - Adenosine Triphosphate -- metabolism KW - Adenosine Triphosphatases -- metabolism KW - Adenosine Triphosphatases -- chemistry KW - Cell Cycle Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72944467?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Hexamerization+of+p97-VCP+is+promoted+by+ATP+binding+to+the+D1+domain+and+required+for+ATPase+and+biological+activities.&rft.au=Wang%2C+Qing%3BSong%2C+Changcheng%3BLi%2C+Chou-Chi+H&rft.aulast=Wang&rft.aufirst=Qing&rft.date=2003-01-10&rft.volume=300&rft.issue=2&rft.spage=253&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 - 2003-02-25 N1 - Date created - 2002-12-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer and other causes of mortality among radiologic technologists in the United States. AN - 72882376; 12455042 AB - Data are limited on the role of chronic exposure to low-dose ionizing radiation in the etiology of cancer. In a nationwide cohort of 146,022 U.S. radiologic technologists (73% female), we evaluated mortality risks in relation to work characteristics. Standardized mortality ratios (SMRs) were computed to compare mortality in the total cohort vs. the general population of the United States. Mortality risks were low for all causes (SMR = 0.76) and for all cancers (SMR = 0.82) among the radiologic technologists. We also calculated relative risks (RR) for the 90,305 technologists who responded to a baseline mailed questionnaire, using Poisson regression models, adjusted for known risk factors. Risks were higher for all cancers (RR = 1.28, 95% confidence interval [CI] = 0.93-1.69) and breast cancer (RR = 2.92, 95% CI = 1.22-7.00) among radiologic technologists first employed prior to 1940 compared to those first employed in 1960 or later, and risks declined with more recent calendar year of first employment (p-trend = 0.04 and 0.002, respectively), irrespective of employment duration. Risk for the combined category of acute lymphocytic, acute myeloid and chronic myeloid leukemias was increased among those first employed prior to 1950 (RR = 1.64, 95% CI = 0.42-6.31) compared to those first employed in 1950 or later. Risks rose for breast cancer (p-trend = 0.018) and for acute lymphocytic, acute myeloid and chronic myeloid leukemias (p-trend = 0.05) with increasing duration of employment as a radiologic technologist prior to 1950. The elevated mortality risks for breast cancer and for the combined group of acute lymphocytic, acute myeloid and chronic myeloid leukemias are consistent with a radiation etiology given greater occupational exposures to ionizing radiation prior to 1950 than in more recent times. Copyright 2002 Wiley-Liss, Inc. JF - International journal of cancer AU - Mohan, Aparna K AU - Hauptmann, Michael AU - Freedman, D Michal AU - Ron, Elaine AU - Matanoski, Genevieve M AU - Lubin, Jay H AU - Alexander, Bruce H AU - Boice, John D AU - Doody, Michele Morin AU - Linet, Martha S AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7244, USA. mohan@cber.fda.gov Y1 - 2003/01/10/ PY - 2003 DA - 2003 Jan 10 SP - 259 EP - 267 VL - 103 IS - 2 SN - 0020-7136, 0020-7136 KW - Index Medicus KW - Risk Factors KW - Humans KW - Cohort Studies KW - Adult KW - Confidence Intervals KW - Lung Neoplasms -- mortality KW - Adolescent KW - United States -- epidemiology KW - Time Factors KW - Male KW - Female KW - Cause of Death KW - Occupational Exposure KW - Mortality KW - Radiology -- manpower KW - Neoplasms, Radiation-Induced -- mortality KW - Technology, Radiologic KW - Radiation, Ionizing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72882376?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cancer+and+other+causes+of+mortality+among+radiologic+technologists+in+the+United+States.&rft.au=Mohan%2C+Aparna+K%3BHauptmann%2C+Michael%3BFreedman%2C+D+Michal%3BRon%2C+Elaine%3BMatanoski%2C+Genevieve+M%3BLubin%2C+Jay+H%3BAlexander%2C+Bruce+H%3BBoice%2C+John+D%3BDoody%2C+Michele+Morin%3BLinet%2C+Martha+S&rft.aulast=Mohan&rft.aufirst=Aparna&rft.date=2003-01-10&rft.volume=103&rft.issue=2&rft.spage=259&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 - 2003-01-07 N1 - Date created - 2002-11-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The in vivo but not the in vitro am3 revertant frequencies increase linearly with increased ethylnitrosourea doses in spleen of mice transgenic for phiX174 am3, cs70 using the single burst assay AN - 18657201; 5546056 AB - The am3 revertant frequencies (RF) in spleens from male mice transgenic for phiX174 am3, cs70 were analyzed 14 weeks after ethylnitrosourea (ENU) treatment, both by the single burst assay (SBA) and the mixed burst assay (MBA). The mean in vivo (burst size >30/assay plate) revertant frequency (MRF) for the vehicle control was 2.610 super(-7). The ENU induced in vivo RF were linear over the dose range 0-150mg/kg, (r super(2)=0.999). The concomitant in (burst size less than or equal to 30/assay plate) was independent of dose (r super(2)=0.216). The only viable revertants are base pair substitutions of the center base pair in the am3 nonsense (TAG) codon in the phiX174 lysis E gene. Sequenced revertants chosen randomly from in vitro plates and in vivo untreated control plates were AG transitions. Sequence analysis of in vivo revertants from ENU treated animals revealed revertants that were 17% AG transitions and 83% AT transversions, the latter being consistent with the reported A:T base pair alterations induced by ENU. No AC transitions were seen. This suggests the occurrence of an ENU-induced O super(2) ET-dT lesion leading to a dT base mismatch. The observations in this report both confirm and validate the use of the SBA for distinguishing between in vivo mutations that are fixed in the animal and in vitro mutations that arise from other sources. The ability of the SBA to distinguish the in vivo from the in vitro origin of mutations has increased the specificity, sensitivity and utility of the phiX transgenic system. JF - Mutation Research-Genetic Toxicology and Environmental Mutagenesis AU - Weaver, R P AU - Malling, H V AD - Mammalian Mutagenesis Group, Laboratory of Toxicology, Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA, malling@niehs.nih.gov Y1 - 2003/01/10/ PY - 2003 DA - 2003 Jan 10 SP - 1 EP - 13 PB - Elsevier Science B.V. VL - 534 IS - 1-2 SN - 1383-5718, 1383-5718 KW - double prime am3 gene KW - double prime cs70 gene KW - in vitro KW - in vivo KW - phiX174 gene KW - Genetics Abstracts; Toxicology Abstracts KW - X 24200:Nitrosamines & related compounds KW - G 07220:General theory/testing systems UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18657201?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+Research-Genetic+Toxicology+and+Environmental+Mutagenesis&rft.atitle=The+in+vivo+but+not+the+in+vitro+am3+revertant+frequencies+increase+linearly+with+increased+ethylnitrosourea+doses+in+spleen+of+mice+transgenic+for+phiX174+am3%2C+cs70+using+the+single+burst+assay&rft.au=Weaver%2C+R+P%3BMalling%2C+H+V&rft.aulast=Weaver&rft.aufirst=R&rft.date=2003-01-10&rft.volume=534&rft.issue=1-2&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Mutation+Research-Genetic+Toxicology+and+Environmental+Mutagenesis&rft.issn=13835718&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Nitric oxide-induced cellular stress and p53 activation in chronic inflammation. AN - 72956204; 12518062 AB - Free radical-induced cellular stress contributes to cancer during chronic inflammation. Here, we investigated mechanisms of p53 activation by the free radical, NO. NO from donor drugs induced both ataxia-telangiectasia mutated (ATM)- and ataxia-telangiectasia mutated and Rad3-related-dependent p53 posttranslational modifications, leading to an increase in p53 transcriptional targets and a G(2)M cell cycle checkpoint. Such modifications were also identified in cells cocultured with NO-releasing macrophages. In noncancerous colon tissues from patients with ulcerative colitis (a cancer-prone chronic inflammatory disease), inducible NO synthase protein levels were positively correlated with p53 serine 15 phosphorylation levels. Immunostaining of HDM-2 and p21(WAF1) was consistent with transcriptionally active p53. Our study highlights a pivotal role of NO in the induction of cellular stress and the activation of a p53 response pathway during chronic inflammation. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Hofseth, Lorne J AU - Saito, Shin'ichi AU - Hussain, S Perwez AU - Espey, Michael G AU - Miranda, Katrina M AU - Araki, Yuzuru AU - Jhappan, Chamelli AU - Higashimoto, Yuichiro AU - He, Peijun AU - Linke, Steven P AU - Quezado, Martha M AU - Zurer, Irit AU - Rotter, Varda AU - Wink, David A AU - Appella, Ettore AU - Harris, Curtis C AD - Laboratories of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/01/07/ PY - 2003 DA - 2003 Jan 07 SP - 143 EP - 148 VL - 100 IS - 1 SN - 0027-8424, 0027-8424 KW - CDKN1A protein, human KW - 0 KW - Cdkn1a protein, mouse KW - Cell Cycle Proteins KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - DNA-Binding Proteins KW - Free Radicals KW - Lipopolysaccharides KW - Tumor Suppressor Protein p53 KW - Tumor Suppressor Proteins KW - Phosphoserine KW - 17885-08-4 KW - Nitric Oxide KW - 31C4KY9ESH KW - Interferon-gamma KW - 82115-62-6 KW - NOS2 protein, human KW - EC 1.14.13.39 KW - Nitric Oxide Synthase KW - Nitric Oxide Synthase Type II KW - Nos2 protein, mouse KW - ATM protein, human KW - EC 2.7.11.1 KW - Ataxia Telangiectasia Mutated Proteins KW - Atm protein, mouse KW - Protein-Serine-Threonine Kinases KW - Index Medicus KW - Coculture Techniques KW - Animals KW - Protein-Serine-Threonine Kinases -- metabolism KW - Humans KW - Lipopolysaccharides -- pharmacology KW - Interferon-gamma -- pharmacology KW - Transcription, Genetic KW - Macrophages -- drug effects KW - Phosphoserine -- metabolism KW - Tumor Cells, Cultured KW - Phosphorylation KW - Cyclins -- metabolism KW - Nitric Oxide Synthase -- metabolism KW - Cell Cycle KW - Comet Assay KW - Protein Processing, Post-Translational KW - Breast Neoplasms KW - Macrophages -- physiology KW - Mice KW - Free Radicals -- metabolism KW - Ataxia Telangiectasia -- genetics KW - Cell Line KW - Female KW - Inflammation -- physiopathology KW - DNA Damage KW - Colitis, Ulcerative -- physiopathology KW - Inflammation -- genetics KW - Nitric Oxide -- physiology KW - Colitis, Ulcerative -- pathology KW - Tumor Suppressor Protein p53 -- genetics KW - Tumor Suppressor Protein p53 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72956204?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Nitric+oxide-induced+cellular+stress+and+p53+activation+in+chronic+inflammation.&rft.au=Hofseth%2C+Lorne+J%3BSaito%2C+Shin%27ichi%3BHussain%2C+S+Perwez%3BEspey%2C+Michael+G%3BMiranda%2C+Katrina+M%3BAraki%2C+Yuzuru%3BJhappan%2C+Chamelli%3BHigashimoto%2C+Yuichiro%3BHe%2C+Peijun%3BLinke%2C+Steven+P%3BQuezado%2C+Martha+M%3BZurer%2C+Irit%3BRotter%2C+Varda%3BWink%2C+David+A%3BAppella%2C+Ettore%3BHarris%2C+Curtis+C&rft.aulast=Hofseth&rft.aufirst=Lorne&rft.date=2003-01-07&rft.volume=100&rft.issue=1&rft.spage=143&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 - 2003-02-21 N1 - Date created - 2003-01-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Exp Med. 1999 Nov 15;190(10):1375-82 [10562313] Cancer Res. 1999 Sep 1;59(17):4375-82 [10485486] Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1584-8 [10677503] J Biol Chem. 2000 Apr 14;275(15):11341-7 [10753947] Nat Cell Biol. 2000 Jun;2(6):339-45 [10854324] Pathol Biol (Paris). 2000 Apr;48(3):227-45 [10858956] Cancer Res. 2000 Jul 1;60(13):3333-7 [10910033] Cell. 2000 Sep 15;102(6):849-62 [11030628] Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12770-5 [11050162] Nature. 2000 Nov 16;408(6810):307-10 [11099028] Oncogene. 2000 Dec 14;19(54):6369-75 [11175352] Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2640-5 [11226292] Gut. 2001 Apr;48(4):468-72 [11247889] Eur J Clin Invest. 2001 Apr;31(4):337-43 [11298781] Science. 2001 Jun 8;292(5523):1910-5 [11397945] Cancer Res. 2001 Sep 1;61(17):6388-93 [11522631] FEBS Lett. 2001 Oct 5;506(2):91-6 [11591378] Nat Cell Biol. 2001 Dec;3(12):E277-86 [11781586] Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):345-50 [11756671] J Biol Chem. 2002 May 3;277(18):15697-702 [11867628] Nat Rev Mol Cell Biol. 2002 Mar;3(3):214-20 [11994742] Am J Gastroenterol. 1987 Dec;82(12):1275-8 [3318403] Dig Dis Sci. 1989 Oct;34(10):1536-41 [2791805] Cell. 1990 Jun 1;61(5):759-67 [2188735] Lancet. 1993 Aug 7;342(8867):338-40 [7687730] Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):9813-7 [8234317] Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5258-65 [7777494] Gut. 1995 May;36(5):718-23 [7541008] Genes Dev. 1996 Apr 15;10(8):934-47 [8608941] Cell. 1996 Oct 18;87(2):159-70 [8861899] Nucleic Acids Res. 1996 Nov 15;24(22):4464-70 [8948636] J Pathol. 1996 Oct;180(2):152-9 [8976873] Nature. 1997 May 15;387(6630):296-9 [9153395] Nature. 1997 May 15;387(6630):299-303 [9153396] J Biol Chem. 1997 Dec 5;272(49):31138-48 [9388267] Genes Dev. 1997 Dec 15;11(24):3471-81 [9407038] EMBO J. 1998 Jan 2;17(1):159-69 [9427750] Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8823-8 [9671763] Nitric Oxide. 1997 Feb;1(1):18-30 [9701041] Science. 1998 Nov 20;282(5393):1497-501 [9822382] Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):3077-80 [10077639] Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3706-11 [10097101] Science. 1999 Apr 23;284(5414):651-4 [10213689] Am J Pathol. 1999 Jun;154(6):1621-6 [10362784] Mod Pathol. 1999 Jun;12(6):604-11 [10392637] Gut. 1999 Aug;45(2):199-209 [10403731] Biochem Biophys Res Commun. 2000 Jan 19;267(2):609-13 [10631110] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Liquid chromatography-mass spectrometry method for the analysis of the anti-cancer agent capecitabine and its nucleoside metabolites in human plasma. AN - 72878318; 12450548 AB - A reversed-phase high-performance liquid chromatography method with electrospray ionization and mass spectral detection is described for the determination of capecitabine, 5'-deoxy-5-fluorocytidine and 5'-deoxy-5-fluorouridine in human plasma with 5-chloro-2'-deoxyuridine as the internal standard. An on-line sample clean-up procedure allows dilution of the plasma sample with the initial mobile phase. The linear dynamic range is 0.0500-10.0 microgram/ml for capecitabine, and 0.0500-25.0 microgram/ml for the metabolites, 5'-deoxy-5-fluorocytidine and 5'-deoxy-5-fluorouridine, respectively. This method has been used to analyze plasma samples from patients receiving capecitabine in combination with oxaliplatin. JF - Journal of chromatography. B, Analytical technologies in the biomedical and life sciences AU - Xu, Yan AU - Grem, Jean L AD - Gastrointestinal Malignancies Section, Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, 20889-5105, Bethesda, MD, USA. Y1 - 2003/01/05/ PY - 2003 DA - 2003 Jan 05 SP - 273 EP - 285 VL - 783 IS - 1 SN - 1570-0232, 1570-0232 KW - Antimetabolites, Antineoplastic KW - 0 KW - Deoxycytidine KW - 0W860991D6 KW - Capecitabine KW - 6804DJ8Z9U KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Humans KW - Fluorouracil -- analogs & derivatives KW - Colorectal Neoplasms -- blood KW - Deoxycytidine -- pharmacokinetics KW - Deoxycytidine -- analogs & derivatives KW - Chromatography, High Pressure Liquid -- methods KW - Antimetabolites, Antineoplastic -- blood KW - Antimetabolites, Antineoplastic -- pharmacokinetics KW - Deoxycytidine -- blood KW - Spectrometry, Mass, Electrospray Ionization -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72878318?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+chromatography.+B%2C+Analytical+technologies+in+the+biomedical+and+life+sciences&rft.atitle=Liquid+chromatography-mass+spectrometry+method+for+the+analysis+of+the+anti-cancer+agent+capecitabine+and+its+nucleoside+metabolites+in+human+plasma.&rft.au=Xu%2C+Yan%3BGrem%2C+Jean+L&rft.aulast=Xu&rft.aufirst=Yan&rft.date=2003-01-05&rft.volume=783&rft.issue=1&rft.spage=273&rft.isbn=&rft.btitle=&rft.title=Journal+of+chromatography.+B%2C+Analytical+technologies+in+the+biomedical+and+life+sciences&rft.issn=15700232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-28 N1 - Date created - 2002-11-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A site in the fourth membrane-associated domain of the N-methyl-D-aspartate receptor regulates desensitization and ion channel gating. AN - 72938086; 12414797 AB - The N-methyl-d-aspartate (NMDA) receptor has four membrane-associated domains, three of which are membrane-spanning (M1, M3, and M4) and one of which is a re-entrant pore loop (M2). The M1-M3 domains have been demonstrated to influence the function of the ion channel, but a similar role for the M4 domain has not been reported. We have identified a methionine residue (Met(823)) in the M4 domain of the NR2A subunit that regulates desensitization and ion channel gating. A tryptophan substitution at this site did not alter the EC(50) for glycine or the peak NMDA EC(50) but decreased the steady-state NMDA EC(50) and markedly increased apparent desensitization, mean open time, and peak current density. Results of rapid solution exchange experiments revealed that changes in microscopic desensitization rates and closing rates could account for the changes in macroscopic desensitization, steady-state NMDA EC(50), and current density. Other amino acid substitutions at this site could increase or decrease the rate of desensitization and mean open time of the ion channel. Both mean open time and desensitization were dependent primarily upon the hydrophobic character of the amino acid at the position. These results demonstrate an important role for hydrophobic interactions at Met(823) in regulation of NMDA receptor function. JF - The Journal of biological chemistry AU - Ren, Hong AU - Honse, Yumiko AU - Karp, Brian J AU - Lipsky, Robert H AU - Peoples, Robert W AD - Unit on Cellular Neuropharmacology, Laboratory of Molecular and Cellular Neurobiology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892-8115, USA. Y1 - 2003/01/03/ PY - 2003 DA - 2003 Jan 03 SP - 276 EP - 283 VL - 278 IS - 1 SN - 0021-9258, 0021-9258 KW - Excitatory Amino Acid Agonists KW - 0 KW - Receptors, N-Methyl-D-Aspartate KW - N-Methylaspartate KW - 6384-92-5 KW - Methionine KW - AE28F7PNPL KW - Glycine KW - TE7660XO1C KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Regression Analysis KW - Protein Structure, Secondary KW - N-Methylaspartate -- metabolism KW - Patch-Clamp Techniques KW - Sequence Alignment KW - Models, Molecular KW - Humans KW - Glycine -- metabolism KW - Molecular Sequence Data KW - Methionine -- metabolism KW - Amino Acid Sequence KW - Protein Structure, Tertiary KW - Excitatory Amino Acid Agonists -- metabolism KW - Cell Line KW - Ion Channel Gating -- physiology KW - Receptors, N-Methyl-D-Aspartate -- metabolism KW - Receptors, N-Methyl-D-Aspartate -- genetics KW - Receptors, N-Methyl-D-Aspartate -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72938086?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+site+in+the+fourth+membrane-associated+domain+of+the+N-methyl-D-aspartate+receptor+regulates+desensitization+and+ion+channel+gating.&rft.au=Ren%2C+Hong%3BHonse%2C+Yumiko%3BKarp%2C+Brian+J%3BLipsky%2C+Robert+H%3BPeoples%2C+Robert+W&rft.aulast=Ren&rft.aufirst=Hong&rft.date=2003-01-03&rft.volume=278&rft.issue=1&rft.spage=276&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 - 2003-02-10 N1 - Date created - 2002-12-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemical oxidation of chlorinated non-aqueous phase liquid by hydrogen peroxide in natural sand systems AN - 19673063; 5584035 AB - This study explored the Fenton-like oxidation of trichloroethylene (TCE) existing as dense non-aqueous phase liquid (DNAPL) in natural silica sand (iron = 0.04 g/kg) and the sand from an aquifer (iron = 2.01 g/kg). Glass bead containing no iron mineral was used as the control. Batch oxidation experiments were conducted to assess interactions between oxidant and TCE DNAPL. Column experiments were performed to evaluate dynamics of TCE and H sub(2)O sub(2) during oxidation. The pH was not altered. In the batch system, a single application of 3% H sub(2)O sub(2) to the aquifer sand oxidized 40% of the added TCE DNAPL in 1 h, which was four times of that by dissolution with the gas purge procedure. This demonstrated the ability of mineral-catalyzed Fenton-like reaction to directly oxidize TCE in non-aqueous liquid. In the column experiments, after passing 7 pore volumes (PVs) of 1.5 and 3% H sub(2)O sub(2) solution, the residual TCE in aquifer sand column was 12.0 and 2.6% of the initial added, respectively. On the other hand, 28.4% of the added TCE still remained in the silica sand column by 7 PVs of 3% H sub(2)O sub(2). The distribution of TCE in column and effluent indicated the occurring of direct oxidation of TCE DNAPL and the increased solubilization, which probably due to size reduction of DNAPL droplets, followed by water-phased TCE oxidation. JF - Journal of Hazardous Materials AU - Yeh, CK-J AU - Wu, H-M AU - Chen, T-C AD - Department of Environmental Science and Engineering, National Pingtung University of Science and Technology, 1 Hseuh Fu Road, Nei Pu, Pingtung 91207, Taiwan, ROC, kjyeh@mail.npust.edu.tw Y1 - 2003/01/03/ PY - 2003 DA - 2003 Jan 03 SP - 29 EP - 51 VL - 96 IS - 1 SN - 0304-3894, 0304-3894 KW - hydrogen peroxide KW - trichloroethylene KW - Toxicology Abstracts; Pollution Abstracts KW - Aquifers KW - Effluents KW - nonaqueous phase liquids KW - Pores KW - Silica KW - Hydrogen peroxide KW - Sand KW - Solubilization KW - Oxidation KW - Dissolution KW - Trichloroethylene KW - pH effects KW - Iron KW - Minerals KW - Oxidants KW - Glass beads KW - P 2000:FRESHWATER POLLUTION KW - X 24360:Metals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19673063?accountid=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+Hazardous+Materials&rft.atitle=Chemical+oxidation+of+chlorinated+non-aqueous+phase+liquid+by+hydrogen+peroxide+in+natural+sand+systems&rft.au=Yeh%2C+CK-J%3BWu%2C+H-M%3BChen%2C+T-C&rft.aulast=Yeh&rft.aufirst=CK-J&rft.date=2003-01-03&rft.volume=96&rft.issue=1&rft.spage=29&rft.isbn=&rft.btitle=&rft.title=Journal+of+Hazardous+Materials&rft.issn=03043894&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2003-04-01 N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Aquifers; Effluents; Pores; Silica; Sand; Hydrogen peroxide; Solubilization; Oxidation; Dissolution; Trichloroethylene; Minerals; Iron; pH effects; Oxidants; Glass beads; nonaqueous phase liquids ER - TY - JOUR T1 - Divalent interaction of the GGAs with the Rabaptin-5-Rabex-5 complex. AN - 72941468; 12505986 AB - Cargo transfer from trans-Golgi network (TGN)-derived transport carriers to endosomes involves a still undefined set of tethering/fusion events. Here we analyze a molecular interaction that may play a role in this process. We demonstrate that the GGAs, a family of Arf-dependent clathrin adaptors involved in selection of TGN cargo, interact with the Rabaptin-5-Rabex-5 complex, a Rab4/Rab5 effector regulating endosome fusion. These interactions are bipartite: GGA-GAE domains recognize an FGPLV sequence (residues 439-443) in a predicted random coil of Rabaptin-5 (a sequence also recognized by the gamma1- and gamma2-adaptin ears), while GGA-GAT domains bind to the C-terminal coiled-coils of Rabaptin-5. The GGA-Rabaptin-5 interaction decreases binding of clathrin to the GGA-hinge domain, and expression of green fluorescent protein (GFP)-Rabaptin-5 shifts the localization of endogenous GGA1 and associated cargo to enlarged early endosomes. These observations thus identify a binding sequence for GAE/gamma-adaptin ear domains and reveal a functional link between proteins regulating TGN cargo export and endosomal tethering/fusion events. JF - The EMBO journal AU - Mattera, Rafael AU - Arighi, Cecilia N AU - Lodge, Robert AU - Zerial, Marino AU - Bonifacino, Juan S AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/01/02/ PY - 2003 DA - 2003 Jan 02 SP - 78 EP - 88 VL - 22 IS - 1 SN - 0261-4189, 0261-4189 KW - Clathrin KW - 0 KW - Guanine Nucleotide Exchange Factors KW - Peptide Fragments KW - RABEP1 protein, human KW - RABGEF1 protein, human KW - Recombinant Fusion Proteins KW - Vesicular Transport Proteins KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Recombinant Fusion Proteins -- metabolism KW - Peptide Fragments -- metabolism KW - Clathrin -- metabolism KW - Peptide Fragments -- chemistry KW - Humans KW - Glutathione Transferase -- metabolism KW - Amino Acid Sequence KW - Biotinylation KW - Recombinant Fusion Proteins -- chemistry KW - Mutagenesis KW - Binding Sites KW - Guanine Nucleotide Exchange Factors -- metabolism KW - trans-Golgi Network -- ultrastructure KW - Vesicular Transport Proteins -- metabolism KW - trans-Golgi Network -- metabolism KW - Vesicular Transport Proteins -- chemistry KW - Guanine Nucleotide Exchange Factors -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72941468?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Divalent+interaction+of+the+GGAs+with+the+Rabaptin-5-Rabex-5+complex.&rft.au=Mattera%2C+Rafael%3BArighi%2C+Cecilia+N%3BLodge%2C+Robert%3BZerial%2C+Marino%3BBonifacino%2C+Juan+S&rft.aulast=Mattera&rft.aufirst=Rafael&rft.date=2003-01-02&rft.volume=22&rft.issue=1&rft.spage=78&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 - 2003-02-12 N1 - Date created - 2002-12-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biochem. 2002 Mar;131(3):327-36 [11872161] Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):8907-12 [10430869] Structure. 2002 Jun;10(6):797-809 [12057195] J Biol Chem. 1999 Dec 31;274(53):37583-90 [10608812] Biochem J. 2000 Mar 15;346 Pt 3:593-601 [10698684] J Biol Chem. 2000 Mar 10;275(10):7176-83 [10702286] J Cell Biol. 2000 Apr 3;149(1):67-80 [10747088] J Cell Biol. 2000 Apr 3;149(1):81-94 [10747089] Mol Biol Cell. 2000 Apr;11(4):1241-55 [10749927] Biochem Biophys Res Commun. 2000 May 19;271(3):719-25 [10814529] Nat Rev Neurosci. 2000 Dec;1(3):161-72 [11257904] Cell. 2001 Apr 6;105(1):93-102 [11301005] J Biol Chem. 2001 Apr 20;276(16):13145-52 [11139587] J Cell Biol. 2001 May 28;153(5):1111-20 [11381094] Science. 2001 Jun 1;292(5522):1712-6 [11387475] Science. 2001 Jun 1;292(5522):1716-8 [11387476] Mol Biol Cell. 2001 Jun;12(6):1885-96 [11408593] Mol Biol Cell. 2001 Jul;12(7):2219-28 [11452015] J Biol Chem. 2001 Jul 27;276(30):28541-5 [11390366] Mol Biol Cell. 2001 Oct;12(10):2907-20 [11598180] Mol Cell Biol. 2001 Dec;21(23):7981-94 [11689690] Exp Cell Res. 2002 Jan 1;272(1):8-14 [11740860] Nat Cell Biol. 2002 Feb;4(2):124-33 [11788822] Nature. 2002 Feb 21;415(6874):933-7 [11859375] Nature. 2002 Feb 21;415(6874):937-41 [11859376] Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):8072-7 [12060753] Nat Struct Biol. 2002 Jul;9(7):527-31 [12042876] Gene. 2002 Jun 12;292(1-2):191-7 [12119113] Structure. 2002 Aug;10(8):1139-48 [12176391] Mol Biol Cell. 2003 Apr;14(4):1545-57 [12686608] Cell. 1995 Nov 3;83(3):423-32 [8521472] EMBO J. 1997 Mar 3;16(5):917-28 [9118953] Cell. 1997 Sep 19;90(6):1149-59 [9323142] EMBO J. 1997 Oct 15;16(20):6182-91 [9321397] Neuroreport. 1997 Nov 10;8(16):3649-54 [9427343] EMBO J. 1998 Apr 1;17(7):1930-40 [9524116] EMBO J. 1998 Apr 1;17(7):1941-51 [9524117] Science. 1998 Apr 17;280(5362):431-4 [9545220] Cell. 1999 Jun 11;97(6):805-15 [10380931] J Cell Biol. 1999 Sep 6;146(5):993-1004 [10477754] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hypersensitivity of DNA polymerase beta null mouse fibroblasts reflects accumulation of cytotoxic repair intermediates from site-specific alkyl DNA lesions. AN - 72938056; 12509266 AB - Monofunctional alkylating agents react with DNA by S(N)1 or S(N)2 mechanisms resulting in formation of a wide spectrum of cytotoxic base adducts. DNA polymerase beta (beta-pol) is required for efficient base excision repair of N-alkyl adducts, and we make use of the hypersensitivity of beta-pol null mouse fibroblasts to investigate such alkylating agents with a view towards understanding the DNA lesions responsible for the cellular phenotype. The inability of O(6)-benzylguanine to sensitize wild-type or beta-pol null cells to S(N)1-type methylating agents indicates that the observed hypersensitivity is not due to differential repair of cytotoxic O-alkyl adducts. Using a 3-methyladenine-specific agent and an inhibitor of such methylation, we find that inefficient repair of 3-methyladenine is not the reason for the hypersensitivity of beta-pol null cells to methylating agents, and further that 3-methyladenine is not the adduct primarily responsible for methyl methanesulfonate (MMS)- and methyl nitrosourea-induced cytotoxicity in wild-type cells. Relating the expected spectrum of DNA adducts and the relative sensitivity of cells to monofunctional alkylating agents, we propose that the hypersensitivity of beta-pol null cells reflects accumulation of cytotoxic repair intermediates, such as the 5'-deoxyribose phosphate group, following removal of 7-alkylguanine from DNA. In support of this conclusion, beta-pol null cells are also hypersensitive to the thymidine analog 5-hydroxymethyl-2'-deoxyuridine (hmdUrd). This agent is incorporated into cellular DNA and elicits cytotoxicity only when removed by glycosylase-initiated base excision repair. Consistent with the hypothesis that there is a common repair intermediate resulting in cytotoxicity following treatment with both types of agents, both MMS and hmdUrd-initiated cell death are preceded by a similar rapid concentration-dependent suppression of DNA synthesis and a later cell cycle arrest in G(0)/G(1) and G(2)M phases. JF - DNA repair AU - Horton, Julie K AU - Joyce-Gray, Donna F AU - Pachkowski, Brian F AU - Swenberg, James A AU - Wilson, Samuel H AD - Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 2003/01/02/ PY - 2003 DA - 2003 Jan 02 SP - 27 EP - 48 VL - 2 IS - 1 SN - 1568-7864, 1568-7864 KW - Alkylating Agents KW - 0 KW - Antineoplastic Agents KW - methyl lexitropsin KW - Netropsin KW - 64B3O0RD7N KW - DNA KW - 9007-49-2 KW - DNA Polymerase beta KW - EC 2.7.7.- KW - Index Medicus KW - Animals KW - Alkylating Agents -- metabolism KW - In Vitro Techniques KW - Antineoplastic Agents -- metabolism KW - DNA -- physiology KW - Mice KW - Time Factors KW - Cell Line KW - Fibroblasts KW - Alkylation KW - DNA Repair -- genetics KW - DNA Repair -- physiology KW - DNA Damage -- physiology KW - DNA Polymerase beta -- genetics KW - Netropsin -- metabolism KW - DNA Damage -- genetics KW - Netropsin -- analogs & derivatives KW - DNA Polymerase beta -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72938056?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+repair&rft.atitle=Hypersensitivity+of+DNA+polymerase+beta+null+mouse+fibroblasts+reflects+accumulation+of+cytotoxic+repair+intermediates+from+site-specific+alkyl+DNA+lesions.&rft.au=Horton%2C+Julie+K%3BJoyce-Gray%2C+Donna+F%3BPachkowski%2C+Brian+F%3BSwenberg%2C+James+A%3BWilson%2C+Samuel+H&rft.aulast=Horton&rft.aufirst=Julie&rft.date=2003-01-02&rft.volume=2&rft.issue=1&rft.spage=27&rft.isbn=&rft.btitle=&rft.title=DNA+repair&rft.issn=15687864&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-10 N1 - Date created - 2003-01-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increasing the Efficacy of Anti-Inflammatory Agents Used in the Treatment of Sepsis AN - 872124702; 14116585 AB - Excessive production of inflammatory mediators during invasive infection plays a key role in the pathogenesis of septic shock. In an attempt to improve survival of patients with this lethal syndrome, agents were developed to selectively inhibit mediators in this inflammatory response. Despite promising preclinical results, several different mediator-specific anti-inflammatory agents failed to demonstrate significant benefit in patients. There was, however, a significant difference in mortality between preclinical and clinical trials. The median control mortality in preclinical trials, performed almost uniformly in highly lethal sepsis models, was 88%. In clinical trials however, the median control mortality rate was much lower, at 41%. A recent meta-regression analysis of these preclinical and clinical trials in combination with prospective confirmatory studies demonstrated that risk of death as assessed by control group mortality rate significantly altered the treatment effect of these agents in both humans and animals. While anti-inflammatory agents were very beneficial in groups with high control mortality rates, they were ineffective or harmful in groups with low control mortality rates. Thus, variation in the risk of death due to sepsis provides a basis for the marked difference in the efficacy of these anti-inflammatory agents in preclinical and clinical trials over the last decade. In contrast to mediator-specific anti-inflammatory agents, glucocorticoids and activated protein C have recently demonstrated significant beneficial effects in individual clinical trials. However, glucocorticoids were studied only in patients with vasopressor-dependent septic shock, which is associated with a high control mortality rate (i.e. 61%) similar to the level at which mediator-specific agents would have been expected to be markedly beneficial. Furthermore, consistent with earlier findings for mediator-specific anti-inflammatory agents, analysis of the activated protein C study also demonstrated a relationship between risk of death and effect of treatment. Developing better methods to define high-risk septic populations for treatment with anti-inflammatory agents will increase the efficacy of this therapeutic approach and minimize its potential for harm. JF - European Journal of Clinical Microbiology & Infectious Diseases AU - Minneci, P AU - Deans, K AU - Natanson, C AU - Eichacker, P Q AD - Department of Surgery, Massachusetts General Hospital, 55 Fruit Street, MA 02114, Boston, USA, Pminneci@mail.cc.nih.gov Y1 - 2003/01// PY - 2003 DA - Jan 2003 SP - 1 EP - 9 PB - Springer-Verlag, Tiergartenstrasse 17 Heidelberg 69121 Germany VL - 22 IS - 1 SN - 0934-9723, 0934-9723 KW - Microbiology Abstracts B: Bacteriology KW - Mortality KW - activated protein C KW - Survival KW - Septic shock KW - Infection KW - Glucocorticoids KW - Clinical trials KW - Models KW - Inflammation KW - Sepsis KW - Risk factors KW - Risk groups KW - Antiinflammatory agents KW - J 02350:Immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/872124702?accountid=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+Clinical+Microbiology+%26+Infectious+Diseases&rft.atitle=Increasing+the+Efficacy+of+Anti-Inflammatory+Agents+Used+in+the+Treatment+of+Sepsis&rft.au=Minneci%2C+P%3BDeans%2C+K%3BNatanson%2C+C%3BEichacker%2C+P+Q&rft.aulast=Minneci&rft.aufirst=P&rft.date=2003-01-01&rft.volume=22&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=European+Journal+of+Clinical+Microbiology+%26+Infectious+Diseases&rft.issn=09349723&rft_id=info:doi/10.1007%2Fs10096-002-0857-3 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2011-06-01 N1 - Last updated - 2012-03-29 N1 - SubjectsTermNotLitGenreText - Mortality; activated protein C; Survival; Septic shock; Infection; Clinical trials; Glucocorticoids; Inflammation; Models; Sepsis; Risk factors; Risk groups; Antiinflammatory agents DO - http://dx.doi.org/10.1007/s10096-002-0857-3 ER - TY - JOUR T1 - Activation of Broca's Area during the Production of Spoken and Signed Language: A Combined Cytoarchitectonic Mapping and PET Analysis AN - 85593706; 200405385 AB - Broca's area in the inferior frontal gyrus consists of two cytoarchitectonically defined regions - Brodmann areas (BA) 44 & 45. Combining probabilistic maps of these two areas with functional neuroimaging data obtained using PET, it is shown that BA45, not BA44, is activated by both speech & signing during the production of language narratives when the generation of complex movements & sounds is taken into account. Subjects were bilinguals fluent from early childhood in both American Sign Language (ASL) & English. It is BA44, not BA45, that is activated by the generation of complex articulatory movements of oral/laryngeal or limb musculature. The same patterns of activation are found for oral language production in a group of English speaking monolingual subjects. These findings implicate BA45 as the part of Broca's area that is fundamental to the modality-independent aspects of language generation. 2 Tables, 2 Figures, 52 References. Adapted from the source document JF - Neuropsychologia AU - Horwitz, Barry AU - Amunts, Katrin AU - Bhattacharyya, Rajan AU - Patkin, Debra AU - Jeffries, Keith AU - Zilles, Karl AU - Braun, Allen R AD - Language Section, National Instit Deafness & Other Communication Disorders, National Instits Health, Bethesda, MD horwitz@helix.nih.gov Y1 - 2003///0, PY - 2003 DA - 0, 2003 SP - 1868 EP - 1876 VL - 41 IS - 14 SN - 0028-3932, 0028-3932 KW - Articulation (04600) KW - Stimulus Modality (84180) KW - Bilingualism (08850) KW - Sign Language (78400) KW - Brain (09350) KW - English (21900) KW - Speech Production (82780) KW - American Sign Language (02350) KW - Neuroimaging Techniques (57245) KW - article KW - 4018: psycholinguistics; neurolinguistics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85593706?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Allba&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychologia&rft.atitle=Activation+of+Broca%27s+Area+during+the+Production+of+Spoken+and+Signed+Language%3A+A+Combined+Cytoarchitectonic+Mapping+and+PET+Analysis&rft.au=Horwitz%2C+Barry%3BAmunts%2C+Katrin%3BBhattacharyya%2C+Rajan%3BPatkin%2C+Debra%3BJeffries%2C+Keith%3BZilles%2C+Karl%3BBraun%2C+Allen+R&rft.aulast=Horwitz&rft.aufirst=Barry&rft.date=2003-01-01&rft.volume=41&rft.issue=14&rft.spage=1868&rft.isbn=&rft.btitle=&rft.title=Neuropsychologia&rft.issn=00283932&rft_id=info:doi/ LA - English DB - Linguistics and Language Behavior Abstracts (LLBA) N1 - Date revised - 2004-05-01 N1 - Last updated - 2016-09-27 N1 - CODEN - NUPSA6 N1 - SubjectsTermNotLitGenreText - Brain (09350); Neuroimaging Techniques (57245); Speech Production (82780); Sign Language (78400); Bilingualism (08850); Articulation (04600); Stimulus Modality (84180); American Sign Language (02350); English (21900) ER - TY - JOUR T1 - Stuttering: A Dynamic Motor Control Disorder AN - 85574778; 200402663 AB - The purpose of this review is to determine what neural mechanisms may be dysfunctional in stuttering. Three sources of evidence are reviewed. First, studies of dynamic inter-relationships among brain regions during normal speech & in persons who stutter (PWS) suggest that the timing of neural activity in different regions may be abnormal in PWS. Second, the brain lesions associated with acquired stuttering are reviewed. These indicate that in a high percentage of cases, the primary speech & language regions are not affected but lesions involve other structures, such as the basal ganglia, which may modulate the primary speech & language regions. Third, to characterize the motor control disorder in stuttering, similarities & differences from focal dystonias such as spasmodic dysphonia (SD) & Tourette's syndrome (TS) are reviewed. This review indicates that the central control abnormalities in stuttering are not due to disturbance in one particular brain region but rather a system dysfunction that interferes with rapid & dynamic speech processing for production. 1 Table, 133 References. Adapted from the source document JF - Journal of Fluency Disorders AU - Ludlow, Christy L AU - Loucks, Torrey AD - Laryngeal & Speech Section, Clinical Neurosciences Program, National Instit Neurological Disorders & Stroke, Bethesda, MD Ludlowc@ninds.nih.gov Y1 - 2003/01// PY - 2003 DA - January 2003 SP - 273 EP - 295 VL - 28 IS - 4 SN - 0094-730X, 0094-730X KW - Stuttering (84850) KW - Speech Pathology (82650) KW - Brain (09350) KW - Neurolinguistics (57250) KW - Speech Motor Control (82600) KW - Neuroimaging Techniques (57245) KW - article KW - 4018: psycholinguistics; neurolinguistics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85574778?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Allba&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Fluency+Disorders&rft.atitle=Stuttering%3A+A+Dynamic+Motor+Control+Disorder&rft.au=Ludlow%2C+Christy+L%3BLoucks%2C+Torrey&rft.aulast=Ludlow&rft.aufirst=Christy&rft.date=2003-01-01&rft.volume=28&rft.issue=4&rft.spage=273&rft.isbn=&rft.btitle=&rft.title=Journal+of+Fluency+Disorders&rft.issn=0094730X&rft_id=info:doi/ LA - English DB - Linguistics and Language Behavior Abstracts (LLBA) N1 - Date revised - 2004-03-01 N1 - Last updated - 2016-09-27 N1 - CODEN - JFDID8 N1 - SubjectsTermNotLitGenreText - Speech Motor Control (82600); Stuttering (84850); Neurolinguistics (57250); Brain (09350); Speech Pathology (82650); Neuroimaging Techniques (57245) ER - TY - JOUR T1 - Auditory function associated with Col11a1 haploinsufficiency in chondrodysplasia (cho) mice. AN - 85413076; pmid-12527136 AB - Heterozygosity for mutations in the fibrillar collagen gene COL11A1 causes sensorineural hearing loss in patients with Stickler syndrome or Marshall syndrome. Chondrodysplasia (cho) is a functional null allele of Col11a1 that causes lethal chondrodysplasia in cho/cho newborn mice, and osteoarthritis in cho/+ heterozygotes. To determine if Col11a1 haploinsufficiency causes hearing loss in cho/+ mice, auditory brainstem response (ABR) thresholds were measured at 2, 4, 6, 8 and 10 months of age. There was no difference in ABR thresholds for click and tone burst stimuli between cho/+ and +/+ mice at all ages. In contrast to the conclusion of a previous report, our results indicate that Col11a1 haploinsufficiency does not cause significant hearing loss on the C57BL/6 strain background. We conclude that Stickler syndrome and Marshall syndrome mutations in COL11A1 cause hearing loss via dominant negative effects upon wild-type fibrillar collagen polypeptides in the extracellular matrices of the cochlea.Copyright 2002 Elsevier Science B.V. JF - Hearing research AU - Szymko-Bennett, Yvonne M AU - Kurima, Kiyoto AU - Olsen, Bjorn AU - Seegmiller, Robert AU - Griffith, Andrew J AD - Hearing Section, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 5 Research Court, Rockville, MD 20850, USA. Y1 - 2003/01// PY - 2003 DA - Jan 2003 SP - 178 EP - 182 VL - 175 IS - 1-2 SN - 0378-5955, 0378-5955 KW - Index Medicus KW - National Library of Medicine KW - Acoustic Stimulation KW - Animals KW - Auditory Threshold KW - *Collagen Type XI: genetics KW - Evoked Potentials, Auditory, Brain Stem KW - *Hearing KW - Mice KW - Mice, Inbred C57BL KW - *Osteochondrodysplasias: genetics KW - *Osteochondrodysplasias: physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85413076?accountid=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=Auditory+function+associated+with+Col11a1+haploinsufficiency+in+chondrodysplasia+%28cho%29+mice.&rft.au=Szymko-Bennett%2C+Yvonne+M%3BKurima%2C+Kiyoto%3BOlsen%2C+Bjorn%3BSeegmiller%2C+Robert%3BGriffith%2C+Andrew+J&rft.aulast=Szymko-Bennett&rft.aufirst=Yvonne&rft.date=2003-01-01&rft.volume=175&rft.issue=1-2&rft.spage=178&rft.isbn=&rft.btitle=&rft.title=Hearing+research&rft.issn=03785955&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Development of Evidence-Based Practice Guidelines: Committee Update AN - 85337868; llba-200510695 AB - The Academy of Neurologic Communication Disorders & Sciences (ANCDS), by way of the mission, purposes, & activities of its Ad Hoc Practice Guidelines Coordinating Committee & respective writing committees, has embarked on a 5-year project to develop a range of evidence-based practice guidelines for specific neurologically impaired patient populations (ie, dysarthria, dementia, acquired apraxia of speech, developmental apraxia of speech, aphasia, cognitive-communication disorders after traumatic brain injury, & cognitive & communication disorders after right-hemisphere brain damage). The project embraces a philosophy that quality of care is best supported by scientific evidence of treatment efficacy. This article, which details & updates the proceedings from the Committee's presentation at the ANCDS annual educational & scientific meeting in 2002 in Atlanta, Georgia, summarizes the progress to date by the various writing committees responsible for developing these evidence-based practice guidelines. 1 Figure, 15 References. Adapted from the source document JF - Journal of Medical Speech-Language Pathology AU - Frattali, Carol AU - Bayles, Kathryn AU - Beeson, Pelagie AU - Kennedy, Mary R T AU - Wambaugh, Julie AU - Yorkston, Kathryn M AD - Dept Rehabilitation Medicine, W. G. Magnuson Clinical Center, National Instits Health, Bethesda, MD carol_frattali@nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - ix EP - xvii VL - 11 IS - 3 SN - 1065-1438, 1065-1438 KW - *Communication Disorders (13625) KW - *Language Therapy (44400) KW - *Aphasia (03400) KW - *Nervous System Disorders (57100) KW - *Cognitive Processes (12950) KW - *Brain Damage (09400) KW - *Dementia (18020) KW - *Language Pathology (43250) KW - article KW - 6812: special education; language therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85337868?accountid=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+Medical+Speech-Language+Pathology&rft.atitle=Development+of+Evidence-Based+Practice+Guidelines%3A+Committee+Update&rft.au=Frattali%2C+Carol%3BBayles%2C+Kathryn%3BBeeson%2C+Pelagie%3BKennedy%2C+Mary+R+T%3BWambaugh%2C+Julie%3BYorkston%2C+Kathryn+M&rft.aulast=Frattali&rft.aufirst=Carol&rft.date=2003-01-01&rft.volume=11&rft.issue=3&rft.spage=ix&rft.isbn=&rft.btitle=&rft.title=Journal+of+Medical+Speech-Language+Pathology&rft.issn=10651438&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2005-10-01 N1 - Last updated - 2014-06-17 N1 - CODEN - JSLPEP N1 - SubjectsTermNotLitGenreText - *Aphasia (03400); *Dementia (18020); *Communication Disorders (13625); *Nervous System Disorders (57100); *Brain Damage (09400); *Language Therapy (44400); *Language Pathology (43250); *Cognitive Processes (12950) ER - TY - JOUR T1 - Common Features of Fluency-Evoking Conditions Studied in Stuttering Subjects and Controls: An H215O PET Study AN - 85332039; llba-200402667 AB - We used H215O PET to characterize the common features of two successful but markedly different fluency-evoking conditions - paced speech & singing - in order to identify brain mechanisms that enable fluent speech in people who stutter. To do so, we compared responses under fluency-evoking conditions with responses elicited by tasks that typically elicit dysfluent speech (quantifying the degree of stuttering & using this measure as a confounding covariate in our analyses). We evaluated task-related activations in both stuttering subjects & age- & gender-matched controls. Areas that were either uniquely activated during fluency-evoking conditions or in which the magnitude of activation was significantly greater during fluency-evoking than dysfluency-evoking tasks included auditory association areas that process speech & voice & motor regions related to control of the larynx & oral articulators. This suggests that a common fluency-evoking mechanism might relate to more effective coupling of auditory & motor systems - ie, more efficient self-monitoring, allowing motor areas to more effectively modify speech. These effects were seen in both PWS & controls, suggesting that they are due to the sensorimotor or cognitive demands of the fluency-evoking tasks themselves. While responses seen in both groups were bilateral, however, the fluency-evoking tasks elicited more robust activation of auditory & motor regions within the left hemisphere of stuttering subjects, suggesting a role for the left hemisphere in compensatory processes that enable fluency. 3 Tables, 3 Figures, 32 References. Adapted from the source document JF - Journal of Fluency Disorders AU - Stager, Sheila V AU - Jeffries, Keith J AU - Braun, Allen R AD - c/o Braun-Language Section, Voice Speech & Language Branch, National Instit Deafness & Other Communication Disorders, National Instits Health, Bethesda, MD brauna@nidcd.nih.gov Y1 - 2003/01// PY - 2003 DA - Jan 2003 SP - 319 EP - 336 VL - 28 IS - 4 SN - 0094-730X, 0094-730X KW - *Speech Production (82780) KW - *Fluency (24910) KW - *Speech Motor Control (82600) KW - *Singing (78950) KW - *Neuroimaging Techniques (57245) KW - *Cerebral Dominance (11500) KW - *Stuttering (84850) KW - article KW - 4018: psycholinguistics; neurolinguistics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85332039?accountid=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+Fluency+Disorders&rft.atitle=Common+Features+of+Fluency-Evoking+Conditions+Studied+in+Stuttering+Subjects+and+Controls%3A+An+H215O+PET+Study&rft.au=Stager%2C+Sheila+V%3BJeffries%2C+Keith+J%3BBraun%2C+Allen+R&rft.aulast=Stager&rft.aufirst=Sheila&rft.date=2003-01-01&rft.volume=28&rft.issue=4&rft.spage=319&rft.isbn=&rft.btitle=&rft.title=Journal+of+Fluency+Disorders&rft.issn=0094730X&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2004-03-01 N1 - Last updated - 2014-06-17 N1 - CODEN - JFDID8 N1 - SubjectsTermNotLitGenreText - *Neuroimaging Techniques (57245); *Stuttering (84850); *Fluency (24910); *Speech Motor Control (82600); *Speech Production (82780); *Singing (78950); *Cerebral Dominance (11500) ER - TY - JOUR T1 - Pathways to Parkinsonism. AN - 85244544; pmid-12526767 AB - A novel gene for Parkinson's disease (PD), DJ-1, has been identified that encodes a multifunctional product with several known protein-protein interactions and effects on gene expression. Here, I outline how it is possible to construct hypotheses that place DJ-1 in different relationships to the other known PD genes, alpha-synuclein and parkin. The identification of multiple genetic causes will provide further impetus to describe the pathway leading to PD. JF - Neuron AU - Cookson, Mark R AD - Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA. PY - 2003 SP - 7 EP - 10 VL - 37 IS - 1 SN - 0896-6273, 0896-6273 KW - Animals KW - Oncogene Proteins KW - Human KW - Oxidative Stress KW - Protein Folding KW - Disease Models, Animal KW - Parkinsonian Disorders KW - Mutation KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85244544?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuron&rft.atitle=Pathways+to+Parkinsonism.&rft.au=Cookson%2C+Mark+R&rft.aulast=Cookson&rft.aufirst=Mark&rft.date=2003-01-01&rft.volume=37&rft.issue=1&rft.spage=7&rft.isbn=&rft.btitle=&rft.title=Neuron&rft.issn=08966273&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - From humble neural beginnings comes knowledge of numbers. AN - 85240014; pmid-12526766 AB - Following a recent report that monkey prefrontal cortex contains cells that represent number concepts, Nieder and Miller investigated the scale used to code numbers. In this issue of Neuron, they report that prefrontal cells use the same scale (Weber's Law) used by sensory neurons to code stimulus intensity, suggesting how abstract cognitive operations may arise from simpler building blocks that humans share with other animals. JF - Neuron AU - Pessoa Luiz AU - Desimone, Robert AD - Laboratory of Brain and Cognition, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA. PY - 2003 SP - 4 EP - 6 VL - 37 IS - 1 SN - 0896-6273, 0896-6273 KW - Human KW - Neural Pathways KW - Animal KW - Psychomotor Performance KW - Prefrontal Cortex KW - Parietal Lobe KW - Cognition KW - Evolution KW - Nerve Net KW - Mathematics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85240014?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuron&rft.atitle=From+humble+neural+beginnings+comes+knowledge+of+numbers.&rft.au=Pessoa+Luiz%3BDesimone%2C+Robert&rft.aulast=Pessoa+Luiz&rft.aufirst=&rft.date=2003-01-01&rft.volume=37&rft.issue=1&rft.spage=4&rft.isbn=&rft.btitle=&rft.title=Neuron&rft.issn=08966273&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - On the persistent sodium current in squid giant axons. AN - 85236118; pmid-12522209 AB - R. F. Rakowski, D. C. Gadsby, and P. DeWeer have reported a persistent, tetrodotoxin-sensitive sodium ion current (I(NaP)) in squid giant axons having a low threshold (-90 mV) and a maximal inward amplitude of -4 microA/cm(2) at -50 mV. This report makes the case that most of I(NaP) is attributable to an ion channel mechanism distinct from the classical rapidly activating and inactivating sodium ion current, I(Na), which is also tetrodotoxin sensitive. The analysis of the contribution of I(Na) to I(NaP) is critically dependent on slow inactivation of I(Na). The results of this gating process reported here demonstrate that inactivation of I(Na) is complete in the steady-state for V > -40 mV, thereby making it unlikely that I(NaP) in this potential range is attributable to I(Na). Moreover, -90 mV is well below I(Na) threshold, as demonstrated by the C. A. Vandenberg and F. Bezanilla model of I(Na) gating in squid giant axons. Their model predicts a persistent current having a threshold of -60 mV and a peak amplitude of -25 microA/cm(2) at -20 mV. Modulation of this component by the slow inactivation process predicts a persistent current that is finite in the -60- to -40-mV range having a peak amplitude of -1 microA/cm(-2) at -50 mV. Subtraction of this current from the I(NaP) measurements yields the portion of I(NaP) that appears to be attributable to an ion channel mechanism distinct from I(Na). JF - Journal of Neurophysiology AU - Clay, John R AD - Ion Channel Biophysics Unit, Basic Neurosciences Program, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 2003 SP - 640 EP - 644 VL - 89 IS - 1 SN - 0022-3077, 0022-3077 KW - Sodium KW - Patch-Clamp Techniques KW - Animal KW - Membrane Potentials KW - Axons KW - Squid KW - Sodium Channels KW - Models, Neurological UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85236118?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Neurophysiology&rft.atitle=On+the+persistent+sodium+current+in+squid+giant+axons.&rft.au=Clay%2C+John+R&rft.aulast=Clay&rft.aufirst=John&rft.date=2003-01-01&rft.volume=89&rft.issue=1&rft.spage=640&rft.isbn=&rft.btitle=&rft.title=Journal+of+Neurophysiology&rft.issn=00223077&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Expression and distribution of tuberoinfundibular peptide of 39 residues in the rat central nervous system. AN - 85235519; pmid-12508326 AB - Tuberoinfundibular peptide of 39 residues (TIP39) has been recently purified and identified as a selective ligand for the parathyroid hormone 2 receptor. As a next step toward understanding its functions, we report the expression and distribution of TIP39 in the rat central nervous system. In situ hybridization histochemistry and immunocytochemistry revealed TIP39-containing cell bodies in three distinct areas. The major one comprises the subparafascicular area posterior through the intralaminar nucleus of the thalamus; a second is the medial paralemniscal nucleus at the pontomesencephalic junction; and a third is in the dorsal and dorsolateral hypothalamic areas, which contained a few, scattered cell bodies. We found, in contrast to the highly restricted localization of TIP39-containing cell bodies, a much more widespread localization of TIP39-containing fibers. The highest density of fibers was observed in limbic areas such as the septum, the amygdala, and the bed nucleus of the stria terminalis; in areas involved in endocrine regulation, such as the hypothalamic dorsomedial, paraventricular, periventricular, and arcuate nuclei; in auditory areas, such as the ectorhinal and temporal cortices, inferior colliculus, medial geniculate body, and some of the nuclei of the superior olivary complex; and in the dorsolateral funiculus of the spinal cord. The localization of TIP39-containing nuclei and fibers provides an anatomical basis for previously demonstrated endocrine and nociceptive effects of TIP39 and suggests additional functions for TIP39, one apparent candidate being the regulation of auditory information processing. JF - The Journal of Comparative Neurology AU - Dobolyi Arpad AU - Palkovits Miklós AU - Usdin Ted Björn AD - Laboratory of Genetics, National Institute of Mental Health, Bethesda, Maryland 20892-4094, USA. PY - 2003 SP - 547 EP - 566 VL - 455 IS - 4 SN - 0021-9967, 0021-9967 KW - Hypothalamus KW - Support, U.S. Gov't, P.H.S. KW - Spinal Cord KW - Cell Count KW - Animal KW - Central Nervous System KW - Limbic System KW - Thalamus KW - Rats KW - RNA, Messenger KW - Mesencephalon KW - In Situ Hybridization KW - Rats, Sprague-Dawley KW - Receptors, Parathyroid Hormone KW - Medulla Oblongata KW - Neuropeptides KW - Immunohistochemistry KW - Male KW - Nerve Fibers UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85235519?accountid=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+Comparative+Neurology&rft.atitle=Expression+and+distribution+of+tuberoinfundibular+peptide+of+39+residues+in+the+rat+central+nervous+system.&rft.au=Dobolyi+Arpad%3BPalkovits+Mikl%C3%B3s%3BUsdin+Ted+Bj%C3%B6rn&rft.aulast=Dobolyi+Arpad&rft.aufirst=&rft.date=2003-01-01&rft.volume=455&rft.issue=4&rft.spage=547&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+Comparative+Neurology&rft.issn=00219967&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Molecular tracking of antigen-specific T cell clones in neurological immune-mediated disorders. AN - 85221721; pmid-12477694 AB - T cells recognizing self or microbial antigens may trigger or reactivate immune-mediated diseases. Monitoring the frequency of specific T cell clonotypes to assess a possible link with the course of disease has been a difficult task with currently available technology. Our goal was to track individual candidate pathogenic T cell clones, selected on the basis of previous extensive studies from patients with immune-mediated disorders of the CNS, including multiple sclerosis, HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) and chronic Lyme neuroborreliosis. We developed and applied a highly specific and sensitive technique to track single CD4(+) and CD8(+) T cell clones through the detection and quantification of T cell receptor (TCR) alpha or beta chain complementarity-determining region 3 transcripts by real-time reverse transcriptase (RT)-PCR. We examined the frequency of the candidate pathogenic T cell clones in the peripheral blood and CSF during the course of neurological disease. Using this approach, we detected variations of clonal frequencies that appeared to be related to clinical course, significant enrichment in the CSF, or both. By integrating clonotype tracking with direct visualization of antigen-specific staining, we showed that a single T cell clone contributed substantially to the overall recognition of the viral peptide/MHC complex in a patient with HAM/TSP. T cell clonotype tracking is a powerful new technology enabling further elucidation of the dynamics of expansion of autoreactive or pathogen-specific T cells that mediate pathological or protective immune responses in neurological disorders. JF - Brain AU - Muraro, Paolo A AU - Klaus-Peter, Wandinger AU - Bielekova Bibiana AU - Gran, Bruno AU - Marques, Adriana AU - Utz, Ursula AU - McFarland, Henry F AU - Jacobson, Steve AU - Martin, Roland AD - Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, MD 20892-1400, USA. PY - 2003 SP - 20 EP - 31 VL - 126 IS - Pt 1 SN - 0006-8950, 0006-8950 KW - Clone Cells KW - Genes, T-Cell Receptor KW - Human KW - Disease Progression KW - Aged KW - Brain Diseases KW - Lymphocyte Count KW - Multiple Sclerosis KW - Adult KW - DNA Primers KW - Molecular Sequence Data KW - Support, Non-U.S. Gov't KW - Flow Cytometry KW - Immunodominant Epitopes KW - Autoimmune Diseases of the Nervous System KW - Male KW - T-Lymphocytes KW - Amino Acid Sequence KW - Reverse Transcriptase Polymerase Chain Reaction KW - Sequence Analysis, DNA KW - Base Sequence KW - Case-Control Studies KW - Borrelia KW - Lyme Neuroborreliosis KW - Case Report KW - Immunophenotyping UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85221721?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain&rft.atitle=Molecular+tracking+of+antigen-specific+T+cell+clones+in+neurological+immune-mediated+disorders.&rft.au=Muraro%2C+Paolo+A%3BKlaus-Peter%2C+Wandinger%3BBielekova+Bibiana%3BGran%2C+Bruno%3BMarques%2C+Adriana%3BUtz%2C+Ursula%3BMcFarland%2C+Henry+F%3BJacobson%2C+Steve%3BMartin%2C+Roland&rft.aulast=Muraro&rft.aufirst=Paolo&rft.date=2003-01-01&rft.volume=126&rft.issue=Pt+1&rft.spage=20&rft.isbn=&rft.btitle=&rft.title=Brain&rft.issn=00068950&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Talking with your doctor: A guide for older people AN - 821468632 JF - Ageing International AU - Anonymous Y1 - 2003///Winter PY - 2003 DA - Winter 2003 SP - 98 EP - 113 CY - New York PB - Springer Science & Business Media VL - 28 IS - 1 SN - 01635158 KW - Gerontology And Geriatrics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/821468632?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aabiglobal&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Ageing+International&rft.atitle=Talking+with+your+doctor%3A+A+guide+for+older+people&rft.au=Anonymous&rft.aulast=Anonymous&rft.aufirst=&rft.date=2003-01-01&rft.volume=28&rft.issue=1&rft.spage=98&rft.isbn=&rft.btitle=&rft.title=Ageing+International&rft.issn=01635158&rft_id=info:doi/10.1007%2Fs12126-003-1018-4 LA - English DB - ProQuest Central N1 - Copyright - Springer 2003 N1 - Last updated - 2014-08-30 DO - http://dx.doi.org/10.1007/s12126-003-1018-4 ER - TY - JOUR T1 - The neuropharmacological basis for the use of memantine in the treatment of Alzheimer's disease. AN - 75755894; 14530799 AB - Memantine has been demonstrated to be safe and effective in the symptomatic treatment of Alzheimer's disease (AD). While the neurobiological basis for the therapeutic activity of memantine is not fully understood, the drug is not a cholinesterase inhibitor and, therefore, acts differently from current AD therapies. Memantine can interact with a variety of ligand-gated ion channels. However, NMDA receptors appear to be a key target of memantine at therapeutic concentrations. Memantine is an uncompetitive (channel blocking) NMDA receptor antagonist. Like other NMDA receptor antagonists, memantine at high concentrations can inhibit mechanisms of synaptic plasticity that are believed to underlie learning and memory. However, at lower, clinically relevant concentrations memantine can under some circumstances promote synaptic plasticity and preserve or enhance memory in animal models of AD. In addition, memantine can protect against the excitotoxic destruction of cholinergic neurons. Blockade of NMDA receptors by memantine could theoretically confer disease-modifying activity in AD by inhibiting the "weak" NMDA receptor-dependent excitotoxicity that has been hypothesized to play a role in the progressive neuronal loss that underlies the evolving dementia. Moreover, recent in vitro studies suggest that memantine abrogates beta-amyloid (Abeta) toxicity and possibly inhibits Abeta production. Considerable attention has focused on the investigation of theories to explain the better tolerability of memantine over other NMDA receptor antagonists, particularly those that act by a similar channel blocking mechanism such as dissociative anesthetic-like agents (phencyclidine, ketamine, MK-801). A variety of channel-level factors could be relevant, including fast channel-blocking kinetics and strong voltage-dependence (allowing rapid relief of block during synaptic activity), as well as reduced trapping (permitting egress from closed channels). These factors may allow memantine to block channel activity induced by low, tonic levels of glutamate--an action that might contribute to symptomatic improvement and could theoretically protect against weak excitotoxicity--while sparing synaptic responses required for normal behavioral functioning, cognition and memory. JF - CNS drug reviews AU - Rogawski, Michael A AU - Wenk, Gary L AD - Epilepsy Research Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-4457, USA. michael.rogawski@nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 275 EP - 308 VL - 9 IS - 3 SN - 1080-563X, 1080-563X KW - Excitatory Amino Acid Antagonists KW - 0 KW - Neuroprotective Agents KW - Receptors, N-Methyl-D-Aspartate KW - Memantine KW - W8O17SJF3T KW - Index Medicus KW - Animals KW - Receptors, N-Methyl-D-Aspartate -- drug effects KW - Memory -- drug effects KW - Humans KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Neuronal Plasticity -- drug effects KW - Molecular Biology -- methods KW - Electrophysiology KW - Receptors, N-Methyl-D-Aspartate -- chemistry KW - Receptors, N-Methyl-D-Aspartate -- classification KW - Memantine -- therapeutic use KW - Neuropharmacology KW - Memantine -- pharmacology KW - Alzheimer Disease -- physiopathology KW - Alzheimer Disease -- drug therapy KW - Excitatory Amino Acid Antagonists -- therapeutic use KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Alzheimer Disease -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75755894?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=CNS+drug+reviews&rft.atitle=The+neuropharmacological+basis+for+the+use+of+memantine+in+the+treatment+of+Alzheimer%27s+disease.&rft.au=Rogawski%2C+Michael+A%3BWenk%2C+Gary+L&rft.aulast=Rogawski&rft.aufirst=Michael&rft.date=2003-01-01&rft.volume=9&rft.issue=3&rft.spage=275&rft.isbn=&rft.btitle=&rft.title=CNS+drug+reviews&rft.issn=1080563X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-23 N1 - Date created - 2003-10-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protofibrils, pores, fibrils, and neurodegeneration: separating the responsible protein aggregates from the innocent bystanders. AN - 75744799; 12704221 AB - Many neurodegenerative diseases, including Alzheimer's and Parkinson's and the transmissible spongiform encephalopathies (prion diseases), are characterized at autopsy by neuronal loss and protein aggregates that are typically fibrillar. A convergence of evidence strongly suggests that protein aggregation is neurotoxic and not a product of cell death. However, the identity of the neurotoxic aggregate and the mechanism by which it disables and eventually kills a neuron are unknown. Both biophysical studies aimed at elucidating the precise mechanism of in vitro aggregation and animal modeling studies support the emerging notion that an ordered prefibrillar oligomer, or protofibril, may be responsible for cell death and that the fibrillar form that is typically observed at autopsy may actually be neuroprotective. A subpopulation of protofibrils may function as pathogenic amyloid pores. An analogous mechanism may explain the neurotoxicity of the prion protein; recent data demonstrates that the disease-associated, infectious form of the prion protein differs from the neurotoxic species. This review focuses on recent experimental studies aimed at identification and characterization of the neurotoxic protein aggregates. JF - Annual review of neuroscience AU - Caughey, Byron AU - Lansbury, Peter T AD - NIAID, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana, USA. bcaughey@niaid.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 267 EP - 298 VL - 26 SN - 0147-006X, 0147-006X KW - Amyloid beta-Peptides KW - 0 KW - Nerve Tissue Proteins KW - PrPSc Proteins KW - Prions KW - SOD1 protein, human KW - Synucleins KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Superoxide Dismutase-1 KW - Index Medicus KW - PrPSc Proteins -- pathogenicity KW - Animals KW - Amyotrophic Lateral Sclerosis -- genetics KW - Amyotrophic Lateral Sclerosis -- metabolism KW - Humans KW - PrPSc Proteins -- metabolism KW - Superoxide Dismutase -- metabolism KW - Disease Models, Animal KW - PrPSc Proteins -- genetics KW - Amyloid beta-Peptides -- metabolism KW - In Vitro Techniques KW - Nerve Tissue Proteins -- metabolism KW - Prions -- metabolism KW - Prions -- pathogenicity KW - Amyotrophic Lateral Sclerosis -- physiopathology KW - Nerve Degeneration KW - Neurodegenerative Diseases KW - Plaque, Amyloid KW - Neurofibrillary Tangles UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75744799?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neuroscience&rft.atitle=Protofibrils%2C+pores%2C+fibrils%2C+and+neurodegeneration%3A+separating+the+responsible+protein+aggregates+from+the+innocent+bystanders.&rft.au=Caughey%2C+Byron%3BLansbury%2C+Peter+T&rft.aulast=Caughey&rft.aufirst=Byron&rft.date=2003-01-01&rft.volume=26&rft.issue=&rft.spage=267&rft.isbn=&rft.btitle=&rft.title=Annual+review+of+neuroscience&rft.issn=0147006X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-10 N1 - Date created - 2003-10-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Shift work sleep disorder]. AN - 75705890; 14503229 JF - Ryoikibetsu shokogun shirizu AU - Uchiyama, Makoto AD - Department of Psychophysiology, National Institute of Mental Health, National Center of Neurology and Psychiatry. Y1 - 2003 PY - 2003 DA - 2003 SP - 133 EP - 136 IS - 39 KW - Index Medicus KW - Humans KW - Sleep Disorders, Circadian Rhythm -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75705890?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Ryoikibetsu+shokogun+shirizu&rft.atitle=%5BShift+work+sleep+disorder%5D.&rft.au=Uchiyama%2C+Makoto&rft.aulast=Uchiyama&rft.aufirst=Makoto&rft.date=2003-01-01&rft.volume=&rft.issue=39&rft.spage=133&rft.isbn=&rft.btitle=&rft.title=Ryoikibetsu+shokogun+shirizu&rft.issn=&rft_id=info:doi/ LA - Japanese DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-17 N1 - Date created - 2003-09-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lessons from chronic renal diseases in African Americans: treatment implications. AN - 73645369; 13677426 AB - End-stage renal disease (ESRD) is a significant public health problem in both developed and developing countries. The magnitude and patterns of renal disease vary among countries, differences that could be due, in part, to regional racial and ethnic composition. The United States is a typical example, with significant racial and ethnic differences in the magnitude and pattern of renal disease. Compared with Caucasians and Asians, African Americans, Native Americans, and Pacific Islanders are disproportionately afflicted with end-stage kidney failure. Whereas diabetes mellitus (primarily type 2) is the predominant cause of renal disease (and ESRD) in the United States, especially in Native Americans, hypertensive kidney disease is a major cause of ESRD in African Americans. Some of the lifestyle and physical characteristics that may be responsible for the increased incidence and prevalence of hypertensive kidney disease in African Americans include: 1) the higher prevalence and severity of hypertension, especially in the early years of life; 2) lower socioeconomic status leading to inadequate health care; 3) a greater propensity toward developing intrinsic renal vascular disease; 4) a greater tendency toward developing target organ damage at "normal" blood pressure levels; 5) illicit drug use; and 6) the use of medication that is less reno-protective to treat their blood pressure. JF - Ethnicity & disease AU - Agodoa, Lawrence AD - Office of Minority Health Research Coordination, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-5454, USA. agodoal@extra.niddk.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - S118 EP - S124 VL - 13 IS - 2 Suppl 2 SN - 1049-510X, 1049-510X KW - Antihypertensive Agents KW - 0 KW - Index Medicus KW - Renal Dialysis -- utilization KW - Humans KW - Delivery of Health Care -- standards KW - Antihypertensive Agents -- standards KW - Kidney Transplantation -- utilization KW - Ethnic Groups -- statistics & numerical data KW - Hypertension -- complications KW - Survival Rate KW - Antihypertensive Agents -- classification KW - Social Class KW - Life Style -- ethnology KW - Diabetes Mellitus -- ethnology KW - Antihypertensive Agents -- therapeutic use KW - Incidence KW - Substance-Related Disorders -- complications KW - Substance-Related Disorders -- ethnology KW - Hypertension -- ethnology KW - United States -- epidemiology KW - Diabetes Complications KW - Prevalence KW - Hypertension, Renal -- drug therapy KW - African Americans -- statistics & numerical data KW - Kidney Failure, Chronic -- therapy KW - Kidney Failure, Chronic -- mortality KW - Hypertension, Renal -- complications KW - Kidney Failure, Chronic -- etiology KW - Kidney Failure, Chronic -- ethnology KW - Hypertension, Renal -- ethnology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73645369?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Ethnicity+%26+disease&rft.atitle=Lessons+from+chronic+renal+diseases+in+African+Americans%3A+treatment+implications.&rft.au=Agodoa%2C+Lawrence&rft.aulast=Agodoa&rft.aufirst=Lawrence&rft.date=2003-01-01&rft.volume=13&rft.issue=2+Suppl+2&rft.spage=S118&rft.isbn=&rft.btitle=&rft.title=Ethnicity+%26+disease&rft.issn=1049510X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-02 N1 - Date created - 2003-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interventions for metabolic and endocrine complications of human immunodeficiency virus/acquired immune deficiency syndrome and illicit drug use. AN - 73608808; 12942372 AB - Illicit drug use and concurrent infection with human immunodeficiency virus (HIV) are associated with metabolic and endocrine complications that may include lipid, carbohydrate, and endocrine metabolism disorders and nutritional deficiencies. Interventions for these metabolic and endocrine complications range from micronutrient supplementation to hormone-replacement therapy. We present the current strategies for the management of metabolic and endocrine disorders of HIV/acquired immunodeficiency virus and drug use. In addition, the panel members (contributing authors of the present supplement) recommend further research to determine the nature and extent of problems and to design better and effective therapies. JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America AU - Khalsa, Jag H AU - Genser, Sander AU - Coates, Paul AU - Francis, Henry AD - Center on AIDS and Other Medical Consequences of Drug Abuse, National Institue on Drug Abuse, National Institues of Health, Bethesda, Maryland, USA. jk98p@nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - S37 EP - S42 VL - 37 Suppl 2 KW - Index Medicus KW - Humans KW - Endocrine System Diseases -- etiology KW - Metabolic Diseases -- prevention & control KW - HIV Infections -- complications KW - Metabolic Diseases -- etiology KW - Substance-Related Disorders -- complications KW - Endocrine System Diseases -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73608808?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.atitle=Interventions+for+metabolic+and+endocrine+complications+of+human+immunodeficiency+virus%2Facquired+immune+deficiency+syndrome+and+illicit+drug+use.&rft.au=Khalsa%2C+Jag+H%3BGenser%2C+Sander%3BCoates%2C+Paul%3BFrancis%2C+Henry&rft.aulast=Khalsa&rft.aufirst=Jag&rft.date=2003-01-01&rft.volume=37+Suppl+2&rft.issue=&rft.spage=S37&rft.isbn=&rft.btitle=&rft.title=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.issn=1537-6591&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-10 N1 - Date created - 2003-08-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of gabapentin to reduce chronic neuropathic pain in Fabry disease. AN - 73555638; 12971431 AB - The effect of the anticonvulsant gabapentin on neuropathic pain was studied in six male patients with Fabry disease, aged 15-45 years. After 4 weeks of treatment, pain, as measured using the Brief Pain Inventory, was decreased compared with baseline. Treatment was generally well tolerated. This study indicates that gabapentin should be considered as a treatment option for the neuropathic pain of Fabry disease. JF - Journal of inherited metabolic disease AU - Ries, M AU - Mengel, E AU - Kutschke, G AU - Kim, K S AU - Birklein, F AU - Krummenauer, F AU - Beck, M AD - Centre for Lysosomal Storage Disorders, Children's Hospital, Mainz, Germany. mr380t@nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 413 EP - 414 VL - 26 IS - 4 SN - 0141-8955, 0141-8955 KW - Acetates KW - 0 KW - Amines KW - Anticonvulsants KW - Cyclohexanecarboxylic Acids KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - gabapentin KW - 6CW7F3G59X KW - Index Medicus KW - Humans KW - Adult KW - Treatment Outcome KW - Pain Measurement KW - Adolescent KW - Male KW - Neuralgia -- physiopathology KW - Neuralgia -- drug therapy KW - Neuralgia -- etiology KW - Acetates -- adverse effects KW - Fabry Disease -- complications KW - Anticonvulsants -- adverse effects KW - Acetates -- therapeutic use KW - Anticonvulsants -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73555638?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+inherited+metabolic+disease&rft.atitle=Use+of+gabapentin+to+reduce+chronic+neuropathic+pain+in+Fabry+disease.&rft.au=Ries%2C+M%3BMengel%2C+E%3BKutschke%2C+G%3BKim%2C+K+S%3BBirklein%2C+F%3BKrummenauer%2C+F%3BBeck%2C+M&rft.aulast=Ries&rft.aufirst=M&rft.date=2003-01-01&rft.volume=26&rft.issue=4&rft.spage=413&rft.isbn=&rft.btitle=&rft.title=Journal+of+inherited+metabolic+disease&rft.issn=01418955&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-04-01 N1 - Date created - 2003-09-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Proteomic approaches to the diagnosis, treatment, and monitoring of cancer. AN - 73544927; 12908550 AB - The field of proteomics holds promise for the discovery of new biomarkers for the early detection and diagnosis of disease, molecular targets for therapy and markers for therapeutic efficacy and toxicity. A variety of proteomics approaches may be used to address these goals. Two-dimensional gel electrophoresis (2D-PAGE) is the cornerstone of many discovery-based proteomics studies. Technologies such as laser capture microdissection (LCM) and highly sensitive MS methods are currently being used together to identify greater numbers of lower abundance proteins that are differentially expressed between defined cell populations. Newer technologies such as reverse phase protein arrays will enable the identification and profiling of target pathways in small biopsy specimens. Surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) analysis enables the high throughput characterization of lysates from very few tumor cells or body fluids and may be best suited for diagnosis and monitoring of disease. Such technologies are expected to supplement our arsenal of mRNA-based assays, and we believe that in the future, entire cellular networks and not just a single deregulated protein will be the target of therapeutics and that we will soon be able to monitor the status of these pathways in diseased cells before, during and after therapy. JF - Advances in experimental medicine and biology AU - Wulfkuhle, Julia D AU - Paweletz, Cloud P AU - Steeg, Patricia S AU - Petricoin, Emanuel F AU - Liotta, Lance AD - FDA/NCI Clinical Proteomics Program, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. wulfkuhle@cher.fda.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 59 EP - 68 VL - 532 SN - 0065-2598, 0065-2598 KW - Biomarkers, Tumor KW - 0 KW - Neoplasm Proteins KW - Proteome KW - RNA, Messenger KW - Index Medicus KW - Microdissection KW - Gene Expression Profiling KW - Biomarkers, Tumor -- genetics KW - RNA, Messenger -- metabolism KW - Phosphorylation KW - Peptide Mapping KW - Humans KW - Electrophoresis, Gel, Two-Dimensional KW - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization KW - Lasers KW - Signal Transduction KW - Proteomics -- methods KW - Neoplasms -- diagnosis KW - Neoplasms -- pathology KW - Neoplasms -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73544927?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Proteomic+approaches+to+the+diagnosis%2C+treatment%2C+and+monitoring+of+cancer.&rft.au=Wulfkuhle%2C+Julia+D%3BPaweletz%2C+Cloud+P%3BSteeg%2C+Patricia+S%3BPetricoin%2C+Emanuel+F%3BLiotta%2C+Lance&rft.aulast=Wulfkuhle&rft.aufirst=Julia&rft.date=2003-01-01&rft.volume=532&rft.issue=&rft.spage=59&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 - 2004-02-03 N1 - Date created - 2003-08-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The ureteric bud. Tissue-culture approaches to branching morphogenesis and inductive signaling. AN - 73541698; 12886769 JF - Methods in molecular medicine AU - Perantoni, Alan O AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick, MD, USA. Y1 - 2003 PY - 2003 DA - 2003 SP - 179 EP - 192 VL - 86 SN - 1543-1894, 1543-1894 KW - Culture Media KW - 0 KW - Collagen KW - 9007-34-5 KW - Index Medicus KW - Rats KW - Animals KW - Morphogenesis KW - Dogs KW - Mice KW - Signal Transduction KW - Cell Line KW - Ureter -- physiology KW - Culture Techniques -- methods KW - Ureter -- embryology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73541698?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+molecular+medicine&rft.atitle=The+ureteric+bud.+Tissue-culture+approaches+to+branching+morphogenesis+and+inductive+signaling.&rft.au=Perantoni%2C+Alan+O&rft.aulast=Perantoni&rft.aufirst=Alan&rft.date=2003-01-01&rft.volume=86&rft.issue=&rft.spage=179&rft.isbn=&rft.btitle=&rft.title=Methods+in+molecular+medicine&rft.issn=15431894&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-11 N1 - Date created - 2003-07-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effects of growth hormone and sex steroid on lean body mass, fat mass, muscle strength, cardiovascular endurance and adverse events in healthy elderly women and men. AN - 73541647; 12955028 AB - Decreases in growth hormone (GH) and insulin-like growth factor I occur with age, in addition to oestrogen deficiency in women and a reduction in the levels of testosterone in men. These age-related hormonal changes may contribute to reductions in lean body mass, muscle strength and cardiac endurance, which can be partially reversed in elderly people with GH treatment, and testosterone supplements and oestrogen/progestin hormone replacement therapy in men and women, respectively. These treatments are, however, thought to have potentially serious adverse effects. We conducted a study to evaluate the separate and interactive effects of GH and sex steroids on body composition, muscle strength and cardiac endurance as well as the rate of adverse events in healthy elderly people. The results of the study showed that although there were beneficial effects with GH and sex steroid treatment, a high percentage of adverse effects occurred after 26 weeks of treatment, demonstrating a need for more research on the safety of hormonal therapy in the elderly population. Copyright 2003 S. Karger AG, Basel JF - Hormone research AU - Harman, S Mitchell AU - Blackman, Marc R AD - National Institute on Aging, National Institutes of Health, Baltimore, MD, USA. Harman@kronosinstitute.org Y1 - 2003 PY - 2003 DA - 2003 SP - 121 EP - 124 VL - 60 SN - 0301-0163, 0301-0163 KW - Gonadal Steroid Hormones KW - 0 KW - Testosterone KW - 3XMK78S47O KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Growth Hormone KW - 9002-72-6 KW - Index Medicus KW - Testosterone -- pharmacology KW - Double-Blind Method KW - Pain -- chemically induced KW - Humans KW - Insulin-Like Growth Factor I -- metabolism KW - Aged KW - Male KW - Female KW - Growth Hormone -- adverse effects KW - Hormone Replacement Therapy KW - Gonadal Steroid Hormones -- pharmacology KW - Body Weight -- drug effects KW - Adipose Tissue -- drug effects KW - Cardiovascular System -- drug effects KW - Muscle, Skeletal -- drug effects KW - Growth Hormone -- pharmacology KW - Body Composition -- drug effects KW - Gonadal Steroid Hormones -- adverse effects KW - Physical Endurance -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73541647?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hormone+research&rft.atitle=The+effects+of+growth+hormone+and+sex+steroid+on+lean+body+mass%2C+fat+mass%2C+muscle+strength%2C+cardiovascular+endurance+and+adverse+events+in+healthy+elderly+women+and+men.&rft.au=Harman%2C+S+Mitchell%3BBlackman%2C+Marc+R&rft.aulast=Harman&rft.aufirst=S&rft.date=2003-01-01&rft.volume=60&rft.issue=&rft.spage=121&rft.isbn=&rft.btitle=&rft.title=Hormone+research&rft.issn=03010163&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-06 N1 - Date created - 2003-09-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemoprevention of lung cancer: new directions. AN - 73526640; 12903853 AB - The refractoriness of advanced lung cancer to current treatment modalities requires new approaches to reduce the public health burden associated with this disease. One strategy that is currently being tested is chemoprevention, which aims to prevent the development of cancer in populations that are at high risk for cancer due to a variety of genetic or environmental factors. The key to the success of this approach, however, requires the identification of appropriately targeted efficacious, non-toxic agents as well as the methodologies to efficiently test them. Given the lack of success of previous phase III definitive lung cancer chemoprevention trials, there is a need for smaller scale phase II trials with molecular, imaging, or histologic endpoints to demonstrate preliminary safety and efficacy. The identification of molecular pathways critical to lung carcinogenesis offers the opportunity to develop targeted therapies for prevention. Means of optimizing the risk/benefit ratio associated with treatment include regional drug delivery that minimizes systemic toxicities and combination therapies. Identification of the most appropriate cohorts, such as former smokers without ongoing DNA damage due to carcinogen exposure, may uncover benefits that are hidden in a mixed population. Equally important is the identification of appropriate study endpoints that are predictive of patient outcomes such as cancer incidence. Further understanding of lung cancer biology will be critical to the success of future clinical trials. JF - Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer AU - Szabo, Eva AU - Kalebic, Thea AD - Lung and Upper Aerodigestive Cancer Research Group, Division of Cancer Prevention, National Cancer Institute, 6130 Executive Blvd., Room 2132, Bethesda, MD 20892, USA. Y1 - 2003 PY - 2003 DA - 2003 SP - 172 EP - 81; discussion 264-6 VL - 163 SN - 0080-0015, 0080-0015 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Mass Screening KW - Risk Factors KW - Humans KW - Clinical Trials as Topic KW - Chemoprevention -- methods KW - Research Design KW - Lung Neoplasms -- prevention & control KW - Lung Neoplasms -- diagnosis KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73526640?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Recent+results+in+cancer+research.+Fortschritte+der+Krebsforschung.+Progres+dans+les+recherches+sur+le+cancer&rft.atitle=Chemoprevention+of+lung+cancer%3A+new+directions.&rft.au=Szabo%2C+Eva%3BKalebic%2C+Thea&rft.aulast=Szabo&rft.aufirst=Eva&rft.date=2003-01-01&rft.volume=163&rft.issue=&rft.spage=172&rft.isbn=&rft.btitle=&rft.title=Recent+results+in+cancer+research.+Fortschritte+der+Krebsforschung.+Progres+dans+les+recherches+sur+le+cancer&rft.issn=00800015&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-18 N1 - Date created - 2003-08-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cardiac toxicity associated with capecitabine therapy. AN - 73518421; 12899507 JF - Acta oncologica (Stockholm, Sweden) AU - Saif, M Wasif AU - Quinn, Mary G AU - Thomas, Rebecca R AU - Ernst, Aaron AU - Grem, Jean L AD - Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NCI-Navy Medical Oncology, National Naval Medical Center, Bethesda 20889-5105, USA. Y1 - 2003 PY - 2003 DA - 2003 SP - 342 EP - 344 VL - 42 IS - 4 SN - 0284-186X, 0284-186X KW - Antimetabolites, Antineoplastic KW - 0 KW - Prodrugs KW - Deoxycytidine KW - 0W860991D6 KW - Capecitabine KW - 6804DJ8Z9U KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Diagnosis, Differential KW - Humans KW - Electrocardiography KW - Fluorouracil -- analogs & derivatives KW - Middle Aged KW - Male KW - Rectal Neoplasms -- drug therapy KW - Deoxycytidine -- toxicity KW - Prodrugs -- toxicity KW - Heart Diseases -- chemically induced KW - Deoxycytidine -- analogs & derivatives KW - Antimetabolites, Antineoplastic -- toxicity KW - Rectal Neoplasms -- pathology KW - Heart Diseases -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73518421?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cardiac+toxicity+associated+with+capecitabine+therapy.&rft.au=Saif%2C+M+Wasif%3BQuinn%2C+Mary+G%3BThomas%2C+Rebecca+R%3BErnst%2C+Aaron%3BGrem%2C+Jean+L&rft.aulast=Saif&rft.aufirst=M&rft.date=2003-01-01&rft.volume=42&rft.issue=4&rft.spage=342&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 - 2003-08-15 N1 - Date created - 2003-08-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vigabatrin and newer interventions in succinic semialdehyde dehydrogenase deficiency. AN - 73511694; 12891656 AB - Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare disorder characterized by an inborn error of the catabolism of the inhibitory neurotransmitter GABA. Because of the deficiency of SSADH, the final enzyme of the GABA degradation pathway, the substrate, succinic semialdehyde, is shunted towards production of 4-hydroxybutyric acid (gamma-hydroxybutyric acid). Elevations of gamma-hydroxybutyric acid can be detected in the physiologic fluids of patients with SSADH deficiency, and forms the mainstay of diagnosis. The clinical features of SSADH deficiency include nonspecific neurologic manifestations such as mental retardation/developmental delay, absent speech, hypotonia, nonprogressive ataxia, features of autism or pervasive developmental delay, developmental language delay (dyspraxia, receptive, and expressive delays), and occasionally, seizures. Although the metabolic pathway has been established, it is not known whether insufficient GABA and/or excess gamma-hydroxybutyric acid contribute to the disease phenotype. Pharmacological therapy in patients with this disorder has been limited to vigabatrin, an anticonvulsant that blocks GABA transaminase. This review will discuss therapeutic options in SSADH deficiency, on the basis of patient experience, and preliminary work using a murine model. Finally, a discussion of adjunctive therapies will be included. JF - Annals of neurology AU - Gropman, Andrea AD - Neurogenetics Branch, Section on Neuronal Migration, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. gropmana@ninds.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - S66 EP - S72 VL - 54 Suppl 6 SN - 0364-5134, 0364-5134 KW - Anticonvulsants KW - 0 KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - Aldehyde Oxidoreductases KW - EC 1.2.- KW - ALDH5A1 protein, human KW - EC 1.2.1.24 KW - Succinate-Semialdehyde Dehydrogenase KW - Vigabatrin KW - GR120KRT6K KW - Index Medicus KW - Drug Therapy, Combination KW - Animals KW - Humans KW - Clinical Trials as Topic KW - Amino Acid Metabolism, Inborn Errors -- drug therapy KW - Aldehyde Oxidoreductases -- genetics KW - Aldehyde Oxidoreductases -- deficiency KW - Anticonvulsants -- adverse effects KW - Amino Acid Metabolism, Inborn Errors -- genetics KW - Vigabatrin -- therapeutic use KW - gamma-Aminobutyric Acid -- metabolism KW - Vigabatrin -- adverse effects KW - Anticonvulsants -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73511694?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Vigabatrin+and+newer+interventions+in+succinic+semialdehyde+dehydrogenase+deficiency.&rft.au=Gropman%2C+Andrea&rft.aulast=Gropman&rft.aufirst=Andrea&rft.date=2003-01-01&rft.volume=54+Suppl+6&rft.issue=&rft.spage=S66&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 - 2003-12-24 N1 - Date created - 2003-07-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I/II study of high-dose tamoxifen in combination with vinblastine in patients with androgen-independent prostate cancer. AN - 73455574; 12852695 AB - In this phase I/II clinical trial the antitumor activity of high-dose tamoxifen when administered in combination with vinblastine was assessed and the toxicity profile of this combination characterized. All 25 patients enrolled in this study were required to have androgen-independent prostate cancer and to maintain androgen ablation during treatment. Vinblastine was given by continuous infusion over 5 days. Doses were increased from 0.9 mg/m2/day to 1.5 mg/m2/day in successive cohorts of at least 3 patients, with no further escalation even in the absence of dose-limiting toxicity. Intra-patient dose escalation was permitted. Tamoxifen was administered at a dose of 200 mg/kg on day 1, then 120 mg/kg/day on day 2. Standard response criteria were utilized to assess antitumor activity and CTC toxicity criteria were used. Quality of life (QOL) pain assessments were evaluated at each visit to the clinic. Most patients tolerated the highest dose of vinblastine at 1.5 mg/m2/day by continuous infusion over 5 days with 200 mg/kg/day of tamoxifen on day 1 and day 2. One patient had a greater than 50% decline in prostate-specific antigen that lasted for 170 days. Two patients received dose reductions because of toxicity. The most common serious toxicities included neutropenia, and fatigue. Reversible neurosensory, neuromotor, neurocortical and neurocerebellar toxicities were reported. Six of the 25 patients enrolled in the study (24%) experienced reversible neurologic toxicity of at least grade III. No statistically significant differences between precycle assessment of QOL and subsequent cycles were observed. It is concluded that vinblastine at 1.5 mg/m2/day continuous i.v. infusion combined with tamoxifen 200 mg/kg/day on day 1 and day 2 is inactive, and not without toxicity in the treatment of advanced metastatic androgen-independent prostate cancer. JF - Acta oncologica (Stockholm, Sweden) AU - Hamilton, Michael AU - Dahut, William AU - Brawley, Otis AU - Davis, Patricia AU - Wells-Jones, Toni AU - Kohler, David AU - Duray, Paul AU - Liewehr, David J AU - Lakhani, Nehal AU - Steinberg, Seth M AU - Figg, William D AU - Reed, Eddie AD - Medicine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003 PY - 2003 DA - 2003 SP - 195 EP - 201 VL - 42 IS - 3 SN - 0284-186X, 0284-186X KW - Androgens KW - 0 KW - Tamoxifen KW - 094ZI81Y45 KW - Vinblastine KW - 5V9KLZ54CY KW - Index Medicus KW - Humans KW - Aged KW - Neutropenia -- chemically induced KW - Quality of Life KW - Pain KW - Androgens -- pharmacology KW - Tamoxifen -- administration & dosage KW - Tamoxifen -- adverse effects KW - Treatment Outcome KW - Vinblastine -- administration & dosage KW - Middle Aged KW - Vinblastine -- adverse effects KW - Male KW - Prostatic Neoplasms -- pathology KW - Prostatic Neoplasms -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73455574?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+phase+I%2FII+study+of+high-dose+tamoxifen+in+combination+with+vinblastine+in+patients+with+androgen-independent+prostate+cancer.&rft.au=Hamilton%2C+Michael%3BDahut%2C+William%3BBrawley%2C+Otis%3BDavis%2C+Patricia%3BWells-Jones%2C+Toni%3BKohler%2C+David%3BDuray%2C+Paul%3BLiewehr%2C+David+J%3BLakhani%2C+Nehal%3BSteinberg%2C+Seth+M%3BFigg%2C+William+D%3BReed%2C+Eddie&rft.aulast=Hamilton&rft.aufirst=Michael&rft.date=2003-01-01&rft.volume=42&rft.issue=3&rft.spage=195&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 - 2003-07-22 N1 - Date created - 2003-07-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Crystallization of the protein kinase Cdelta C1B domain. AN - 73432947; 12840517 JF - Methods in molecular biology (Clifton, N.J.) AU - Zhang, Gongyi AU - Hurley, James H AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. Y1 - 2003 PY - 2003 DA - 2003 SP - 299 EP - 304 VL - 233 SN - 1064-3745, 1064-3745 KW - Isoenzymes KW - 0 KW - Phorbol Esters KW - Protein Kinase C KW - EC 2.7.11.13 KW - Protein Kinase C-delta KW - Index Medicus KW - Crystallization KW - Phorbol Esters -- chemistry KW - Phorbol Esters -- metabolism KW - Models, Molecular KW - Protein Kinase C -- metabolism KW - Isoenzymes -- chemistry KW - Protein Kinase C -- chemistry KW - Protein Structure, Tertiary KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73432947?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.atitle=Crystallization+of+the+protein+kinase+Cdelta+C1B+domain.&rft.au=Zhang%2C+Gongyi%3BHurley%2C+James+H&rft.aulast=Zhang&rft.aufirst=Gongyi&rft.date=2003-01-01&rft.volume=233&rft.issue=&rft.spage=299&rft.isbn=&rft.btitle=&rft.title=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.issn=10643745&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-12 N1 - Date created - 2003-07-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [3H]Phorbol 12,13-dibutyrate binding assay for protein kinase C and related proteins. AN - 73427576; 12840504 JF - Methods in molecular biology (Clifton, N.J.) AU - Lewin, Nancy E AU - Blumberg, Peter M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 2003 PY - 2003 DA - 2003 SP - 129 EP - 156 VL - 233 SN - 1064-3745, 1064-3745 KW - Ligands KW - 0 KW - Tritium KW - 10028-17-8 KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Index Medicus KW - Protein Binding KW - Protein Kinase C -- metabolism KW - Phorbol 12,13-Dibutyrate -- chemistry KW - Tritium -- metabolism KW - Phorbol 12,13-Dibutyrate -- metabolism KW - Radioligand Assay -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73427576?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.atitle=%5B3H%5DPhorbol+12%2C13-dibutyrate+binding+assay+for+protein+kinase+C+and+related+proteins.&rft.au=Lewin%2C+Nancy+E%3BBlumberg%2C+Peter+M&rft.aulast=Lewin&rft.aufirst=Nancy&rft.date=2003-01-01&rft.volume=233&rft.issue=&rft.spage=129&rft.isbn=&rft.btitle=&rft.title=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.issn=10643745&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-12 N1 - Date created - 2003-07-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 is present in synapses where it mediates mitochondrial dysfunction and synaptic degeneration in response to DNA damage, and oxidative and excitotoxic insults. AN - 73424644; 12835511 AB - A form of programmed cell-death called apoptosis occurs in neurons during development of the nervous system, and may also occur in a variety of neuropathological conditions. Here we present evidence obtained in studies of adult mice and neuronal cell cultures showing that p53 protein is present in synapses where its level and amount of phosphorylation are increased following exposure of the cells to the DNA-damaging agent etoposide. We also show that levels of active p53 increase in isolated cortical synaptosomes exposed to oxidative and excitotoxic insults. Increased levels of p53 also precede loss of synapsin I immunoreactive terminals in cultured hippocampal neurons exposed to etoposide. Synaptosomes from p53-deficient mice exhibit increased resistance to oxidative and excitotoxic insults as indicated by stabilization of mitochondrial membrane potential and decreased production of reactive oxygen species. Finally, we show that a synthetic inhibitor of p53 (PFT-alpha) protects synaptosomes from wild-type mice against oxidative and excitotoxic injuries, and preserves presynaptic terminals in cultured hippocampal neurons exposed to etoposide. Collectively, these findings provide the first evidence for a local transcription-independent action of p53 in synapses, and suggest that such a local action of p53 may contribute to the dysfunction and degeneration of synapses that occurs in various neurodegenerative disorders. JF - Neuromolecular medicine AU - Gilman, Charles P AU - Chan, Sic L AU - Guo, Zhihong AU - Zhu, Xiaoxiang AU - Greig, Nigel AU - Mattson, Mark P AD - Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, USA. Y1 - 2003 PY - 2003 DA - 2003 SP - 159 EP - 172 VL - 3 IS - 3 SN - 1535-1084, 1535-1084 KW - Benzothiazoles KW - 0 KW - Neuroprotective Agents KW - Neurotoxins KW - Nucleic Acid Synthesis Inhibitors KW - Reactive Oxygen Species KW - Synapsins KW - Thiazoles KW - Tumor Suppressor Protein p53 KW - Toluene KW - 3FPU23BG52 KW - Etoposide KW - 6PLQ3CP4P3 KW - pifithrin KW - D213B92S1Y KW - Index Medicus KW - Etoposide -- pharmacology KW - Reactive Oxygen Species -- metabolism KW - Animals KW - Synaptosomes KW - Neurotoxins -- pharmacology KW - Oxidative Stress -- genetics KW - Mice KW - Synapsins -- metabolism KW - DNA Damage -- genetics KW - DNA Damage -- drug effects KW - Neuroprotective Agents -- pharmacology KW - Thiazoles -- pharmacology KW - Nucleic Acid Synthesis Inhibitors -- pharmacology KW - Membrane Potentials -- genetics KW - Phosphorylation KW - Cells, Cultured KW - Oxidative Stress -- drug effects KW - Membrane Potentials -- drug effects KW - Toluene -- analogs & derivatives KW - Neurodegenerative Diseases -- physiopathology KW - Brain -- drug effects KW - Presynaptic Terminals -- pathology KW - Brain -- metabolism KW - Tumor Suppressor Protein p53 -- metabolism KW - Presynaptic Terminals -- metabolism KW - Brain -- physiopathology KW - Neurodegenerative Diseases -- genetics KW - Toluene -- pharmacology KW - Presynaptic Terminals -- drug effects KW - Mitochondria -- drug effects KW - Neurodegenerative Diseases -- metabolism KW - Mitochondria -- metabolism KW - Tumor Suppressor Protein p53 -- genetics KW - Mitochondria -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73424644?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuromolecular+medicine&rft.atitle=p53+is+present+in+synapses+where+it+mediates+mitochondrial+dysfunction+and+synaptic+degeneration+in+response+to+DNA+damage%2C+and+oxidative+and+excitotoxic+insults.&rft.au=Gilman%2C+Charles+P%3BChan%2C+Sic+L%3BGuo%2C+Zhihong%3BZhu%2C+Xiaoxiang%3BGreig%2C+Nigel%3BMattson%2C+Mark+P&rft.aulast=Gilman&rft.aufirst=Charles&rft.date=2003-01-01&rft.volume=3&rft.issue=3&rft.spage=159&rft.isbn=&rft.btitle=&rft.title=Neuromolecular+medicine&rft.issn=15351084&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-26 N1 - Date created - 2003-07-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Wegener's granulomatosis: current and upcoming therapies. AN - 73403190; 12823849 AB - Wegener's granulomatosis is a complex multisystem disease that can be associated with morbidity and mortality. The introduction of cyclophosphamide and glucocorticoids brought about the potential for long-term survival and provided the opportunity and impetus to explore treatment options that can reduce the toxicity of therapy and lessen the likelihood of relapse. With the growth of knowledge regarding disease pathophysiology and the increasing ability to selectively target the immune system, the potential options for therapeutic investigation have continued to expand. Careful study of new agents through rigorously designed trials is essential to answering questions of safety and efficacy in Wegener's granulomatosis. JF - Arthritis research & therapy AU - Langford, Carol A AD - Immunologic Diseases Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. clangford@niaid.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 180 EP - 191 VL - 5 IS - 4 KW - Immunosuppressive Agents KW - 0 KW - Index Medicus KW - Humans KW - Clinical Trials as Topic KW - Immunosuppressive Agents -- therapeutic use KW - Remission Induction KW - Granulomatosis with Polyangiitis -- therapy KW - Granulomatosis with Polyangiitis -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73403190?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+research+%26+therapy&rft.atitle=Wegener%27s+granulomatosis%3A+current+and+upcoming+therapies.&rft.au=Langford%2C+Carol+A&rft.aulast=Langford&rft.aufirst=Carol&rft.date=2003-01-01&rft.volume=5&rft.issue=4&rft.spage=180&rft.isbn=&rft.btitle=&rft.title=Arthritis+research+%26+therapy&rft.issn=1478-6362&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-07 N1 - Date created - 2003-06-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Arthritis Rheum. 1999 Dec;42(12):2666-73 [10616016] Arthritis Rheum. 2000 May;43(5):1021-32 [10817555] QJM. 2000 Jul;93(7):433-9 [10874052] Arthritis Rheum. 2000 Aug;43(8):1836-40 [10943874] Curr Opin Rheumatol. 2001 Jan;13(1):48-55 [11148715] Arthritis Rheum. 2001 May;44(5):1149-54 [11352248] Ther Apher. 2001 Jun;5(3):176-81 [11467753] Nephrol Dial Transplant. 2001 Oct;16(10):2018-27 [11572891] Arthritis Rheum. 2001 Dec;44(12):2836-40 [11762944] Curr Opin Rheumatol. 2002 Jan;14(1):23-8 [11790992] Arthritis Res. 2002;4(2):77-9 [11879541] Ann Rheum Dis. 2002 Jun;61(6):559 [12006335] J Am Soc Nephrol. 2002 Jul;13(7):1977-9 [12089397] Arthritis Res. 2002;4(4):266-73 [12106498] Rheumatology (Oxford). 2002 Oct;41(10):1126-32 [12364631] J Clin Invest. 2002 Oct;110(7):955-63 [12370273] J Am Soc Nephrol. 2003 Feb;14(2):440-7 [12538745] Am J Med. 2003 Apr 15;114(6):463-9 [12727579] Ann Intern Med. 1967 Aug;67(2):393-8 [6036397] Medicine (Baltimore). 1973 Nov;52(6):535-61 [4748591] Ann Intern Med. 1983 Jan;98(1):76-85 [6336643] Mayo Clin Proc. 1985 Jan;60(1):27-32 [3871238] Am J Med. 1990 Oct;89(4):403-10 [2220874] Ann Intern Med. 1990 Nov 1;113(9):656-63 [2221646] Lancet. 1991 May 11;337(8750):1137-9 [1674023] Ann Intern Med. 1992 Mar 15;116(6):488-98 [1739240] Arthritis Rheum. 1992 Nov;35(11):1322-9 [1445449] Curr Opin Rheumatol. 1993 Jan;5(1):11-7 [8435284] J Autoimmun. 1993 Apr;6(2):207-19 [8499059] Ann Intern Med. 1994 Jan 1;120(1):12-7 [8250451] Adv Exp Med Biol. 1993;336:473-6 [8296660] Arthritis Rheum. 1994 Jun;37(6):919-24 [8003065] Arthritis Rheum. 1995 May;38(5):608-13 [7748215] Clin Exp Immunol. 1995 Jul;101(1):2-7 [7621588] Arthritis Rheum. 1996 Jan;39(1):87-92 [8546743] Rheumatology (Oxford). 2002 Nov;41(11):1303-7 [12422004] Ann Intern Med. 1996 Mar 1;124(5):477-84 [8602705] N Engl J Med. 1996 Jul 4;335(1):16-20 [8637536] QJM. 1996 Jan;89(1):15-23 [8730339] Arthritis Rheum. 1996 Oct;39(10):1754-60 [8843868] Sarcoidosis Vasc Diffuse Lung Dis. 1996 Oct;13(3):249-52 [8946594] Br J Rheumatol. 1996 Nov;35(11):1150-3 [8948304] QJM. 1996 Dec;89(12):903-12 [9015484] QJM. 1997 Jun;90(6):401-9 [9205678] Rheum Dis Clin North Am. 1997 Nov;23(4):841-53 [9361158] Arthritis Rheum. 1997 Dec;40(12):2187-98 [9416856] J Rheumatol. 1998 Mar;25(3):492-5 [9517769] J Immunol. 1998 Apr 1;160(7):3602-9 [9531324] Nephrol Dial Transplant. 1998 Aug;13(8):2074-6 [9719168] Arthritis Rheum. 1998 Sep;41(9):1521-37 [9751084] Arthritis Rheum. 1998 Oct;41(10):1835-44 [9778225] Arthritis Rheum. 1999 Apr;42(4):742-50 [10211889] J Rheumatol. 1999 May;26(5):1134-9 [10332980] J Am Soc Nephrol. 1999 Sep;10(9):1965-71 [10477149] Br Med J. 1958 Aug 2;2(5091):265-70 [13560836] Arthritis Rheum. 2002 Jun 15;47(3):326-32 [12115164] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Platelet-derived growth factor-producing cells immortalized from rat mesencephalon with SV40 large T antigen transduced by an AAV vector. AN - 73386060; 12808197 AB - Adeno-associated virus (AAV) can infect a wide variety of mammalian cell types and is capable of infecting both dividing and non-dividing cell populations. Here we report the construction of a recombinant AAV vector which expresses the SV40 large T protein (AAV-T) and the use of this vector to immortalize primary cells from embryonic rat mesencephalon. The AAV-T vector was constructed by introducing the BamH1 fragment of the pCMV/SVE/Neo plasmid containing T antigen and SV40 regulatory elements into the JM48 plasmid containing the inverted terminal repeats of AAV. Neuronal cultures from E-12 rat mesencephalon were grown in defined media supplemented with basic fibroblast growth factor. These cells were infected with the AAV-T vector. A cell line (designated RMAT) and six subclones were established from these cultures through multiple passages. This cell line was immunoreactive for SV40 large T antigen and the cytoskeletal proteins nestin and vimentin. Morphological differentiation and expression of neurofilament 160 kDa were induced by exposure to dibutyrl cyclic AMP. Immunoassays performed to measure endogenous production of growth factors showed that RMAT cells produced high levels of platelet-derived growth factor (PDGF). AAV may be a useful vector for the transduction of oncogenes to produce cell lines. JF - Restorative neurology and neuroscience AU - Phillips, André W AU - Zhang, Peisu AU - Truckenmiller, Mary Ellen AU - Keir, Stuart D AU - Bouvier, Margaret AU - Tornatore, Carlo AU - Freed, William J AD - Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health, DHHS, 9000 Rockville Pike, Bethesda, MD 20892, USA. Y1 - 2003 PY - 2003 DA - 2003 SP - 1 EP - 10 VL - 21 IS - 1-2 SN - 0922-6028, 0922-6028 KW - Antigens, Polyomavirus Transforming KW - 0 KW - Antineoplastic Agents KW - Intermediate Filament Proteins KW - Nerve Growth Factors KW - Nerve Tissue Proteins KW - Nes protein, rat KW - Nestin KW - Phosphodiesterase Inhibitors KW - Platelet-Derived Growth Factor KW - Tretinoin KW - 5688UTC01R KW - Fibroblast Growth Factors KW - 62031-54-3 KW - Bucladesine KW - 63X7MBT2LQ KW - 1-Methyl-3-isobutylxanthine KW - TBT296U68M KW - Index Medicus KW - Tretinoin -- pharmacology KW - Animals KW - Drug Interactions KW - Gene Expression Regulation, Viral KW - Nerve Growth Factors -- pharmacology KW - Bucladesine -- pharmacology KW - Intermediate Filament Proteins -- metabolism KW - Cell Size -- drug effects KW - Rats KW - Enzyme-Linked Immunosorbent Assay KW - Cell Differentiation -- drug effects KW - Time Factors KW - Embryo, Mammalian KW - Phosphodiesterase Inhibitors -- pharmacology KW - Dependovirus -- genetics KW - Cells, Cultured -- microbiology KW - Fibroblast Growth Factors -- metabolism KW - Pregnancy KW - Blotting, Western KW - Neurons -- cytology KW - Genetic Vectors -- genetics KW - 1-Methyl-3-isobutylxanthine -- pharmacology KW - Antineoplastic Agents -- pharmacology KW - Immunohistochemistry KW - Female KW - Mesencephalon -- metabolism KW - Cell Transformation, Viral -- physiology KW - Mesencephalon -- virology KW - Transduction, Genetic KW - Antigens, Polyomavirus Transforming -- metabolism KW - Antigens, Polyomavirus Transforming -- chemistry KW - Platelet-Derived Growth Factor -- biosynthesis KW - Mesencephalon -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73386060?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Restorative+neurology+and+neuroscience&rft.atitle=Platelet-derived+growth+factor-producing+cells+immortalized+from+rat+mesencephalon+with+SV40+large+T+antigen+transduced+by+an+AAV+vector.&rft.au=Phillips%2C+Andr%C3%A9+W%3BZhang%2C+Peisu%3BTruckenmiller%2C+Mary+Ellen%3BKeir%2C+Stuart+D%3BBouvier%2C+Margaret%3BTornatore%2C+Carlo%3BFreed%2C+William+J&rft.aulast=Phillips&rft.aufirst=Andr%C3%A9&rft.date=2003-01-01&rft.volume=21&rft.issue=1-2&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Restorative+neurology+and+neuroscience&rft.issn=09226028&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-24 N1 - Date created - 2003-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Female-specific reproductive toxicities following preconception exposure to xenobiotics. AN - 73382199; 12817672 AB - Females do differ from males in their germ cell and general reproductive responses to toxicants. Chromatin structure is perhaps one factor that contributes to sex differences in germ cell response to toxicants. Differences in available targets likely contribute to response differences between sexes as well as to within sex differences between germ cell stages. It is important to consider these differences when conducting reproductive toxicity studies and interpreting the results. JF - Advances in experimental medicine and biology AU - Bishop, Jack B AD - NIEHS, Laboratory of Toxicology, 111 TW Alexander Dr., Research Triangle Park, NC 27709, USA. bishop@niehs.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 1 EP - 9 VL - 518 SN - 0065-2598, 0065-2598 KW - Teratogens KW - 0 KW - Xenobiotics KW - Index Medicus KW - Rats KW - Animals KW - Genes, Dominant KW - Germ Cells -- drug effects KW - Teratogens -- toxicity KW - Time Factors KW - Maternal Exposure KW - Male KW - Female KW - Pregnancy KW - Mutagenesis KW - Abnormalities, Drug-Induced KW - Reproduction -- drug effects KW - Xenobiotics -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73382199?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Female-specific+reproductive+toxicities+following+preconception+exposure+to+xenobiotics.&rft.au=Bishop%2C+Jack+B&rft.aulast=Bishop&rft.aufirst=Jack&rft.date=2003-01-01&rft.volume=518&rft.issue=&rft.spage=1&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 - 2004-01-28 N1 - Date created - 2003-06-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chapter 18: Statistical issues in the design and analysis of studies of human papillomavirus and cervical neoplasia. AN - 73381240; 12807956 AB - Appropriately sophisticated statistical approaches are crucial for addressing the increasingly complex set of critical questions that follow from the recognition that human papillomavirus (HPV) is a necessary causal factor for cervical cancer. Cervical cancer researchers have defined the major stages of cervical carcinogenesis, with HPV infection as the necessary cause. Focus of etiologic studies is shifting from establishing causality to determining risk factors for HPV persistence and neoplastic progression using serially collected biomarkers. Prevention-oriented epidemiology and trials of new screening strategies and vaccines will rely on surrogate endpoints because we cannot let women develop cancer when it can be prevented. Future epidemiologic and prevention studies of HPV infection and cervical carcinogenesis will exploit subtle pathologic distinctions and will employ improved measurements of complex molecular biologic phenomena. The anticipated statistical issues are highlighted in this discussion. JF - Journal of the National Cancer Institute. Monographs AU - Wacholder, Sholom AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health/DHHS, EPS 8046, Bethesda, MD 20892-7244, USA. wacholder@nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 125 EP - 130 IS - 31 SN - 1052-6773, 1052-6773 KW - Index Medicus KW - Mass Screening KW - Reproducibility of Results KW - Humans KW - Cohort Studies KW - Case-Control Studies KW - Cervical Intraepithelial Neoplasia -- virology KW - Observer Variation KW - Epidemiologic Research Design KW - Female KW - Papillomavirus Infections -- complications KW - Papillomaviridae KW - Data Interpretation, Statistical KW - Uterine Cervical Neoplasms -- virology KW - Tumor Virus Infections -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73381240?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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.+Monographs&rft.atitle=Chapter+18%3A+Statistical+issues+in+the+design+and+analysis+of+studies+of+human+papillomavirus+and+cervical+neoplasia.&rft.au=Wacholder%2C+Sholom&rft.aulast=Wacholder&rft.aufirst=Sholom&rft.date=2003-01-01&rft.volume=&rft.issue=31&rft.spage=125&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute.+Monographs&rft.issn=10526773&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-27 N1 - Date created - 2003-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chapter 2: Natural history of anogenital human papillomavirus infection and neoplasia. AN - 73375930; 12807940 AB - This chapter suggests promising areas of future epidemiologic research on human papillomavirus (HPV) and anogenital cancer, organized around our understanding of cervical carcinogenesis. The major steps in cervical carcinogenesis include HPV infection, HPV persistence over a certain period of time, progression to precancer, and invasion. Backward steps include clearance of HPV infection and regression of precancer. Additional studies of incident HPV infections among virgins initiating sexual activity could clarify the earliest aspects of transmission and immune response. Research on older women and their male partners should focus on understanding the determinants of varying age-specific HPV prevalence curves and underlying dynamics of viral persistence, clearance, and latency. It will be particularly important for epidemiologists to define HPV persistence rigorously in order to guide clinical management and vaccine trials. Intensive longitudinal studies that collect visual, microscopic (cytologic and histologic), and molecular data will be needed to understand the fate of individual HPV infections and to clarify whether multiple, concurrent infections act independently on the cervix. Case-control designs will be useful mainly in searching for new biomarkers of risk of progression among HPV-infected women that could then be validated prospectively. Prospective confirmation is also needed for the etiologic cofactors established by case-control studies of invasive cervical cancer. Much of the knowledge about cervical cancer might apply to anal neoplasia. Epidemiologic studies of other genital tumors such as penile neoplasia are still needed, but multicentric groups must place great emphasis on measurement technology, given the difficulty in obtaining reliable comprehensive measurements. JF - Journal of the National Cancer Institute. Monographs AU - Schiffman, Mark AU - Kjaer, Susanne Krüger AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 6120 Executive Boulevard, Rm. 7066, Rockville, MD 20852, USA. schiffman@mail.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 14 EP - 19 IS - 31 SN - 1052-6773, 1052-6773 KW - Index Medicus KW - Neoplasm Invasiveness KW - Genital Neoplasms, Female -- epidemiology KW - Humans KW - Disease Progression KW - Genital Neoplasms, Female -- virology KW - Male KW - Female KW - Cell Transformation, Neoplastic KW - Age Distribution KW - Uterine Cervical Neoplasms -- epidemiology KW - Papillomavirus Infections -- complications KW - Papillomaviridae KW - Anus Neoplasms -- epidemiology KW - Sexually Transmitted Diseases, Viral -- epidemiology KW - Sexually Transmitted Diseases, Viral -- virology KW - Anus Neoplasms -- virology KW - Uterine Cervical Neoplasms -- virology KW - Tumor Virus Infections -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73375930?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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.+Monographs&rft.atitle=Chapter+2%3A+Natural+history+of+anogenital+human+papillomavirus+infection+and+neoplasia.&rft.au=Schiffman%2C+Mark%3BKjaer%2C+Susanne+Kr%C3%BCger&rft.aulast=Schiffman&rft.aufirst=Mark&rft.date=2003-01-01&rft.volume=&rft.issue=31&rft.spage=14&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute.+Monographs&rft.issn=10526773&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-27 N1 - Date created - 2003-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chapter 4: Genital tract infections, cervical inflammation, and antioxidant nutrients--assessing their roles as human papillomavirus cofactors. AN - 73373760; 12807942 AB - Cervical infections by approximately 15 human papillomavirus (HPV) types are the necessary cause of cervical cancer and its immediate precursor lesions. However, oncogenic HPV infections are usually benign and usually resolve within 1-2 years. A few of these infections persist and progress to cervical precancer and cancer. A number of cervical factors, such as infection by sexually transmitted pathogens other than HPV, cervical inflammation, and antioxidant nutrients, may influence the natural history of HPV infection along the pathways of persistence and progression or resolution. We examine the possible roles of these HPV cofactors in cervical carcinogenesis and discuss new methodologies that may enable researchers to measure relevant markers of the cervical microenvironment in which these cofactors may be active. JF - Journal of the National Cancer Institute. Monographs AU - Castle, Philip E AU - Giuliano, Anna R AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health/DHHS, 6120 Executive Boulevard, Rm. 7074, EPS MSC 7234, Bethesda, MD 20892-7234, USA. castlep@mail.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 29 EP - 34 IS - 31 SN - 1052-6773, 1052-6773 KW - Antioxidants KW - 0 KW - Biomarkers KW - Index Medicus KW - Risk Factors KW - Humans KW - Biomarkers -- analysis KW - Vaginal Smears KW - Female KW - Antioxidants -- metabolism KW - Uterine Cervical Neoplasms -- metabolism KW - Tumor Virus Infections -- metabolism KW - Papillomavirus Infections -- complications KW - Papillomaviridae KW - Uterine Cervicitis -- metabolism KW - Uterine Cervicitis -- virology KW - Uterine Cervicitis -- complications KW - Papillomavirus Infections -- metabolism KW - Uterine Cervical Neoplasms -- virology KW - Tumor Virus Infections -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73373760?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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.+Monographs&rft.atitle=Chapter+4%3A+Genital+tract+infections%2C+cervical+inflammation%2C+and+antioxidant+nutrients--assessing+their+roles+as+human+papillomavirus+cofactors.&rft.au=Castle%2C+Philip+E%3BGiuliano%2C+Anna+R&rft.aulast=Castle&rft.aufirst=Philip&rft.date=2003-01-01&rft.volume=&rft.issue=31&rft.spage=29&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute.+Monographs&rft.issn=10526773&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-27 N1 - Date created - 2003-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inflammatory joint disease: clinical, histological, and molecular parameters of acute and chronic inflammation and tissue destruction. AN - 73342184; 12769484 JF - Methods in molecular biology (Clifton, N.J.) AU - McCartney-Francis, Nancy L AU - Chan, James AU - Wahl, Sharon M AD - NIDCR, NIH, Bethesda, MD, USA. Y1 - 2003 PY - 2003 DA - 2003 SP - 147 EP - 159 VL - 225 SN - 1064-3745, 1064-3745 KW - Peptidoglycan KW - 0 KW - Polysaccharides, Bacterial KW - RNA, Messenger KW - streptococcal group A cell wall carbohydrate KW - streptococcal polysaccharide group A KW - Index Medicus KW - Severity of Illness Index KW - Animals KW - Rats, Inbred Lew KW - Ankle Joint -- pathology KW - Specimen Handling KW - Cell Wall -- chemistry KW - RNA, Messenger -- analysis KW - Immunohistochemistry -- methods KW - Reverse Transcriptase Polymerase Chain Reaction -- methods KW - Gene Expression Profiling -- methods KW - Rats KW - Blotting, Western KW - Foot KW - Blotting, Northern -- methods KW - Electrophoretic Mobility Shift Assay -- methods KW - Female KW - Peptidoglycan -- toxicity KW - Arthritis -- pathology KW - Arthritis, Rheumatoid KW - Streptococcus pyogenes -- physiology KW - Polysaccharides, Bacterial -- toxicity KW - Disease Models, Animal KW - Arthritis -- chemically induced KW - Arthritis -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73342184?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.atitle=Inflammatory+joint+disease%3A+clinical%2C+histological%2C+and+molecular+parameters+of+acute+and+chronic+inflammation+and+tissue+destruction.&rft.au=McCartney-Francis%2C+Nancy+L%3BChan%2C+James%3BWahl%2C+Sharon+M&rft.aulast=McCartney-Francis&rft.aufirst=Nancy&rft.date=2003-01-01&rft.volume=225&rft.issue=&rft.spage=147&rft.isbn=&rft.btitle=&rft.title=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.issn=10643745&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-07 N1 - Date created - 2003-05-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Non-steroidal anti-inflammatory and cyclooxygenase-2-selective inhibitors in clinical cancer prevention trials. AN - 73332697; 12795057 JF - Progress in experimental tumor research AU - Hawk, Ernest T AU - Viner, Jaye L AU - Umar, Asad AD - Gastrointestinal & Other Cancers Research Group, National Cancer Institute, Division of Cancer Prevention, Bethesda, Md., USA. eh51p@nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 210 EP - 242 VL - 37 SN - 0079-6263, 0079-6263 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Cyclooxygenase 2 Inhibitors KW - Cyclooxygenase Inhibitors KW - Isoenzymes KW - Membrane Proteins KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - PTGS2 protein, human KW - Prostaglandin-Endoperoxide Synthases KW - Aspirin KW - R16CO5Y76E KW - Index Medicus KW - Humans KW - Aspirin -- therapeutic use KW - Clinical Trials as Topic KW - Skin Neoplasms -- prevention & control KW - Colorectal Neoplasms -- prevention & control KW - Isoenzymes -- antagonists & inhibitors KW - Cyclooxygenase Inhibitors -- therapeutic use KW - Cyclooxygenase Inhibitors -- adverse effects KW - Anti-Inflammatory Agents, Non-Steroidal -- therapeutic use KW - Anti-Inflammatory Agents, Non-Steroidal -- adverse effects KW - Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73332697?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+experimental+tumor+research&rft.atitle=Non-steroidal+anti-inflammatory+and+cyclooxygenase-2-selective+inhibitors+in+clinical+cancer+prevention+trials.&rft.au=Hawk%2C+Ernest+T%3BViner%2C+Jaye+L%3BUmar%2C+Asad&rft.aulast=Hawk&rft.aufirst=Ernest&rft.date=2003-01-01&rft.volume=37&rft.issue=&rft.spage=210&rft.isbn=&rft.btitle=&rft.title=Progress+in+experimental+tumor+research&rft.issn=00796263&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-14 N1 - Date created - 2003-06-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The genetic relationship to periodontal disease. AN - 73324261; 12756032 JF - Periodontology 2000 AU - Nares, Salvador AD - National Institutes of Health, National Institute of Dental and Cranofacial Research, Oral Infection and Immunity Branch, Bethesda, Maryland, USA. Y1 - 2003 PY - 2003 DA - 2003 SP - 36 EP - 49 VL - 32 SN - 0906-6713, 0906-6713 KW - Dental Implants KW - 0 KW - HLA Antigens KW - Interleukin-1 KW - Receptors, Formyl Peptide KW - Receptors, IgG KW - Receptors, Immunologic KW - Receptors, Peptide KW - Dentistry KW - Continental Population Groups -- genetics KW - HLA Antigens -- genetics KW - Polymorphism, Single Nucleotide KW - Human Genome Project KW - Humans KW - Terminology as Topic KW - Dental Implants -- adverse effects KW - Receptors, Immunologic -- genetics KW - Twin Studies as Topic KW - Receptors, Peptide -- genetics KW - Interleukin-1 -- genetics KW - Receptors, IgG -- genetics KW - Periodontitis -- genetics KW - Periodontitis -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73324261?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Periodontology+2000&rft.atitle=The+genetic+relationship+to+periodontal+disease.&rft.au=Nares%2C+Salvador&rft.aulast=Nares&rft.aufirst=Salvador&rft.date=2003-01-01&rft.volume=32&rft.issue=&rft.spage=36&rft.isbn=&rft.btitle=&rft.title=Periodontology+2000&rft.issn=09066713&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-21 N1 - Date created - 2003-05-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A comparative immunohistochemical study of spontaneous and chemically induced pheochromocytomas in B6C3F1 mice. AN - 73301014; 12746566 AB - Spontaneously occurring and chemically induced pheochromocytomas are rare in mice. That the mouse pheochromocytoma is a more appropriate animal model than that of the rat for study of human medullary adrenal tumors has been suggested. The expression of phenylethanolamine-N-methyltransferase (PNMT), the enzyme responsible for production of epinephrine from norepinephrine, is common to both mouse and human pheochromocytomas. This investigation assessed the expression of the immunohistochemical markers PNMT, tyrosine hydroxylase (TH), and chromogranin A (CGA) in spontaneously occurring and chemically induced pheochromocytomas in the B6C3F1 mouse. Spontaneous tumors were derived from control animals from 10 different studies and the pheochromocytomas from treated groups from 4 different studies. All tumors were positive for maximal TH expression. A highly significant difference in PNMT expression (p < 0.01) occurred between spontaneously occurring pheochromocytomas classified as benign or "malignant" by the criteria of toxicologic pathology. Chemically induced tumors showed intermediate PNMT staining. A marked reduction in CGA expression occurred in pheochromocytomas induced by technical grade pentachlorophenol, compared to the other three chemicals and the spontaneously occurring tumors. These findings suggest that immunohistochemistry is a reliable tool in investigating the functional capabilities of pheochromocytomas in mice. PNMT expression is a tightly regulated component of the chromaffin cell phenotype and appears to be readily lost in mouse pheochromocytomas, particularly those with aggressive characteristics. JF - Endocrine pathology AU - Hill, Georgette D AU - Pace, Virgilio AU - Persohn, Elke AU - Bresser, Christina AU - Haseman, Joseph K AU - Tischler, Arthur S AU - Nyska, Abraham AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Science (NIEHS), Research Triangle Park, North Carolina 27709, USA. Y1 - 2003 PY - 2003 DA - 2003 SP - 81 EP - 91 VL - 14 IS - 1 SN - 1046-3976, 1046-3976 KW - Chromogranin A KW - 0 KW - Chromogranins KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - Phenylethanolamine N-Methyltransferase KW - EC 2.1.1.28 KW - Index Medicus KW - Rats KW - Animals KW - Neoplasms KW - Mice KW - Immunohistochemistry KW - Male KW - Female KW - Pheochromocytoma -- chemically induced KW - Adrenal Gland Neoplasms -- metabolism KW - Phenylethanolamine N-Methyltransferase -- biosynthesis KW - Adrenal Gland Neoplasms -- chemically induced KW - Chromogranins -- biosynthesis KW - Adrenal Gland Neoplasms -- pathology KW - Tyrosine 3-Monooxygenase -- biosynthesis KW - Pheochromocytoma -- pathology KW - Pheochromocytoma -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73301014?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Endocrine+pathology&rft.atitle=A+comparative+immunohistochemical+study+of+spontaneous+and+chemically+induced+pheochromocytomas+in+B6C3F1+mice.&rft.au=Hill%2C+Georgette+D%3BPace%2C+Virgilio%3BPersohn%2C+Elke%3BBresser%2C+Christina%3BHaseman%2C+Joseph+K%3BTischler%2C+Arthur+S%3BNyska%2C+Abraham&rft.aulast=Hill&rft.aufirst=Georgette&rft.date=2003-01-01&rft.volume=14&rft.issue=1&rft.spage=81&rft.isbn=&rft.btitle=&rft.title=Endocrine+pathology&rft.issn=10463976&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-17 N1 - Date created - 2003-05-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Systems toxicology and the Chemical Effects in Biological Systems (CEBS) knowledge base. AN - 73285857; 12735106 AB - The National Center for Toxicogenomics is developing the first public toxicogenomics knowledge base that combines molecular expression data sets from transcriptomics, proteomics, metabonomics, and conventional toxicology with metabolic, toxicologcal pathway, and gene regulatory network information relevant to environmental toxicology and human disease. It is called the Chemical Effects in Biological Systems (CEBS) knowledge base and is designed to meet the information needs of "systems toxicology," involving the study of perturbation by chemicals and stressors, monitoring changes in molecular expression and conventional toxicological parameters, and iteratively integrating biological response data to describe the functioning organism. Based upon functional genomics approaches used successfully in analyzing yeast gene expression data sets, relational and descriptive compendia will be assembled for toxicologically important genes, groups of genes, single nucleotide polymorphisms (SNPs), and mutant and knockout phenotypes. CEBS data sets will be fully documented in the experimental protocol and therefore searchable by compound, structure, toxicity end point, pathology and point, gene, gene group, SNP, pathway, and network as a function of dose, time, and the phenotype of the target tissue. A knowledge base is being developed by assimilating toxicological, biological, and chemical information from multiple public domain databases and by progressively refining that information about gene, protein, and metabolite expression for classes of chemicals and their biological effects in various species. By analogy to the GenBank database for genome sequences, researchers will globally query (or BLAST) CEBS using a transcriptome of a tissue of interest (or a list of outliers) to have the knowledge base return information on genes, groups of genes, metabolic and toxicological pathways, and contextually associated phenotypic information for compounds that display similar response profiles. With high-quality data content, CEBS will ultimately become a resource to support hypothesis-driven and discovery research that contributes effectively to drug safety and the improvement of risk assessments for chemicals in the environment. The CEBS development effort will span a decade or more. JF - EHP toxicogenomics : journal of the National Institute of Environmental Health Sciences AU - Waters, Michael AU - Boorman, Gary AU - Bushel, Pierre AU - Cunningham, Michael AU - Irwin, Rick AU - Merrick, Alex AU - Olden, Kenneth AU - Paules, Richard AU - Selkirk, James AU - Stasiewicz, Stanley AU - Weis, Brenda AU - Van Houten, Ben AU - Walker, Nigel AU - Tennant, Raymond AD - National Center for Toxicogenomics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. waters2@niehs.nih.gov Y1 - 2003/01// PY - 2003 DA - January 2003 SP - 15 EP - 28 VL - 111 IS - 1T SN - 1542-4359, 1542-4359 KW - Index Medicus KW - Protein Array Analysis KW - Phenotype KW - Gene Expression Profiling KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - Proteomics KW - Computational Biology KW - Databases as Topic KW - Pharmacogenetics KW - Knowledge UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73285857?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=EHP+toxicogenomics+%3A+journal+of+the+National+Institute+of+Environmental+Health+Sciences&rft.atitle=Systems+toxicology+and+the+Chemical+Effects+in+Biological+Systems+%28CEBS%29+knowledge+base.&rft.au=Waters%2C+Michael%3BBoorman%2C+Gary%3BBushel%2C+Pierre%3BCunningham%2C+Michael%3BIrwin%2C+Rick%3BMerrick%2C+Alex%3BOlden%2C+Kenneth%3BPaules%2C+Richard%3BSelkirk%2C+James%3BStasiewicz%2C+Stanley%3BWeis%2C+Brenda%3BVan+Houten%2C+Ben%3BWalker%2C+Nigel%3BTennant%2C+Raymond&rft.aulast=Waters&rft.aufirst=Michael&rft.date=2003-01-01&rft.volume=111&rft.issue=1T&rft.spage=15&rft.isbn=&rft.btitle=&rft.title=EHP+toxicogenomics+%3A+journal+of+the+National+Institute+of+Environmental+Health+Sciences&rft.issn=15424359&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-26 N1 - Date created - 2003-05-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identifying related L1 retrotransposons by analyzing 3' transduced sequences. AN - 73280699; 12734010 AB - A large fraction of the human genome is attributable to L1 retrotransposon sequences. Not only do L1s themselves make up a significant portion of the genome, but L1-encoded proteins are thought to be responsible for the transposition of other repetitive elements and processed pseudogenes. In addition, L1s can mobilize non-L1, 3'-flanking DNA in a process called 3' transduction. Using computational methods, we collected DNA sequences from the human genome for which we have high confidence of their mobilization through L1-mediated 3' transduction. The precursors of L1s with transduced sequence can often be identified, allowing us to reconstruct L1 element families in which a single parent L1 element begot many progeny L1s. Of the L1s exhibiting a sequence structure consistent with 3' transduction (L1 with transduction-derived sequence, L1-TD), the vast majority were located in duplicated regions of the genome and thus did not necessarily represent unique insertion events. Of the remaining L1-TDs, some lack a clear polyadenylation signal, but the alignment between the parent-progeny sequences nevertheless ends in an A-rich tract of DNA. Sequence data suggest that during the integration into the genome of RNA representing an L1-TD, reverse transcription may be primed internally at A-rich sequences that lie downstream of the L1 3' untranslated region. The occurrence of L1-mediated transduction in the human genome may be less frequent than previously thought, and an accurate estimate is confounded by the frequent occurrence of segmental genomic duplications. JF - Genome biology AU - Szak, Suzanne T AU - Pickeral, Oxana K AU - Landsman, David AU - Boeke, Jef D AD - National Center for Biotechnology Information (NCBI), National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA. Y1 - 2003 PY - 2003 DA - 2003 SP - 1 VL - 4 IS - 5 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Base Sequence KW - Genome, Human KW - Sequence Homology, Nucleic Acid KW - Humans KW - Recombination, Genetic KW - Computational Biology -- methods KW - Molecular Sequence Data KW - Mutagenesis, Insertional KW - DNA -- genetics KW - Long Interspersed Nucleotide Elements -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73280699?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genome+biology&rft.atitle=Identifying+related+L1+retrotransposons+by+analyzing+3%27+transduced+sequences.&rft.au=Szak%2C+Suzanne+T%3BPickeral%2C+Oxana+K%3BLandsman%2C+David%3BBoeke%2C+Jef+D&rft.aulast=Szak&rft.aufirst=Suzanne&rft.date=2003-01-01&rft.volume=4&rft.issue=5&rft.spage=R30&rft.isbn=&rft.btitle=&rft.title=Genome+biology&rft.issn=1474-760X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-22 N1 - Date created - 2003-05-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Curr Opin Genet Dev. 1999 Dec;9(6):657-63 [10607616] Immunol Res. 1999;19(2-3):169-82 [10493171] Nat Genet. 2000 Apr;24(4):363-7 [10742098] Genome Res. 2000 Apr;10(4):411-5 [10779482] Eur J Hum Genet. 2000 Sep;8(9):697-703 [10980575] Mol Cell Biol. 2001 Feb;21(4):1429-39 [11158327] Nature. 2001 Feb 15;409(6822):860-921 [11237011] Mol Biol Evol. 2001 Jun;18(6):926-35 [11371580] Genome Res. 2001 Jun;11(6):1005-17 [11381028] Genome Biol. 2001;2(6):REVIEWS0005 [11423011] Trends Genet. 2001 Nov;17(11):619-21 [11672845] Annu Rev Genet. 2001;35:501-38 [11700292] Genome Res. 2001 Dec;11(12):2050-8 [11731495] Genome Res. 2001 Dec;11(12):2059-65 [11731496] Cell. 2002 Aug 9;110(3):315-25 [12176319] Cell. 2002 Aug 9;110(3):327-38 [12176320] Genome Biol. 2002 Sep 19;3(10):research0052 [12372140] EMBO J. 2002 Nov 1;21(21):5899-910 [12411507] Nucleic Acids Res. 1985 Nov 11;13(21):7813-27 [2999705] Biochim Biophys Acta. 1987 Dec 8;910(3):203-12 [2445384] Genomics. 1987 Oct;1(2):113-25 [3692483] Science. 1991 Dec 20;254(5039):1805-8 [1662412] Science. 1991 Dec 20;254(5039):1808-10 [1722352] Cancer Res. 1992 Feb 1;52(3):643-5 [1310068] Cell. 1993 Feb 26;72(4):595-605 [7679954] Mol Cell Biol. 1994 Jul;14(7):4485-92 [7516468] Nat Genet. 1994 Jun;7(2):143-8 [7920631] Science. 1995 Oct 13;270(5234):253-4 [7569973] Science. 1996 Mar 15;271(5255):1592-4 [8599117] Cell. 1996 Nov 29;87(5):905-16 [8945517] Cell. 1996 Nov 29;87(5):917-27 [8945518] Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1872-7 [9050872] Nat Genet. 1997 May;16(1):6-7 [9140383] Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):7704-11 [9223252] Nucleic Acids Res. 1997 Sep 1;25(17):3389-402 [9254694] EMBO J. 1997 Oct 1;16(19):6034-43 [9312060] Genes Dev. 1997 Nov 1;11(21):2755-66 [9353246] Genomics. 1997 Nov 1;45(3):554-61 [9367680] Nucleic Acids Res. 1997 Dec 15;25(24):4876-82 [9396791] EMBO J. 1997 Nov 3;16(21):6590-602 [9351839] Genetica. 1997;100(1-3):261-70 [9440279] Gene. 1997 Dec 31;205(1-2):177-82 [9461392] Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2083-8 [9482842] Cell. 1998 Aug 21;94(4):463-70 [9727489] Biochemistry. 1998 Dec 22;37(51):18081-93 [9922177] Science. 1999 Mar 5;283(5407):1530-4 [10066175] Nature. 1999 Mar 11;398(6723):108-9, 111 [10086353] Science. 1999 Mar 5;283(5407):1465;1467 [10206876] FEMS Microbiol Lett. 1999 May 15;174(2):247-50 [10339815] Hum Mol Genet. 2000 Mar 1;9(4):653-7 [10699189] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Excitotoxic and excitoprotective mechanisms: abundant targets for the prevention and treatment of neurodegenerative disorders. AN - 73266083; 12728191 AB - Activation of glutamate receptors can trigger the death of neurons and some types of glial cells, particularly when the cells are coincidentally subjected to adverse conditions such as reduced levels of oxygen or glucose, increased levels of oxidative stress, exposure to toxins or other pathogenic agents, or a disease-causing genetic mutation. Such excitotoxic cell death involves excessive calcium influx and release from internal organelles, oxyradical production, and engagement of programmed cell death (apoptosis) cascades. Apoptotic proteins such as p53, Bax, and Par-4 induce mitochondrial membrane permeability changes resulting in the release of cytochrome c and the activation of proteases, such as caspase-3. Events occurring at several subcellular sites, including the plasma membrane, endoplasmic reticulum, mitochondria and nucleus play important roles in excitotoxicity. Excitotoxic cascades are initiated in postsynaptic dendrites and may either cause local degeneration or plasticity of those synapses, or may propagate the signals to the cell body resulting in cell death. Cells possess an array of antiexcitotoxic mechanisms including neurotrophic signaling pathways, intrinsic stress-response pathways, and survival proteins such as protein chaperones, calcium-binding proteins, and inhibitor of apoptosis proteins. Considerable evidence supports roles for excitotoxicity in acute disorders such as epileptic seizures, stroke and traumatic brain and spinal cord injury, as well as in chronic age-related disorders such as Alzheimer's, Parkinson's, and Huntington's disease and amyotrophic lateral sclerosis. A better understanding of the excitotoxic process is not only leading to the development of novel therapeutic approaches for neurodegenerative disorders, but also to unexpected insight into mechanisms of synaptic plasticity. JF - Neuromolecular medicine AU - Mattson, Mark P AD - Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. mattsonm@grc.nia.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 65 EP - 94 VL - 3 IS - 2 SN - 1535-1084, 1535-1084 KW - Neurotoxins KW - 0 KW - Receptors, Glutamate KW - Index Medicus KW - Signal Transduction -- physiology KW - Animals KW - Oxidative Stress -- physiology KW - Humans KW - Signal Transduction -- drug effects KW - Oxidative Stress -- drug effects KW - Cell Death -- physiology KW - Central Nervous System -- metabolism KW - Neurodegenerative Diseases -- physiopathology KW - Neurons -- metabolism KW - Receptors, Glutamate -- drug effects KW - Neurons -- drug effects KW - Receptors, Glutamate -- metabolism KW - Neurotoxins -- pharmacology KW - Cell Death -- drug effects KW - Neurodegenerative Diseases -- prevention & control KW - Neurons -- pathology KW - Neurodegenerative Diseases -- drug therapy KW - Central Nervous System -- physiopathology KW - Cell Survival -- drug effects KW - Central Nervous System -- drug effects KW - Cell Survival -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73266083?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuromolecular+medicine&rft.atitle=Excitotoxic+and+excitoprotective+mechanisms%3A+abundant+targets+for+the+prevention+and+treatment+of+neurodegenerative+disorders.&rft.au=Mattson%2C+Mark+P&rft.aulast=Mattson&rft.aufirst=Mark&rft.date=2003-01-01&rft.volume=3&rft.issue=2&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Neuromolecular+medicine&rft.issn=15351084&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-13 N1 - Date created - 2003-05-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Substance abuse and HIV infection. AN - 73263769; 12717047 AB - Substance abuse facilitates the spread of HIV infection and complicates its management. Successful treatment of HIV disease and other comorbidities in substance abusers requires treatment of substance abuse. At the Clinical Pathway of the Ryan White CARE Act 2002 All Grantee Conference held in Washington, DC, in August 2002, Henry Francis, MD, discussed characteristics of substance abuse in the United States and obstacles and approaches to successful treatment. JF - Topics in HIV medicine : a publication of the International AIDS Society, USA AU - Francis, Henry AD - National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA. PY - 2003 SP - 20 EP - 24 VL - 11 IS - 1 SN - 1542-8826, 1542-8826 KW - Anti-HIV Agents KW - 0 KW - Narcotics KW - Methadone KW - UC6VBE7V1Z KW - Index Medicus KW - Models, Organizational KW - Drug Interactions KW - Methadone -- therapeutic use KW - Humans KW - Methadone -- pharmacokinetics KW - Narcotics -- pharmacokinetics KW - Child KW - Methadone -- blood KW - Population Surveillance KW - Age Distribution KW - Anti-HIV Agents -- therapeutic use KW - Substance Abuse Treatment Centers -- organization & administration KW - Comprehensive Health Care -- organization & administration KW - Narcotics -- blood KW - Adult KW - Narcotics -- therapeutic use KW - Adolescent KW - United States -- epidemiology KW - Sex Distribution KW - Female KW - Male KW - Prevalence KW - Substance-Related Disorders -- blood KW - HIV Infections -- complications KW - HIV Infections -- drug therapy KW - Substance-Related Disorders -- drug therapy KW - Substance-Related Disorders -- complications KW - HIV Infections -- epidemiology KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73263769?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Topics+in+HIV+medicine+%3A+a+publication+of+the+International+AIDS+Society%2C+USA&rft.atitle=Substance+abuse+and+HIV+infection.&rft.au=Francis%2C+Henry&rft.aulast=Francis&rft.aufirst=Henry&rft.date=2003-01-01&rft.volume=11&rft.issue=1&rft.spage=20&rft.isbn=&rft.btitle=&rft.title=Topics+in+HIV+medicine+%3A+a+publication+of+the+International+AIDS+Society%2C+USA&rft.issn=15428826&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-23 N1 - Date created - 2003-04-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunocytochemical detection of p21ras, Raf-1, ERK1/MAP kinase and PKC isoforms in a 20-methylcholanthrene-induced transformed murine embryonal fibroblast cells in culture. AN - 73257486; 12740648 AB - An immunocytochemical study using antibodies against p21ras, Raf-1, MAP kinase/ERK1 and PKCalpha, beta, gamma, delta, epsilon, zeta, isoforms were performed on a 20-methylcholanthrene-induced transformed murine embryonal fibroblast cells in both in vitro and in vivo growth conditions. Altered expression of p21ras, Raf-1, MAP kinase in this particular cell line strongly supported the previous findings of the activation of one component of signal transduction under the influence of the other in the MAP kinase cascade of signal transduction during neoplastic transformation and which also seemed to be involved in CNCI-PM-20 cell line. The altered expression of PKCalpha, beta, and delta was thought to be an epigenetic event occurring under the indirect influence of other changes in these cells. Host physiology and metabolism did not have much impact on the expression of these gene products after biological incubation of these cells in syngenic host. JF - Neoplasma AU - Banerjee, K AU - Das, S K AU - Mukherjee, P AD - Department of In Vitro Carcinogenesis and Cellular Chemotherapy, Chittaranjan National Cancer Institute, Calcutta 700026, India. Y1 - 2003 PY - 2003 DA - 2003 SP - 131 EP - 138 VL - 50 IS - 2 SN - 0028-2685, 0028-2685 KW - Isoenzymes KW - 0 KW - Methylcholanthrene KW - 56-49-5 KW - Proto-Oncogene Proteins c-raf KW - EC 2.7.11.1 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Mitogen-Activated Protein Kinase 3 KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinases KW - Oncogene Protein p21(ras) KW - EC 3.6.5.2 KW - Index Medicus KW - Fibroblasts -- drug effects KW - Animals KW - Embryo, Mammalian -- cytology KW - Mice KW - Immunohistochemistry KW - Protein Kinase C -- analysis KW - Isoenzymes -- analysis KW - Cell Transformation, Neoplastic -- chemistry KW - Mitogen-Activated Protein Kinases -- analysis KW - Oncogene Protein p21(ras) -- analysis KW - Proto-Oncogene Proteins c-raf -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73257486?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neoplasma&rft.atitle=Immunocytochemical+detection+of+p21ras%2C+Raf-1%2C+ERK1%2FMAP+kinase+and+PKC+isoforms+in+a+20-methylcholanthrene-induced+transformed+murine+embryonal+fibroblast+cells+in+culture.&rft.au=Banerjee%2C+K%3BDas%2C+S+K%3BMukherjee%2C+P&rft.aulast=Banerjee&rft.aufirst=K&rft.date=2003-01-01&rft.volume=50&rft.issue=2&rft.spage=131&rft.isbn=&rft.btitle=&rft.title=Neoplasma&rft.issn=00282685&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-01 N1 - Date created - 2003-05-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phorbol ester uncouples adenosine inhibition of presynaptic Ca2+ transients at hippocampal synapses. AN - 73257245; 12722976 AB - Synaptic transmission involves Ca2+ influx at presynaptic terminals. Adenosine receptors inhibit transmission, and this effect can be abolished by activation of PKC with phorbol esters. Whether protein kinase C (PKC) acts via alterations in Ca2+ entry at the presynaptic terminal is unknown. In the present study, we recorded the presynaptic Ca2+ transients (preCa(delta)) in hippocampal stratum radiatum, using fluorescence photometry. The calcium dye Fura-2 AM was used to load the Schaffer collateral/commissural tract and its terminals. Tetrodotoxin (TTX)-sensitive Na+ channels and Cd2+-sensitive, high-voltage activated Ca2+ channels (HVACCs) were required to elicit the preCa(delta). Application of the phorbol ester phorbol-12,13-dibutyrate (PDBu) abolished the adenosine inhibition of both preCa(delta) and the field excitatory postsynaptic potentials (fEPSPs). PDBu consistently potentiated fEPSPs, and also increased preCa(delta) in a large majority of the slices examined. Regardless of whether potentiation was observed, PDBu always prevented adenosine inhibition of preCa(delta). In contrast, the inactive phorbol ester, 4alpha-phorbol, did not alter adenosine inhibition of preCa(delta), indicating that PKC activation is necessary for the occurrence of the observed effects. Our findings suggest that PKC activation abolishes adenosine's inhibitory effect on synaptic activity involving presynaptic Ca2+ entry. JF - Hippocampus AU - Stocca, Gabriella AU - Lovinger, David M AD - Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. gstocca@mail.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 355 EP - 360 VL - 13 IS - 3 SN - 1050-9631, 1050-9631 KW - Calcium Channels KW - 0 KW - Phorbol Esters KW - Receptors, Purinergic P1 KW - Tetrodotoxin KW - 4368-28-9 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Adenosine KW - K72T3FS567 KW - Calcium KW - SY7Q814VUP KW - Fura-2 KW - TSN3DL106G KW - Index Medicus KW - Animals KW - Calcium Channels -- metabolism KW - Receptors, Purinergic P1 -- metabolism KW - Calcium -- metabolism KW - Rats KW - Phorbol Esters -- pharmacology KW - Rats, Sprague-Dawley KW - Excitatory Postsynaptic Potentials -- drug effects KW - Receptors, Purinergic P1 -- drug effects KW - Photometry KW - Calcium Channels -- drug effects KW - Tetrodotoxin -- pharmacology KW - Organ Culture Techniques KW - Excitatory Postsynaptic Potentials -- physiology KW - Protein Kinase C -- drug effects KW - Synaptic Transmission -- drug effects KW - Neural Inhibition -- drug effects KW - Synaptic Transmission -- physiology KW - Neural Inhibition -- physiology KW - Neural Pathways -- drug effects KW - Hippocampus -- drug effects KW - Protein Kinase C -- metabolism KW - Calcium Signaling -- drug effects KW - Presynaptic Terminals -- drug effects KW - Calcium Signaling -- physiology KW - Presynaptic Terminals -- enzymology KW - Hippocampus -- enzymology KW - Neural Pathways -- enzymology KW - Adenosine -- antagonists & inhibitors KW - Adenosine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73257245?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hippocampus&rft.atitle=Phorbol+ester+uncouples+adenosine+inhibition+of+presynaptic+Ca2%2B+transients+at+hippocampal+synapses.&rft.au=Stocca%2C+Gabriella%3BLovinger%2C+David+M&rft.aulast=Stocca&rft.aufirst=Gabriella&rft.date=2003-01-01&rft.volume=13&rft.issue=3&rft.spage=355&rft.isbn=&rft.btitle=&rft.title=Hippocampus&rft.issn=10509631&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-10 N1 - Date created - 2003-04-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Homocysteine and folate deficiency sensitize oligodendrocytes to the cell death-promoting effects of a presenilin-1 mutation and amyloid beta-peptide. AN - 73237883; 12728194 AB - Although damage to white matter occurs in the brains of patients with Alzheimer's disease (AD), the underlying mechanisms are unknown. Recent findings suggest that individuals with elevated levels of homocysteine are at increased risk of AD. Here we show that oligodendrocytes from mice expressing a mutant form of presenilin-1 (PS1) that causes familial AD exhibit increased sensitivity to death induced by homocysteine compared to oligodendrocytes from wild-type control mice. Homocysteine also sensitized oligodendrocytes to the cytotoxicity of amyloid beta-peptide. Folate deficiency, which is known to result in elevated levels of homocysteine in vivo, also sensitized oligodendrocytes to the cell-death-promoting actions of mutant PS1 and amyloid beta-peptide. Inhibitors of poly (ADP-ribose) polymerase and p53 protected oligodendrocytes against cell death induced by homocysteine and amyloid beta-peptide, consistent with a role for a DNA-damage response in the cell death process. These findings demonstrate an adverse effect of homocysteine on oligodendrocytes, and suggest roles for homocysteine and folate deficiency in the white matter damage in AD and related neurodegenerative disorders. JF - Neuromolecular medicine AU - Pak, Kirk J AU - Chan, Sic L AU - Mattson, Mark P AD - Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2003 PY - 2003 DA - 2003 SP - 119 EP - 128 VL - 3 IS - 2 SN - 1535-1084, 1535-1084 KW - Amyloid beta-Peptides KW - 0 KW - Enzyme Inhibitors KW - Membrane Proteins KW - Poly(ADP-ribose) Polymerase Inhibitors KW - Presenilin-1 KW - Tumor Suppressor Protein p53 KW - Homocysteine KW - 0LVT1QZ0BA KW - Poly(ADP-ribose) Polymerases KW - EC 2.4.2.30 KW - Index Medicus KW - Animals KW - Membrane Proteins -- metabolism KW - Disease Models, Animal KW - Mice KW - Membrane Proteins -- genetics KW - Tumor Suppressor Protein p53 -- metabolism KW - Poly(ADP-ribose) Polymerases -- metabolism KW - DNA Damage -- genetics KW - DNA Damage -- drug effects KW - Up-Regulation -- physiology KW - Tumor Suppressor Protein p53 -- antagonists & inhibitors KW - Mice, Mutant Strains KW - Amyloid beta-Peptides -- metabolism KW - Cells, Cultured KW - Amyloid beta-Peptides -- toxicity KW - Up-Regulation -- drug effects KW - Mutation -- genetics KW - Enzyme Inhibitors -- pharmacology KW - Oligodendroglia -- drug effects KW - Alzheimer Disease -- genetics KW - Oligodendroglia -- pathology KW - Alzheimer Disease -- physiopathology KW - Brain -- metabolism KW - Cell Death -- drug effects KW - Folic Acid Deficiency -- physiopathology KW - Brain -- physiopathology KW - Oligodendroglia -- metabolism KW - Homocysteine -- metabolism KW - Nerve Fibers, Myelinated -- metabolism KW - Brain -- pathology KW - Folic Acid Deficiency -- metabolism KW - Folic Acid Deficiency -- genetics KW - Cell Death -- genetics KW - Nerve Fibers, Myelinated -- pathology KW - Alzheimer Disease -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73237883?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuromolecular+medicine&rft.atitle=Homocysteine+and+folate+deficiency+sensitize+oligodendrocytes+to+the+cell+death-promoting+effects+of+a+presenilin-1+mutation+and+amyloid+beta-peptide.&rft.au=Pak%2C+Kirk+J%3BChan%2C+Sic+L%3BMattson%2C+Mark+P&rft.aulast=Pak&rft.aufirst=Kirk&rft.date=2003-01-01&rft.volume=3&rft.issue=2&rft.spage=119&rft.isbn=&rft.btitle=&rft.title=Neuromolecular+medicine&rft.issn=15351084&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-13 N1 - Date created - 2003-05-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutagenicity of the drinking water supply in Bangkok. AN - 73235165; 12718698 AB - Seventeen samples of tap water in Bangkok and 2 neighboring provinces were collected in winter and summer, concentrated and tested for mutagenic activity using the Ames Salmonella mutagenesis assay. Preliminary results demonstrated that concentrated tap water exhibited clear mutagenicity towards S. typhimurium TA100 and YG1029, but not towards TA98 and YG1024, in the absence of S9 mix, and the addition of S9 mix markedly decreased the mutagenicity to both tester strains. Amberlite( ) XAD-2 resin, but not blue rayon, was able to adsorb mutagens from water at pH 2. Our data clearly demonstrated that all tap water samples prepared by chlorination of Chao Phraya River water were mutagenic to strain TA100 without S9 mix, inducing 3,351 + 741 and 2,216 + 770 revertants/l, in winter and summer, respectively. On the other hand, however, tap water samples prepared from ground water were not mutagenic. Furthermore, it was found that boiling for only 5 min and filtration through home purifying system containing activated charcoal and mixed resin units were very effective to abolish the mutagenicity of water. Storage of water also significantly decreased the mutagenicity, however, it took 2-3 weeks to totally abolish it. Additionally, we also found 1 out of 6 brands of commercially available bottled drinking water to be mutagenic, with about 26 % of the average mutagenicity of tap water. The results in the present study clearly demonstrated that chlorinated tap water in Bangkok and neighboring provinces contain direct-acting mutagens causing capable of causing base-pair substitution. Boiling and filtration of tap water through home purifying systems may be the most effective means to abolish the mutagenicity. Some brands of commercial bottled waters may also contain mutagens which may be derived from tap water. JF - Asian Pacific journal of cancer prevention : APJCP AU - Kusamran, Wannee R AU - Tanthasri, Nopsarun AU - Meesiripan, Nuntana AU - Tepsuwan, Anong AD - Biochemistry and Chemical Carcinogenesis Section, Research Division, National Cancer Institute, Bangkok 10400, Thailand. waroran@health.moph.go.th PY - 2003 SP - 31 EP - 38 VL - 4 IS - 1 SN - 1513-7368, 1513-7368 KW - Mutagens KW - 0 KW - Water Pollutants KW - Index Medicus KW - Mutagenicity Tests -- methods KW - Seasons KW - Thailand -- epidemiology KW - Salmonella typhimurium -- drug effects KW - Water Purification -- methods KW - Water Supply -- analysis KW - Water Pollutants -- analysis KW - Water Pollutants -- adverse effects KW - Mutagens -- analysis KW - Mutagens -- adverse effects KW - Environmental Exposure -- analysis KW - Environmental Exposure -- adverse effects KW - Water Supply -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73235165?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Asian+Pacific+journal+of+cancer+prevention+%3A+APJCP&rft.atitle=Mutagenicity+of+the+drinking+water+supply+in+Bangkok.&rft.au=Kusamran%2C+Wannee+R%3BTanthasri%2C+Nopsarun%3BMeesiripan%2C+Nuntana%3BTepsuwan%2C+Anong&rft.aulast=Kusamran&rft.aufirst=Wannee&rft.date=2003-01-01&rft.volume=4&rft.issue=1&rft.spage=31&rft.isbn=&rft.btitle=&rft.title=Asian+Pacific+journal+of+cancer+prevention+%3A+APJCP&rft.issn=15137368&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-28 N1 - Date created - 2003-04-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Anti-mouse mesangial cell serum induces acute glomerulonephropathy in mice. AN - 73135527; 12660412 AB - In order to develop a model in mouse similar to anti- Thy-1 nephritis in the rat, we prepared sheep antiserum against SV40-transformed mouse mesangial (MES 13) cells. In vivo, the anti-mouse mesangial cell serum-treated mice showed severe azotemia that peaked at day 6 and proteinuria that peaked at day 8, in a dose-dependent fashion. Light microscopy and electron microscopy showed duplication of glomerular basement membranes, mesangiolysis, subendothelial and mesangial electron-dense deposits, and foot process effacement. Intraglomerular tuft cell number was significantly reduced at day 4 and there were increased numbers of apoptotic cells at days 2 and 4. SCID mice and mice lacking C3 manifested similar responses to anti-mouse mesangial cell serum, suggesting that T cells, B cells and complement are not required for glomerular injury in this model. In vitro, anti-mouse mesangial cell serum treated mesangial cells showed greater release of lactate dehydrogenase, decreased cell survival, and increased apoptotic cell death. Anti-mouse mesangial cell serum induces glomerulopathy characterized by mesangiolysis and mesangial cell apoptosis, and followed by cellular proliferation. Copyright 2003 S. Karger AG, Basel JF - Nephron. Experimental nephrology AU - Yo, Yoshikage AU - Braun, Michael C AU - Barisoni, Laura AU - Mobaraki, Hideko AU - Lu, Huiyan AU - Shrivastav, Shashi AU - Owens, Jennie AU - Kopp, Jeffrey B AD - Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892-1268, USA. Y1 - 2003 PY - 2003 DA - 2003 SP - e92 EP - 106 VL - 93 IS - 3 KW - Antigens, Surface KW - 0 KW - Endotoxins KW - Immune Sera KW - Immunoglobulins KW - Index Medicus KW - Acute Disease KW - Animals KW - Lung -- chemistry KW - Disease Models, Animal KW - Kidney -- chemistry KW - Kidney -- immunology KW - Mice, Inbred BALB C KW - Antigens, Surface -- immunology KW - Lung -- immunology KW - Antibody Specificity KW - Sheep -- immunology KW - Mice, Congenic KW - Cell Division -- immunology KW - Time Factors KW - Endotoxins -- blood KW - 3T3 Cells KW - Apoptosis -- immunology KW - Mice KW - Organ Specificity KW - Mice, Inbred Strains KW - Dose-Response Relationship, Immunologic KW - Immunoglobulins -- metabolism KW - Endotoxins -- adverse effects KW - Mice, SCID KW - Cell Line KW - Female KW - Glomerular Mesangium -- chemistry KW - Glomerulonephritis, Membranous -- blood KW - Glomerular Mesangium -- cytology KW - Glomerular Mesangium -- pathology KW - Glomerular Mesangium -- immunology KW - Glomerulonephritis, Membranous -- immunology KW - Immune Sera -- toxicity KW - Immune Sera -- metabolism KW - Glomerulonephritis, Membranous -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73135527?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nephron.+Experimental+nephrology&rft.atitle=Anti-mouse+mesangial+cell+serum+induces+acute+glomerulonephropathy+in+mice.&rft.au=Yo%2C+Yoshikage%3BBraun%2C+Michael+C%3BBarisoni%2C+Laura%3BMobaraki%2C+Hideko%3BLu%2C+Huiyan%3BShrivastav%2C+Shashi%3BOwens%2C+Jennie%3BKopp%2C+Jeffrey+B&rft.aulast=Yo&rft.aufirst=Yoshikage&rft.date=2003-01-01&rft.volume=93&rft.issue=3&rft.spage=e92&rft.isbn=&rft.btitle=&rft.title=Nephron.+Experimental+nephrology&rft.issn=1660-2129&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-11 N1 - Date created - 2003-03-27 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 ER - TY - JOUR T1 - Synergism of Fas-mediated apoptosis and tumor necrosis factor on adriamycin cytotoxicity to transitional cell carcinoma. AN - 73127440; 12660450 AB - To explore the accurate Fas antigenic expression in transitional cell carcinoma (TCC) cells and and compare its synergistic modulation on adriamycin cytotoxicity with alpha-tumor necrosis factor (TNF-alpha). The expression of Fas antigen in normal urothelium and TCC cell lines was measured by flow cytometry. The Fas/Fas ligand reaction-induced cytotoxic changes in tumor cells were evaluated by microculture MTT technique. The synergism efficacy of Fas-mediated apoptosis and TNF-alpha on adriamycin cytotoxicity of TCC cells was analyzed. The Fas/Fas ligand-induced apoptosis in tumor cells was studied by annexin-V apoptotic cell expression and DNA ladder fragmentation analysis. 75% of TCC cell lines showed Fas antigen expression. The Fas expression was not influenced by in vitro growth density of tumor cells. Apoptosis of TCC cells was observed during 48 h of treatment after activation of the Fas/Fas ligand pathway. TNF-alpha had a higher cytotoxicity activity on TCC cells than Fas ligand (17 vs. 0.7%) while combination of both reagents had 30% increased synergistic cytotoxicity. The increasing rate of apoptotic body after 3 days of treatment was 74% in adriamycin, 32% in Fas ligand, 60% in TNF-alpha, 69% in Fas and adriamycin combination and Fas and TNF-alpha combination, 103% in combination of TNF-alpha and adriamycin, and 136% in combination of these three reagents individually. In the DNA ladder analysis, Fas ligand had a 1.5-fold increase of DNA fragmentation when compared with adriamycin while TNF-alpha had a 4.4-fold increase and triple combination had a 5.5-fold increase after 3 days of treatment. Although the Fas antigen expression is common in TCC cells and apoptosis can be activated by the Fas/Fas ligand pathway activation, the synergistic cytotoxicity of adriamycin by the Fas/Fas ligand pathway is lower than that of TNF-alpha. Copyright 2003 S. Karger AG, Basel JF - Urologia internationalis AU - Yu, Dah-Shyong AU - Hsieh, Dar-Shih AU - Chen, Hong-I AU - Chang, Sun-Yran AD - Uro-Oncology Laboratory, Division of Urology, Department of Surgery, Tri-Service General Hospital, No. 325, Sec. 2 Cheng-Gung Road, Nei-Hu, Taipei 114, Taiwan/ROC. yuds@ms21.hinet.net Y1 - 2003 PY - 2003 DA - 2003 SP - 161 EP - 166 VL - 70 IS - 3 SN - 0042-1138, 0042-1138 KW - Antigens, CD95 KW - 0 KW - FASLG protein, human KW - Fas Ligand Protein KW - Membrane Glycoproteins KW - Tumor Necrosis Factor-alpha KW - Doxorubicin KW - 80168379AG KW - Index Medicus KW - Humans KW - Carcinoma, Transitional Cell -- pathology KW - Urinary Bladder Neoplasms -- pathology KW - Apoptosis KW - Antigens, CD95 -- pharmacology KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Doxorubicin -- toxicity KW - Membrane Glycoproteins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73127440?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Urologia+internationalis&rft.atitle=Synergism+of+Fas-mediated+apoptosis+and+tumor+necrosis+factor+on+adriamycin+cytotoxicity+to+transitional+cell+carcinoma.&rft.au=Yu%2C+Dah-Shyong%3BHsieh%2C+Dar-Shih%3BChen%2C+Hong-I%3BChang%2C+Sun-Yran&rft.aulast=Yu&rft.aufirst=Dah-Shyong&rft.date=2003-01-01&rft.volume=70&rft.issue=3&rft.spage=161&rft.isbn=&rft.btitle=&rft.title=Urologia+internationalis&rft.issn=00421138&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-08 N1 - Date created - 2003-03-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The search for a rational basis for treatment selection. AN - 73110688; 12638633 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 - Mattson, Margaret E AD - Treatment Research Branch, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892, USA. Y1 - 2003 PY - 2003 DA - 2003 SP - 97 EP - 113 VL - 16 SN - 0738-422X, 0738-422X KW - Index Medicus KW - Multicenter Studies as Topic KW - Psychotherapy KW - Cognitive Therapy KW - Humans KW - Prognosis KW - Outcome and Process Assessment (Health Care) KW - Clinical Trials as Topic KW - Alcoholics Anonymous KW - Personality Assessment KW - Patient Selection KW - Social Environment KW - Alcoholism -- rehabilitation KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73110688?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Recent+developments+in+alcoholism+%3A+an+official+publication+of+the+American+Medical+Society+on+Alcoholism%2C+the+Research+Society+on+Alcoholism%2C+and+the+National+Council+on+Alcoholism&rft.atitle=The+search+for+a+rational+basis+for+treatment+selection.&rft.au=Mattson%2C+Margaret+E&rft.aulast=Mattson&rft.aufirst=Margaret&rft.date=2003-01-01&rft.volume=16&rft.issue=&rft.spage=97&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 - 2003-04-07 N1 - Date created - 2003-03-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Research on alcoholism treatment. AN - 73106657; 12638628 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 - Gordis, Enoch AD - National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003 PY - 2003 DA - 2003 SP - 3 EP - 6 VL - 16 SN - 0738-422X, 0738-422X KW - Index Medicus KW - Humans KW - Clinical Trials as Topic KW - Research KW - Alcoholism -- rehabilitation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73106657?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Research+on+alcoholism+treatment.&rft.au=Gordis%2C+Enoch&rft.aulast=Gordis&rft.aufirst=Enoch&rft.date=2003-01-01&rft.volume=16&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 - 2003-04-07 N1 - Date created - 2003-03-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biomarkers as aids to identification of relapse in alcoholic patients. AN - 73104556; 12638630 AB - Since return to drinking is common in patients recovering from alcoholism, recognition of relapse should be an important component of treatment. Recurrent assessment with biochemical measures can provide clinicians with useful information on the drinking status of their patients. This chapter addresses issues surrounding the importance of early detection of relapse, describes biochemical markers that may assist in this, reviews relevant scientific investigations, and offers recommendations to researchers and clinicians. 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 - Allen, John P AU - Anton, Raymond AD - National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892, USA. Y1 - 2003 PY - 2003 DA - 2003 SP - 25 EP - 38 VL - 16 SN - 0738-422X, 0738-422X KW - Biomarkers KW - 0 KW - Index Medicus KW - Humans KW - Follow-Up Studies KW - Recurrence KW - Alcoholism -- rehabilitation KW - Alcoholism -- diagnosis KW - Alcohol Drinking -- blood KW - Biomarkers -- blood KW - Alcoholism -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73104556?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Biomarkers+as+aids+to+identification+of+relapse+in+alcoholic+patients.&rft.au=Allen%2C+John+P%3BAnton%2C+Raymond&rft.aulast=Allen&rft.aufirst=John&rft.date=2003-01-01&rft.volume=16&rft.issue=&rft.spage=25&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 - 2003-04-07 N1 - Date created - 2003-03-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Association analysis of exonic variants of the GABA(B)-receptor gene and alpha electroencephalogram voltage in normal subjects and alcohol-dependent patients. AN - 73100370; 12645817 AB - Based on pharmacologic evidence, it has been suggested that GABA(B) receptors may play a crucial role in the generation of alpha-electroencephalogram (EEG) oscillations. We tested whether three exonic variants of the gene encoding the human GABA(B) receptor (GABA(B)R1) modify scalp-recorded alpha-EEG voltage. One hundred twenty-eight patients suffering from alcoholism and 114 normal subjects were investigated. Alcohol-dependent patients were included because evidence exists that the frequently observed alpha low voltage in these subjects is at least partly a trait variable. Logistic regression analyses revealed no associations between alpha-EEG voltage and polymorphic variations in exon 1a1 or exon 11. A significant interaction was observed for an exon 7 substitution polymorphism and diagnosis (P = 0.009). Post hoc analyses showed an association between EEG phenotype and exon 7 genotype in normal subjects only. It is concluded that this particular association may only be observable under physiologic conditions and that alpha low voltage in alcohol-dependent subjects is under the control of either different genes or that it is related to the disease process. JF - Behavior genetics AU - Winterer, Georg AU - Mahlberg, Richard AU - Smolka, Michael N AU - Samochowiec, Jerzy AU - Ziller, Mario AU - Rommelspacher, Hans-Peter AU - Herrmann, Werner M AU - Schmidt, Lutz G AU - Sander, Thomas AD - Department of Psychiatry, Benjamin Franklin University Hospital, Free University of Berlin, Berlin, Germany. wintereg@intra.nimh.nih.gov Y1 - 2003/01// PY - 2003 DA - January 2003 SP - 7 EP - 15 VL - 33 IS - 1 SN - 0001-8244, 0001-8244 KW - GABA type B receptor, subunit 1 KW - 0 KW - Receptors, GABA-B KW - Index Medicus KW - Phenotype KW - Alleles KW - Sex Factors KW - Polymorphism, Restriction Fragment Length KW - Humans KW - Adult KW - Regression (Psychology) KW - Middle Aged KW - Mutation KW - Male KW - Female KW - Receptors, GABA-B -- genetics KW - Genetic Variation KW - Exons KW - Alcoholism -- physiopathology KW - Alcoholism -- genetics KW - Alpha Rhythm UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73100370?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Behavior+genetics&rft.atitle=Association+analysis+of+exonic+variants+of+the+GABA%28B%29-receptor+gene+and+alpha+electroencephalogram+voltage+in+normal+subjects+and+alcohol-dependent+patients.&rft.au=Winterer%2C+Georg%3BMahlberg%2C+Richard%3BSmolka%2C+Michael+N%3BSamochowiec%2C+Jerzy%3BZiller%2C+Mario%3BRommelspacher%2C+Hans-Peter%3BHerrmann%2C+Werner+M%3BSchmidt%2C+Lutz+G%3BSander%2C+Thomas&rft.aulast=Winterer&rft.aufirst=Georg&rft.date=2003-01-01&rft.volume=33&rft.issue=1&rft.spage=7&rft.isbn=&rft.btitle=&rft.title=Behavior+genetics&rft.issn=00018244&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-17 N1 - Date created - 2003-03-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intraocular hemorrhage after systemic thrombolytic therapy in a patient with exudative macular degeneration. AN - 73099263; 12635684 AB - To report a hemorrhagic complication from thrombolytic therapy in a patient with exudative macular degeneration. A 75 year old patient with exudative macular degeneration developed pain and loss of vision in the left eye shortly after receiving tissue plasminogen activator (t-PA) for a myocardial infarction. Examination revealed the patient to be in angle closure. A CT scan revealed the etiology of the angle closure to be a dense vitreous hemorrhage pushing the iris-lens diaphragm forward. Intraocular pressure was treated successfully, but the final visual acuity was only light perception. Thrombolytic therapy can lead to devastating intraocular hemorrhages. The presence of exudative macular degeneration may potentially increase the risk of developing such complications. JF - European journal of ophthalmology AU - Djalilian, A R AU - Cantrill, H C AU - Samuelson, T W AD - Department of Ophthalmology, Regions Hospital, St. Paul, Minnesota, USA. djaliliana@nei.nih.gov PY - 2003 SP - 96 EP - 98 VL - 13 IS - 1 SN - 1120-6721, 1120-6721 KW - Antihypertensive Agents KW - 0 KW - Fibrinolytic Agents KW - Tissue Plasminogen Activator KW - EC 3.4.21.68 KW - Index Medicus KW - Intraocular Pressure KW - Humans KW - Treatment Outcome KW - Antihypertensive Agents -- therapeutic use KW - Aged KW - Exudates and Transudates KW - Visual Acuity KW - Female KW - Myocardial Infarction -- drug therapy KW - Tissue Plasminogen Activator -- adverse effects KW - Fibrinolytic Agents -- adverse effects KW - Eye Hemorrhage -- drug therapy KW - Thrombolytic Therapy -- adverse effects KW - Eye Hemorrhage -- chemically induced KW - Macular Degeneration -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73099263?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+ophthalmology&rft.atitle=Intraocular+hemorrhage+after+systemic+thrombolytic+therapy+in+a+patient+with+exudative+macular+degeneration.&rft.au=Djalilian%2C+A+R%3BCantrill%2C+H+C%3BSamuelson%2C+T+W&rft.aulast=Djalilian&rft.aufirst=A&rft.date=2003-01-01&rft.volume=13&rft.issue=1&rft.spage=96&rft.isbn=&rft.btitle=&rft.title=European+journal+of+ophthalmology&rft.issn=11206721&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-09 N1 - Date created - 2003-03-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Assessment of alcoholic patients: advances and future challenges. AN - 73094737; 12638629 AB - Noteworthy advances have been made in methods of assessing patients suffering alcohol problems. More than one hundred measures are now available to assist clinicians and researchers in screening for such problems, diagnosing them, and developing treatment plans individualized according to relevant patient characteristics. This chapter reviews progress in assessment supporting each of these activities and suggests directions for future research. It concludes by identifying a series of research issues that cut across multiple domains of alcohol assessment. 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 - Allen, John P AD - National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892, USA. Y1 - 2003 PY - 2003 DA - 2003 SP - 13 EP - 24 VL - 16 SN - 0738-422X, 0738-422X KW - Biomarkers KW - 0 KW - Index Medicus KW - Humans KW - Outcome and Process Assessment (Health Care) KW - Patient Care Planning KW - Outcome Assessment (Health Care) KW - Personality Assessment KW - Biomarkers -- blood KW - Alcoholism -- rehabilitation KW - Alcoholism -- diagnosis KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73094737?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Assessment+of+alcoholic+patients%3A+advances+and+future+challenges.&rft.au=Allen%2C+John+P&rft.aulast=Allen&rft.aufirst=John&rft.date=2003-01-01&rft.volume=16&rft.issue=&rft.spage=13&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 - 2003-04-07 N1 - Date created - 2003-03-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of hazardous exposure by protective exposure: modulation of phase II detoxification and lipid peroxidation by Camellia sinensis and Swertia chirata. AN - 73082352; 12616622 AB - Many natural compounds are now known to have a modulatory role on physiological functions and biotransformation reactions involved in the detoxification process, thereby affording protection from cytotoxic, genotoxic, and metabolic actions of environmental toxicants. As part of a programme on evaluation of food, beverage, and traditional medicinal plants for their anticarcinogenic activity, their effects on detoxification enzymes were also studied. The present report deals with Camellia sinensis and Swertia chirata. The effect of water infusions as well as crude and purified components of these plants on glutathione-S-transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) was analyzed in mice that were exposed to the chemical carcinogen DMBA. All the four enzymes were found to be activated in different degrees following treatment. The effect of Theaflavin, a component of black tea, was highly significant. The activation of the enzymes was accompanied by significant reduction in lipid peroxidation. The observation suggest the chemopreventive potential of both Camellia sinensis and Swertia chirata. Copyright 2003 Wiley-Liss, Inc. JF - Teratogenesis, carcinogenesis, and mutagenesis AU - Saha, Prosenjit AU - Das, Sukta AD - Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, Kolkata, India. Y1 - 2003 PY - 2003 DA - 2003 SP - 313 EP - 322 VL - Suppl 1 SN - 0270-3211, 0270-3211 KW - Antioxidants KW - 0 KW - Biflavonoids KW - Carcinogens KW - Hazardous Substances KW - Plant Extracts KW - Tea KW - theaflavin KW - 1IA46M0D13 KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Catechin KW - 8R1V1STN48 KW - epigallocatechin gallate KW - BQM438CTEL KW - Catalase KW - EC 1.11.1.6 KW - Glutathione Peroxidase KW - EC 1.11.1.9 KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Animals KW - Carcinogens -- pharmacology KW - Liver -- enzymology KW - Plants, Medicinal -- enzymology KW - Glutathione Transferase -- metabolism KW - Superoxide Dismutase -- metabolism KW - Liver -- metabolism KW - Tea -- chemistry KW - Mice KW - Plant Extracts -- chemistry KW - Plants, Medicinal -- chemistry KW - Carcinogens -- antagonists & inhibitors KW - Catalase -- metabolism KW - Plant Extracts -- pharmacology KW - Glutathione Peroxidase -- metabolism KW - 9,10-Dimethyl-1,2-benzanthracene -- pharmacology KW - Antioxidants -- pharmacology KW - Liver -- drug effects KW - Enzyme Activation -- drug effects KW - Tea -- metabolism KW - Male KW - 9,10-Dimethyl-1,2-benzanthracene -- antagonists & inhibitors KW - Camellia sinensis -- chemistry KW - Inactivation, Metabolic KW - Camellia sinensis -- enzymology KW - Hazardous Substances -- antagonists & inhibitors KW - Catechin -- analogs & derivatives KW - Lipid Peroxidation -- drug effects KW - Hazardous Substances -- pharmacology KW - Swertia -- enzymology KW - Catechin -- pharmacology KW - Swertia -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73082352?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Regulation+of+hazardous+exposure+by+protective+exposure%3A+modulation+of+phase+II+detoxification+and+lipid+peroxidation+by+Camellia+sinensis+and+Swertia+chirata.&rft.au=Saha%2C+Prosenjit%3BDas%2C+Sukta&rft.aulast=Saha&rft.aufirst=Prosenjit&rft.date=2003-01-01&rft.volume=Suppl+1&rft.issue=&rft.spage=313&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 - 2003-09-16 N1 - Date created - 2003-03-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nicaraven Chugai. AN - 73081110; 12625035 AB - Chugai (the Japanese subsidiary of Roche) is developing nicaraven (Antevas), a water-soluble antioxidant, for the potential treatment of disorders caused by acute cerebrovascular diseases. A registration application was filed in April 1995, and in April 2002, nicaraven was still awaiting registration in Japan. By August 2002, Chugai had filed an NDA in Japan for the additional indication of subarachnoidal bleeding. JF - Current opinion in investigational drugs (London, England : 2000) AU - Leker, Ronen R AD - Laboratory of Molecular Biology, NIH/NINDS Building 36, Room 3c12, 36 Convent Drive, MSC 4092, Bethesda, MD 20892, USA. lekerr@nih.ninds.gov Y1 - 2003/01// PY - 2003 DA - January 2003 SP - 83 EP - 90 VL - 4 IS - 1 SN - 1472-4472, 1472-4472 KW - Antioxidants KW - 0 KW - Neuroprotective Agents KW - Niacinamide KW - 25X51I8RD4 KW - nicaraven KW - UD8PEV6JBD KW - Index Medicus KW - Stroke -- drug therapy KW - Animals KW - Brain Ischemia -- drug therapy KW - Clinical Trials, Phase II as Topic KW - Clinical Trials, Phase III as Topic KW - Humans KW - Clinical Trials, Phase I as Topic KW - Cerebral Hemorrhage -- drug therapy KW - Structure-Activity Relationship KW - Brain Edema -- drug therapy KW - Antioxidants -- adverse effects KW - Niacinamide -- pharmacology KW - Niacinamide -- therapeutic use KW - Antioxidants -- pharmacology KW - Niacinamide -- adverse effects KW - Antioxidants -- therapeutic use KW - Niacinamide -- analogs & derivatives KW - Neuroprotective Agents -- adverse effects KW - Neuroprotective Agents -- therapeutic use KW - Neuroprotective Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73081110?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+investigational+drugs+%28London%2C+England+%3A+2000%29&rft.atitle=Nicaraven+Chugai.&rft.au=Leker%2C+Ronen+R&rft.aulast=Leker&rft.aufirst=Ronen&rft.date=2003-01-01&rft.volume=4&rft.issue=1&rft.spage=83&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+investigational+drugs+%28London%2C+England+%3A+2000%29&rft.issn=14724472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-10 N1 - Date created - 2003-03-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transcriptional profiling in the human prefrontal cortex: evidence for two activational states associated with cocaine abuse. AN - 73076314; 12629581 AB - CNS-focused cDNA microarrays were used to examine gene expression profiles in dorsolateral prefrontal cortex (dlPFC, Area 46) from seven individual sets of age- and post-mortem interval-matched male cocaine abusers and controls. The presence of cocaine and related metabolites was confirmed by gas chromatography-mass spectrometry. Sixty-five transcripts were differentially expressed, indicating alterations in energy metabolism, mitochondria and oligodendrocyte function, cytoskeleton and related signaling, and neuronal plasticity. There was evidence for two distinct states of transcriptional regulation, with increases in gene expression predominating in subjects testing positive for a metabolite indicative of recent 'crack' cocaine abuse and decreased expression profiles in the remaining cocaine subjects. This pattern was confirmed by quantitative polymerase chain reaction for select transcripts. These data suggest that cocaine abuse targets a distinct subset of genes in the dlPFC, resulting in either a state of acute activation in which increased gene expression predominates, or a relatively destimulated, refractory phase. JF - The pharmacogenomics journal AU - Lehrmann, E AU - Oyler, J AU - Vawter, M P AU - Hyde, T M AU - Kolachana, B AU - Kleinman, J E AU - Huestis, M A AU - Becker, K G AU - Freed, W J AD - Cellular Neurobiology Research Branch, National Institute on Drug Abuse, NIH, DHHS, Baltimore, MD 21224, USA. elehrman@intra.nida.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 27 EP - 40 VL - 3 IS - 1 SN - 1470-269X, 1470-269X KW - Crack Cocaine KW - 0 KW - Index Medicus KW - Genotype KW - Transcription, Genetic -- drug effects KW - Humans KW - Polymerase Chain Reaction -- methods KW - Adult KW - Middle Aged KW - Crack Cocaine -- adverse effects KW - Cluster Analysis KW - Male KW - Cocaine-Related Disorders -- genetics KW - Gene Expression Profiling -- statistics & numerical data KW - Prefrontal Cortex -- physiology KW - Oligonucleotide Array Sequence Analysis -- methods KW - Transcriptional Activation -- drug effects KW - Oligonucleotide Array Sequence Analysis -- statistics & numerical data KW - Gene Expression Profiling -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73076314?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+pharmacogenomics+journal&rft.atitle=Transcriptional+profiling+in+the+human+prefrontal+cortex%3A+evidence+for+two+activational+states+associated+with+cocaine+abuse.&rft.au=Lehrmann%2C+E%3BOyler%2C+J%3BVawter%2C+M+P%3BHyde%2C+T+M%3BKolachana%2C+B%3BKleinman%2C+J+E%3BHuestis%2C+M+A%3BBecker%2C+K+G%3BFreed%2C+W+J&rft.aulast=Lehrmann&rft.aufirst=E&rft.date=2003-01-01&rft.volume=3&rft.issue=1&rft.spage=27&rft.isbn=&rft.btitle=&rft.title=The+pharmacogenomics+journal&rft.issn=1470269X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-14 N1 - Date created - 2003-03-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Neurosci. 2001 Nov 1;21(21):8655-63 [11606653] Neuroscience. 2001;108(3):371-80 [11738252] Mol Cell Biol. 2002 Jan;22(2):587-98 [11756554] Genome Res. 2002 Feb;12(2):292-7 [11827948] Restor Neurol Neurosci. 2001;18(2-3):127-35 [11847435] Eur J Neurosci. 2002 Jan;15(2):269-80 [11849294] Neuropsychopharmacology. 2002 Mar;26(3):376-86 [11850152] J Neurosci. 2002 Apr 1;22(7):2718-29 [11923437] J Neurochem. 2002 Apr;81(2):292-300 [12064476] J Neurochem. 2002 May;81(4):802-13 [12065639] Anesthesiology. 1983 Jun;58(6):495-9 [6859579] Nature. 1990 Apr 26;344(6269):836-41 [2158629] J Neurochem. 1990 Sep;55(3):1079-82 [2117048] J Biol Chem. 1991 Nov 25;266(33):22465-71 [1834672] J Neurosci. 1992 Jun;12(6):2165-76 [1376774] Brain Res. 1992 May 8;579(2):181-6 [1628210] Genomics. 1992 Dec;14(4):1104-6 [1478653] Synapse. 1992 Nov;12(3):242-53 [1362292] J Neurosci. 1993 Jan;13(1):276-84 [8380850] J Neurochem. 1993 Jul;61(1):1-11 [7685811] FEBS Lett. 1993 Sep 6;330(1):85-9 [7690334] Brain Res Mol Brain Res. 1993 Oct;20(1-2):91-100 [8255186] Brain Res. 1993 Oct 29;626(1-2):117-26 [8281422] Am J Psychiatry. 1994 Jul;151(7):1074-6 [8010366] J Neurosci. 1994 Jul;14(7):4289-98 [8027779] Neuron. 1994 Nov;13(5):1235-44 [7946359] Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6542-6 [7604029] Mol Neurobiol. 1995 Aug-Dec;11(1-3):47-53 [8561967] Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):12040-5 [8876259] Biol Psychiatry. 1997 Mar 15;41(6):633-5 [9066985] Neuroreport. 1997 May 6;8(7):1561-5 [9189892] J Neurosci. 1997 Aug 1;17(15):5993-6000 [9221795] J Biol Chem. 1997 Sep 26;272(39):24333-8 [9305890] Neuron. 1997 Sep;19(3):591-611 [9331351] Proc Natl Acad Sci U S A. 1997 Oct 28;94(22):12210-7 [9342388] Brain Res Mol Brain Res. 1997 Oct 3;49(1-2):15-28 [9387859] Am J Psychiatry. 1998 Jan;155(1):124-6 [9433350] Am J Psychiatry. 1998 Feb;155(2):207-13 [9464199] Neuroscience. 1998 Feb;82(4):1103-14 [9466434] Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3269-74 [9501252] Prog Neurobiol. 1998 Apr;54(6):679-720 [9560846] Pharmacol Biochem Behav. 1998 May;60(1):237-44 [9610948] Neuropharmacology. 1998;37(3):339-47 [9681932] Neuron. 1998 Sep;21(3):467-76 [9768834] Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863-8 [9843981] J Neurochem. 1999 Jan;72(1):157-65 [9886066] Am J Psychiatry. 1999 Jan;156(1):11-8 [9892292] Genet Anal. 1999 Feb;14(5-6):143-9 [10084106] Eur J Neurosci. 1999 May;11(5):1598-604 [10215912] Chem Phys Lipids. 1999 Apr;98(1-2):119-26 [10358934] Brain Res. 1999 Jul 3;833(2):133-41 [10375688] Ann N Y Acad Sci. 1999 Jun 29;877:412-38 [10415662] Psychopharmacology (Berl). 1999 Oct;146(4):373-90 [10550488] Brain Res Mol Brain Res. 1999 Nov 10;73(1-2):181-5 [10581411] Cereb Cortex. 2000 Mar;10(3):318-25 [10731226] Eur J Pharmacol. 2000 Mar 30;393(1-3):249-53 [10771021] Neuropsychologia. 2000;38(8):1180-7 [10838152] J Neurosci Res. 2000 Aug 1;61(3):338-49 [10900081] Psychopharmacology (Berl). 2000 Aug;151(2-3):99-120 [10972458] Am J Psychiatry. 2000 Nov;157(11):1789-98 [11058476] Neuron. 2000 Oct;28(1):53-67 [11086983] J Neurosci. 2000 Dec 1;20(23):8701-9 [11102476] Alcohol Clin Exp Res. 2000 Dec;24(12):1873-82 [11141048] Neuropsychologia. 2001;39(4):376-89 [11164876] Synapse. 2001 Mar 1;39(3):257-66 [11169774] Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3577-82 [11248120] Nat Rev Neurosci. 2001 Feb;2(2):119-28 [11252991] J Neurochem. 2001 Apr;77(2):542-9 [11299316] Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6917-22 [11381111] Anal Biochem. 2001 Aug 1;295(1):17-21 [11476540] Brain Res Bull. 2001 Jul 15;55(5):641-50 [11576761] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Natural dietary agents can protect against DMBA genotoxicity in lymphocytes as revealed by single cell gel electrophoresis assay. AN - 73075288; 12616598 AB - Many natural agents including fruits and vegetables are known to provide protection from different degenerative diseases including cancer, by preventing damage to the cellular components. The effect of two important dietary agents, alpha tocopherol, and the flavonoid quercetin, along with two commonly consumed vegetables, bitter gourd and tomato, were investigated on spontaneous and dimethylbenz(a)anthracene (DMBA)-induced DNA damage in murine lymphocytes in vitro. DNA damage was determined by single cell gel electrophoresis (comet assay). The rationale for such an approach for this study is that DNA damage can lead to genetic disorders that occur at different stages of carcinogenesis and protection from such damages may in the long run help to prevent development of cancer. Both alpha tocopherol and quercetin as single agents were found to be potent inhibitors of DNA damage (spontaneous and carcinogen induced) in a dose-dependent manner. Fresh juices of bitter gourd and tomato could also protect from DMBA-induced DNA damage but not as effectively as the single agents. The anticarcinogenic role of nutrients as well as non-nutrient dietary components need to be explored more extensively. The Comet assay is a simple, fast, and reliable method to determine the protective effect against DNA damage, one of the prerequisites for carcinogenesis. Copyright 2003 Wiley-Liss, Inc. JF - Teratogenesis, carcinogenesis, and mutagenesis AU - De, Sarmishtha AU - Ganguly, Chaiti AU - Das, Sukta AD - Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, Kolkata, India. Y1 - 2003 PY - 2003 DA - 2003 SP - 71 EP - 78 VL - Suppl 1 SN - 0270-3211, 0270-3211 KW - Antineoplastic Agents KW - 0 KW - Carcinogens KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Quercetin KW - 9IKM0I5T1E KW - alpha-Tocopherol KW - H4N855PNZ1 KW - Index Medicus KW - Animals KW - Lycopersicon esculentum -- chemistry KW - Dose-Response Relationship, Drug KW - Mice KW - Cell Separation KW - Momordica charantia -- chemistry KW - Carcinogens -- pharmacology KW - Antineoplastic Agents -- metabolism KW - Quercetin -- metabolism KW - Lymphocytes -- metabolism KW - Comet Assay -- methods KW - Carcinogens -- antagonists & inhibitors KW - DNA Damage -- drug effects KW - Lymphocytes -- chemistry KW - alpha-Tocopherol -- pharmacology KW - 9,10-Dimethyl-1,2-benzanthracene -- pharmacology KW - Diet KW - alpha-Tocopherol -- metabolism KW - Antineoplastic Agents -- pharmacology KW - Lymphocytes -- drug effects KW - Quercetin -- pharmacology KW - 9,10-Dimethyl-1,2-benzanthracene -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73075288?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Natural+dietary+agents+can+protect+against+DMBA+genotoxicity+in+lymphocytes+as+revealed+by+single+cell+gel+electrophoresis+assay.&rft.au=De%2C+Sarmishtha%3BGanguly%2C+Chaiti%3BDas%2C+Sukta&rft.aulast=De&rft.aufirst=Sarmishtha&rft.date=2003-01-01&rft.volume=Suppl+1&rft.issue=&rft.spage=71&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 - 2003-09-16 N1 - Date created - 2003-03-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Slowing tumorigenic progression in TRAMP mice and prostatic carcinoma cell lines using natural anti-oxidant from spinach, NAO--a comparative study of three anti-oxidants. AN - 73040097; 12597448 AB - The TRAMP model and human prostatic cancer (PCA) cell lines DU145 and PC3 are useful forchemopreventive studies. We compared the efficacy of 3 anti-oxidants [a water-soluble natural anti-oxidant. NAO (200 mg/kg). found in spinach leaves; epigallocatechin-3 gallate, EGCG (200 mg/kg), a major green tea polyphenol; and N-acetylcysteine, NAC (125 mg/kg)] plus vehicle in slowing spontaneous tumorigenic progression in TRAMP and wild-type male mice. Sacrifices occurred on weeks 5, 9, and 13. Prostatic histopathology and oxidative-stress blood markers were evaluated. Hyperplasias were ranked by a combination of severity grade and distribution (focal, multifocal, and diffuse). The effectivity of each tested compound in reducing the severity/focalness of hyperplasia varied from lobe to lobe. NAO exerted a significant effect on the dorsal and lateral lobes; NAC, on the anterior and ventral lobes, and EGCG, on the ventral lobe. When the most severe hyperplasia in all 4 lobes of TRAMPs was evaluated, only NAO reduced hyperplasia at weeks 9 and 13. Plasma peroxide levels in TRAMPs were reduced following oral administration of NAO or NAC for 13 weeks; EGCG only slightly reduced these levels. In NAO-treated DU 145 and PC3 PCA cells, inhibition of cellular proliferation occurred in a dose-dependent manner, increasing numbers of G1 cells and reducing ROS levels. The anti-oxidative and antiproliferative properties of NAO may explain its efficacy in slowing the spontaneous prostatic carcinogenic process in the TRAMP and its effects in the cell lines. JF - Toxicologic pathology AU - Nyska, Abraham AU - Suttie, Andrew AU - Bakshi, Shlomo AU - Lomnitski, Liat AU - Grossman, Sholomo AU - Bergman, Margalit AU - Ben-Shaul, Varda AU - Crocket, Patrick AU - Haseman, Joseph K AU - Moser, Glenda AU - Goldsworthy, Thomas L AU - Maronpot, Robert R AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina 27709, USA. nyska@niehs.nih.gov PY - 2003 SP - 39 EP - 51 VL - 31 IS - 1 SN - 0192-6233, 0192-6233 KW - Antioxidants KW - 0 KW - Reactive Oxygen Species KW - Catechin KW - 8R1V1STN48 KW - epigallocatechin gallate KW - BQM438CTEL KW - Acetylcysteine KW - WYQ7N0BPYC KW - Index Medicus KW - Administration, Oral KW - Reactive Oxygen Species -- metabolism KW - Animals KW - Drug Screening Assays, Antitumor KW - Acetylcysteine -- therapeutic use KW - Humans KW - Cell Division -- drug effects KW - Disease Progression KW - Mice KW - Mice, Transgenic KW - Acetylcysteine -- isolation & purification KW - Tumor Cells, Cultured KW - Mice, Inbred C57BL KW - G1 Phase -- drug effects KW - Male KW - Prostatic Neoplasms -- metabolism KW - Spinacia oleracea -- chemistry KW - Antioxidants -- isolation & purification KW - Catechin -- analogs & derivatives KW - Catechin -- isolation & purification KW - Catechin -- therapeutic use KW - Prostatic Neoplasms -- drug therapy KW - Prostatic Neoplasms -- pathology KW - Carcinoma -- pathology KW - Carcinoma -- drug therapy KW - Antioxidants -- therapeutic use KW - Prostatic Hyperplasia -- metabolism KW - Prostatic Hyperplasia -- pathology KW - Carcinoma -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73040097?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Slowing+tumorigenic+progression+in+TRAMP+mice+and+prostatic+carcinoma+cell+lines+using+natural+anti-oxidant+from+spinach%2C+NAO--a+comparative+study+of+three+anti-oxidants.&rft.au=Nyska%2C+Abraham%3BSuttie%2C+Andrew%3BBakshi%2C+Shlomo%3BLomnitski%2C+Liat%3BGrossman%2C+Sholomo%3BBergman%2C+Margalit%3BBen-Shaul%2C+Varda%3BCrocket%2C+Patrick%3BHaseman%2C+Joseph+K%3BMoser%2C+Glenda%3BGoldsworthy%2C+Thomas+L%3BMaronpot%2C+Robert+R&rft.aulast=Nyska&rft.aufirst=Abraham&rft.date=2003-01-01&rft.volume=31&rft.issue=1&rft.spage=39&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 - 2003-07-28 N1 - Date created - 2003-02-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Loss of CDC5 function in Saccharomyces cerevisiae leads to defects in Swe1p regulation and Bfa1p/Bub2p-independent cytokinesis. AN - 73018691; 12586693 AB - In many organisms, polo kinases appear to play multiple roles during M-phase progression. To provide new insights into the function of budding yeast polo kinase Cdc5p, we generated novel temperature-sensitive cdc5 mutants by mutagenizing the C-terminal domain. Here we show that, at a semipermissive temperature, the cdc5-3 mutant exhibited a synergistic bud elongation and growth defect with loss of HSL1, a component important for normal G(2)/M transition. Loss of SWE1, which phosphorylates and inactivates the budding yeast Cdk1 homolog Cdc28p, suppressed the cdc5-3 hsl1Delta defect, suggesting that Cdc5p functions at a point upstream of Swe1p. In addition, the cdc5-4 and cdc5-7 mutants exhibited chained cell morphologies with shared cytoplasms between the connected cell bodies, indicating a cytokinetic defect. Close examination of these mutants revealed delayed septin assembly at the incipient bud site and loosely organized septin rings at the mother-bud neck. Components in the mitotic exit network (MEN) play important roles in normal cytokinesis. However, loss of BFA1 or BUB2, negative regulators of the MEN, failed to remedy the cytokinetic defect of these mutants, indicating that Cdc5p promotes cytokinesis independently of Bfa1p and Bub2p. Thus, Cdc5p contributes to the activation of the Swe1p-dependent Cdc28p/Clb pathway, normal septin function, and cytokinesis. JF - Genetics AU - Park, Chong Jin AU - Song, Sukgil AU - Lee, Philip R AU - Shou, Wenying AU - Deshaies, Raymond J AU - Lee, Kyung S AD - Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/01// PY - 2003 DA - January 2003 SP - 21 EP - 33 VL - 163 IS - 1 SN - 0016-6731, 0016-6731 KW - BFA1 protein, S cerevisiae KW - 0 KW - BUB2 protein, S cerevisiae KW - CLB2 protein, S cerevisiae KW - Cell Cycle Proteins KW - Cyclin B KW - Cytoskeletal Proteins KW - Saccharomyces cerevisiae Proteins KW - Protein Kinases KW - EC 2.7.- KW - SWE1 protein, S cerevisiae KW - EC 2.7.1.- KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - CDC5 protein, S cerevisiae KW - EC 2.7.11.21 KW - CDC28 Protein Kinase, S cerevisiae KW - EC 2.7.11.22 KW - Index Medicus KW - Gene Expression Regulation, Fungal KW - Saccharomyces cerevisiae Proteins -- metabolism KW - CDC28 Protein Kinase, S cerevisiae -- metabolism KW - Mitosis -- genetics KW - Cyclin B -- metabolism KW - Mitosis -- physiology KW - Cytoskeletal Proteins -- metabolism KW - Mutation KW - Cell Cycle Proteins -- metabolism KW - Saccharomyces cerevisiae -- genetics KW - Protein Kinases -- metabolism KW - Protein-Tyrosine Kinases -- genetics KW - Saccharomyces cerevisiae -- metabolism KW - Protein Kinases -- genetics KW - Saccharomyces cerevisiae -- enzymology KW - Protein-Tyrosine Kinases -- metabolism KW - Cell Division -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73018691?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Loss+of+CDC5+function+in+Saccharomyces+cerevisiae+leads+to+defects+in+Swe1p+regulation+and+Bfa1p%2FBub2p-independent+cytokinesis.&rft.au=Park%2C+Chong+Jin%3BSong%2C+Sukgil%3BLee%2C+Philip+R%3BShou%2C+Wenying%3BDeshaies%2C+Raymond+J%3BLee%2C+Kyung+S&rft.aulast=Park&rft.aufirst=Chong&rft.date=2003-01-01&rft.volume=163&rft.issue=1&rft.spage=21&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-12 N1 - Date created - 2003-02-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Cell Biol. 1998 Nov 2;143(3):709-17 [9813092] J Cell Biol. 1998 Nov 2;143(3):659-71 [9813088] J Cell Biol. 1998 Dec 14;143(6):1603-16 [9852154] J Cell Biol. 1998 Dec 14;143(6):1617-34 [9852155] J Cell Biol. 1998 Dec 28;143(7):1947-60 [9864366] Genes Dev. 1998 Dec 15;12(24):3777-87 [9869630] Mol Cell Biol. 1999 Feb;19(2):1369-80 [9891070] Genes Dev. 1999 Jan 15;13(2):176-87 [9925642] Mol Cell Biol. 1999 Oct;19(10):6929-39 [10490630] Mol Cell Biol. 1999 Oct;19(10):7123-37 [10490648] J Cell Biol. 1997 Oct 6;139(1):75-93 [9314530] J Cell Biol. 1998 Jan 26;140(2):355-66 [9442111] Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14360-5 [10588710] Mol Cell Biol. 2000 Jan;20(1):286-98 [10594031] Mol Cell Biol. 2000 Jun;20(11):4049-61 [10805747] Mol Cell. 2000 May;5(5):841-51 [10882120] J Cell Sci. 2000 Oct;113 Pt 19:3399-408 [10984431] Science. 2000 Oct 13;290(5490):341-4 [11030653] J Cell Biol. 2001 Feb 5;152(3):451-69 [11157974] Nature. 2001 Mar 8;410(6825):215-20 [11242082] EMBO J. 2001 Mar 15;20(6):1259-70 [11250892] J Cell Sci. 2001 Apr;114(Pt 7):1379-86 [11257003] Mol Cell Biol. 2001 Aug;21(15):4949-59 [11438652] J Cell Sci. 2001 Jun;114(Pt 12):2345-54 [11493673] Cell. 2001 Nov 30;107(5):655-65 [11733064] J Bacteriol. 1983 Jan;153(1):163-8 [6336730] Yeast. 1992 Feb;8(2):79-82 [1561838] J Cell Biol. 1993 Mar;120(6):1305-20 [8449978] EMBO J. 1993 Sep;12(9):3417-26 [8253069] J Cell Biol. 1995 May;129(3):767-78 [7730410] Genes Dev. 1996 Jun 1;10(11):1327-40 [8647431] Science. 1996 Sep 6;273(5280):1377-80 [8703070] Curr Opin Cell Biol. 1996 Feb;8(1):106-19 [8791410] Mol Biol Cell. 1997 Jun;8(6):987-98 [9201710] EMBO J. 1998 Mar 2;17(5):1328-35 [9482730] EMBO J. 1998 Mar 2;17(5):1336-49 [9482731] Curr Biol. 1998 Apr 23;8(9):497-507 [9560342] Genes Dev. 1998 May 15;12(10):1483-94 [9585508] Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9301-6 [9689075] Yeast. 1998 Jul;14(10):953-61 [9717241] J Cell Biol. 1998 Sep 7;142(5):1301-12 [9732290] Curr Biol. 1998 Aug 27;8(17):947-54 [9742395] J Cell Biol. 1998 Nov 2;143(3):737-49 [9813094] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Autopsy: coaxing secrets from the dead. Every drug is a poison; every poison, a drug. AN - 73017638; 12585747 JF - Journal of the American Pharmaceutical Association (Washington,D.C. : 1996) AU - Wick, Jeannette Y AU - Zanni, Guido R AD - National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. PY - 2003 SP - 18 EP - 23 VL - 43 IS - 1 SN - 1086-5802, 1086-5802 KW - Index Medicus KW - History, 20th Century KW - Humans KW - History, Ancient KW - History, 19th Century KW - History, 17th Century KW - History, Medieval KW - Male KW - Female KW - Poisoning -- diagnosis KW - Autopsy -- methods KW - Autopsy -- history UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73017638?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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+Pharmaceutical+Association+%28Washington%2CD.C.+%3A+1996%29&rft.atitle=Autopsy%3A+coaxing+secrets+from+the+dead.+Every+drug+is+a+poison%3B+every+poison%2C+a+drug.&rft.au=Wick%2C+Jeannette+Y%3BZanni%2C+Guido+R&rft.aulast=Wick&rft.aufirst=Jeannette&rft.date=2003-01-01&rft.volume=43&rft.issue=1&rft.spage=18&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Pharmaceutical+Association+%28Washington%2CD.C.+%3A+1996%29&rft.issn=10865802&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-18 N1 - Date created - 2003-02-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transplacental carcinogenicity of inorganic arsenic in the drinking water: induction of hepatic, ovarian, pulmonary, and adrenal tumors in mice. AN - 73013912; 12583988 AB - Arsenic is a known human carcinogen, but development of rodent models of inorganic arsenic carcinogenesis has been problematic. Since gestation is often a period of high sensitivity to chemical carcinogenesis, we performed a transplacental carcinogenicity study in mice using inorganic arsenic. Groups (n = 10) of pregnant C3H mice were given drinking water containing sodium arsenite (NaAsO(2)) at 0 (control), 42.5, and 85 ppm arsenite ad libitum from day 8 to 18 of gestation. These doses were well tolerated and body weights of the dams during gestation and of the offspring subsequent to birth were not reduced. Dams were allowed to give birth, and offspring were weaned at 4 weeks and then put into separate gender-based groups (n = 25) according to maternal exposure level. The offspring received no additional arsenic treatment. The study lasted 74 weeks in males and 90 weeks in females. A complete necropsy was performed on all mice and tissues were examined by light microscopy in a blind fashion. In male offspring, there was a marked increase in hepatocellular carcinoma incidence in a dose- related fashion (control, 12%; 42.5 ppm, 38%; 85 ppm, 61%) and in liver tumor multiplicity (tumors per liver; 5.6-fold over control at 85 ppm). In males, there was also a dose-related increase in adrenal tumor incidence and multiplicity. In female offspring, dose-related increases occurred in ovarian tumor incidence (control, 8%; 42.5 ppm, 26%; 85 ppm, 38%) and lung carcinoma incidence (control, 0%; 42.5 ppm, 4%; 85 ppm, 21%). Arsenic exposure also increased the incidence of proliferative lesions of the uterus and oviduct. These results demonstrate that oral inorganic arsenic exposure, as a single agent, can induce tumor formation in rodents and establishes inorganic arsenic as a complete transplacental carcinogen in mice. The development of this rodent model of inorganic arsenic carcinogenesis has important implications in defining the mechanism of action for this common environmental carcinogen. Copyright 2003 Elsevier Science (USA) JF - Toxicology and applied pharmacology AU - Waalkes, Michael P AU - Ward, Jerrold M AU - Liu, Jie AU - Diwan, Bhalchandra A AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at the National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. waalkes@niehs.nih.gov Y1 - 2003/01/01/ PY - 2003 DA - 2003 Jan 01 SP - 7 EP - 17 VL - 186 IS - 1 SN - 0041-008X, 0041-008X KW - Arsenites KW - 0 KW - Sodium Compounds KW - Water Pollutants, Chemical KW - sodium arsenite KW - 48OVY2OC72 KW - Index Medicus KW - Animals KW - Mice, Inbred C57BL KW - Mice KW - Male KW - Female KW - Pregnancy KW - Arsenic Poisoning -- etiology KW - Chemical and Drug Induced Liver Injury -- pathology KW - Water Pollutants, Chemical -- toxicity KW - Arsenites -- toxicity KW - Ovarian Neoplasms -- chemically induced KW - Maternal-Fetal Exchange KW - Chemical and Drug Induced Liver Injury -- etiology KW - Ovarian Neoplasms -- pathology KW - Adrenal Gland Neoplasms -- chemically induced KW - Sodium Compounds -- toxicity KW - Adrenal Gland Neoplasms -- pathology KW - Lung Neoplasms -- chemically induced KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73013912?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Transplacental+carcinogenicity+of+inorganic+arsenic+in+the+drinking+water%3A+induction+of+hepatic%2C+ovarian%2C+pulmonary%2C+and+adrenal+tumors+in+mice.&rft.au=Waalkes%2C+Michael+P%3BWard%2C+Jerrold+M%3BLiu%2C+Jie%3BDiwan%2C+Bhalchandra+A&rft.aulast=Waalkes&rft.aufirst=Michael&rft.date=2003-01-01&rft.volume=186&rft.issue=1&rft.spage=7&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 - 2003-03-12 N1 - Date created - 2003-02-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alcohol dependence and the price of alcoholic beverages. AN - 72998247; 12564720 AB - This study estimates the impact of the price of alcoholic beverages on latent dimensions of current alcohol dependence and abuse. A three-part econometric model is used to estimate the impact of price on three latent dimensions (factors). For heavier drinking, the estimated price elasticity is -1.325 (P = 0.027); for physical and other consequences of drinking, -1.895 (P = 0.003); for increased salience of drinking, -0.411 (P = 0.339). For a single latent factor characterized simply as dependence/abuse, estimated price elasticity is -1.487 (P = 0.012). These results suggest that higher prices for alcohol reduce important dimensions of current alcohol dependence and abuse. JF - Journal of health economics AU - Farrell, Susan AU - Manning, Willard G AU - Finch, Michael D AD - University of Minnesota, USA. sfarrell@willco.niaaa.nih.gov Y1 - 2003/01// PY - 2003 DA - January 2003 SP - 117 EP - 147 VL - 22 IS - 1 SN - 0167-6296, 0167-6296 KW - Health administration KW - Regression Analysis KW - Chronic Disease -- economics KW - Risk-Taking KW - Humans KW - Income KW - Demography KW - Choice Behavior KW - Taxes KW - Drug and Narcotic Control KW - Cost of Illness KW - Models, Econometric KW - United States -- epidemiology KW - Family Health KW - Alcoholism -- epidemiology KW - Alcoholic Beverages -- economics KW - Fees and Charges KW - Health Behavior KW - Alcoholism -- economics KW - Alcoholism -- complications KW - Alcoholic Beverages -- supply & distribution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72998247?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+health+economics&rft.atitle=Alcohol+dependence+and+the+price+of+alcoholic+beverages.&rft.au=Farrell%2C+Susan%3BManning%2C+Willard+G%3BFinch%2C+Michael+D&rft.aulast=Farrell&rft.aufirst=Susan&rft.date=2003-01-01&rft.volume=22&rft.issue=1&rft.spage=117&rft.isbn=&rft.btitle=&rft.title=Journal+of+health+economics&rft.issn=01676296&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-25 N1 - Date created - 2003-02-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Docetaxel-related skin, nail, and vascular toxicity. AN - 72993105; 12564432 JF - The Annals of pharmacotherapy AU - Leonard, Gregory D AU - Zujewski, Jo Anne AD - Medical Oncology Clinical Research Unit, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1960, USA. leonardg@mail.nih.gov Y1 - 2003/01// PY - 2003 DA - January 2003 SP - 148 VL - 37 IS - 1 SN - 1060-0280, 1060-0280 KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Taxoids KW - docetaxel KW - 15H5577CQD KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Toes KW - Infusions, Intravenous KW - Humans KW - Middle Aged KW - Forearm KW - Female KW - Nail Diseases -- chemically induced KW - Paclitaxel -- adverse effects KW - Antineoplastic Agents, Phytogenic -- adverse effects KW - Phlebitis -- chemically induced KW - Antineoplastic Agents, Phytogenic -- therapeutic use KW - Paclitaxel -- analogs & derivatives KW - Paclitaxel -- therapeutic use KW - Skin Diseases -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72993105?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Annals+of+pharmacotherapy&rft.atitle=Docetaxel-related+skin%2C+nail%2C+and+vascular+toxicity.&rft.au=Leonard%2C+Gregory+D%3BZujewski%2C+Jo+Anne&rft.aulast=Leonard&rft.aufirst=Gregory&rft.date=2003-01-01&rft.volume=37&rft.issue=1&rft.spage=148&rft.isbn=&rft.btitle=&rft.title=The+Annals+of+pharmacotherapy&rft.issn=10600280&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-24 N1 - Date created - 2003-02-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chronic lithium treatment antagonizes glutamate-induced decrease of phosphorylated CREB in neurons via reducing protein phosphatase 1 and increasing MEK activities. AN - 72992386; 12559097 AB - The cyclic AMP response element binding protein (CREB) has major roles in mediating adaptive responses at glutamatergic synapses and in the neuroprotective effects of neurotrophins. CREB has been implicated as a potential mediator of antidepressant actions. In vitro, chronic lithium treatment has been shown to promote neuronal cell survival. In the present study, we have used cultures of cerebellar granule neurons to analyze the effects of acute and chronic lithium treatment on the response to toxic concentrations of glutamate. Such concentrations of glutamate decrease the phosphorylation of CREB at serine(133) in an N-methyl-D-aspartate (NMDA) receptor-dependent manner. Chronic, but not acute, lithium treatment suppresses glutamate-induced decreases in phosphorylated CREB, and transfection studies indicate that chronic lithium, in the presence of a glutamate stimulus, markedly increases CRE-driven gene expression. Experiments with selected pharmacological reagents indicate that the glutamate-induced decreases in phosphorylated CREB are regulated primarily by protein phosphatase 1. Chronic lithium treatment not only decreases protein phosphatase 1 activity under these circumstances, but also augments glutamate-induced increases in MEK activity. PD 98059, a MEK inhibitor, prevents chronic lithium treatment from increasing phosphorylated CREB levels in glutamate-treated neurons. We conclude from these results that chronic lithium treatment is permissive for maintaining higher phosphorylated CREB levels in the presence of glutamate in part by decreasing protein phosphatase 1 activity and in part by increasing MEK activity. Higher levels of phosphorylated CREB and CRE-responsive genes such as bcl-2 may be responsible for lithium's reported effects on neuronal survival. JF - Neuroscience AU - Kopnisky, K L AU - Chalecka-Franaszek, E AU - Gonzalez-Zulueta, M AU - Chuang, D-M AD - Molecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, Building 10 Center Drive, Room 4C206, MSC 1363 Bethesda, MD 20892-1363, USA. Y1 - 2003 PY - 2003 DA - 2003 SP - 425 EP - 435 VL - 116 IS - 2 SN - 0306-4522, 0306-4522 KW - Chromones KW - 0 KW - Cyclic AMP Response Element-Binding Protein KW - Enzyme Inhibitors KW - Excitatory Amino Acid Antagonists KW - Morpholines KW - 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one KW - 31M2U1DVID KW - Glutamic Acid KW - 3KX376GY7L KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - 6-Cyano-7-nitroquinoxaline-2,3-dione KW - 6OTE87SCCW KW - Lithium KW - 9FN79X2M3F KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Mitogen-Activated Protein Kinase 1 KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinase 3 KW - Mitogen-Activated Protein Kinases KW - Phosphoprotein Phosphatases KW - EC 3.1.3.16 KW - Protein Phosphatase 1 KW - Index Medicus KW - Animals KW - Drug Interactions KW - Mitogen-Activated Protein Kinases -- metabolism KW - Morpholines -- pharmacology KW - 6-Cyano-7-nitroquinoxaline-2,3-dione -- pharmacology KW - Dizocilpine Maleate -- pharmacology KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Rats KW - Rats, Sprague-Dawley KW - Cerebellum -- cytology KW - Phosphorylation KW - Chromones -- pharmacology KW - Cells, Cultured KW - Mitogen-Activated Protein Kinase 1 -- metabolism KW - Enzyme Inhibitors -- pharmacology KW - Cyclic AMP Response Element-Binding Protein -- metabolism KW - Protein-Serine-Threonine Kinases -- metabolism KW - Neurons -- metabolism KW - Neurons -- drug effects KW - Phosphoprotein Phosphatases -- metabolism KW - Glutamic Acid -- pharmacology KW - Lithium -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72992386?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chronic+lithium+treatment+antagonizes+glutamate-induced+decrease+of+phosphorylated+CREB+in+neurons+via+reducing+protein+phosphatase+1+and+increasing+MEK+activities.&rft.au=Kopnisky%2C+K+L%3BChalecka-Franaszek%2C+E%3BGonzalez-Zulueta%2C+M%3BChuang%2C+D-M&rft.aulast=Kopnisky&rft.aufirst=K&rft.date=2003-01-01&rft.volume=116&rft.issue=2&rft.spage=425&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-17 N1 - Date created - 2003-01-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fluctuations in neural activity during cocaine self-administration: clues provided by brain thermorecording. AN - 72986634; 12559108 AB - Since metabolic neural activity is accompanied by heat release, measurement of local brain temperature offers a method for assessing alterations in neural activity. This approach, continuous monitoring of local brain (ventral tegmental area, ventral striatum, and hippocampus) and body (temporal muscle) temperature, was used to study intravenous cocaine self-administration in trained rats. The first self-administration of a session was preceded by a strong temperature increase that continued after the drug infusion. After peaking at the time of the second self-administration, temperature plateaued (+0.7 degrees C) with biphasic fluctuations (+/-0.10-0.15 degrees C) around each subsequent self-administration. Temperature gradually increased before and for 30-50 s after the lever-press, but then abruptly decreased to a minimum at 180-240 s, when it began to increase to reach another peak immediately after the next lever-press. Doubling the dose of injected cocaine significantly potentiated the post-cocaine temperature decrease and increased time to the next lever-press. In contrast to drug-reinforced lever-presses, temperatures phasically increased after non-reinforced lever-presses and at the end of a session when the lever was blocked and the rat was hyperactive, trying to reach the inaccessible lever. While temperature changes in each recording location were generally correlative, the initial temperature elevation was stronger in all brain structures than in muscle and ventral striatum was the structure that showed the most pronounced and consistent temperature fluctuations. These data suggest a generalized brain activation associated with cocaine-seeking and cocaine-taking behavior with its phasic fluctuations around individual drug self-injections. While the initial component of brain activation preceding the first lever-press for cocaine is internally determined and closely related to behavioral search, subsequent biphasic fluctuations in neural activity associated with repeated drug intakes appear to be drug-mediated. Cocaine-induced potentiation of monoamine transmission is a possible factor for gradual increases in neural activity that drive cocaine seeking, while a rapid, brain concentration-dependent action on Na(+) transport (local anesthetic action) is the most probable factor determining an abrupt, transient cessation of neural activation associated with cocaine reward. JF - Neuroscience AU - Kiyatkin, E A AU - Brown, P L AD - Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. ekiyatki@intra.nida.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 525 EP - 538 VL - 116 IS - 2 SN - 0306-4522, 0306-4522 KW - Dopamine Uptake Inhibitors KW - 0 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Rats KW - Animals KW - Self Administration KW - Rats, Long-Evans KW - Reward KW - Motivation KW - Energy Metabolism -- physiology KW - Cocaine-Related Disorders -- metabolism KW - Male KW - Brain -- drug effects KW - Body Temperature -- physiology KW - Cocaine -- pharmacology KW - Brain -- physiology KW - Dopamine Uptake Inhibitors -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72986634?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Fluctuations+in+neural+activity+during+cocaine+self-administration%3A+clues+provided+by+brain+thermorecording.&rft.au=Kiyatkin%2C+E+A%3BBrown%2C+P+L&rft.aulast=Kiyatkin&rft.aufirst=E&rft.date=2003-01-01&rft.volume=116&rft.issue=2&rft.spage=525&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-17 N1 - Date created - 2003-01-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Progress toward clinical application of the nitric oxide-releasing diazeniumdiolates. AN - 72983206; 12415121 AB - Diazeniumdiolates, compounds of structure R(1)R(2)NN(O)=NOR(3), which have also been called NONOates, have proven useful for treating an increasing diversity of medical disorders in relevant animal models. Here, I review the chemical features that make them such excellent starting points for designing materials capable of targeting reliable and controllable fluxes of bioactive NO for in vitro and in vivo applications. This is followed by a consideration of recent proof-of-concept studies that underscore what I believe to be the substantial clinical promise of such materials. Examples covered include progress toward inhibiting restenosis after angioplasty, preparing thromboresistant medical devices, reversing vasospasm, and relieving pulmonary hypertension. Together with a very recent report describing the beneficial effects of diazeniumdiolate therapy in a patient with acute respiratory distress syndrome, the results of the animal experiments support the prediction that a broad selection of problems in clinical medicine can be solved by judiciously mining the enormous variety of possible R(1)R(2)NN(O)=NOR(3) structures. JF - Annual review of pharmacology and toxicology AU - Keefer, Larry K AD - Chemistry Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA. keefer@ncifcrf.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 585 EP - 607 VL - 43 SN - 0362-1642, 0362-1642 KW - Azo Compounds KW - 0 KW - Nitric Oxide Donors KW - diazeniumdiolate KW - Nitric Oxide KW - 31C4KY9ESH KW - Index Medicus KW - Humans KW - Structure-Activity Relationship KW - Nitric Oxide Donors -- therapeutic use KW - Azo Compounds -- chemistry KW - Nitric Oxide -- physiology KW - Drug Design KW - Azo Compounds -- therapeutic use KW - Nitric Oxide Donors -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72983206?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Progress+toward+clinical+application+of+the+nitric+oxide-releasing+diazeniumdiolates.&rft.au=Keefer%2C+Larry+K&rft.aulast=Keefer&rft.aufirst=Larry&rft.date=2003-01-01&rft.volume=43&rft.issue=&rft.spage=585&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 - 2003-09-09 N1 - Date created - 2003-01-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombinant human activated protein C in sepsis: inconsistent trial results, an unclear mechanism of action, and safety concerns resulted in labeling restrictions and the need for phase IV trials. AN - 72978487; 12544982 JF - Critical care medicine AU - Eichacker, Peter Q AU - Natanson, Charles AD - Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/01// PY - 2003 DA - January 2003 SP - S94 EP - S96 VL - 31 IS - 1 Suppl SN - 0090-3493, 0090-3493 KW - Anti-Infective Agents KW - 0 KW - Protein C KW - Recombinant Proteins KW - drotrecogin alfa activated KW - JGH8MYC891 KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Animals KW - Humans KW - Disease Models, Animal KW - Protein C -- therapeutic use KW - Clinical Trials, Phase IV as Topic KW - Anti-Infective Agents -- pharmacokinetics KW - Clinical Trials, Phase II as Topic KW - Clinical Trials, Phase III as Topic KW - Protein C -- pharmacokinetics KW - Sepsis -- drug therapy KW - Recombinant Proteins -- pharmacokinetics KW - Anti-Infective Agents -- therapeutic use KW - Anti-Infective Agents -- adverse effects KW - Drug Approval KW - Recombinant Proteins -- adverse effects KW - Protein C -- adverse effects KW - Drug Labeling KW - Recombinant Proteins -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72978487?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Critical+care+medicine&rft.atitle=Recombinant+human+activated+protein+C+in+sepsis%3A+inconsistent+trial+results%2C+an+unclear+mechanism+of+action%2C+and+safety+concerns+resulted+in+labeling+restrictions+and+the+need+for+phase+IV+trials.&rft.au=Eichacker%2C+Peter+Q%3BNatanson%2C+Charles&rft.aulast=Eichacker&rft.aufirst=Peter&rft.date=2003-01-01&rft.volume=31&rft.issue=1+Suppl&rft.spage=S94&rft.isbn=&rft.btitle=&rft.title=Critical+care+medicine&rft.issn=00903493&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-12 N1 - Date created - 2003-01-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Crit Care Med. 2004 Jan;32(1):311-2 [14707611] Crit Care Med. 2003 Aug;31(8):2249 [12973192] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Extended mortality follow-up of a cohort of dry cleaners. AN - 72973486; 12547485 AB - The mortality follow-up of a cohort of dry cleaners was extended to further evaluate cancers risks associated with organic solvents. The underlying and contributing causes of death among 5,369 members of a dry cleaning union in St. Louis were determined through December 31, 1993. The mortality experience of the cohort was compared to that of the US population adjusted for age at entry, year of death, race and gender. The total mortality was about as expected (SMR = 1.0, N = 2351, 95% CI = 1.0-1.1). Excesses were observed for emphysema (SMR = 1.7, N = 21, 95% CI = 1.0-2.5), Hodgkin's disease (SMR = 2.0, N = 5, 95% CI = 0.6-4.6) and cancers of the esophagus (SMR = 2.2, N = 26, 95% CI = 1.5-3.3), larynx (SMR = 1.7, N = 6, 95% CI = 0.6-3.7), lung (SMR = 1.4, N = 125), 95% CI = 1.1-1.6), and cervix (SMR = 1.6, N = 27, 95% CI = 1.0-2.3). These excesses occurred among men and women and blacks and whites. Bladder cancer was elevated among white men and women and kidney cancer among black men and women, but not significantly so. None of these causes of death showed strong relationships with duration or estimated level of exposure to dry cleaning solvents, although relative risks for cancers of the larynx, lung and kidney were larger among subjects estimated to have higher levels of exposure and risks from bladder cancer and chronic nephritis were greater among persons who entered the union after 1960. The excesses observed are unlikely to be due to chance because most occurred in earlier as well as the recent follow-up. The specific factors contributing the excesses, however, are not clear. Socioeconomic, lifestyle, and occupational exposures are all possibilities. Lack of information on socioeconomic and lifestyle factors hampers evaluation. JF - Annals of epidemiology AU - Blair, Aaron AU - Petralia, Sandra A AU - Stewart, Patricia A AD - Department of Occupational Epidemiology, Branch Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2003/01// PY - 2003 DA - January 2003 SP - 50 EP - 56 VL - 13 IS - 1 SN - 1047-2797, 1047-2797 KW - Solvents KW - 0 KW - Index Medicus KW - Risk Factors KW - Humans KW - Confounding Factors (Epidemiology) KW - African Americans -- statistics & numerical data KW - European Continental Ancestry Group -- statistics & numerical data KW - Follow-Up Studies KW - United States -- epidemiology KW - Sex Distribution KW - Male KW - Female KW - Neoplasms -- mortality KW - Solvents -- adverse effects KW - Occupational Exposure -- adverse effects KW - Occupational Diseases -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72973486?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Extended+mortality+follow-up+of+a+cohort+of+dry+cleaners.&rft.au=Blair%2C+Aaron%3BPetralia%2C+Sandra+A%3BStewart%2C+Patricia+A&rft.aulast=Blair&rft.aufirst=Aaron&rft.date=2003-01-01&rft.volume=13&rft.issue=1&rft.spage=50&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 - 2003-03-25 N1 - Date created - 2003-01-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Progressive and extensive dopaminergic degeneration induced by convection-enhanced delivery of 6-hydroxydopamine into the rat striatum: a novel rodent model of Parkinson disease. AN - 72972693; 12546362 AB - A striatal dopamine lesion induces progressive nigral degeneration in rodents; however, intrastriatal injection of 6-hydroxydopamine (6-OHDA) causes only limited lesions due to spontaneous regeneration of the neurons that survive. To make an extensive lesion, the authors used a convection-enhanced delivery (CED) method for intrastriatal infusion of 6-OHDA and evaluated the animals for a model of Parkinson disease (PD). Different doses of 6-OHDA were infused into the unilateral striatum in rats by using the CED method. The dopaminergic neuronal degeneration was evaluated based on morphological, biochemical, and behavioral measurements until 8 weeks postlesion. Due to the wide distribution of the drug, CED of 20 microg of 6-OHDA into the striatum was sufficient to obtain a progressive and extensive nigrostriatal lesion as defined by morphological (> 80% cell loss in the substantia nigra [SN]) and biochemical (> 95% decrease in striatal dopamine) criteria. The extent of the lesion manifested as a stable turning behavior with amphetamine (> 6 turns/minute) and apomorphine (> 4 turns/minute). It also appeared that at I week postlesion the apoptotic markers were maximal in neurons of the SN. A rat model of PD with a progressive and extensive dopamine lesion was successfully made by intrastriatal CED of 6-OHDA. In this model, the therapeutic value can be assessed using behavioral, biochemical, and histochemical measurements. The delay of nigral neuronal death with respect to the time of 6-OHDA administration may provide a therapeutic window for testing neuroprotective strategies. JF - Journal of neurosurgery AU - Oiwa, Yoshitsugu AU - Sanchez-Pernaute, Rosario AU - Harvey-White, Judith AU - Bankiewicz, Krys S AD - Molecular Therapeutics Section, Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. oiwa@wakayama-med.ac.jp Y1 - 2003/01// PY - 2003 DA - January 2003 SP - 136 EP - 144 VL - 98 IS - 1 SN - 0022-3085, 0022-3085 KW - Adrenergic Agents KW - 0 KW - Cardiotonic Agents KW - Oxidopamine KW - 8HW4YBZ748 KW - Dopamine KW - VTD58H1Z2X KW - Abridged Index Medicus KW - Index Medicus KW - Severity of Illness Index KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Cardiotonic Agents -- analysis KW - Substantia Nigra -- pathology KW - Substantia Nigra -- drug effects KW - Dopamine -- analysis KW - Disease Models, Animal KW - Time Factors KW - Convection KW - Adrenergic Agents -- adverse effects KW - Parkinson Disease, Secondary -- chemically induced KW - Drug Delivery Systems KW - Parkinson Disease, Secondary -- pathology KW - Oxidopamine -- administration & dosage KW - Nerve Degeneration -- pathology KW - Nerve Degeneration -- chemically induced KW - Corpus Striatum -- drug effects KW - Oxidopamine -- adverse effects KW - Corpus Striatum -- pathology KW - Adrenergic Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72972693?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Progressive+and+extensive+dopaminergic+degeneration+induced+by+convection-enhanced+delivery+of+6-hydroxydopamine+into+the+rat+striatum%3A+a+novel+rodent+model+of+Parkinson+disease.&rft.au=Oiwa%2C+Yoshitsugu%3BSanchez-Pernaute%2C+Rosario%3BHarvey-White%2C+Judith%3BBankiewicz%2C+Krys+S&rft.aulast=Oiwa&rft.aufirst=Yoshitsugu&rft.date=2003-01-01&rft.volume=98&rft.issue=1&rft.spage=136&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 - 2003-02-12 N1 - Date created - 2003-01-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - NPY Leu7Pro and alcohol dependence in Finnish and Swedish populations. AN - 72969937; 12544000 AB - Neuropeptide Y (NPY) is a modulator of alcohol intake in animal models of alcoholism, and is potentially involved in alcohol dependence. A coding Leu7Pro polymorphism in the signal peptide of preproNPY has been described, and the Pro7 allele has been reported to correlate with increased alcohol consumption in non-dependent Finnish males. Recently, this polymorphism was also reported to be associated with an actual diagnosis of alcohol dependence. We compared Pro7 allele frequencies in one Finnish (n = 135) and one Swedish (n = 472) population of alcohol dependent individuals, and ethnically matched controls (Finns: n = 213; Swedes: n = 177) in whom alcohol dependence was established, or any diagnosis of substance disorder was excluded, respectively, through the use of structured face-to-face interviews. Pro7 frequencies in alcoholics were 5.2 and 4.1% in Finns and Swedes, respectively, similar to the 5.0-5.5% recently reported in European Americans in a Yale study. However, corresponding frequencies in the control populations were similar, at 6.1 and 5.9% in Finns and Swedes, respectively, yielding no association, in contrast with the Yale study, where an association was reported based on a 2.0% Pro7 frequency in European American controls. A meta-analysis of available data yields Pro7 frequencies of 4.7% both in Caucasian alcoholics and Caucasian controls. Pro7 does not seem to be associated with a diagnosis of alcoholism in Caucasian populations. JF - Alcoholism, clinical and experimental research AU - Zhu, Guanshan AU - Pollak, Lotta AU - Mottagui-Tabar, Salim AU - Wahlestedt, Claes AU - Taubman, Julie AU - Virkkunen, Matti AU - Goldman, David AU - Heilig, Markus AD - Laboratory of Neurogenetics, National Institute on Alcoholism and Alcohol Abuse, National Institutes of Health, USA. Y1 - 2003/01// PY - 2003 DA - January 2003 SP - 19 EP - 24 VL - 27 IS - 1 SN - 0145-6008, 0145-6008 KW - Neuropeptide Y KW - 0 KW - Protein Precursors KW - preproneuropeptide Y KW - 92307-59-0 KW - Index Medicus KW - Humans KW - Chi-Square Distribution KW - Sweden -- epidemiology KW - Gene Frequency -- genetics KW - Finland -- epidemiology KW - Male KW - Female KW - Amino Acid Substitution -- genetics KW - Polymorphism, Genetic -- genetics KW - Protein Precursors -- genetics KW - Alcoholism -- genetics KW - Neuropeptide Y -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72969937?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=NPY+Leu7Pro+and+alcohol+dependence+in+Finnish+and+Swedish+populations.&rft.au=Zhu%2C+Guanshan%3BPollak%2C+Lotta%3BMottagui-Tabar%2C+Salim%3BWahlestedt%2C+Claes%3BTaubman%2C+Julie%3BVirkkunen%2C+Matti%3BGoldman%2C+David%3BHeilig%2C+Markus&rft.aulast=Zhu&rft.aufirst=Guanshan&rft.date=2003-01-01&rft.volume=27&rft.issue=1&rft.spage=19&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 - 2003-07-01 N1 - Date created - 2003-01-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Microarray analysis reveals distinct gene expression profiles among different histologic types of endometrial cancer. AN - 72955802; 12517768 AB - Previous studies of oncogene and tumor suppressor gene alterations have suggested that differences exist in the molecular pathogenesis of the various histological types of endometrial cancer. To elucidate further the molecular events involved in endometrial carcinogenesis, we examined global expression patterns of 16 nonendometrioid cancers (13 serous papillary and 3 clear cell), 19 endometrioid cancers, and 7 age-matched normal endometria using cDNA microarrays. Unsupervised analysis of gene expression identified 191 genes that exhibited >2-fold differences (P < 0.001) between the histological groups. Many genes were similarly dysregulated in both nonendometrioid and endometrioid cancers relative to normal endometria. Gene expression differences in only 24 transcripts could distinguish serous from endometrioid cancers, the two most common subgroups. These data provide the basis for investigation of previously unrecognized novel pathways involved in the development of endometrial cancers. JF - Cancer research AU - Risinger, John I AU - Maxwell, G Larry AU - Chandramouli, G V R AU - Jazaeri, Amir AU - Aprelikova, Olga AU - Patterson, Tricia AU - Berchuck, Andrew AU - Barrett, J Carl AD - Laboratory of Biosystems and Cancer, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2003/01/01/ PY - 2003 DA - 2003 Jan 01 SP - 6 EP - 11 VL - 63 IS - 1 SN - 0008-5472, 0008-5472 KW - Index Medicus KW - Reference Values KW - Humans KW - Endometrium -- cytology KW - Endometrium -- physiology KW - Female KW - Gene Expression Regulation, Neoplastic KW - Gene Expression Profiling KW - Endometrial Neoplasms -- pathology KW - Endometrial Neoplasms -- classification KW - Endometrial Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72955802?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Microarray+analysis+reveals+distinct+gene+expression+profiles+among+different+histologic+types+of+endometrial+cancer.&rft.au=Risinger%2C+John+I%3BMaxwell%2C+G+Larry%3BChandramouli%2C+G+V+R%3BJazaeri%2C+Amir%3BAprelikova%2C+Olga%3BPatterson%2C+Tricia%3BBerchuck%2C+Andrew%3BBarrett%2C+J+Carl&rft.aulast=Risinger&rft.aufirst=John&rft.date=2003-01-01&rft.volume=63&rft.issue=1&rft.spage=6&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 - 2003-03-27 N1 - Date created - 2003-01-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Promising molecular targets for cancer prevention: AP-1, NF-kappa B and Pdcd4. AN - 72955480; 12524209 AB - There are still many unanswered questions regarding the processes by which extracellular signals are transduced from plasma-membrane receptors to the transcription machinery in the nucleus and the translation machinery in the cytoplasm. Some of these gene expression events become misregulated as a result of environmental or endogenous exposure to agents that cause multistage carcinogenesis. We are now beginning to identify and validate the crucial molecular events that drive the rate-limiting steps of carcinogenesis and to target these events for cancer prevention. Transcription factors AP-1 and nuclear factor kappa B can be specifically targeted to prevent cancer induction in mouse models. A protein known as programmed-cell-death-4 is a new potential molecular target that has a surprising mode of action. JF - Trends in molecular medicine AU - Young, Matthew R AU - Yang, Hsin-Sheng AU - Colburn, Nancy H AD - The Gene Regulation Section, Basic Research Laboratory, National Cancer Institute - Frederick, National Institutes of Health, Frederick, MD 21702, USA. youngm@ncifcrf.gov Y1 - 2003/01// PY - 2003 DA - January 2003 SP - 36 EP - 41 VL - 9 IS - 1 SN - 1471-4914, 1471-4914 KW - Apoptosis Regulatory Proteins KW - 0 KW - NF-kappa B KW - PDCD4 protein, human KW - Pdcd4 protein, mouse KW - Peptide Fragments KW - Proteins KW - Proto-Oncogene Proteins c-jun KW - RNA-Binding Proteins KW - TAM67 peptide KW - Transcription Factor AP-1 KW - Index Medicus KW - Peptide Fragments -- metabolism KW - Protein Biosynthesis KW - Animals KW - Cytoplasm -- metabolism KW - Humans KW - Disease Progression KW - Proto-Oncogene Proteins c-jun -- metabolism KW - Mice KW - Time Factors KW - Models, Biological KW - Transcription Factor AP-1 -- metabolism KW - Neoplasms -- prevention & control KW - Proteins -- metabolism KW - Signal Transduction KW - Neoplasms -- metabolism KW - NF-kappa B -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72955480?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+molecular+medicine&rft.atitle=Promising+molecular+targets+for+cancer+prevention%3A+AP-1%2C+NF-kappa+B+and+Pdcd4.&rft.au=Young%2C+Matthew+R%3BYang%2C+Hsin-Sheng%3BColburn%2C+Nancy+H&rft.aulast=Young&rft.aufirst=Matthew&rft.date=2003-01-01&rft.volume=9&rft.issue=1&rft.spage=36&rft.isbn=&rft.btitle=&rft.title=Trends+in+molecular+medicine&rft.issn=14714914&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-11 N1 - Date created - 2003-01-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Calorie restriction, aging, and cancer prevention: mechanisms of action and applicability to humans. AN - 72953183; 12525670 AB - Calorie restriction (CR) is the most effective and reproducible intervention for increasing lifespan in a variety of animal species, including mammals. CR is also the most potent, broadly acting cancer-prevention regimen in experimental carcinogenesis models. Translation of the knowledge gained from CR research to human chronic disease prevention and the promotion of healthy aging is critical, especially because obesity, which is an important risk factor for several chronic diseases, including many cancers, is alarmingly increasing in the Western world. This review synthesizes the key biological mechanisms underlying many of the beneficial effects of CR, with a particular focus on the insulin-like growth factor-1 pathway. We also describe some of the opportunities now available for investigations, including gene expression profiling studies, the development of pharmacological mimetics of CR, and the integration of CR regimens with targeted, mechanism-based interventions. These approaches will facilitate the translation of CR research into strategies for effective human chronic disease prevention. JF - Annual review of medicine AU - Hursting, Stephen D AU - Lavigne, Jackie A AU - Berrigan, David AU - Perkins, Susan N AU - Barrett, J Carl AD - Laboratory of Biosystems and Cancer, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA. sh63v@nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 131 EP - 152 VL - 54 SN - 0066-4219, 0066-4219 KW - Reactive Oxygen Species KW - 0 KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Index Medicus KW - Risk KW - Reactive Oxygen Species -- metabolism KW - Animals KW - Insulin-Like Growth Factor I -- physiology KW - Humans KW - Apoptosis -- physiology KW - Aging -- physiology KW - Caloric Restriction KW - Neoplasms -- prevention & control KW - Neoplasms -- etiology KW - Health Promotion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72953183?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Calorie+restriction%2C+aging%2C+and+cancer+prevention%3A+mechanisms+of+action+and+applicability+to+humans.&rft.au=Hursting%2C+Stephen+D%3BLavigne%2C+Jackie+A%3BBerrigan%2C+David%3BPerkins%2C+Susan+N%3BBarrett%2C+J+Carl&rft.aulast=Hursting&rft.aufirst=Stephen&rft.date=2003-01-01&rft.volume=54&rft.issue=&rft.spage=131&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 - 2003-06-03 N1 - Date created - 2003-01-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structure of DNA polymerase beta with the mutagenic DNA lesion 8-oxodeoxyguanine reveals structural insights into its coding potential. AN - 72950077; 12517346 AB - Oxidative damage to DNA generates 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG). During DNA replication and repair synthesis, 8-oxodG can pair with cytosine or adenine. The ability to accurately replicate through this lesion depends on the DNA polymerase. We report the first structure of a polymerase with a promutagenic DNA lesion, 8-oxodG, in the confines of its active site. The modified guanine residue is in an anti conformation and forms Watson-Crick hydrogen bonds with an incoming dCTP. To accommodate the oxygen at C8, the 5'-phosphate backbone of the templating nucleotide flips 180 degrees. Thus, the flexibility of the template sugar-phosphate backbone near the polymerase active site is one parameter that influences the anti-syn equilibrium of 8-oxodG. Our results provide insights into the mechanisms employed by polymerases to select the complementary dNTP. JF - Structure (London, England : 1993) AU - Krahn, Joseph M AU - Beard, William A AU - Miller, Holly AU - Grollman, Arthur P AU - Wilson, Samuel H AD - Laboratory of Structural Biology, National Institute of Environmental Health Sciences, NIH, P.O. Box 12233, Research Triangle Park, NC 27709, USA. Y1 - 2003/01// PY - 2003 DA - January 2003 SP - 121 EP - 127 VL - 11 IS - 1 SN - 0969-2126, 0969-2126 KW - Deoxyadenine Nucleotides KW - 0 KW - 8-hydroxyguanine KW - 5614-64-2 KW - Guanine KW - 5Z93L87A1R KW - DNA Polymerase beta KW - EC 2.7.7.- KW - 2'-deoxyadenosine triphosphate KW - K8KCC8SH6N KW - Index Medicus KW - Molecular Structure KW - DNA Repair KW - Models, Molecular KW - DNA Damage KW - Humans KW - Nucleic Acid Conformation KW - Deoxyadenine Nucleotides -- metabolism KW - DNA Replication KW - Binding Sites KW - Guanine -- chemistry KW - DNA Polymerase beta -- chemistry KW - Guanine -- analogs & derivatives KW - Protein Structure, Tertiary KW - DNA Polymerase beta -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72950077?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Structure+%28London%2C+England+%3A+1993%29&rft.atitle=Structure+of+DNA+polymerase+beta+with+the+mutagenic+DNA+lesion+8-oxodeoxyguanine+reveals+structural+insights+into+its+coding+potential.&rft.au=Krahn%2C+Joseph+M%3BBeard%2C+William+A%3BMiller%2C+Holly%3BGrollman%2C+Arthur+P%3BWilson%2C+Samuel+H&rft.aulast=Krahn&rft.aufirst=Joseph&rft.date=2003-01-01&rft.volume=11&rft.issue=1&rft.spage=121&rft.isbn=&rft.btitle=&rft.title=Structure+%28London%2C+England+%3A+1993%29&rft.issn=09692126&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-12 N1 - Date created - 2003-01-08 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 1MQ3; PDB; 1MQ2 N1 - SuppNotes - Comment In: Structure. 2003 Jan;11(1):1-2 [12517331] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rapid Akt activation by nicotine and a tobacco carcinogen modulates the phenotype of normal human airway epithelial cells. AN - 72948870; 12511591 AB - Tobacco-related diseases such as lung cancer cause over 4.2 million deaths annually, with approximately 400,000 deaths per year occurring in the US. Genotoxic effects of tobacco components have been described, but effects on signaling pathways in normal cells have not been described. Here, we show activation of the serine/threonine kinase Akt in nonimmortalized human airway epithelial cells in vitro by two components of cigarette smoke, nicotine and the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Activation of Akt by nicotine or NNK occurred within minutes at concentrations achievable by smokers and depended upon alpha(3)-/alpha(4)-containing or alpha(7)-containing nicotinic acetylcholine receptors, respectively. Activated Akt increased phosphorylation of downstream substrates such as GSK-3, p70(S6K), 4EBP-1, and FKHR. Treatment with nicotine or NNK attenuated apoptosis caused by etoposide, ultraviolet irradiation, or hydrogen peroxide and partially induced a transformed phenotype manifest as loss of contact inhibition and loss of dependence on exogenous growth factors or adherence to ECM. In vivo, active Akt was detected in airway epithelial cells and lung tumors from NNK-treated A/J mice, and in human lung cancers derived from smokers. Redundant Akt activation by nicotine and NNK could contribute to tobacco-related carcinogenesis by regulating two processes critical for tumorigenesis, cell growth and apoptosis. JF - The Journal of clinical investigation AU - West, Kip A AU - Brognard, John AU - Clark, Amy S AU - Linnoila, Ilona R AU - Yang, Xiaowei AU - Swain, Sandra M AU - Harris, Curtis AU - Belinsky, Steven AU - Dennis, Phillip A AD - Cancer Therapeutics Branch, Cell and Cancer Biology Branch, National Cancer Institute, Bethesda, Maryland 20889, USA. Y1 - 2003/01// PY - 2003 DA - January 2003 SP - 81 EP - 90 VL - 111 IS - 1 SN - 0021-9738, 0021-9738 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - Carcinogens KW - Carrier Proteins KW - DNA-Binding Proteins KW - EIF4EBP1 protein, human KW - FOXO1 protein, human KW - Forkhead Box Protein O1 KW - Forkhead Transcription Factors KW - Nitrosamines KW - Phosphoproteins KW - Proto-Oncogene Proteins KW - Transcription Factors KW - Nicotine KW - 6M3C89ZY6R KW - 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone KW - 7S395EDO61 KW - AKT1 protein, human KW - EC 2.7.11.1 KW - Protein-Serine-Threonine Kinases KW - Proto-Oncogene Proteins c-akt KW - Ribosomal Protein S6 Kinases, 70-kDa KW - Glycogen Synthase Kinase 3 KW - EC 2.7.11.26 KW - Abridged Index Medicus KW - Index Medicus KW - Ultraviolet Rays KW - Apoptosis KW - Transcription Factors -- metabolism KW - Humans KW - Cell Survival KW - Phenotype KW - Phosphorylation KW - Enzyme-Linked Immunosorbent Assay KW - Time Factors KW - DNA-Binding Proteins -- metabolism KW - Lung Neoplasms -- metabolism KW - Phosphoproteins -- metabolism KW - Immunoblotting KW - Carrier Proteins -- metabolism KW - Enzyme Activation KW - Reverse Transcriptase Polymerase Chain Reaction KW - Ribosomal Protein S6 Kinases, 70-kDa -- metabolism KW - Protein Binding KW - Cells, Cultured KW - Cell Death KW - Glycogen Synthase Kinase 3 -- metabolism KW - Immunohistochemistry KW - Epithelial Cells -- drug effects KW - Tobacco KW - Proto-Oncogene Proteins -- metabolism KW - Bronchi -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72948870?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Rapid+Akt+activation+by+nicotine+and+a+tobacco+carcinogen+modulates+the+phenotype+of+normal+human+airway+epithelial+cells.&rft.au=West%2C+Kip+A%3BBrognard%2C+John%3BClark%2C+Amy+S%3BLinnoila%2C+Ilona+R%3BYang%2C+Xiaowei%3BSwain%2C+Sandra+M%3BHarris%2C+Curtis%3BBelinsky%2C+Steven%3BDennis%2C+Phillip+A&rft.aulast=West&rft.aufirst=Kip&rft.date=2003-01-01&rft.volume=111&rft.issue=1&rft.spage=81&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 - 2003-03-03 N1 - Date created - 2003-01-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1999 Mar 19;96(6):857-68 [10102273] Chem Res Toxicol. 1999 Sep;12(9):840-9 [10490506] Clin Cancer Res. 2000 May;6(5):1616-25 [10815878] J Dent Res. 2000 Apr;79(4):939-49 [10831096] Mol Cell Biol. 2000 Jul;20(14):5010-8 [10866658] Neuropharmacology. 2000 Oct;39(13):2543-60 [11044726] Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3501-6 [11248107] Curr Med Chem. 2001 May;8(6):651-74 [11281847] J Biol Chem. 2001 Apr 27;276(17):13541-6 [11278378] Genomics. 2001 May 1;73(3):272-83 [11350119] Cancer Res. 2001 May 15;61(10):3986-97 [11358816] Nat Med. 2001 Jul;7(7):833-9 [11433349] J Natl Cancer Inst. 2001 Jul 18;93(14):1081-8 [11459869] Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10320-5 [11504907] Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10314-9 [11504908] Cell Prolif. 2001 Aug;34(4):199-210 [11529878] FEBS Lett. 2001 Aug 31;504(3):118-25 [11532443] Nat Rev Mol Cell Biol. 2001 Oct;2(10):760-8 [11584303] J Cell Sci. 2001 Aug;114(Pt 16):2903-10 [11686294] Mol Pharmacol. 2001 Dec;60(6):1201-9 [11723227] Br Med J. 1975 Nov 8;4(5992):313-6 [1192046] Br Med J. 1980 Apr 5;280(6219):972-6 [7417765] Carcinogenesis. 1988 Jun;9(6):875-84 [3286030] Cancer Res. 1989 Oct 1;49(19):5305-11 [2670201] Proc Natl Acad Sci U S A. 1990 May;87(9):3294-8 [2159143] Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3258-62 [2014250] Exp Lung Res. 1991 Mar-Apr;17(2):485-99 [2050045] Am J Clin Pathol. 1992 Feb;97(2):233-43 [1372146] Scand J Gastroenterol. 1993 Jun;28(6):487-94 [8322024] J Biol Chem. 1994 Feb 18;269(7):5241-8 [8106507] J Cell Biol. 1994 Feb;124(4):619-26 [8106557] Cell Growth Differ. 1994 Oct;5(10):1033-40 [7848904] Brain Res Mol Brain Res. 1995 Jan;28(1):101-9 [7707862] Gene. 1995 Apr 3;155(2):189-93 [7721089] Nature. 1995 Aug 17;376(6541):599-602 [7637810] Nature. 1995 Dec 21-28;378(6559):785-9 [8524413] J Invest Dermatol. 1996 Sep;107(3):412-8 [8751979] Mol Neurobiol. 1997 Oct;15(2):193-222 [9396010] Carcinogenesis. 1998 Apr;19(4):551-6 [9600337] Eur J Pharmacol. 1998 Apr 17;347(1):131-9 [9650859] Exp Lung Res. 1998 Jul-Aug;24(4):541-55 [9659582] Clin Dermatol. 1998 Sep-Oct;16(5):557-64 [9787965] Mol Pharmacol. 1998 Nov;54(5):779-88 [9804613] J Biol Chem. 1998 Nov 13;273(46):30336-43 [9804796] Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13513-8 [9811831] J Clin Invest. 1999 Mar;103(5):637-47 [10074480] Exp Cell Res. 1999 Dec 15;253(2):663-72 [10585289] CA Cancer J Clin. 1999 Jan-Feb;49(1):8-31, 1 [10200775] Comment In: J Clin Invest. 2003 Jan;111(1):31-3 [12511585] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Strategies for pharmacologic treatment of high functioning autism and Asperger syndrome. AN - 72946085; 12512397 AB - The treatment of complex, polymorphous disorders like HFA/AS always brings a particular challenge to pharmacotherapy. Additionally, the specific characteristics presented by HFA/AS introduce unique complications to patient care and place unusual demands on a clinician's skill and experience. To provide safe and effective treatment, the clinician must understand the core features of the disorder and the manifestations of the condition in his or her patient. Furthermore, a thorough understanding of the family, school, and community resources and limitations is necessary. Once an assessment has been made, focusing on target symptoms provides a crucial framework for care. Knowing manifestations of symptoms and characterizing their distribution and behavior in that patient is most important. For patients with HFA/AS it is particularly essential to coordinate behavioral and pharmacologic objectives. The target symptoms should be tracked carefully and placed into a priority system that is based on the risks and disability they create for the patient. The skill of pharmacotherapy also means setting out realistic expectations, keeping track of the larger systems of care at school and home, and collaboration with parents and care providers. There is an expanding range and pace of biologic and intervention research into HFA/AS. The genetic work has produced exciting leads that are likely to be helpful to future generations [82-84], but the task of clinicians is to tend to today's patients. As we discover more about the complex neural circuitry subserving repetitive behaviors, reward systems, and social cognition, there are good reasons to believe our treatments will become more sophisticated and specific. Psychopharmacology is also moving to design medications that target more specific populations of receptor and brain functions. This is likely to produce medicines that have fewer side effects, are more effective, and are more symptom-specific. Pharmacotherapy is not the ultimate treatment for HFA/AS but it has a definite place. Medication can be a critical element in a comprehensive treatment plan. There is a wider range of medications with more specific biologic effects than ever before. For patients with HFA/AS these newer agents are safer and less disruptive. When paired with clinicians who are becoming more skilled at recognizing and managing symptoms, patients have a greater opportunity to reach their potential and lead pleasurable lives. JF - Child and adolescent psychiatric clinics of North America AU - Towbin, Kenneth E AD - Departments of Psychiatry and Behavioral Sciences, and Pediatrics, George Washington University School of Medicine, Children's National Medical Center, 111 Michigan Avenue NW, Washington, DC 20010, USA. Kenneth.Towbin@nih.gov Y1 - 2003/01// PY - 2003 DA - January 2003 SP - 23 EP - 45 VL - 12 IS - 1 SN - 1056-4993, 1056-4993 KW - Psychotropic Drugs KW - 0 KW - Index Medicus KW - Patient Care Team KW - Combined Modality Therapy KW - Humans KW - Child KW - Adolescent KW - Male KW - Female KW - Intelligence -- drug effects KW - Asperger Syndrome -- psychology KW - Autistic Disorder -- diagnosis KW - Psychotropic Drugs -- therapeutic use KW - Autistic Disorder -- drug therapy KW - Asperger Syndrome -- diagnosis KW - Psychotropic Drugs -- adverse effects KW - Autistic Disorder -- psychology KW - Asperger Syndrome -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72946085?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Child+and+adolescent+psychiatric+clinics+of+North+America&rft.atitle=Strategies+for+pharmacologic+treatment+of+high+functioning+autism+and+Asperger+syndrome.&rft.au=Towbin%2C+Kenneth+E&rft.aulast=Towbin&rft.aufirst=Kenneth&rft.date=2003-01-01&rft.volume=12&rft.issue=1&rft.spage=23&rft.isbn=&rft.btitle=&rft.title=Child+and+adolescent+psychiatric+clinics+of+North+America&rft.issn=10564993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-27 N1 - Date created - 2003-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Beta-carotene and lung cancer: a lesson for future chemoprevention investigations? AN - 72945610; 12509411 JF - Journal of the National Cancer Institute AU - Greenwald, Peter AD - Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. greenwap@dcpc31.nci.nih.gov Y1 - 2003/01/01/ PY - 2003 DA - 2003 Jan 01 SP - 1 VL - 95 IS - 1 SN - 0027-8874, 0027-8874 KW - Anticarcinogenic Agents KW - 0 KW - Carcinogens KW - beta Carotene KW - 01YAE03M7J KW - Index Medicus KW - Treatment Failure KW - Randomized Controlled Trials as Topic KW - Humans KW - Chemoprevention -- methods KW - Dietary Supplements KW - Male KW - beta Carotene -- administration & dosage KW - Lung Neoplasms -- prevention & control KW - Lung Neoplasms -- etiology KW - Carcinogens -- administration & dosage KW - Smoking -- adverse effects KW - Anticarcinogenic Agents -- adverse effects KW - beta Carotene -- adverse effects KW - Lung Neoplasms -- chemically induced KW - Anticarcinogenic Agents -- administration & dosage KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72945610?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Beta-carotene+and+lung+cancer%3A+a+lesson+for+future+chemoprevention+investigations%3F&rft.au=Greenwald%2C+Peter&rft.aulast=Greenwald&rft.aufirst=Peter&rft.date=2003-01-01&rft.volume=95&rft.issue=1&rft.spage=E1&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 - 2003-01-24 N1 - Date created - 2003-01-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Natl Cancer Inst. 2003 May 21;95(10):E4 [12759404] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of polychlorinated biphenyl levels across studies of human neurodevelopment. AN - 72943431; 12515680 AB - Polychlorinated biphenyls (PCBs) are persistent pollutants that are ubiquitous in the food chain, and detectable amounts are in the blood of almost every person in most populations that have been examined. Extensive evidence from animal studies shows that PCBs are neurotoxins, even at low doses. Interpretation of human data regarding low-level, early-life PCB exposure and subsequent neurodevelopment is problematic because levels of exposure were not similarly quantified across studies. We expressed the exposure levels from 10 studies of PCB and neurodevelopment in a uniform manner using a combination of data from original investigators, laboratory reanalyses, calculations based on published data, and expert opinion. The mainstay of our comparison was the median level of PCB 153 in maternal pregnancy serum. The median concentration of PCB 153 in the 10 studies ranged from 30 to 450 ng/g serum lipid, and the median of the 10 medians was 110 ng/g. We found that (a)) the distribution of PCB 153 exposure in most studies overlapped substantially, (b)) exposure levels in the Faroe Islands study were about 3-4-fold higher than in most other studies, and (c)) the exposure levels in the two recent U.S. studies were about one-third of those in the four earlier U.S. studies or recent Dutch, German, and northern Québec studies. Our results will facilitate a direct comparison of the findings on PCBs and neurodevelopment when they are published for all 10 studies. JF - Environmental health perspectives AU - Longnecker, Matthew P AU - Wolff, Mary S AU - Gladen, Beth C AU - Brock, John W AU - Grandjean, Philippe AU - Jacobson, Joseph L AU - Korrick, Susan A AU - Rogan, Walter J AU - Weisglas-Kuperus, Nynke AU - Hertz-Picciotto, Irva AU - Ayotte, Pierre AU - Stewart, Paul AU - Winneke, Gerhard AU - Charles, M Judith AU - Jacobson, Sandra W AU - Dewailly, Eric AU - Boersma, E Rudy AU - Altshul, Larisa M AU - Heinzow, Birger AU - Pagano, James J AU - Jensen, Allan A AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. longnecker@niehs.nih.gov Y1 - 2003/01// PY - 2003 DA - January 2003 SP - 65 EP - 70 VL - 111 IS - 1 SN - 0091-6765, 0091-6765 KW - Environmental Pollutants KW - 0 KW - Polychlorinated Biphenyls KW - DFC2HB4I0K KW - 2,4,5,2',4',5'-hexachlorobiphenyl KW - ZRU0C9E32O KW - Index Medicus KW - United States KW - Sensitivity and Specificity KW - Quebec KW - Humans KW - Food Contamination KW - Europe KW - Female KW - Chromatography, Gas -- methods KW - Pregnancy KW - Maternal Exposure -- adverse effects KW - Milk, Human -- chemistry KW - Polychlorinated Biphenyls -- blood KW - Nervous System -- drug effects KW - Nervous System -- embryology KW - Environmental Pollutants -- blood KW - Milk, Human -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72943431?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Comparison+of+polychlorinated+biphenyl+levels+across+studies+of+human+neurodevelopment.&rft.au=Longnecker%2C+Matthew+P%3BWolff%2C+Mary+S%3BGladen%2C+Beth+C%3BBrock%2C+John+W%3BGrandjean%2C+Philippe%3BJacobson%2C+Joseph+L%3BKorrick%2C+Susan+A%3BRogan%2C+Walter+J%3BWeisglas-Kuperus%2C+Nynke%3BHertz-Picciotto%2C+Irva%3BAyotte%2C+Pierre%3BStewart%2C+Paul%3BWinneke%2C+Gerhard%3BCharles%2C+M+Judith%3BJacobson%2C+Sandra+W%3BDewailly%2C+Eric%3BBoersma%2C+E+Rudy%3BAltshul%2C+Larisa+M%3BHeinzow%2C+Birger%3BPagano%2C+James+J%3BJensen%2C+Allan+A&rft.aulast=Longnecker&rft.aufirst=Matthew&rft.date=2003-01-01&rft.volume=111&rft.issue=1&rft.spage=65&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 - 2003-10-15 N1 - Date created - 2003-01-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Int Arch Occup Environ Health. 2001 Apr;74(3):184-8 [11355292] J Natl Cancer Inst. 2001 May 16;93(10):768-76 [11353787] Neurotoxicol Teratol. 2001 Jul-Aug;23(4):305-17 [11485834] Lancet. 2001 Nov 10;358(9293):1602-7 [11716887] Environ Health Perspect. 2001 Dec;109(12):1291-9 [11748038] Environ Health Perspect. 2002 Jul;110(7):617-24 [12117636] Am J Public Health. 1983 Mar;73(3):293-6 [6401943] J Assoc Off Anal Chem. 1984 Jan-Feb;67(1):122-9 [6321428] Am J Public Health. 1986 Feb;76(2):172-7 [3080910] J Pediatr. 1986 Aug;109(2):335-41 [3090217] Sci Total Environ. 1987 Jul;64(3):259-93 [3110947] Science. 1988 Jul 15;241(4863):334-6 [3133768] Arch Environ Contam Toxicol. 1989 Jul-Aug;18(4):495-500 [2505694] Am J Public Health. 1989 Oct;79(10):1401-4 [2551196] Neurotoxicol Teratol. 1990 May-Jun;12(3):239-48 [2115098] Arch Toxicol. 1990;64(7):567-71 [2127352] J Pediatr. 1991 Jul;119(1 Pt 1):58-63 [1906100] N Engl J Med. 1996 Sep 12;335(11):783-9 [8703183] Chemosphere. 1996 Oct;33(8):1485-94 [8856955] J Anal Toxicol. 1996 Nov-Dec;20(7):528-36 [8934301] Crit Rev Toxicol. 1996 Nov;26(6):709-37 [8958469] Arch Environ Contam Toxicol. 1997 Apr;32(3):329-36 [9096084] Am J Ind Med. 1997 Dec;32(6):606-13 [9358917] J Pediatr. 1999 Jan;134(1):33-41 [9880446] Am J Ind Med. 1999 Jan;35(1):15-20 [9884741] Environ Res. 1999 Feb;80(2 Pt 2):S113-S121 [10092425] Environ Health Perspect. 1999 Aug;107 Suppl 4:639-49 [10421775] Arch Environ Contam Toxicol. 1999 Oct;37(3):408-14 [10473799] Epidemiology. 2000 May;11(3):249-54 [10784239] J Pediatr. 2000 May;136(5):599-605 [10802490] Arch Environ Contam Toxicol. 2000 Aug;39(2):265-70 [10871430] Arch Environ Health. 2000 May-Jun;55(3):195-200 [10908103] J Expo Anal Environ Epidemiol. 2000 Nov-Dec;10(6 Pt 2):743-54 [11138666] Sci Total Environ. 2000 Dec 18;263(1-3):197-208 [11194153] Neurotoxicology. 2000 Dec;21(6):1029-38 [11233749] Diabetes Care. 2001 Jun;24(6):1099-101 [11375377] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characteristics of the PAH emissions from the incineration of livestock wastes with/without APCD. AN - 72942917; 12504163 AB - This study was conducted on two batch-type livestock waste incinerators, including the one with an air-pollution control device (APCD)-one wet scrubber (WSB) and the other without APCD for the disposal of livestock wastes. The concentration and composition of 21 individual polycyclic aromatic hydrocarbons (PAHs) in the stack flue gas (gas and particle phases), bottom ash, and effluent of WSB were determined. Stack flue gas samples were collected by a PAH stack-sampling system. Twenty-one individual PAHs were analyzed by a gas chromatography/mass spectrometer (GC/MS). Due to the low combustion temperature, a remarkable and significant increase in the total-PAH concentration of emission from the stack with APCD was observed when compared with the case without APCD. Measured total-PAH emission factors were 285 and 2.86 mg/kg waste for the incineration with and without APCD, respectively, while BaP (the most carcinogenic PAH) emission factors were 0.79 and 0.12 mg/kg waste for the incineration with and without APCD. The total-PAH output/input mass ratios averaged 0.011 and 0.004 with and without APCD, respectively. The result reveals that the PAH content in the auxiliary fuel during the incinerating process could affect the emission of PAH. JF - Environment international AU - Chen, Shui-Jen AU - Hsieh, Lien-Te AU - Chiu, Shui-Chi AD - Department of Environmental Engineering and Science, National Pingtung University of Science and Technology, Nei Pu 91207, Ping Tung, Taiwan. chensj@mail.npust.edu.tw Y1 - 2003/01// PY - 2003 DA - January 2003 SP - 659 EP - 668 VL - 28 IS - 7 SN - 0160-4120, 0160-4120 KW - Gases KW - 0 KW - Polycyclic Aromatic Hydrocarbons KW - Index Medicus KW - Environmental Monitoring KW - Animals, Domestic KW - Animals KW - Incineration KW - Gas Chromatography-Mass Spectrometry KW - Polycyclic Aromatic Hydrocarbons -- analysis KW - Refuse Disposal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72942917?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environment+international&rft.atitle=Characteristics+of+the+PAH+emissions+from+the+incineration+of+livestock+wastes+with%2Fwithout+APCD.&rft.au=Chen%2C+Shui-Jen%3BHsieh%2C+Lien-Te%3BChiu%2C+Shui-Chi&rft.aulast=Chen&rft.aufirst=Shui-Jen&rft.date=2003-01-01&rft.volume=28&rft.issue=7&rft.spage=659&rft.isbn=&rft.btitle=&rft.title=Environment+international&rft.issn=01604120&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-22 N1 - Date created - 2002-12-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Decision making in adolescents with behavior disorders and adults with substance abuse. AN - 72937498; 12505799 AB - The study assessed the validity of the Gambling Task as a test of decision-making ability in adolescents and examined whether adolescents with behavior disorders, who are at risk for substance abuse, have deficits in decision making similar to those exhibited by adults with substance abuse. Performance on the Gambling Task in two testing sessions separated by 1 week was assessed in 64 12-14-year-old adolescents (31 healthy, 33 with externalizing behavior disorders) and 52 adults (22 healthy, 30 with substance abuse). The healthy adolescents and the healthy adults had similar performance on the Gambling Task. Adolescents with behavior disorders performed more poorly than healthy adolescents, but only in the second testing session. In adults, overall Gambling Task performance did not differ between the healthy and substance abuse groups at either testing session, indicating no difference in learning of decision-making strategies between groups. However, adults with substance abuse performed more poorly than healthy adults during an early stage of the task, when participants presumably begin to understand the rewards and penalties involved in the task but are not yet sure of the actual risk of incurring penalities. The Gambling Task can be used with adolescents. Testing with the Gambling Task revealed a deficit in decision making in adolescents with behavior disorders, who are at risk for substance abuse. This deficit may represent a vulnerability factor for the development of substance abuse. JF - The American journal of psychiatry AU - Ernst, Monique AU - Grant, Steven J AU - London, Edythe D AU - Contoreggi, Carlo S AU - Kimes, Alane S AU - Spurgeon, Loretta AD - NIH NIMH/MAP, 15K North Dr., Room 118, MSC 2670, Bethesda, MD 20892-2670, USA. ernstm@intra.nimh.nih.gov Y1 - 2003/01// PY - 2003 DA - January 2003 SP - 33 EP - 40 VL - 160 IS - 1 SN - 0002-953X, 0002-953X KW - Abridged Index Medicus KW - Index Medicus KW - Gambling -- psychology KW - Reference Values KW - Risk-Taking KW - Humans KW - Impulsive Behavior -- diagnosis KW - Child KW - Attention Deficit Disorder with Hyperactivity -- diagnosis KW - Attention Deficit Disorder with Hyperactivity -- psychology KW - Discrimination Learning KW - Risk Factors KW - Impulsive Behavior -- psychology KW - Practice (Psychology) KW - Adult KW - Personality Assessment KW - Neuropsychological Tests KW - Adolescent KW - Female KW - Male KW - Substance-Related Disorders -- diagnosis KW - Internal-External Control KW - Probability Learning KW - Child Behavior Disorders -- psychology KW - Substance-Related Disorders -- psychology KW - Decision Making KW - Child Behavior Disorders -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72937498?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Decision+making+in+adolescents+with+behavior+disorders+and+adults+with+substance+abuse.&rft.au=Ernst%2C+Monique%3BGrant%2C+Steven+J%3BLondon%2C+Edythe+D%3BContoreggi%2C+Carlo+S%3BKimes%2C+Alane+S%3BSpurgeon%2C+Loretta&rft.aulast=Ernst&rft.aufirst=Monique&rft.date=2003-01-01&rft.volume=160&rft.issue=1&rft.spage=33&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 - 2003-01-30 N1 - Date created - 2002-12-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Am J Psychiatry. 2003 Jan;160(1):1-2 [12505792] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of microglia in inflammation-mediated neurodegenerative diseases: mechanisms and strategies for therapeutic intervention. AN - 72900647; 12490568 AB - Evidence from postmortem analysis implicates the involvement of microglia in the neurodegenerative process of several degenerative neurological diseases, including Alzheimer's disease and Parkinson's disease. It remains to be determined, however, whether microglial activation plays a role in the initiation stage of disease progression or occurs merely as a response to neuronal death. Activated microglia secrete a variety of proinflammatory and neurotoxic factors that are believed to induce and/or exacerbate neurodegeneration. In this article, we summarize recent advances on the study of the role of microglia based on findings from animal and cell culture models in the pathogenesis of neurodegenerative diseases, with particular emphasis on Parkinson's disease. In addition, we also discuss novel approaches to potential therapeutic strategies. JF - The Journal of pharmacology and experimental therapeutics AU - Liu, Bin AU - Hong, Jau-Shyong AD - Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. liu3@niehs.nih.gov Y1 - 2003/01// PY - 2003 DA - January 2003 SP - 1 EP - 7 VL - 304 IS - 1 SN - 0022-3565, 0022-3565 KW - Anti-Inflammatory Agents KW - 0 KW - Neuroprotective Agents KW - Naloxone KW - 36B82AMQ7N KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Naloxone -- pharmacology KW - Animals KW - Humans KW - Dopamine -- physiology KW - Parkinson Disease -- pathology KW - Neuroprotective Agents -- pharmacology KW - Inflammation -- pathology KW - Nerve Degeneration -- drug therapy KW - Microglia -- physiology KW - Nerve Degeneration -- pathology KW - Microglia -- pathology KW - Microglia -- drug effects KW - Anti-Inflammatory Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72900647?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Role+of+microglia+in+inflammation-mediated+neurodegenerative+diseases%3A+mechanisms+and+strategies+for+therapeutic+intervention.&rft.au=Liu%2C+Bin%3BHong%2C+Jau-Shyong&rft.aulast=Liu&rft.aufirst=Bin&rft.date=2003-01-01&rft.volume=304&rft.issue=1&rft.spage=1&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 - 2003-01-23 N1 - Date created - 2002-12-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Direct estimates of human per nucleotide mutation rates at 20 loci causing Mendelian diseases. AN - 72896543; 12497628 AB - I estimate per nucleotide rates of spontaneous mutations of different kinds in humans directly from the data on per locus mutation rates and on sequences of de novo nonsense nucleotide substitutions, deletions, insertions, and complex events at eight loci causing autosomal dominant diseases and 12 loci causing X-linked diseases. The results are in good agreement with indirect estimates, obtained by comparison of orthologous human and chimpanzee pseudogenes. The average direct estimate of the combined rate of all mutations is 1.8x10(-8) per nucleotide per generation, and the coefficient of variation of this rate across the 20 loci is 0.53. Single nucleotide substitutions are approximately 25 times more common than all other mutations, deletions are approximately three times more common than insertions, complex mutations are very rare, and CpG context increases substitution rates by an order of magnitude. There is only a moderate tendency for loci with high per locus mutation rates to also have higher per nucleotide substitution rates, and per nucleotide rates of deletions and insertions are statistically independent on the per locus mutation rate. Rates of different kinds of mutations are strongly correlated across loci. Mutational hot spots with per nucleotide rates above 5x10(-7) make only a minor contribution to human mutation. In the next decade, direct measurements will produce a rather precise, quantitative description of human spontaneous mutation at the DNA level. Published 2002 Wiley-Liss, Inc. JF - Human mutation AU - Kondrashov, Alexey S AD - National Center for Biotechnology Information, NIH, Bethesda, Maryland 20892, USA. Kondrashov@ncbi.nlm.nih.gov Y1 - 2003/01// PY - 2003 DA - January 2003 SP - 12 EP - 27 VL - 21 IS - 1 KW - Codon, Nonsense KW - 0 KW - Index Medicus KW - Genetic Variation KW - Kinetics KW - Humans KW - Point Mutation KW - Genetic Diseases, X-Linked -- genetics KW - Mutagenesis, Insertional KW - Gene Deletion KW - DNA Mutational Analysis -- methods KW - Genetic Diseases, Inborn -- genetics KW - Genetic Predisposition to Disease KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72896543?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Direct+estimates+of+human+per+nucleotide+mutation+rates+at+20+loci+causing+Mendelian+diseases.&rft.au=Kondrashov%2C+Alexey+S&rft.aulast=Kondrashov&rft.aufirst=Alexey&rft.date=2003-01-01&rft.volume=21&rft.issue=1&rft.spage=12&rft.isbn=&rft.btitle=&rft.title=Human+mutation&rft.issn=1098-1004&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-01-29 N1 - Date created - 2002-12-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Coexpression of CD58 or CD48 with intercellular adhesion molecule 1 on target cells enhances adhesion of resting NK cells. AN - 72895613; 12496412 AB - The beta2 integrin LFA-1 (CD11a/CD18) mediates adhesion of lymphocytes to cells expressing ICAM. The strength of this adhesion is regulated by different signals delivered by cytokines and chemokines, and by the TCR in the case of T cells. To determine the receptor-ligand interactions required for adhesion of resting NK cells, Drosophila cells expressing different combinations of ligands of human NK cell receptors were generated. Expression of ICAM-1 alone was sufficient for an adhesion of resting NK cells that was sensitive to inhibitors of src family kinase and of phosphatidylinositol 3-kinase. Binding of resting NK cells to solid-phase ICAM-1 showed similar signaling requirements. A pulse of either IL-2 or IL-15 to resting NK cells resulted in strongly enhanced, actin-dependent adhesion to insect cells expressing ICAM-1 alone. Coexpression of either LFA-3 (CD58) or CD48 with ICAM-1 resulted in strong adhesion by resting NK cells, even in the absence of cytokines. Therefore, receptors for LFA-3 and CD48 on resting NK cells strengthen the adhesion mediated by LFA-1. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Barber, Domingo F AU - Long, Eric O AD - Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852-1727, USA. Y1 - 2003/01/01/ PY - 2003 DA - 2003 Jan 01 SP - 294 EP - 299 VL - 170 IS - 1 SN - 0022-1767, 0022-1767 KW - Adjuvants, Immunologic KW - 0 KW - Antigens, CD KW - Antigens, CD58 KW - CD48 Antigen KW - CD48 protein, human KW - Interleukin-15 KW - Interleukin-2 KW - Intercellular Adhesion Molecule-1 KW - 126547-89-5 KW - Abridged Index Medicus KW - Index Medicus KW - Interleukin-2 -- pharmacology KW - Animals KW - Transfection KW - Humans KW - Drosophila melanogaster KW - Interleukin-15 -- pharmacology KW - Signal Transduction -- immunology KW - Cell Adhesion -- immunology KW - Drug Synergism KW - Cell Line KW - Intercellular Adhesion Molecule-1 -- physiology KW - Antigens, CD -- biosynthesis KW - Antigens, CD -- physiology KW - Adjuvants, Immunologic -- physiology KW - Antigens, CD58 -- physiology KW - Interphase -- immunology KW - Killer Cells, Natural -- physiology KW - Killer Cells, Natural -- cytology KW - Adjuvants, Immunologic -- pharmacology KW - Antigens, CD58 -- biosynthesis KW - Killer Cells, Natural -- immunology KW - Adjuvants, Immunologic -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72895613?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Coexpression+of+CD58+or+CD48+with+intercellular+adhesion+molecule+1+on+target+cells+enhances+adhesion+of+resting+NK+cells.&rft.au=Barber%2C+Domingo+F%3BLong%2C+Eric+O&rft.aulast=Barber&rft.aufirst=Domingo&rft.date=2003-01-01&rft.volume=170&rft.issue=1&rft.spage=294&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 - 2003-03-05 N1 - Date created - 2002-12-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carbendazim: disposition, cellular permeability, metabolite identification, and pharmacokinetic comparison with its nanoparticle. AN - 72893860; 12486692 AB - The purpose of this study was to systematically evaluate the pharmacokinetic profiles of carbendazim, a novel anticancer drug. Carbendazim reached the highest concentrations in stomach and small intestine by 1 h after oral administration (500 mg/kg) to tumor-bearing nude mice. Four hours later, carbendazim in the large intestine reached maximum concentrations, probably because of pH-induced precipitation of the drug in the large intestine. The highest concentrations of carbendazim in well-perfused tissues, solid tumor, and blood ranged from 63 to 164 microg/g by 4 h. The percentage of carbendazim distributed to solid tumor by 4 h was higher than most well-perfused tissues. Carbendazim concentrations in blood were similar to, or somewhat lower than, those in tumor and other tissues. By 24 h post-dosing, carbendazim concentrations in tissues and blood declined to almost basal levels. The total percentage of administered carbendazim eliminated in urine was 25.7%, and in feces 16.6% within 24 h. Carbendazim exhibited fast permeation across Caco-2 and HT-29 carcinoma cell lines with corresponding permeability coefficients 7.74-8.06 x 10(-5) and 6.8-8.42 x 10(-5) (cm/s). The overall plasma protein binding of carbendazim (0.2-125 microg/mL) assessed by ultrafiltration ranged from 60 to 74%. Comparative pharmacokinetics was conducted in rats by high-pressure liquid chromatography to evaluate the relative bioavailability of carbendazim versus its nanoparticle formulation. Carbendazim and its nanoparticle reached T(max) at 2.01 and 1.57 h, respectively. The relative bioavailability of nanoparticle carbendazim versus regular carbendazim was 166%. High-pressure liquid chromatography analysis of the rat serum obtained at 20 h after oral dosing revealed a carbendazim metabolite, which was identified by mass spectroscopy analysis as 2-aminobenzimidazole, a hydrolyzed product of carbendazim. Incubation of carbendazim with human and rat liver microsomes produced a metabolite identified by mass spectrometry as 5(6)- or 4(7)-hydroxyl carbendazim. The comprehensive pharmacokinetic information is important to the current clinical investigation of carbendazim. Copyright 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association JF - Journal of pharmaceutical sciences AU - Jia, Lee AU - Wong, Hong AU - Wang, Yao AU - Garza, Mark AU - Weitman, Steve D AD - Institute for Drug Development, 14960 Omicron Drive, San Antonio, Texas 78245, USA. Jiale@mail.nih.gov Y1 - 2003/01// PY - 2003 DA - January 2003 SP - 161 EP - 172 VL - 92 IS - 1 SN - 0022-3549, 0022-3549 KW - Benzimidazoles KW - 0 KW - Carbamates KW - carbendazim KW - H75J14AA89 KW - Index Medicus KW - Tissue Distribution -- physiology KW - Rats KW - Protein Binding -- physiology KW - Animals KW - Rats, Sprague-Dawley KW - Caco-2 Cells -- metabolism KW - Xenograft Model Antitumor Assays -- methods KW - Humans KW - HT29 Cells -- metabolism KW - Mice, Nude KW - Mice KW - Benzimidazoles -- metabolism KW - Cell Membrane Permeability -- physiology KW - Benzimidazoles -- chemistry KW - Nanotechnology -- methods KW - Benzimidazoles -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72893860?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+pharmaceutical+sciences&rft.atitle=Carbendazim%3A+disposition%2C+cellular+permeability%2C+metabolite+identification%2C+and+pharmacokinetic+comparison+with+its+nanoparticle.&rft.au=Jia%2C+Lee%3BWong%2C+Hong%3BWang%2C+Yao%3BGarza%2C+Mark%3BWeitman%2C+Steve+D&rft.aulast=Jia&rft.aufirst=Lee&rft.date=2003-01-01&rft.volume=92&rft.issue=1&rft.spage=161&rft.isbn=&rft.btitle=&rft.title=Journal+of+pharmaceutical+sciences&rft.issn=00223549&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-11 N1 - Date created - 2002-12-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Noninvasive measurement of iron: report of an NIDDK workshop. AN - 72891882; 12393526 AB - An international workshop on the noninvasive measurement of iron was conducted by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) on April 17, 2001, to assess the current state of the science and to identify areas needing further investigation. The workshop concluded that a clear clinical need is evident for quantitative, noninvasive, safe, accurate, and readily available means of measuring body storage iron to improve the diagnosis and management of patients with iron overload from such disorders as hereditary hemochromatosis, thalassemia major, sickle cell disease, aplastic anemia, and myelodysplasia, among others. Magnetic resonance imaging (MRI) potentially provides the best available technique for examining the 3-dimensional distribution of excess iron in the body, but further research is needed to develop means of making measurements quantitative. Biomagnetic susceptometry provides the only noninvasive method to measure tissue iron stores that has been calibrated, validated, and used in clinical studies, but the complexity, cost, and technical demands of the liquid-helium-cooled superconducting instruments required at present have restricted clinical access to the method. The workshop identified basic and clinical research opportunities for deepening our understanding of the physical properties of iron and iron toxicity, for further investigation of MRI as a method for quantitative determinations of tissue iron, especially in liver, heart and brain, and for development of improved methods and more widely available instrumentation for biomagnetic susceptometry. JF - Blood AU - Brittenham, Gary M AU - Badman, David G AU - National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Workshop AD - Columbia University College of Physicians and Surgeons, New York, NY, USA. ; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Workshop Y1 - 2003/01/01/ PY - 2003 DA - 2003 Jan 01 SP - 15 EP - 19 VL - 101 IS - 1 SN - 0006-4971, 0006-4971 KW - Iron KW - E1UOL152H7 KW - Abridged Index Medicus KW - Index Medicus KW - Magnetic Resonance Imaging -- standards KW - Magnetics KW - Magnetic Resonance Imaging -- methods KW - Diagnostic Imaging -- standards KW - Humans KW - Iron Overload -- etiology KW - Organ Specificity KW - Tissue Distribution KW - Iron Overload -- diagnosis KW - Diagnostic Imaging -- methods KW - Iron -- analysis KW - Iron -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72891882?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Noninvasive+measurement+of+iron%3A+report+of+an+NIDDK+workshop.&rft.au=Brittenham%2C+Gary+M%3BBadman%2C+David+G%3BNational+Institute+of+Diabetes+and+Digestive+and+Kidney+Diseases+%28NIDDK%29Workshop&rft.aulast=Brittenham&rft.aufirst=Gary&rft.date=2003-01-01&rft.volume=101&rft.issue=1&rft.spage=15&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-18 N1 - Date created - 2002-12-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Common sites of retroviral integration in mouse hematopoietic tumors identified by high-throughput, single nucleotide polymorphism-based mapping and bacterial artificial chromosome hybridization. AN - 72890098; 12502872 AB - Retroviral insertional mutagenesis in mouse hematopoietic tumors provides a powerful cancer gene discovery tool. Here, we describe a high-throughput, single nucleotide polymorphism (SNP)-based method, for mapping retroviral integration sites cloned from mouse tumors, and a bacterial artificial chromosome (BAC) hybridization method, for localizing these retroviral integration sites to common sites of retroviral integration (CISs). Several new CISs were identified, including one CIS that mapped near Notch1, a gene that has been causally associated with human T-cell tumors. This mapping method is applicable to many different species, including ones where few genetic markers and little genomic sequence information are available. It can also be used to map endogenous proviruses. JF - Journal of virology AU - Shen, Haifa AU - Suzuki, Takeshi AU - Munroe, David J AU - Stewart, Claudia AU - Rasmussen, Lynn AU - Gilbert, Debra J AU - Jenkins, Nancy A AU - Copeland, Neal G AD - Mouse Cancer Genetics Program, National Cancer Institute-Frederick, Maryland 21702, USA. Y1 - 2003/01// PY - 2003 DA - January 2003 SP - 1584 EP - 1588 VL - 77 IS - 2 SN - 0022-538X, 0022-538X KW - Index Medicus KW - Animals KW - Mice KW - Chromosome Mapping KW - Mutagenesis, Insertional KW - Polymorphism, Single Nucleotide KW - Retroviridae -- physiology KW - Hematologic Neoplasms -- virology KW - Chromosomes, Artificial, Bacterial KW - Virus Integration KW - Retroviridae -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72890098?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Common+sites+of+retroviral+integration+in+mouse+hematopoietic+tumors+identified+by+high-throughput%2C+single+nucleotide+polymorphism-based+mapping+and+bacterial+artificial+chromosome+hybridization.&rft.au=Shen%2C+Haifa%3BSuzuki%2C+Takeshi%3BMunroe%2C+David+J%3BStewart%2C+Claudia%3BRasmussen%2C+Lynn%3BGilbert%2C+Debra+J%3BJenkins%2C+Nancy+A%3BCopeland%2C+Neal+G&rft.aulast=Shen&rft.aufirst=Haifa&rft.date=2003-01-01&rft.volume=77&rft.issue=2&rft.spage=1584&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 - 2003-01-22 N1 - Date created - 2002-12-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nat Genet. 1999 Nov;23(3):348-53 [10610183] Prog Exp Tumor Res. 1999;35:53-63 [10377751] Genome Res. 2000 Jan;10(1):137-47 [10645958] Science. 2000 May 26;288(5470):1439-41 [10827957] Mamm Genome. 2001 Jun;12(6):436-41 [11353390] J Virol. 1982 Jul;43(1):26-36 [6287001] J Virol. 1984 Sep;51(3):586-94 [6088784] Curr Top Microbiol Immunol. 1986;127:19-34 [3731841] Nature. 1988 Jan 21;331(6153):277-80 [2827041] Proc Natl Acad Sci U S A. 1990 Jan;87(1):170-3 [1688653] J Virol. 1991 Jan;65(1):464-7 [1985210] Trends Genet. 1991 Apr;7(4):113-8 [2068781] Cell. 1991 Aug 23;66(4):649-61 [1831692] J Virol. 1993 Apr;67(4):2083-90 [8383230] Oncogene. 1996 Jul 4;13(1):183-91 [8700545] Hum Mol Genet. 1998 Jul;7(7):1169-78 [9618176] Nat Genet. 2000 Jan;24(1):23-5 [10615122] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Attenuation of the stimulant and convulsant effects of cocaine by 17-substituted-3-hydroxy and 3-alkoxy derivatives of dextromethorphan. AN - 72889851; 12479950 AB - Pharmacological evidence has suggested a role for both sigma and N-methyl-D-aspartate (NMDA) receptors in the behavioral stimulant effects of cocaine and its convulsant effects observed at higher doses. A series of dextromethorphan (DM) analogs with a range of affinities for sigma-1 binding sites and for the NMDA receptor ion channel were used to explore the contribution of these two mechanisms in controlling the stimulant and convulsant effects of cocaine. These compounds were potent and efficacious blockers of both stimulant and convulsant effects produced by acute cocaine administration in mice (cocaine 10 or 75 mg/kg ip for locomotor activity or convulsions, respectively). Generally, the DM analogs blocked these effects of cocaine at doses that did not display ataxic and sedative side effects as measured in the inverted screen test. In contrast to the high-affinity NMDA blockers, (+)-MK-801 (dizocilpine) and dextrorphan (DX), DM and analogs did not stimulate locomotor activity. There was no significant correlation between the affinities of the DM analogs for the sigma-1 or the phencyclidine (PCP) binding site and their potencies to produce behavioral effects on their own or to attenuate the behavioral or toxic effects of cocaine. The present study has identified a series of agents that have cocaine-blocking effects that appear to be distinct from that of classical sigma-1 receptor ligands and that of traditional uncompetitive NMDA receptor antagonists. These findings point to potentially novel pharmacological strategies for blocking cocaine stimulant and toxic effects. JF - Pharmacology, biochemistry, and behavior AU - Zapata, Agustin AU - Gasior, Maciej AU - Geter-Douglass, Beth AU - Tortella, Frank C AU - Newman, Amy Hauck AU - Witkin, Jeffrey M AD - Drug Development Group, National Institute on Drug Abuse-Intramural Research Program, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. azapata@intra.nida.nih.gov Y1 - 2003/01// PY - 2003 DA - January 2003 SP - 313 EP - 323 VL - 74 IS - 2 SN - 0091-3057, 0091-3057 KW - Anticonvulsants KW - 0 KW - Central Nervous System Stimulants KW - Convulsants KW - Excitatory Amino Acid Antagonists KW - Receptors, sigma KW - Dextromethorphan KW - 7355X3ROTS KW - Cocaine KW - I5Y540LHVR KW - Phencyclidine KW - J1DOI7UV76 KW - Index Medicus KW - Behavior, Animal -- drug effects KW - Animals KW - Receptors, sigma -- drug effects KW - Dose-Response Relationship, Drug KW - Phencyclidine -- pharmacology KW - Motor Activity -- drug effects KW - Mice KW - Male KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Dextromethorphan -- analogs & derivatives KW - Dextromethorphan -- pharmacology KW - Central Nervous System Stimulants -- antagonists & inhibitors KW - Cocaine -- pharmacology KW - Convulsants -- toxicity KW - Cocaine -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72889851?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Attenuation+of+the+stimulant+and+convulsant+effects+of+cocaine+by+17-substituted-3-hydroxy+and+3-alkoxy+derivatives+of+dextromethorphan.&rft.au=Zapata%2C+Agustin%3BGasior%2C+Maciej%3BGeter-Douglass%2C+Beth%3BTortella%2C+Frank+C%3BNewman%2C+Amy+Hauck%3BWitkin%2C+Jeffrey+M&rft.aulast=Zapata&rft.aufirst=Agustin&rft.date=2003-01-01&rft.volume=74&rft.issue=2&rft.spage=313&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 - 2003-06-18 N1 - Date created - 2002-12-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - How I treat heparin-induced thrombocytopenia and thrombosis. AN - 72889386; 12393689 JF - Blood AU - Alving, Barbara M AD - National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. alvingb@nih.gov Y1 - 2003/01/01/ PY - 2003 DA - 2003 Jan 01 SP - 31 EP - 37 VL - 101 IS - 1 SN - 0006-4971, 0006-4971 KW - Anticoagulants KW - 0 KW - Heparin KW - 9005-49-6 KW - Abridged Index Medicus KW - Index Medicus KW - Anticoagulants -- therapeutic use KW - Humans KW - Time Factors KW - Comorbidity KW - Thrombosis -- chemically induced KW - Thrombocytopenia -- drug therapy KW - Thrombosis -- drug therapy KW - Thrombocytopenia -- diagnosis KW - Thrombocytopenia -- chemically induced KW - Thrombosis -- diagnosis KW - Heparin -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72889386?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=How+I+treat+heparin-induced+thrombocytopenia+and+thrombosis.&rft.au=Alving%2C+Barbara+M&rft.aulast=Alving&rft.aufirst=Barbara&rft.date=2003-01-01&rft.volume=101&rft.issue=1&rft.spage=31&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-18 N1 - Date created - 2002-12-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High-dose cyclophosphamide with autologous lymphocyte-depleted peripheral blood stem cell (PBSC) support for treatment of refractory chronic autoimmune thrombocytopenia. AN - 72889334; 12393623 AB - Patients with refractory chronic autoimmune thrombocytopenia (AITP) have a significant risk of morbidity and mortality related to hemorrhage. High-dose (HD) cytotoxic therapy may produce remissions but entails risks related to myelosuppression. Hematopoietic stem cell support with lymphocyte-depleted grafts may accelerate hematologic recovery and concomitantly reduce repopulation by autoreactive immunocytes. Fourteen patients with chronic AITP, in whom multiple prior therapies including corticosteroids, splenectomy, intravenous immunoglobulin, and various cytotoxic or immunomodulatory regimens had failed, were treated with HD cyclophosphamide (50 mg/kg/d) and autologous granulocyte colony-stimulating factor (G-CSF)-mobilized leukocytes depleted of lymphocytes by immunomagnetic CD34(+) selection. There were no significant adverse events related to G-CSF, intravenous device insertion, or leukapheresis. Treatment-related complications included transient hemorrhagic cystitis (1 patient), vaginal bleeding (2 patients), gastrointestinal bleeding (1 patient), epistaxis (1 patient), and antibiotic-responsive febrile neutropenia (all patients). The mean time to absolute neutrophil count (ANC) more than 500/mm(3) was 9 +/- 0.6 days. Eight patients experienced antibiotic-responsive gram-positive bacteremia. A median of 2 platelet transfusions was required for stem cell mobilization, intravenous catheter insertion, and apheresis and a median of 9 platelet transfusions was required during hematopoietic recovery. Six patients obtained durable complete responses (platelet counts > 100 000/mm(3) without other therapy) with maximum follow-up of 42 months. Two additional patients obtained durable partial responses (platelet counts significantly increased over baseline with reduced medication requirements and cessation of bleeding complications). This therapeutic approach is feasible for patients with severe chronic AITP, a substantial proportion of whom may obtain durable remissions. Larger controlled trials are recommended. JF - Blood AU - Huhn, Richard D AU - Fogarty, Patrick F AU - Nakamura, Ryotaro AU - Read, Elizabeth J AU - Leitman, Susan F AU - Rick, Margaret E AU - Kimball, Janice AU - Greene, Adeira AU - Hansmann, Kristin AU - Gratwohl, Alois AU - Young, Neal AU - Barrett, A John AU - Dunbar, Cynthia E AD - Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. rhuhn@cimr.umdnj.edu Y1 - 2003/01/01/ PY - 2003 DA - 2003 Jan 01 SP - 71 EP - 77 VL - 101 IS - 1 SN - 0006-4971, 0006-4971 KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Cyclophosphamide KW - 8N3DW7272P KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Salvage Therapy KW - Leukapheresis -- methods KW - Pilot Projects KW - Platelet Transfusion KW - Graft Survival KW - Adult KW - Chronic Disease KW - Granulocyte Colony-Stimulating Factor -- administration & dosage KW - Middle Aged KW - Adolescent KW - Transplantation, Autologous -- adverse effects KW - Time Factors KW - Female KW - Male KW - Platelet Count KW - Cyclophosphamide -- administration & dosage KW - Purpura, Thrombocytopenic, Idiopathic -- therapy KW - Purpura, Thrombocytopenic, Idiopathic -- complications KW - Lymphocyte Depletion KW - Cyclophosphamide -- toxicity KW - Peripheral Blood Stem Cell Transplantation -- adverse effects KW - Peripheral Blood Stem Cell Transplantation -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72889334?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=High-dose+cyclophosphamide+with+autologous+lymphocyte-depleted+peripheral+blood+stem+cell+%28PBSC%29+support+for+treatment+of+refractory+chronic+autoimmune+thrombocytopenia.&rft.au=Huhn%2C+Richard+D%3BFogarty%2C+Patrick+F%3BNakamura%2C+Ryotaro%3BRead%2C+Elizabeth+J%3BLeitman%2C+Susan+F%3BRick%2C+Margaret+E%3BKimball%2C+Janice%3BGreene%2C+Adeira%3BHansmann%2C+Kristin%3BGratwohl%2C+Alois%3BYoung%2C+Neal%3BBarrett%2C+A+John%3BDunbar%2C+Cynthia+E&rft.aulast=Huhn&rft.aufirst=Richard&rft.date=2003-01-01&rft.volume=101&rft.issue=1&rft.spage=71&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-18 N1 - Date created - 2002-12-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of the enzymatic activity of prostate-specific antigen by boric acid and 3-nitrophenyl boronic acid. AN - 72887753; 12481254 AB - Prostate specific antigen (PSA) is a well-established marker of prostate cancer, but it can also degrade extracellular matrix proteins such as fibronectin and could be involved in tumor progression and metastasis. In this study, we have addressed the use of boric acid and 3-nitrophenyl boronic acid (NPBA) as PSA inhibitors in vitro. The inhibition of PSA by boric acid was studied by using specific fluorogenic substrates. Fibronectin, a biologically relevant substrate for PSA, was used as a substrate in a zymographic assay, and the degradation of fibronectin by PSA in the presence of boric acid and NPBA was followed by Western Blot. Low concentrations of boric acid partially inhibited the proteolytic activity of PSA toward a synthetic fluorogenic substrate. Also, by Western blot, we have found significant inhibition in the proteolysis of fibronectin by PSA in the presence of boric acid as well as NPBA. Results indicate that the boronated compounds used in this study can be used for the modulation of PSA activity. PSA activity is inhibited in vitro by boric acid and NPBA. If degradation of fibronectin by PSA were, in fact, an important step in the progression of prostate cancer, then borate-induced inhibition of PSA activity should help reduce the development and proliferation of prostate carcinomas. Copyright 2002 Wiley-Liss, Inc. JF - The Prostate AU - Gallardo-Williams, Maria T AU - Maronpot, Robert R AU - Wine, Robert N AU - Brunssen, Susan H AU - Chapin, Robert E AD - Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. gallardo@niehs.nih.gov Y1 - 2003/01/01/ PY - 2003 DA - 2003 Jan 01 SP - 44 EP - 49 VL - 54 IS - 1 SN - 0270-4137, 0270-4137 KW - Boric Acids KW - 0 KW - Boronic Acids KW - Enzyme Inhibitors KW - Fibronectins KW - Insecticides KW - 3-nitrobenzeneboronic acid KW - 13331-27-6 KW - Serine Endopeptidases KW - EC 3.4.21.- KW - Prostate-Specific Antigen KW - EC 3.4.21.77 KW - boric acid KW - R57ZHV85D4 KW - Index Medicus KW - Serine Endopeptidases -- pharmacology KW - Blotting, Western KW - Humans KW - Disease Progression KW - Fibronectins -- metabolism KW - Enzyme Inhibitors -- pharmacology KW - Male KW - Cell Division KW - Boronic Acids -- pharmacology KW - Boric Acids -- pharmacology KW - Prostatic Neoplasms -- physiopathology KW - Prostate-Specific Antigen -- pharmacology KW - Insecticides -- pharmacology KW - Prostate-Specific Antigen -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72887753?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Prostate&rft.atitle=Inhibition+of+the+enzymatic+activity+of+prostate-specific+antigen+by+boric+acid+and+3-nitrophenyl+boronic+acid.&rft.au=Gallardo-Williams%2C+Maria+T%3BMaronpot%2C+Robert+R%3BWine%2C+Robert+N%3BBrunssen%2C+Susan+H%3BChapin%2C+Robert+E&rft.aulast=Gallardo-Williams&rft.aufirst=Maria&rft.date=2003-01-01&rft.volume=54&rft.issue=1&rft.spage=44&rft.isbn=&rft.btitle=&rft.title=The+Prostate&rft.issn=02704137&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-01-29 N1 - Date created - 2002-12-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A multicentre randomised double masked clinical trial of a new formulation of topical cysteamine for the treatment of corneal cystine crystals in cystinosis. AN - 72885809; 12488257 AB - To evaluate the safety and efficacy of a new topical cysteamine formulation, stable at room temperature, for the treatment of corneal cystine crystals in cystinosis. 20 study subjects were enrolled in the safety study and 16 in the efficacy study. Both studies were randomised and double blind. The primary outcome for the safety study was the occurrence of predefined serious adverse reactions over 6 months and for the efficacy study the reduction of corneal cystine crystal score (CCCS) by 1.00 or more units on photographs graded by a reading centre using a standardised protocol. No study subject developed any serious adverse reactions. In the efficacy study, 47% of eyes receiving the standard formulation experienced a reduction in the CCCS of >/=1.00 after 1 year, while 7% of eyes on the new formulation experienced such a decrease (p=0.04). Although no serious adverse reactions were observed with either formulation, the new formulation was not as effective as the standard formulation. JF - The British journal of ophthalmology AU - Tsilou, E T AU - Thompson, D AU - Lindblad, A S AU - Reed, G F AU - Rubin, B AU - Gahl, W AU - Thoene, J AU - Del Monte, M AU - Schneider, J A AU - Granet, D B AU - Kaiser-Kupfer, M I AD - Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA. tsiloue@nei.nih.gov Y1 - 2003/01// PY - 2003 DA - January 2003 SP - 28 EP - 31 VL - 87 IS - 1 SN - 0007-1161, 0007-1161 KW - Radiation-Protective Agents KW - 0 KW - Cysteamine KW - 5UX2SD1KE2 KW - Index Medicus KW - Prospective Studies KW - Double-Blind Method KW - Humans KW - Adult KW - Treatment Outcome KW - Child KW - Adolescent KW - Male KW - Female KW - Administration, Topical KW - Child, Preschool KW - Radiation-Protective Agents -- administration & dosage KW - Cysteamine -- administration & dosage KW - Cystinosis -- drug therapy KW - Cysteamine -- adverse effects KW - Corneal Diseases -- pathology KW - Radiation-Protective Agents -- adverse effects KW - Corneal Diseases -- drug therapy KW - Cystinosis -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72885809?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+British+journal+of+ophthalmology&rft.atitle=A+multicentre+randomised+double+masked+clinical+trial+of+a+new+formulation+of+topical+cysteamine+for+the+treatment+of+corneal+cystine+crystals+in+cystinosis.&rft.au=Tsilou%2C+E+T%3BThompson%2C+D%3BLindblad%2C+A+S%3BReed%2C+G+F%3BRubin%2C+B%3BGahl%2C+W%3BThoene%2C+J%3BDel+Monte%2C+M%3BSchneider%2C+J+A%3BGranet%2C+D+B%3BKaiser-Kupfer%2C+M+I&rft.aulast=Tsilou&rft.aufirst=E&rft.date=2003-01-01&rft.volume=87&rft.issue=1&rft.spage=28&rft.isbn=&rft.btitle=&rft.title=The+British+journal+of+ophthalmology&rft.issn=00071161&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-20 N1 - Date created - 2002-12-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: N Engl J Med. 1987 Mar 26;316(13):775-9 [3821824] Arch Ophthalmol. 1986 May;104(5):706-11 [3518682] Arch Ophthalmol. 1990 May;108(5):689-93 [2185723] Pediatr Nephrol. 1987 Jul;1(3):260-8 [3153286] Biochem Med Metab Biol. 1992 Dec;48(3):275-85 [1476793] N Engl J Med. 1993 Apr 22;328(16):1157-62 [8455682] J Clin Endocrinol Metab. 1995 Nov;80(11):3257-61 [7593434] Nat Genet. 1998 Apr;18(4):319-24 [9537412] Mol Genet Metab. 1998 Aug;64(4):237-42 [9758713] Mol Genet Metab. 2000 Sep-Oct;71(1-2):100-20 [11001803] J Biol Chem. 1982 Aug 25;257(16):9570-5 [7107582] Science. 1982 Sep 24;217(4566):1263-5 [7112129] J Biol Chem. 1982 Nov 25;257(22):13185-8 [6292178] Am J Ophthalmol. 1983 May;95(5):713-4 [6846466] N Engl J Med. 1987 Apr 16;316(16):971-7 [3550461] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Downregulation of hnRNP A2/B1 expression in tumor cells under prolonged hypoxia. AN - 72885708; 12495935 AB - Heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 has been previously shown to be overexpressed in breast and lung tumors. Because hypoxia is a feature inherent in solid tumors, the regulation of hnRNP A2/B1 expression and subcellular localization under hypoxic conditions was studied on human lung and breast carcinoma cell lines. We found that sustained hypoxic treatment downregulated hnRNP A2/B1 expression in MCF7 and H157 cell lines. Northern blot analysis showed that this decay: (i) was observed as a marked diminution of transcript levels after 24-48 h of exposure to low oxygen tension; (ii) is not mediated by the transcription factor, hypoxia inducible factor-1; and (iii) is partially dependent on a higher hnRNP A2/B1 messenger RNA turnover under hypoxic than normoxic conditions. Immunocytochemical staining also showed a significant diminution of hnRNP A2/B1 staining in these cell lines after 24-48 h of hypoxia, together with a predominant loss of cytoplasmic staining. Further investigations are warranted to evaluate the relevance of modulation of hnRNP A2/B1 in hypoxic environments relative to its previously reported utility as a marker of early lung carcinogenesis. JF - American journal of respiratory cell and molecular biology AU - Garayoa, Mercedes AU - Man, Yan-Gao AU - Martínez, Alfredo AU - Cuttitta, Frank AU - Mulshine, James L AD - Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/01// PY - 2003 DA - January 2003 SP - 80 EP - 85 VL - 28 IS - 1 SN - 1044-1549, 1044-1549 KW - DNA-Binding Proteins KW - 0 KW - HIF1A protein, human KW - Heterogeneous-Nuclear Ribonucleoprotein Group A-B KW - Hypoxia-Inducible Factor 1 KW - Hypoxia-Inducible Factor 1, alpha Subunit KW - Nuclear Proteins KW - RNA, Messenger KW - Transcription Factors KW - hnRNP A2 KW - Index Medicus KW - Base Sequence KW - Blotting, Northern KW - Tumor Cells, Cultured KW - RNA, Messenger -- metabolism KW - Humans KW - RNA, Messenger -- genetics KW - Nuclear Proteins -- metabolism KW - Immunohistochemistry KW - DNA-Binding Proteins -- metabolism KW - Heterogeneous-Nuclear Ribonucleoprotein Group A-B -- metabolism KW - Down-Regulation KW - Heterogeneous-Nuclear Ribonucleoprotein Group A-B -- genetics KW - Cell Hypoxia UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72885708?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Downregulation+of+hnRNP+A2%2FB1+expression+in+tumor+cells+under+prolonged+hypoxia.&rft.au=Garayoa%2C+Mercedes%3BMan%2C+Yan-Gao%3BMart%C3%ADnez%2C+Alfredo%3BCuttitta%2C+Frank%3BMulshine%2C+James+L&rft.aulast=Garayoa&rft.aufirst=Mercedes&rft.date=2003-01-01&rft.volume=28&rft.issue=1&rft.spage=80&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 - 2003-01-30 N1 - Date created - 2002-12-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biologic therapies in the vasculitides. AN - 72884756; 12496503 AB - Monoclonal antibody and recombinant DNA technologies have led to the development of biologic therapies capable of directly targeting selected components of the immune response. With the steady expansion of knowledge regarding the mechanisms of vascular inflammation, the safety and efficacy of biologic agents in the vasculitic diseases are being increasingly investigated. By targeting specific effector mechanisms involved in the pathogenesis of vasculitis, these agents may provide a less toxic means of inducing remission and lessening relapse. However, the study of biologic therapies in the vasculitides must be approached with caution, as unanticipated effects on disease activity and disease-specific toxicities can occur. Studies to examine these agents must recognize the potential for active vasculitis to be organ- or life-threatening as well as the current existence of effective therapies. In the research setting, investigation of biologic agents in the treatment of vasculitic diseases may also provide important insights into pathogenesis of these syndromes. JF - Current opinion in rheumatology AU - Langford, Carol A AU - Sneller, Michael C AD - Immunologic Diseases Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. clangford@niaid.nih.gov Y1 - 2003/01// PY - 2003 DA - January 2003 SP - 3 EP - 10 VL - 15 IS - 1 SN - 1040-8711, 1040-8711 KW - Antibodies, Monoclonal KW - 0 KW - Immunosuppressive Agents KW - Index Medicus KW - Animals KW - Humans KW - Clinical Trials as Topic KW - Mice KW - Immunosuppressive Agents -- therapeutic use KW - Antibodies, Monoclonal -- therapeutic use KW - Biological Therapy -- methods KW - Vasculitis -- immunology KW - Vasculitis -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72884756?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+opinion+in+rheumatology&rft.atitle=Biologic+therapies+in+the+vasculitides.&rft.au=Langford%2C+Carol+A%3BSneller%2C+Michael+C&rft.aulast=Langford&rft.aufirst=Carol&rft.date=2003-01-01&rft.volume=15&rft.issue=1&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+rheumatology&rft.issn=10408711&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-03 N1 - Date created - 2002-12-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retroviral mutation rates and reverse transcriptase fidelity. AN - 72882639; 12456349 AB - Genetic variation in retroviral populations provides a mechanism for retroviruses to escape host immune responses and develop resistance to all known antiretroviral drugs. Retroviruses, like all RNA viruses, exhibit a high mutation rate. Polymerization errors during DNA synthesis by reverse transcriptase, which lacks a proofreading activity, is a major mechanism for generating genetic variation within retroviral populations. In this review, we summarize our current understanding of the processes that contribute to the generation of mutations in retroviruses. An overview of in vivo and in vitro studies of retroviral mutation rates determined by various fidelity assays is provided. Extensive mutational analyses of RTs are beginning to elucidate the relationship between structural determinants of RTs and fidelity of DNA synthesis. Recently, it was observed that the Y586F mutation in MLV RT results in a dramatic increase in the mutation rate in the vicinity of adenine-thymie tracts (AAAA, TTTT, and AATT), which are associated with bends in DNA. These results indicate that the template-primer duplex is a component of the polymerase active site and its structure can influence nucleotide selectivity and the mutation rate. Additionally, the results also suggest that the Y586 residue and the RNase H primer grip are structural determinants of RT that have evolved to attenuate the effects of unusual conformations of the template-primer duplex, such as bends in DNA, on fidelity of DNA synthesis. JF - Frontiers in bioscience : a journal and virtual library AU - Svarovskaia, Evguenia S AU - Cheslock, Sara R AU - Zhang, Wen-Hui AU - Hu, Wei-Shau AU - Pathak, Vinay K AD - HIV Drug Resistance Program, CCR, NCI-Frederick, Frederick, Maryland 21702, USA. Y1 - 2003/01/01/ PY - 2003 DA - 2003 Jan 01 SP - d117 EP - d134 VL - 8 SN - 1093-9946, 1093-9946 KW - RNA-Directed DNA Polymerase KW - EC 2.7.7.49 KW - Index Medicus KW - Animals KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - RNA-Directed DNA Polymerase -- chemistry KW - Retroviridae -- genetics KW - RNA-Directed DNA Polymerase -- genetics KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72882639?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Frontiers+in+bioscience+%3A+a+journal+and+virtual+library&rft.atitle=Retroviral+mutation+rates+and+reverse+transcriptase+fidelity.&rft.au=Svarovskaia%2C+Evguenia+S%3BCheslock%2C+Sara+R%3BZhang%2C+Wen-Hui%3BHu%2C+Wei-Shau%3BPathak%2C+Vinay+K&rft.aulast=Svarovskaia&rft.aufirst=Evguenia&rft.date=2003-01-01&rft.volume=8&rft.issue=&rft.spage=d117&rft.isbn=&rft.btitle=&rft.title=Frontiers+in+bioscience+%3A+a+journal+and+virtual+library&rft.issn=10939946&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-02 N1 - Date created - 2002-11-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Construction and characterization of RNase-based targeted therapeutics. AN - 72882522; 12412481 JF - Methods in molecular biology (Clifton, N.J.) AU - Newton, Dianne L AU - Futami, Junichiro AU - Ruby, Dale AU - Rybak, Susanna M AD - SAIC-Frederick, National Cancer Institute, Frederick, MD, USA. Y1 - 2003 PY - 2003 DA - 2003 SP - 283 EP - 304 VL - 207 SN - 1064-3745, 1064-3745 KW - DNA Primers KW - 0 KW - Immunoglobulin Variable Region KW - Receptors, Transferrin KW - Recombinant Fusion Proteins KW - Ribonuclease, Pancreatic KW - EC 3.1.27.5 KW - Index Medicus KW - Humans KW - Gene Expression KW - Genetic Engineering -- methods KW - Mutagenesis KW - DNA Primers -- chemistry KW - Immunoglobulin Variable Region -- genetics KW - Recombinant Fusion Proteins -- immunology KW - Immunoglobulin Variable Region -- immunology KW - Receptors, Transferrin -- therapeutic use KW - Recombinant Fusion Proteins -- isolation & purification KW - Ribonuclease, Pancreatic -- therapeutic use KW - Immunoglobulin Variable Region -- chemistry KW - Ribonuclease, Pancreatic -- isolation & purification KW - Receptors, Transferrin -- genetics KW - Polymerase Chain Reaction -- methods KW - Recombinant Fusion Proteins -- genetics KW - Receptors, Transferrin -- immunology KW - Recombinant Fusion Proteins -- therapeutic use KW - Ribonuclease, Pancreatic -- chemistry KW - Ribonuclease, Pancreatic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72882522?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.atitle=Construction+and+characterization+of+RNase-based+targeted+therapeutics.&rft.au=Newton%2C+Dianne+L%3BFutami%2C+Junichiro%3BRuby%2C+Dale%3BRybak%2C+Susanna+M&rft.aulast=Newton&rft.aufirst=Dianne&rft.date=2003-01-01&rft.volume=207&rft.issue=&rft.spage=283&rft.isbn=&rft.btitle=&rft.title=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.issn=10643745&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-28 N1 - Date created - 2002-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Study of P450 function using gene knockout and transgenic mice. AN - 72880245; 12464254 AB - The xenobiotic-metabolizing P450s have been extensively studied for their ability to metabolize endogenous and exogenous chemicals. The latter include drugs and dietary and environmentally derived toxicants and carcinogens. These enzymes also metabolize endogenous steroids and fatty acids. P450s are thought to be required for efficient removal of most xenobiotics from the body and to be responsible for the hazardous effects of toxicants and carcinogens based on their ability to convert chemicals to electrophilic metabolites that can cause cellular damage and gene mutations. P450 catalytic activities have been extensively studied in vitro and in cell culture, yielding considerable information on their mechanisms of catalysis, substrate specificities, and metabolic products. Targeted gene disruption has been used to determine the roles of P450s in intact animals and their contributions to the mechanisms of toxicity and carcinogenesis. The P450s chosen for study, CYP1A1, CYP1B1, CYP1A2, and CYP2E1, are conserved in mammals and are known to metabolize most toxicants and chemical carcinogens. Mice lacking expression of these enzymes do not differ from wild-type mice, indicating that these P450s are not required for development and physiological homeostasis. However, the P450 null mice have altered responses to the toxic and carcinogenic effects of chemicals as compared with wild-type mice. These studies establish that P450s mediate the adverse effects of drugs and dietary, environmental, and industrial chemicals and serve to validate molecular epidemiology studies that seek to determine links between P450 polymorphisms and susceptibility to chemically associated diseases. More recently, P450 humanized mice have been produced. JF - Archives of biochemistry and biophysics AU - Gonzalez, Frank J AU - Kimura, Shioko AD - Building 37, Room 3E-24, Laboratory of Metabolism, National Cancer Institute, Bethesda, MD 20892, USA. fjgonz@helix.nih.gov Y1 - 2003/01/01/ PY - 2003 DA - 2003 Jan 01 SP - 153 EP - 158 VL - 409 IS - 1 SN - 0003-9861, 0003-9861 KW - Analgesics, Non-Narcotic KW - 0 KW - Carcinogens KW - Xenobiotics KW - Acetaminophen KW - 362O9ITL9D KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Carcinogens -- pharmacology KW - Animals KW - Analgesics, Non-Narcotic -- pharmacology KW - Dose-Response Relationship, Drug KW - Humans KW - Xenobiotics -- pharmacology KW - Models, Chemical KW - Mice KW - Mice, Transgenic KW - Models, Biological KW - Mice, Knockout KW - Acetaminophen -- pharmacology KW - Cytochrome P-450 Enzyme System -- genetics KW - Cytochrome P-450 Enzyme System -- physiology KW - Cytochrome P-450 Enzyme System -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72880245?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Study+of+P450+function+using+gene+knockout+and+transgenic+mice.&rft.au=Gonzalez%2C+Frank+J%3BKimura%2C+Shioko&rft.aulast=Gonzalez&rft.aufirst=Frank&rft.date=2003-01-01&rft.volume=409&rft.issue=1&rft.spage=153&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 - 2003-02-14 N1 - Date created - 2002-12-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Renaissance of amantadine in the treatment of Parkinson's disease. AN - 72879756; 12442683 JF - Advances in neurology AU - Blanchet, Pierre J AU - Metman, Leo Verhagen AU - Chase, Thomas N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2003 PY - 2003 DA - 2003 SP - 251 EP - 257 VL - 91 SN - 0091-3952, 0091-3952 KW - Antiparkinson Agents KW - 0 KW - Receptors, N-Methyl-D-Aspartate KW - Glutamic Acid KW - 3KX376GY7L KW - Levodopa KW - 46627O600J KW - Amantadine KW - BF4C9Z1J53 KW - Index Medicus KW - Drug Therapy, Combination KW - Animals KW - Glutamic Acid -- metabolism KW - Dyskinesia, Drug-Induced -- drug therapy KW - Receptors, N-Methyl-D-Aspartate -- drug effects KW - Humans KW - Dyskinesia, Drug-Induced -- prevention & control KW - Treatment Outcome KW - Receptors, N-Methyl-D-Aspartate -- metabolism KW - Levodopa -- adverse effects KW - Antiparkinson Agents -- adverse effects KW - Amantadine -- administration & dosage KW - Antiparkinson Agents -- administration & dosage KW - Parkinson Disease -- metabolism KW - Amantadine -- adverse effects KW - Parkinson Disease -- physiopathology KW - Parkinson Disease -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72879756?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neurology&rft.atitle=Renaissance+of+amantadine+in+the+treatment+of+Parkinson%27s+disease.&rft.au=Blanchet%2C+Pierre+J%3BMetman%2C+Leo+Verhagen%3BChase%2C+Thomas+N&rft.aulast=Blanchet&rft.aufirst=Pierre&rft.date=2003-01-01&rft.volume=91&rft.issue=&rft.spage=251&rft.isbn=&rft.btitle=&rft.title=Advances+in+neurology&rft.issn=00913952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-01-07 N1 - Date created - 2002-11-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I study of intravesical suramin for the treatment of superficial transitional cell carcinoma of the bladder. AN - 72876026; 12478189 AB - Suramin is a polysulfonated naphthylurea that inhibits proliferation and DNA synthesis of transitional cell carcinoma cell lines. Its large molecular size and negative charge inhibit bladder absorption, making suramin an excellent candidate for intravesical chemotherapy. Intravesical suramin was evaluated in a phase I study to define dose limiting toxicity and systemic absorption, determine a starting dose and regimen for phase II studies and provide a preliminary assessment of in vivo antitumor activity. Intravesical suramin treatment was administered in 9 patients with histologically identified transitional cell carcinoma (Tcis, Ta or T1) in whom at least 1 course of standard intravesical chemotherapy (bacillus Calmette-Guerin, thiotepa or mitomycin C) had failed. Suramin was administered once weekly for 6 weeks. Patients were treated in groups of 3 using a 60 cc volume and intrapatient dose escalation schedule. Suramin doses of 0.3 to 614.4 mg./ml. were administered intravesically. The last group was treated with the same weekly dose for 6 weeks. The 9 patients underwent 54 treatments with suramin. Plasma suramin concentration after treatment was 1.9 to 38.0 microg./ml. and was not related to treatment dose. The dose escalation phase was limited by the solubility of suramin in solution. Complications included self-limited bladder spasms (less than 24 hours) in 4 of 54 treatments (7%) and new or worsening vesicoureteral reflux in 3 ureters (17%). Another patient who was treated after the Foley balloon was inflated in the urethra experienced bladder spasms, skin flushing and fever (39C). Mean bladder capacity before and after treatment was 600 and 540 ml., respectively. At followup 7 patients had stage Ta tumors and 2 had carcinoma in situ. An intravesical suramin dose of 153 mg./ml was defined as a safe treatment parameter with acceptable plasma concentrations and minimal side effects. Phase II studies are needed to assess the antitumor activity of suramin in patients with transitional cell carcinoma of the bladder. JF - The Journal of urology AU - Uchio, Edward M AU - Linehan, W Marston AU - Figg, William D AU - Walther, McClellan M AD - Urologic Oncology Therapeutic Branch, Center for Cancer Research, National Cancer Institute/NIH, Bethesda, MD, USA. Y1 - 2003/01// PY - 2003 DA - January 2003 SP - 357 EP - 360 VL - 169 IS - 1 SN - 0022-5347, 0022-5347 KW - Antineoplastic Agents KW - 0 KW - Suramin KW - 6032D45BEM KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Aged KW - Middle Aged KW - Male KW - Female KW - Administration, Intravesical KW - Carcinoma, Transitional Cell -- pathology KW - Suramin -- adverse effects KW - Urinary Bladder Neoplasms -- pathology KW - Antineoplastic Agents -- administration & dosage KW - Urinary Bladder Neoplasms -- drug therapy KW - Suramin -- administration & dosage KW - Carcinoma, Transitional Cell -- drug therapy KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72876026?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=A+phase+I+study+of+intravesical+suramin+for+the+treatment+of+superficial+transitional+cell+carcinoma+of+the+bladder.&rft.au=Uchio%2C+Edward+M%3BLinehan%2C+W+Marston%3BFigg%2C+William+D%3BWalther%2C+McClellan+M&rft.aulast=Uchio&rft.aufirst=Edward&rft.date=2003-01-01&rft.volume=169&rft.issue=1&rft.spage=357&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 - 2003-01-09 N1 - Date created - 2002-12-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of the nuclear receptor CAR as a coordinate regulator of hepatic gene expression in defense against chemical toxicity. AN - 72874921; 12464260 AB - The nuclear receptor CAR (constitutive active receptor) mediates the induction of transcription of cytochrome P450 (CYP) genes by phenobarbital (PB) and PB-type inducers. A recent study using CAR-null mice has shown that CAR regulates not only the CYP genes but also other genes encoding various drug/steroid-metabolizing enzymes. In addition to coordinating these enzymes, CAR plays other roles in hepatic gene expression: CAR represses various genes including carnitine palmitoyltransferase 1a and phosphoenolpyruvate carboxykinase 1 in response to PB, and the receptor regulates the constitutive expression of genes such as squalene epoxidase. On the other hand, induction of certain genes such as amino levulinate synthase 1 by PB is not regulated by CAR. Here we describe diverse roles of CAR in hepatic gene expression with a particular focus on endogenous substances such as cholesterol, bilirubin, and steroid hormones. JF - Archives of biochemistry and biophysics AU - Yamamoto, Yukio AU - Kawamoto, Takeshi AU - Negishi, Masahiko AD - Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 2003/01/01/ PY - 2003 DA - 2003 Jan 01 SP - 207 EP - 211 VL - 409 IS - 1 SN - 0003-9861, 0003-9861 KW - Estrogens KW - 0 KW - RNA, Messenger KW - Receptors, Cytoplasmic and Nuclear KW - Transcription Factors KW - constitutive androstane receptor KW - KN 62 KW - 63HM46XPOW KW - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine KW - 84477-87-2 KW - Cholesterol KW - 97C5T2UQ7J KW - Oxygenases KW - EC 1.13.- KW - Squalene Monooxygenase KW - EC 1.14.14.17 KW - Carnitine O-Palmitoyltransferase KW - EC 2.3.1.21 KW - 5-Aminolevulinate Synthetase KW - EC 2.3.1.37 KW - Phosphoenolpyruvate Carboxykinase (ATP) KW - EC 4.1.1.49 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Carnitine O-Palmitoyltransferase -- metabolism KW - Blotting, Northern KW - Oxygenases -- metabolism KW - Oligonucleotide Array Sequence Analysis KW - Dose-Response Relationship, Drug KW - Two-Hybrid System Techniques KW - 5-Aminolevulinate Synthetase -- metabolism KW - Transcription, Genetic KW - Mice KW - Mice, Transgenic KW - Models, Biological KW - Calcium -- metabolism KW - Phosphoenolpyruvate Carboxykinase (ATP) -- metabolism KW - RNA, Messenger -- metabolism KW - Estrogens -- pharmacology KW - Cells, Cultured KW - Cholesterol -- metabolism KW - Cytoplasm -- metabolism KW - Protein Structure, Tertiary KW - Male KW - Receptors, Cytoplasmic and Nuclear -- physiology KW - Transcription Factors -- physiology KW - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine -- pharmacology KW - Transcription Factors -- metabolism KW - Receptors, Cytoplasmic and Nuclear -- metabolism KW - Liver -- metabolism KW - Gene Expression Regulation KW - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72874921?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+biochemistry+and+biophysics&rft.atitle=The+role+of+the+nuclear+receptor+CAR+as+a+coordinate+regulator+of+hepatic+gene+expression+in+defense+against+chemical+toxicity.&rft.au=Yamamoto%2C+Yukio%3BKawamoto%2C+Takeshi%3BNegishi%2C+Masahiko&rft.aulast=Yamamoto&rft.aufirst=Yukio&rft.date=2003-01-01&rft.volume=409&rft.issue=1&rft.spage=207&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 - 2003-02-14 N1 - Date created - 2002-12-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Medical applications of transforming growth factor-beta. AN - 71603552; 15931280 AB - Transforming growth factor-beta (TGF-beta) proteins and their antagonists have entered clinical trials. These multi-functional regulators of cell growth and differentiation induce extracellular matrix proteins and suppress the immune system making TGF-betas useful in treatment of wounds with impaired healing, mucositis, fractures, ischemia-reperfusion injuries, and autoimmune disease. In diseases such as keloids, glomerulonephritis and pulmonary fibrosis, excessive expression of TGF-beta has been implicated as being responsible for accumulation of detrimental scar tissue. In these conditions, agents that block TGF-beta have prevented or reversed disease. Similarly, in carcinogenesis, blocking TGF-beta activity may be valuable in stimulating an immune response towards metastasis. As these blocking agents receive approval, we will likely have new therapies for previously recalcitrant diseases. JF - Clinical medicine & research AU - Flanders, Kathleen C AU - Burmester, James K AD - Laboratory of Cell Regulation and Carcinogenesis, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2003/01// PY - 2003 DA - January 2003 SP - 13 EP - 20 VL - 1 IS - 1 SN - 1539-4182, 1539-4182 KW - Transforming Growth Factor beta KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Wounds and Injuries -- drug therapy KW - Reperfusion Injury -- drug therapy KW - Autoimmune Diseases -- drug therapy KW - Transforming Growth Factor beta -- chemistry KW - Transforming Growth Factor beta -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71603552?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+medicine+%26+research&rft.atitle=Medical+applications+of+transforming+growth+factor-beta.&rft.au=Flanders%2C+Kathleen+C%3BBurmester%2C+James+K&rft.aulast=Flanders&rft.aufirst=Kathleen&rft.date=2003-01-01&rft.volume=1&rft.issue=1&rft.spage=13&rft.isbn=&rft.btitle=&rft.title=Clinical+medicine+%26+research&rft.issn=15394182&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-11-07 N1 - Date created - 2005-10-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8628-32 [7690965] Proteins. 1993 Oct;17(2):176-92 [8265565] Development. 1995 Jun;121(6):1845-54 [7600998] J Cell Sci. 1995 Mar;108 ( Pt 3):985-1002 [7542672] Cancer Res. 1995 Sep 15;55(18):3982-7 [7664267] J Immunol. 1995 Sep 15;155(6):3205-12 [7673733] J Cell Physiol. 1995 Oct;165(1):201-11 [7559802] Cancer Res. 1995 Dec 1;55(23):5545-7 [7585631] Cancer Res. 1995 Dec 1;55(23):5548-50 [7585632] Nat Genet. 1995 Dec;11(4):415-21 [7493022] Cancer Immunol Immunother. 1995 Nov;41(5):302-8 [8536276] Science. 1996 Jan 19;271(5247):350-3 [8553070] Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2909-14 [8610141] Nat Med. 1996 Apr;2(4):418-23 [8597951] Nat Genet. 1996 Jun;13(2):189-95 [8640225] Nat Genet. 1996 Jul;13(3):343-6 [8673134] Biochemistry. 1996 Jul 2;35(26):8517-34 [8679613] Protein Sci. 1996 Jul;5(7):1261-71 [8819159] Neurology. 1998 Jul;51(1):289-92 [9674825] J Natl Cancer Inst. 2000 Sep 6;92(17):1388-402 [10974075] Am J Ophthalmol. 2000 Oct;130(4):516-7 [11024425] Kidney Int. 2000 Nov;58(5):1885-92 [11044208] Cell. 2000 Oct 13;103(2):295-309 [11057902] Gastroenterology. 2000 Nov;119(5):1286-96 [11054386] Gene Ther. 2000 Nov;7(22):1915-24 [11127579] Ann Surg Oncol. 2001 Jan-Feb;8(1):32-7 [11206222] Clin Oral Implants Res. 2000 Apr;11(2):107-15 [11168201] Stroke. 2001 Feb;32(2):544-52 [11157195] Nat Rev Mol Cell Biol. 2000 Dec;1(3):169-78 [11252892] Am J Respir Crit Care Med. 2001 Mar;163(3 Pt 1):770-7 [11254537] Ciba Found Symp. 1991;157:194-207; 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AN - 71600742; 15301405 AB - This study examines the prevalence and patterns of mortality resulting from unintentional poisoning by alcohol (ICD-9 code E860) in the United States. Relevant data for the most recently available years (1996 through 1998) were derived from the Multiple Cause of Death public-use computer data files compiled by the National Center for Health Statistics (NCHS). Data on deaths ascribed to alcohol poisoning as either the underlying cause or as 1 of up to 20 contributing causes were selected and analyzed. The annual average number of deaths for which alcohol poisoning was listed as an underlying cause was 317, with an age-adjusted death rate of 0.11 per 100,000 population. An average of 1,076 additional deaths included alcohol poisoning as a contributing cause, bringing the total number of deaths with any mention of alcohol poisoning to 1,393 per year (0.49 per 100,000 population). Males accounted for more than 80 percent of these deaths. The rate was lower among married than unmarried people (i.e., never married, divorced, or widowed) and was inversely related to education. Among males, the alcohol poisoning death rate was higher for Hispanics and non-Hispanic Blacks than non-Hispanic Whites. Among females, racial/ethnic differences were small, but Black women had higher alcohol poisoning death rates than White or Hispanic women. Alcohol poisoning deaths tended to be most prevalent among people ages 35 to 54; only 2 percent of alcohol poisoning decedents were younger than age 21. Among deaths with a contributing cause of alcohol poisoning, almost 90 percent had an underlying cause related to some type of poisoning from other drugs. JF - Alcohol research & health : the journal of the National Institute on Alcohol Abuse and Alcoholism AU - Yoon, Young-Hee AU - Stinson, Frederick S AU - Yi, Hsiao-Ye AU - Dufour, Mary C AD - Alcohol Epidemiologic Data System of the National Institute on Alcohol Abuse and Alcoholism, Arlington, VA, USA. Y1 - 2003 PY - 2003 DA - 2003 SP - 110 EP - 118 VL - 27 IS - 1 SN - 1535-7414, 1535-7414 KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Educational Status KW - Humans KW - African Americans -- statistics & numerical data KW - European Continental Ancestry Group -- statistics & numerical data KW - National Center for Health Statistics (U.S.) KW - Age Distribution KW - Marital Status KW - Hispanic Americans -- statistics & numerical data KW - Adult KW - Databases, Factual KW - Middle Aged KW - United States -- epidemiology KW - Sex Distribution KW - Female KW - Male KW - Alcohol Drinking -- mortality KW - Alcohol Drinking -- ethnology KW - Ethanol -- poisoning KW - Accidents -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71600742?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+research+%26+health+%3A+the+journal+of+the+National+Institute+on+Alcohol+Abuse+and+Alcoholism&rft.atitle=Accidental+alcohol+poisoning+mortality+in+the+United+States%2C+1996-1998.&rft.au=Yoon%2C+Young-Hee%3BStinson%2C+Frederick+S%3BYi%2C+Hsiao-Ye%3BDufour%2C+Mary+C&rft.aulast=Yoon&rft.aufirst=Young-Hee&rft.date=2003-01-01&rft.volume=27&rft.issue=1&rft.spage=110&rft.isbn=&rft.btitle=&rft.title=Alcohol+research+%26+health+%3A+the+journal+of+the+National+Institute+on+Alcohol+Abuse+and+Alcoholism&rft.issn=15357414&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-31 N1 - Date created - 2004-08-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Delitto perfetto targeted mutagenesis in yeast with oligonucleotides. AN - 71599338; 15260239 JF - Genetic engineering AU - Storici, Francesca AU - Resnick, Michael A AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, NIH, 111 Alexander Dr., Research Triangle Park, NC 27709, USA. Y1 - 2003 PY - 2003 DA - 2003 SP - 189 EP - 207 VL - 25 SN - 0196-3716, 0196-3716 KW - DNA Primers KW - 0 KW - Oligonucleotides KW - Index Medicus KW - Base Sequence KW - Saccharomyces cerevisiae -- genetics KW - Mutagenesis, Site-Directed KW - Oligonucleotides -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71599338?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genetic+engineering&rft.atitle=Delitto+perfetto+targeted+mutagenesis+in+yeast+with+oligonucleotides.&rft.au=Storici%2C+Francesca%3BResnick%2C+Michael+A&rft.aulast=Storici&rft.aufirst=Francesca&rft.date=2003-01-01&rft.volume=25&rft.issue=&rft.spage=189&rft.isbn=&rft.btitle=&rft.title=Genetic+engineering&rft.issn=01963716&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-12 N1 - Date created - 2004-07-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Radiolabeled somatostaitin analogs in the treatment of neuroendocrine tumors: experience of the National Cancer Institute of Milano using high dose of 111In-pentetreotide in metastatic neuroendocrine gastroenteropancreatic tumors. AN - 71589416; 15233216 JF - Journal of endocrinological investigation AU - Bombardieri, E AU - Seregni, E AU - Savelli, G AU - Villano, C AU - Castellani, M R AU - Cirillo, F AU - Pallotti, F AU - Fracassi, S AU - Chiesa, C AU - Chiti, A AU - Bajetta, E AD - Nuclear Medicine Division, Italian Trials of Medical Oncology, National Cancer Institute, Milan, Italy. bombardieri@istitutotumori.mi.it Y1 - 2003 PY - 2003 DA - 2003 SP - 63 EP - 69 VL - 26 IS - 8 Suppl SN - 0391-4097, 0391-4097 KW - Antineoplastic Agents, Hormonal KW - 0 KW - Indium Radioisotopes KW - Radiopharmaceuticals KW - Somatostatin KW - 51110-01-1 KW - pentetreotide KW - G083B71P98 KW - Index Medicus KW - Radiopharmaceuticals -- therapeutic use KW - Radiation Dosage KW - Humans KW - Male KW - Italy KW - Female KW - Radionuclide Imaging KW - Neuroendocrine Tumors -- diagnostic imaging KW - Somatostatin -- therapeutic use KW - Indium Radioisotopes -- therapeutic use KW - Neuroendocrine Tumors -- drug therapy KW - Pancreatic Neoplasms -- diagnostic imaging KW - Gastrointestinal Neoplasms -- drug therapy KW - Somatostatin -- analogs & derivatives KW - Pancreatic Neoplasms -- drug therapy KW - Gastrointestinal Neoplasms -- diagnostic imaging KW - Antineoplastic Agents, Hormonal -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71589416?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+endocrinological+investigation&rft.atitle=Radiolabeled+somatostaitin+analogs+in+the+treatment+of+neuroendocrine+tumors%3A+experience+of+the+National+Cancer+Institute+of+Milano+using+high+dose+of+111In-pentetreotide+in+metastatic+neuroendocrine+gastroenteropancreatic+tumors.&rft.au=Bombardieri%2C+E%3BSeregni%2C+E%3BSavelli%2C+G%3BVillano%2C+C%3BCastellani%2C+M+R%3BCirillo%2C+F%3BPallotti%2C+F%3BFracassi%2C+S%3BChiesa%2C+C%3BChiti%2C+A%3BBajetta%2C+E&rft.aulast=Bombardieri&rft.aufirst=E&rft.date=2003-01-01&rft.volume=26&rft.issue=8+Suppl&rft.spage=63&rft.isbn=&rft.btitle=&rft.title=Journal+of+endocrinological+investigation&rft.issn=03914097&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-13 N1 - Date created - 2004-07-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Male and female sensitivity to alcohol-induced brain damage. AN - 71581869; 15303629 AB - Women are more vulnerable than men to many of the medical consequences of alcohol use. Although research has shown that male alcoholics generally have smaller brain volumes than nonalcoholic males, the few studies that have compared brain structure in alcoholic men and women have had mixed results. To adequately compare brain damage between alcoholic women and men, it is necessary to control for age and to have separate control groups of nonalcoholic men and women. Although the majority of studies suggest that women are more vulnerable to alcohol-induced brain damage than men, the evidence remains inconclusive. JF - Alcohol research & health : the journal of the National Institute on Alcohol Abuse and Alcoholism AU - Hommer, Daniel W AD - Section of Brain Electrophysiology and Imaging, Laboratory of Clinical Studies, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA. Y1 - 2003 PY - 2003 DA - 2003 SP - 181 EP - 185 VL - 27 IS - 2 SN - 1535-7414, 1535-7414 KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Hypoxia, Brain -- physiopathology KW - Ethanol -- adverse effects KW - Age Factors KW - Humans KW - Hypoxia, Brain -- chemically induced KW - Atrophy KW - Hypoxia, Brain -- pathology KW - Male KW - Female KW - Brain -- physiopathology KW - Alcoholism -- pathology KW - Sex Characteristics KW - Brain -- pathology KW - Brain -- drug effects KW - Alcoholism -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71581869?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+research+%26+health+%3A+the+journal+of+the+National+Institute+on+Alcohol+Abuse+and+Alcoholism&rft.atitle=Male+and+female+sensitivity+to+alcohol-induced+brain+damage.&rft.au=Hommer%2C+Daniel+W&rft.aulast=Hommer&rft.aufirst=Daniel&rft.date=2003-01-01&rft.volume=27&rft.issue=2&rft.spage=181&rft.isbn=&rft.btitle=&rft.title=Alcohol+research+%26+health+%3A+the+journal+of+the+National+Institute+on+Alcohol+Abuse+and+Alcoholism&rft.issn=15357414&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-26 N1 - Date created - 2004-08-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Medication use in children and adolescents treated in the community for bipolar disorder. AN - 71542740; 14977464 AB - We assessed the use of mood stabilizers, stimulants, antipsychotic medication, and selective serotonin reuptake inhibitors in children being treated in the community for bipolar disorder (BPD). One hundred eleven patients were screened via parent phone interview for possible inclusion in a phenomenological study of BPD. Data were obtained on the patients' medication trials and side effects. The results of the study indicated that children and adolescents who carry a diagnosis of BPD are treated with a mean of 3.40 +/- 1.48 medications and have had a mean of 6.32 +/- 3.67 trials of psychotropic medication in the past. Ninety-eight percent have had a trial of a mood stabilizer or anticonvulsant, with the most common being valproate (79%), lithium (51%), and gabapentin (29%). JF - Journal of child and adolescent psychopharmacology AU - Bhangoo, Robinder K AU - Lowe, Catherine H AU - Myers, Frances S AU - Treland, Julia AU - Curran, Justin AU - Towbin, Kenneth E AU - Leibenluft, Ellen AD - The Mood and Anxiety Program, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA. Y1 - 2003 PY - 2003 DA - 2003 SP - 515 EP - 522 VL - 13 IS - 4 SN - 1044-5463, 1044-5463 KW - Anticonvulsants KW - 0 KW - Antimanic Agents KW - Serotonin Uptake Inhibitors KW - Index Medicus KW - Drug Therapy, Combination KW - Humans KW - Data Collection KW - Child KW - Anticonvulsants -- therapeutic use KW - Adolescent KW - United States -- epidemiology KW - Male KW - Female KW - Bipolar Disorder -- epidemiology KW - Serotonin Uptake Inhibitors -- therapeutic use KW - Bipolar Disorder -- drug therapy KW - Antimanic Agents -- adverse effects KW - Bipolar Disorder -- psychology KW - Antimanic Agents -- therapeutic use KW - Serotonin Uptake Inhibitors -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71542740?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+child+and+adolescent+psychopharmacology&rft.atitle=Medication+use+in+children+and+adolescents+treated+in+the+community+for+bipolar+disorder.&rft.au=Bhangoo%2C+Robinder+K%3BLowe%2C+Catherine+H%3BMyers%2C+Frances+S%3BTreland%2C+Julia%3BCurran%2C+Justin%3BTowbin%2C+Kenneth+E%3BLeibenluft%2C+Ellen&rft.aulast=Bhangoo&rft.aufirst=Robinder&rft.date=2003-01-01&rft.volume=13&rft.issue=4&rft.spage=515&rft.isbn=&rft.btitle=&rft.title=Journal+of+child+and+adolescent+psychopharmacology&rft.issn=10445463&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-03-08 N1 - Date created - 2004-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interactive effects of excitotoxic injury and dietary restriction on microgliosis and neurogenesis in the hippocampus of adult mice. AN - 71507449; 14716025 AB - Responses to neuronal degeneration are complex, involving activation of microglia, astrocytes, and synaptic remodeling. It has also been suggested that neuronal injury stimulates neurogenesis, the production of new neurons from neural stem cells. Because dietary restriction (DR) can increase hippocampal neurogenesis and promotes the survival of neurons following injury, we determined the effects of DR on the responses of neural stem cells, microglia, and astrocytes in the hippocampus to seizure-induced hippocampal damage. Mice on ad libitum or DR diets were given an intrahippocampal injection of kainate, administered the DNA precursor bromodeoxyuridine (BrdU) during a 5-d period, and euthanized 1 d or 3 wk later. Although kainate greatly increased the numbers of BrdU-labeled cells, it did not enhance neurogenesis and damaged neurons were not replaced. Instead, most BrdU-labeled cells were either proliferating microglia or neural progenitor cells that subsequently died. Microgliosis was transient and was strongly correlated with the amount of damage to CA3 neurons, whereas astrocytosis was delayed and not correlated with neuronal loss. Surprisingly, neurogenesis was not increased in response to seizure-induced damage, and although DR increased basal neurogenesis, it did not promote neurogenesis following brain injury. DR significantly decreased seizure-induced microgliosis, but did not affect astrocytosis. Our findings show that DR suppresses injuryinduced microgliosis suggesting a contribution of a reduced microglial response to the neuroprotective effects of DR. JF - Neuromolecular medicine AU - Lee, Jaewon AU - Auyeung, Wendy W AU - Mattson, Mark P AD - Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2003 PY - 2003 DA - 2003 SP - 179 EP - 196 VL - 4 IS - 3 SN - 1535-1084, 1535-1084 KW - Neurotoxins KW - 0 KW - Bromodeoxyuridine KW - G34N38R2N1 KW - Kainic Acid KW - SIV03811UC KW - Index Medicus KW - Animals KW - Kainic Acid -- pharmacology KW - Neurons -- metabolism KW - Neurons -- drug effects KW - Nerve Degeneration -- physiopathology KW - Cell Division -- drug effects KW - Cell Division -- physiology KW - Neurotoxins -- pharmacology KW - Nerve Degeneration -- chemically induced KW - Mice KW - Stem Cells -- metabolism KW - Down-Regulation -- physiology KW - Mice, Inbred C57BL KW - Down-Regulation -- drug effects KW - Male KW - Gliosis -- physiopathology KW - Epilepsy -- physiopathology KW - Food Deprivation -- physiology KW - Epilepsy -- therapy KW - Hippocampus -- drug effects KW - Gliosis -- prevention & control KW - Epilepsy -- chemically induced KW - Hippocampus -- cytology KW - Microglia -- cytology KW - Nerve Regeneration -- physiology KW - Hippocampus -- physiopathology KW - Gliosis -- chemically induced KW - Microglia -- drug effects KW - Microglia -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71507449?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuromolecular+medicine&rft.atitle=Interactive+effects+of+excitotoxic+injury+and+dietary+restriction+on+microgliosis+and+neurogenesis+in+the+hippocampus+of+adult+mice.&rft.au=Lee%2C+Jaewon%3BAuyeung%2C+Wendy+W%3BMattson%2C+Mark+P&rft.aulast=Lee&rft.aufirst=Jaewon&rft.date=2003-01-01&rft.volume=4&rft.issue=3&rft.spage=179&rft.isbn=&rft.btitle=&rft.title=Neuromolecular+medicine&rft.issn=15351084&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-03-09 N1 - Date created - 2004-01-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Automated indexing of the Hazardous Substances Data Bank (HSDB). AN - 71506852; 14728459 AB - The Hazardous Substances Data Bank (HSDB), produced and maintained by the National Library of Medicine (NLM), contains over 4600 records on potentially hazardous chemicals. To enhance information retrieval from HSDB, NLM has undertaken the development of an automated HSDB indexing protocol as part of its Indexing Initiative. The NLM Indexing Initiative investigates methods whereby automated indexing may partially or completely substitute for human indexing. The poster's purpose is to describe the HSDB Automated Indexing Project. JF - AMIA ... Annual Symposium proceedings. AMIA Symposium AU - Nuss, Carlo AU - Chang, Hua Florence AU - Moore, Dorothy AU - Fonger, George C AD - National Library of Medicine, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA. Y1 - 2003 PY - 2003 DA - 2003 SP - 954 KW - Hazardous Substances KW - 0 KW - Index Medicus KW - United States KW - National Library of Medicine (U.S.) KW - Medical Subject Headings KW - Abstracting and Indexing as Topic -- methods KW - Databases, Factual KW - Automatic Data Processing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71506852?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AMIA+...+Annual+Symposium+proceedings.+AMIA+Symposium&rft.atitle=Automated+indexing+of+the+Hazardous+Substances+Data+Bank+%28HSDB%29.&rft.au=Nuss%2C+Carlo%3BChang%2C+Hua+Florence%3BMoore%2C+Dorothy%3BFonger%2C+George+C&rft.aulast=Nuss&rft.aufirst=Carlo&rft.date=2003-01-01&rft.volume=&rft.issue=&rft.spage=954&rft.isbn=&rft.btitle=&rft.title=AMIA+...+Annual+Symposium+proceedings.+AMIA+Symposium&rft.issn=1942-597X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-14 N1 - Date created - 2004-01-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutational analysis of Drosophila RNA polymerase II. AN - 71504624; 14712733 JF - Methods in enzymology AU - Mortin, Mark A AD - Laboratory of Molecular Genetics, NICHD, NIH, Building 6B, Room 3B-331, Bethesda, Maryland 20892-4255, USA. Y1 - 2003 PY - 2003 DA - 2003 SP - 615 EP - 629 VL - 371 SN - 0076-6879, 0076-6879 KW - RNA Polymerase II KW - EC 2.7.7.- KW - Index Medicus KW - Phenotype KW - Animals KW - RNA Polymerase II -- genetics KW - Genetic Techniques KW - Drosophila melanogaster -- genetics KW - Biochemistry -- methods KW - DNA Mutational Analysis KW - RNA Polymerase II -- chemistry KW - Drosophila melanogaster -- enzymology KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71504624?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutational+analysis+of+Drosophila+RNA+polymerase+II.&rft.au=Mortin%2C+Mark+A&rft.aulast=Mortin&rft.aufirst=Mark&rft.date=2003-01-01&rft.volume=371&rft.issue=&rft.spage=615&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 - 2004-02-09 N1 - Date created - 2004-01-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alterations in cyclin A, B, and D1 in mouse dentate gyrus following TMT-induced hippocampal damage. AN - 71502637; 14715453 AB - The interactions of glia and neurons during injury and subsequent neurodegeneration are a subject of interest both in disease and chemical-induced brain injury. One such model is the prototypical hippocampal toxicant trimethyltin (TMT). An acute injection of TMT (2.0 mg/kg, i.p.) to postnatal day 21 CD-1 male mice produced neuronal necrosis and loss of dentate granule cells, astrocyte hypertrophy, and microglia activation in the hippocampus within 24 hrs. Neuronal necrosis and microglia differentiation to a phagocytic phenotype is temporally correlated with peak elevations in TNF-alpha, cyclin A2, cyclin B1 and cyclin D1 at 72 h post-TMT. TNF-alpha mRNA levels were significantly elevated in the hippocampus by 12 h and remained elevated for 72 h. mRNA levels for cyclin A2 and cyclin B1 were elevated by approximately 2-fold at 72 h. Immunohistochemistry suggested a cellular localization of cyclin A to microglia in the region of neuronal necrosis in the dentate, cyclin B in glial cells in juxtaposition to neurons in the hilus of the hippocampus and cyclin D1 to non-glial cells in the dentate. mRNA levels for cyclin D1 were elevated approximately 1.5-fold by 72 h as determined by RNase protection assay. No changes were seen in mRNA levels for cyclins E, F, G1, G2, H or I nor cyclin dependent kinases. These elevations are not associated with proliferation of microglia as determined by BrdU incorporation and Ki-67 immunohistochemistry. Upregulation of cell cycle genes was associated with cellular processes other than proliferation and may contribute to the differentiation of microglia to a phagocytic phenotype. These data suggest an integrated role for cell cycle regulation of neural cells in the manifestation of hippocampal pathophysiology. JF - Neurotoxicity research AU - McPherson, Christopher A AU - Kubik, Julie AU - Wine, Robert N AU - D'Hellencourt, Christian Lefebvre AU - Harry, G Jean AD - Neurotoxicology Group, National Institute of Environmental Health Sciences,Research Triangle Park, NC 27709, USA. Y1 - 2003 PY - 2003 DA - 2003 SP - 339 EP - 354 VL - 5 IS - 5 SN - 1029-8428, 1029-8428 KW - Cyclin A KW - 0 KW - Cyclin B KW - Nerve Tissue Proteins KW - RNA, Messenger KW - Trimethyltin Compounds KW - Tumor Necrosis Factor-alpha KW - Cyclin D1 KW - 136601-57-5 KW - trimethyltin KW - 1631-73-8 KW - Index Medicus KW - Animals KW - Astrocytes -- drug effects KW - Nuclease Protection Assays KW - Cell Division -- drug effects KW - Tumor Necrosis Factor-alpha -- biosynthesis KW - Mice KW - Nerve Tissue Proteins -- biosynthesis KW - Neuroglia -- drug effects KW - RNA, Messenger -- biosynthesis KW - Neuroglia -- metabolism KW - In Situ Hybridization KW - Neuroglia -- pathology KW - Astrocytes -- pathology KW - Fluorescent Antibody Technique KW - Male KW - Astrocytes -- metabolism KW - Cyclin A -- metabolism KW - Cyclin A -- biosynthesis KW - Cyclin D1 -- metabolism KW - Dentate Gyrus -- drug effects KW - Hippocampus -- metabolism KW - Dentate Gyrus -- metabolism KW - Cyclin B -- metabolism KW - Cyclin B -- biosynthesis KW - Cyclin D1 -- biosynthesis KW - Hippocampus -- pathology KW - Trimethyltin Compounds -- toxicity KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71502637?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurotoxicity+research&rft.atitle=Alterations+in+cyclin+A%2C+B%2C+and+D1+in+mouse+dentate+gyrus+following+TMT-induced+hippocampal+damage.&rft.au=McPherson%2C+Christopher+A%3BKubik%2C+Julie%3BWine%2C+Robert+N%3BD%27Hellencourt%2C+Christian+Lefebvre%3BHarry%2C+G+Jean&rft.aulast=McPherson&rft.aufirst=Christopher&rft.date=2003-01-01&rft.volume=5&rft.issue=5&rft.spage=339&rft.isbn=&rft.btitle=&rft.title=Neurotoxicity+research&rft.issn=10298428&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-28 N1 - Date created - 2004-01-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Three origins of phiX174 am3 revertants in transgenic cell culture. AN - 71502060; 14673871 AB - Transgenic systems for measuring mammalian mutagenesis often use recoverable viral vectors. We hypothesize that mutations in these transgenic systems can arise from three different origins of DNA damage and replication errors and that these three origins of mutations (in vivo, ex vivo, and in vitro) can be differentiated in the PhiX174 am3, cs70 single burst assay (SBA) on the basis of burst size (BS). In vivo mutations are fixed in the animal, ex vivo mutations are fixed in bacterial cells during recovery of the phage, and in vitro revertants arise during the first replications of nonmutant phages under selective conditions. PX-2 cells, derived from a homozygous embryo of a PhiX174 transgenic mouse, were treated with vehicle or N-ethyl-N-nitrosourea (ENU). An algorithm was developed to estimate the BS that resulted in the highest induced revertant frequency; the estimate was 56. In vivo revertants were defined as having BS >55, ex vivo revertants as having a BS of 13-56, and in vitro revertants as having a BS of <14. The frequencies of in vivo revertants at 0, 100, and 200 mg/kg ENU were 0.06, 0.36, and 4.10 x 10(-6) (dose response, P = 0.004); ex vivo revertants were 0.36, 0.46, and 0.41 x 10(-6) (P = 0.37), and in vitro revertants were 0.39, 0.46, and 0.41 x 10(-6) (P = 0.55), respectively. These results show that only in vivo revertants reflect mutagen treatment. They also provide a basis for identifying PhiX174 am3 revertants induced in vivo and may increase the sensitivity of the assay for in vivo mutation. JF - Environmental and molecular mutagenesis AU - Malling, Heinrich V AU - Delongchamp, Robert R AU - Valentine, Carrie R AD - Mammalian Mutagenesis Group, Laboratory of Toxicology, Environmental Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709-2233, USA. malling@niehs.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 258 EP - 273 VL - 42 IS - 4 SN - 0893-6692, 0893-6692 KW - Mutagens KW - 0 KW - Ethylnitrosourea KW - P8M1T4190R KW - Index Medicus KW - Animals KW - Escherichia coli -- metabolism KW - Homozygote KW - Electroporation KW - Dose-Response Relationship, Drug KW - DNA Mutational Analysis KW - Algorithms KW - Cell Culture Techniques KW - Mice KW - Animals, Genetically Modified KW - Mice, Transgenic KW - Polymerase Chain Reaction KW - Mutation KW - Mutagenicity Tests -- methods KW - Bacteriophage phi X 174 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71502060?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Three+origins+of+phiX174+am3+revertants+in+transgenic+cell+culture.&rft.au=Malling%2C+Heinrich+V%3BDelongchamp%2C+Robert+R%3BValentine%2C+Carrie+R&rft.aulast=Malling&rft.aufirst=Heinrich&rft.date=2003-01-01&rft.volume=42&rft.issue=4&rft.spage=258&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 - 2004-02-12 N1 - Date created - 2003-12-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tumor Young Investigator Award: induction of glioblastoma multiforme in primates after fractionated whole-brain irradiation in the therapeutic dose range. AN - 71457035; 14677452 JF - Clinical neurosurgery AU - Lonser, Russell R AU - Walbridge, Stuart AU - Vortmeyer, Alexander O AU - Pack, Svetlana D AU - Nguyen, Tung T AU - Gogate, Nitin AU - Olson, Jeffery J AU - Akbasak, Aytac AU - Bobo, R Hunt AU - Goffman, Thomas AU - Zhuang, Zhengping AU - Oldfield, Edward H AD - Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2003 PY - 2003 DA - 2003 SP - 350 EP - 373 VL - 50 SN - 0069-4827, 0069-4827 KW - Index Medicus KW - Animals KW - Disease Models, Animal KW - Macaca mulatta KW - Time Factors KW - Male KW - Glioblastoma -- genetics KW - Neoplasms, Radiation-Induced -- etiology KW - Brain Neoplasms -- genetics KW - Glioblastoma -- etiology KW - Dose Fractionation KW - Brain -- radiation effects KW - Neoplasms, Radiation-Induced -- genetics KW - Glioblastoma -- diagnosis KW - Brain Neoplasms -- diagnosis KW - Neoplasms, Radiation-Induced -- diagnosis KW - Brain Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71457035?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neurosurgery&rft.atitle=Tumor+Young+Investigator+Award%3A+induction+of+glioblastoma+multiforme+in+primates+after+fractionated+whole-brain+irradiation+in+the+therapeutic+dose+range.&rft.au=Lonser%2C+Russell+R%3BWalbridge%2C+Stuart%3BVortmeyer%2C+Alexander+O%3BPack%2C+Svetlana+D%3BNguyen%2C+Tung+T%3BGogate%2C+Nitin%3BOlson%2C+Jeffery+J%3BAkbasak%2C+Aytac%3BBobo%2C+R+Hunt%3BGoffman%2C+Thomas%3BZhuang%2C+Zhengping%3BOldfield%2C+Edward+H&rft.aulast=Lonser&rft.aufirst=Russell&rft.date=2003-01-01&rft.volume=50&rft.issue=&rft.spage=350&rft.isbn=&rft.btitle=&rft.title=Clinical+neurosurgery&rft.issn=00694827&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-03-05 N1 - Date created - 2003-12-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clozapine-induced neutropenia in children: management with lithium carbonate. AN - 71406420; 14642024 AB - Clozapine, an atypical antipsychotic, is the most effective medication for treatment-resistant schizophrenia, but its use is limited by the high risk of neutropenia and agranulocytosis. In children, the rate of clozapine-induced neutropenia is even higher than in adults. We report two cases of children 7- and 12-years old diagnosed with very early onset schizophrenia, who developed neutropenia when treated with clozapine. In both cases addition of lithium carbonate elevated the white blood count (WBC) allowing clozapine rechallenge. WBC and total neutrophil count remained stable long-term with coadministration of clozapine (400-425 mg per day) and lithium with the blood level of 0.8-1.1 microg/mL. This report supports the use of adjunct lithium for clozapine-induced neutropenia as a safe and successful strategy in children. JF - Journal of child and adolescent psychopharmacology AU - Sporn, Alexandra AU - Gogtay, Nitin AU - Ortiz-Aguayo, Roberto AU - Alfaro, Cara AU - Tossell, Julia AU - Lenane, Marge AU - Gochman, Peter AU - Rapoport, Judith L AD - Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003 PY - 2003 DA - 2003 SP - 401 EP - 404 VL - 13 IS - 3 SN - 1044-5463, 1044-5463 KW - Antipsychotic Agents KW - 0 KW - Lithium Carbonate KW - 2BMD2GNA4V KW - Clozapine KW - J60AR2IKIC KW - Index Medicus KW - Drug Therapy, Combination KW - Schizophrenia, Childhood -- complications KW - Humans KW - Schizophrenia, Childhood -- drug therapy KW - Child KW - Male KW - Leukocyte Count KW - Lithium Carbonate -- therapeutic use KW - Neutropenia -- blood KW - Clozapine -- therapeutic use KW - Antipsychotic Agents -- therapeutic use KW - Neutropenia -- chemically induced KW - Neutropenia -- drug therapy KW - Clozapine -- adverse effects KW - Antipsychotic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71406420?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+child+and+adolescent+psychopharmacology&rft.atitle=Clozapine-induced+neutropenia+in+children%3A+management+with+lithium+carbonate.&rft.au=Sporn%2C+Alexandra%3BGogtay%2C+Nitin%3BOrtiz-Aguayo%2C+Roberto%3BAlfaro%2C+Cara%3BTossell%2C+Julia%3BLenane%2C+Marge%3BGochman%2C+Peter%3BRapoport%2C+Judith+L&rft.aulast=Sporn&rft.aufirst=Alexandra&rft.date=2003-01-01&rft.volume=13&rft.issue=3&rft.spage=401&rft.isbn=&rft.btitle=&rft.title=Journal+of+child+and+adolescent+psychopharmacology&rft.issn=10445463&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-19 N1 - Date created - 2003-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Opioid-related disorders]. AN - 71397166; 14626165 JF - Ryoikibetsu shokogun shirizu AU - Funada, Masahiko AD - National Institute of Mental Health, National Center of Neurology and Psychiatry. Y1 - 2003 PY - 2003 DA - 2003 SP - 480 EP - 483 IS - 40 KW - Narcotic Antagonists KW - 0 KW - Narcotics KW - Naloxone KW - 36B82AMQ7N KW - Buprenorphine KW - 40D3SCR4GZ KW - Methadone KW - UC6VBE7V1Z KW - Index Medicus KW - Methadone -- therapeutic use KW - Buprenorphine -- therapeutic use KW - Narcotic Antagonists -- therapeutic use KW - International Classification of Diseases KW - Humans KW - Naloxone -- therapeutic use KW - Narcotics -- therapeutic use KW - Behavior Therapy -- methods KW - Diagnostic and Statistical Manual of Mental Disorders KW - Opioid-Related Disorders -- diagnosis KW - Opioid-Related Disorders -- therapy KW - Opioid-Related Disorders -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71397166?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Ryoikibetsu+shokogun+shirizu&rft.atitle=%5BOpioid-related+disorders%5D.&rft.au=Funada%2C+Masahiko&rft.aulast=Funada&rft.aufirst=Masahiko&rft.date=2003-01-01&rft.volume=&rft.issue=40&rft.spage=480&rft.isbn=&rft.btitle=&rft.title=Ryoikibetsu+shokogun+shirizu&rft.issn=&rft_id=info:doi/ LA - Japanese DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-29 N1 - Date created - 2003-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Psychoactive substance-related disorders: general remarks from the epidemiological point of view]. AN - 71397120; 14626164 JF - Ryoikibetsu shokogun shirizu AU - Wada, Kiyoshi AD - National Institute of Mental Health, NCNP. Y1 - 2003 PY - 2003 DA - 2003 SP - 474 EP - 479 IS - 40 KW - Index Medicus KW - Japan -- epidemiology KW - Humans KW - Adolescent KW - Time Factors KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71397120?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Ryoikibetsu+shokogun+shirizu&rft.atitle=%5BPsychoactive+substance-related+disorders%3A+general+remarks+from+the+epidemiological+point+of+view%5D.&rft.au=Wada%2C+Kiyoshi&rft.aulast=Wada&rft.aufirst=Kiyoshi&rft.date=2003-01-01&rft.volume=&rft.issue=40&rft.spage=474&rft.isbn=&rft.btitle=&rft.title=Ryoikibetsu+shokogun+shirizu&rft.issn=&rft_id=info:doi/ LA - Japanese DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-29 N1 - Date created - 2003-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Methylphenidate-induced psychiatric disorders]. AN - 71387993; 14626175 JF - Ryoikibetsu shokogun shirizu AU - Ozaki, Shigeru AD - Division of Drug Dependence Research, Section of Psycho-Social Factors Research, National Institute of Mental Health, NCNP. Y1 - 2003 PY - 2003 DA - 2003 SP - 522 EP - 526 IS - 40 KW - Antipsychotic Agents KW - 0 KW - Central Nervous System Stimulants KW - Methylphenidate KW - 207ZZ9QZ49 KW - Haloperidol KW - J6292F8L3D KW - Index Medicus KW - Haloperidol -- therapeutic use KW - International Classification of Diseases KW - Humans KW - Antipsychotic Agents -- therapeutic use KW - Adult KW - Middle Aged KW - Male KW - Female KW - Drug Prescriptions KW - Amphetamine-Related Disorders -- epidemiology KW - Methylphenidate -- adverse effects KW - Amphetamine-Related Disorders -- diagnosis KW - Central Nervous System Stimulants -- adverse effects KW - Amphetamine-Related Disorders -- etiology KW - Amphetamine-Related Disorders -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71387993?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Ryoikibetsu+shokogun+shirizu&rft.atitle=%5BMethylphenidate-induced+psychiatric+disorders%5D.&rft.au=Ozaki%2C+Shigeru&rft.aulast=Ozaki&rft.aufirst=Shigeru&rft.date=2003-01-01&rft.volume=&rft.issue=40&rft.spage=522&rft.isbn=&rft.btitle=&rft.title=Ryoikibetsu+shokogun+shirizu&rft.issn=&rft_id=info:doi/ LA - Japanese DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-29 N1 - Date created - 2003-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Error-prone DNA polymerases: when making a mistake is the only way to get ahead. AN - 71374386; 14616055 AB - Cells have high-fidelity polymerases whose task is to accurately replicate the genome, and low-fidelity polymerases with specialized functions. Although some of these low-fidelity polymerases are exceptional in their ability to replicate damaged DNA and restore the undamaged sequence, they are error prone on undamaged DNA. In fact, these error-prone polymerases are sometimes used in circumstances where the capacity to make errors has a selective advantage. The mutagenic potential of the error-prone polymerases requires that their expression, activity, and access to undamaged DNA templates be regulated. Here we review these specialized polymerases with an emphasis on their biological roles. JF - Annual review of genetics AU - Rattray, Alison J AU - Strathern, Jeffrey N AD - Gene Regulation and Chromosome Biology Laboratory, NCI-Frederick, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702, USA. rattray@ncifcrf.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 31 EP - 66 VL - 37 SN - 0066-4197, 0066-4197 KW - DNA KW - 9007-49-2 KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Index Medicus KW - Eukaryotic Cells -- metabolism KW - Escherichia coli -- metabolism KW - Escherichia coli -- genetics KW - Mutation KW - DNA -- biosynthesis KW - DNA-Directed DNA Polymerase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71374386?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+genetics&rft.atitle=Error-prone+DNA+polymerases%3A+when+making+a+mistake+is+the+only+way+to+get+ahead.&rft.au=Rattray%2C+Alison+J%3BStrathern%2C+Jeffrey+N&rft.aulast=Rattray&rft.aufirst=Alison&rft.date=2003-01-01&rft.volume=37&rft.issue=&rft.spage=31&rft.isbn=&rft.btitle=&rft.title=Annual+review+of+genetics&rft.issn=00664197&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-19 N1 - Date created - 2003-11-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Apportioning causes, targeting populations and predicting risks: population attributable fractions. AN - 71339146; 14598922 JF - European journal of epidemiology AU - Chatterjee, Nilanjan AU - Hartge, Patricia AD - Biostatistics Branch, Epidemiology and Biostatistics Program, National Cancer Institute, NIH, DHHS, USA. chattern@mail.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 933 EP - 935 VL - 18 IS - 10 SN - 0393-2990, 0393-2990 KW - Asbestos KW - 1332-21-4 KW - Index Medicus KW - Occupational Exposure KW - Lung Neoplasms -- epidemiology KW - Humans KW - Environmental Exposure KW - Sweden -- epidemiology KW - Lung Neoplasms -- chemically induced KW - Asbestos -- toxicity KW - Epidemiologic Studies KW - Risk Assessment -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71339146?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+epidemiology&rft.atitle=Apportioning+causes%2C+targeting+populations+and+predicting+risks%3A+population+attributable+fractions.&rft.au=Chatterjee%2C+Nilanjan%3BHartge%2C+Patricia&rft.aulast=Chatterjee&rft.aufirst=Nilanjan&rft.date=2003-01-01&rft.volume=18&rft.issue=10&rft.spage=933&rft.isbn=&rft.btitle=&rft.title=European+journal+of+epidemiology&rft.issn=03932990&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-26 N1 - Date created - 2003-11-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Eur J Epidemiol. 2003;18(10):937-40 [14598923] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Attitudes of Social Work Students about Substance Abuse: Can a Brief Educational Program Make a Difference? AN - 61501757; 200304213 AB - This study examined whether a brief educational program could modify attitudes of master's level social work students about substance abuse. Study methodology involved a two-group pre-test & post-test quasi-experimental design. The Substance Abuse Attitude Survey, a standardized assessment instrument, was used to measure attitudes based on five distinct factors. No significant changes in student attitudes were found after participating in the educational session. Recommendations are offered for how social work schools may enhance their efforts to prepare students to effectively work with substance abusing clients & their families. 3 Tables, 42 References. Adapted from the source document. COPIES ARE AVAILABLE FROM: HAWORTH DOCUMENT DELIVERY CENTER, The Haworth Press, Inc., 10 Alice Street, Binghamton, NY 13904-1580 JF - Journal of Social Work Practice in the Addictions AU - Stein, Jack B AD - Office Science Policy & Communications, National Instit Drug Abuse, National Instits Health, Bethesda, MD js413y@nih.gov Y1 - 2003///0, PY - 2003 DA - 0, 2003 SP - 77 EP - 90 VL - 3 IS - 1 SN - 1533-256X, 1533-256X KW - Drug Addiction KW - Substance Abuse KW - Student Attitudes KW - Educational Programs KW - Professional Training KW - Social Work Education KW - Drug Abuse KW - article KW - 6113: social work education UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61501757?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocialservices&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Social+Work+Practice+in+the+Addictions&rft.atitle=Attitudes+of+Social+Work+Students+about+Substance+Abuse%3A+Can+a+Brief+Educational+Program+Make+a+Difference%3F&rft.au=Stein%2C+Jack+B&rft.aulast=Stein&rft.aufirst=Jack&rft.date=2003-01-01&rft.volume=3&rft.issue=1&rft.spage=77&rft.isbn=&rft.btitle=&rft.title=Journal+of+Social+Work+Practice+in+the+Addictions&rft.issn=1533256X&rft_id=info:doi/ LA - English DB - Social Services Abstracts N1 - Date revised - 2007-05-01 N1 - Last updated - 2016-09-28 N1 - SubjectsTermNotLitGenreText - Social Work Education; Educational Programs; Student Attitudes; Professional Training; Substance Abuse; Drug Abuse; Drug Addiction ER - TY - JOUR T1 - A Telephone Support Group Intervention for Non-HIV-Infected Fathers of HIV-Infected Children AN - 61501452; 200400081 AB - Fathers of HIV-infected children are rarely targeted as a group for specific psychosocial support & intervention. This paper is intended to provide an in-depth case description of a specific telephone group intervention & its perceived effectiveness by group members. Themes covered during the group intervention included diagnosis disclosure, coping, relationship issues, stigma, need for social & concrete support, medical care, & losses. The group was perceived to be effective in bringing together fathers of HIV-infected children. The fathers came from geographically diverse regions & without the group they might not have the opportunity to talk openly with others. All of the participants believed the group to be a valuable resource & would recommend it to others. The findings suggest that this is a cost-effective intervention that provides support to people who are either geographically distanced from each other or who are not emotionally ready to participate in a face-to-face support group. 31 References. Adapted from the source document. COPIES ARE AVAILABLE FROM: HAWORTH DOCUMENT DELIVERY CENTER, The Haworth Press, Inc., 10 Alice Street, Binghamton, NY 13904-1580 JF - Journal of HIV/AIDS & Social Services AU - Battles, Haven B AU - Wiener, Lori S AU - Lewis, Eleesha M AU - Patel, Rita AU - Grant, Shelma Middleton AD - HIV/AIDS Malignancy Branch, National Cancer Instit, National Instits Health, Bethesda, MD battlesh@mail.nih.gov Y1 - 2003///0, PY - 2003 DA - 0, 2003 SP - 63 EP - 78 VL - 2 IS - 1 SN - 1538-1501, 1538-1501 KW - Acquired Immune Deficiency Syndrome KW - Self Help Groups KW - Children KW - Fathers KW - Telephone Communications KW - article KW - 6126: acquired immune deficiency syndrome (AIDS) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61501452?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocialservices&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+HIV%2FAIDS+%26+Social+Services&rft.atitle=A+Telephone+Support+Group+Intervention+for+Non-HIV-Infected+Fathers+of+HIV-Infected+Children&rft.au=Battles%2C+Haven+B%3BWiener%2C+Lori+S%3BLewis%2C+Eleesha+M%3BPatel%2C+Rita%3BGrant%2C+Shelma+Middleton&rft.aulast=Battles&rft.aufirst=Haven&rft.date=2003-01-01&rft.volume=2&rft.issue=1&rft.spage=63&rft.isbn=&rft.btitle=&rft.title=Journal+of+HIV%2FAIDS+%26+Social+Services&rft.issn=15381501&rft_id=info:doi/ LA - English DB - Social Services Abstracts N1 - Date revised - 2007-05-01 N1 - Number of references - 31 N1 - Last updated - 2016-09-28 N1 - SubjectsTermNotLitGenreText - Fathers; Acquired Immune Deficiency Syndrome; Children; Self Help Groups; Telephone Communications ER - TY - JOUR T1 - Work and Housework Conditions and Depressive Symptoms among Married Women: The Importance of Occupational Status AN - 60472085; 200413525 AB - Using the American Changing Lives Survey, a nationally representative sample of adults residing in the US, this research examines housewives' subjective evaluations of their housework & the subjective evaluations of paid employment among three groups of married women-professionals, sales-clerical, & service-blue collar wives. A major goal was to assess the usefulness of disaggregating employed women by occupational status. Depressive symptoms were regressed on five work conditions -- autonomy, physical & time demands, boredom, & feeling appreciated -- along with sociodemographic characteristics. The results indicate professional wives report fewer symptoms than homemakers, sales-clerical, & service-blue collar wives. Differences between professionals & homemakers are largely accounted for by professional women's more advantaged economic position. Nonprofessional employed women are more depressed than professionals even when their disadvantaged working conditions are controlled. We discuss the findings in view of research on the stress of combining full-time employment with homemaking & argue that balancing these two roles may be more difficult for some employed women than for others. 2 Tables, 31 References. Adapted from the source document. COPIES ARE AVAILABLE FROM: HAWORTH DOCUMENT DELIVERY CENTER, The Haworth Press, Inc., 10 Alice Street, Binghamton, NY 13904-1580 JF - Women & Health AU - Riley, Anna L AU - Keith, Verna M AD - Center Scientific Review, National Instits Health, Bethesda, MD rileyann@csr.nih.gov Y1 - 2003///0, PY - 2003 DA - 0, 2003 SP - 1 EP - 17 VL - 38 IS - 4 SN - 0363-0242, 0363-0242 KW - Housework KW - Depression (Psychology) KW - Occupational Status KW - Working Women KW - United States of America KW - Homemakers KW - article KW - 2046: sociology of health and medicine; social psychiatry (mental health) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/60472085?accountid=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=Women+%26+Health&rft.atitle=Work+and+Housework+Conditions+and+Depressive+Symptoms+among+Married+Women%3A+The+Importance+of+Occupational+Status&rft.au=Riley%2C+Anna+L%3BKeith%2C+Verna+M&rft.aulast=Riley&rft.aufirst=Anna&rft.date=2003-01-01&rft.volume=38&rft.issue=4&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Women+%26+Health&rft.issn=03630242&rft_id=info:doi/ LA - English DB - Sociological Abstracts N1 - Date revised - 2007-04-01 N1 - Number of references - 31 N1 - Last updated - 2016-09-28 N1 - CODEN - WOHEDI N1 - SubjectsTermNotLitGenreText - United States of America; Working Women; Homemakers; Housework; Depression (Psychology); Occupational Status ER - TY - JOUR T1 - Estimating ground water arsenic concentrations for exposure assessment in cancer epidemiology AN - 51945195; 2003-065889 JF - Open-File Report - U. S. Geological Survey AU - Ayotte, Joseph D AU - Nuckols, John R AU - Ryker, Sarah J AU - Baris, Dalsu AU - Welch, Alan H AU - Cantor, Kenneth P AU - Robinson, Gilpin R, Jr AU - Karagas, Margaret R AU - Ward, Mary H AU - Hayes, Laura AU - Colt, Joanne AU - Silverman, Debra T AU - Lubin, Jay Y1 - 2003 PY - 2003 DA - 2003 SP - 26 PB - U. S. Geological Survey, Reston, VA SN - 0196-1497, 0196-1497 KW - United States KW - concentration KW - pollutants KW - statistical analysis KW - arsenic KW - pollution KW - diseases KW - ground water KW - carcinogens KW - geographic information systems KW - metals KW - New England KW - risk assessment KW - information systems KW - ecology KW - USGS KW - public health KW - 22:Environmental geology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/51945195?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ageorefmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Open-File+Report+-+U.+S.+Geological+Survey&rft.atitle=Estimating+ground+water+arsenic+concentrations+for+exposure+assessment+in+cancer+epidemiology&rft.au=Ayotte%2C+Joseph+D%3BNuckols%2C+John+R%3BRyker%2C+Sarah+J%3BBaris%2C+Dalsu%3BWelch%2C+Alan+H%3BCantor%2C+Kenneth+P%3BRobinson%2C+Gilpin+R%2C+Jr%3BKaragas%2C+Margaret+R%3BWard%2C+Mary+H%3BHayes%2C+Laura%3BColt%2C+Joanne%3BSilverman%2C+Debra+T%3BLubin%2C+Jay&rft.aulast=Ayotte&rft.aufirst=Joseph&rft.date=2003-01-01&rft.volume=&rft.issue=&rft.spage=26&rft.isbn=&rft.btitle=&rft.title=Open-File+Report+-+U.+S.+Geological+Survey&rft.issn=01961497&rft_id=info:doi/ L2 - http://pubs.usgs.gov/of/2003/of03-097/ https://pubs.er.usgs.gov/browse/usgs-publications/OFR LA - English DB - GeoRef N1 - Conference title - Natural science and public health; prescription for a better environment N1 - Copyright - GeoRef, Copyright 2016, American Geosciences Institute. N1 - Date revised - 2003-01-01 N1 - PubXState - VA N1 - SuppNotes - Accessed on Sept. 3, 2003 N1 - Last updated - 2016-10-25 N1 - CODEN - XGROAG N1 - SubjectsTermNotLitGenreText - arsenic; carcinogens; concentration; diseases; ecology; geographic information systems; ground water; information systems; metals; New England; pollutants; pollution; public health; risk assessment; statistical analysis; United States; USGS ER - TY - JOUR T1 - Regional, seasonal, and ethnic differences in the NHANES III pesticide epidemiology (PEPI) study AN - 51945164; 2003-065888 JF - Open-File Report - U. S. Geological Survey AU - Allen, Ruth H AU - Ward, Mary H AU - Gondy, Gauthami AU - Mage, David T AU - Alavanja, Michael C Y1 - 2003 PY - 2003 DA - 2003 SP - 25 PB - U. S. Geological Survey, Reston, VA SN - 0196-1497, 0196-1497 KW - United States KW - programs KW - agriculture KW - epidemiology KW - spatial variations KW - agrochemicals KW - seasonal variations KW - pesticides KW - USGS KW - NHANES III KW - land use KW - public health KW - 22:Environmental geology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/51945164?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ageorefmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Open-File+Report+-+U.+S.+Geological+Survey&rft.atitle=Regional%2C+seasonal%2C+and+ethnic+differences+in+the+NHANES+III+pesticide+epidemiology+%28PEPI%29+study&rft.au=Allen%2C+Ruth+H%3BWard%2C+Mary+H%3BGondy%2C+Gauthami%3BMage%2C+David+T%3BAlavanja%2C+Michael+C&rft.aulast=Allen&rft.aufirst=Ruth&rft.date=2003-01-01&rft.volume=&rft.issue=&rft.spage=25&rft.isbn=&rft.btitle=&rft.title=Open-File+Report+-+U.+S.+Geological+Survey&rft.issn=01961497&rft_id=info:doi/ L2 - http://pubs.usgs.gov/of/2003/of03-097/ https://pubs.er.usgs.gov/browse/usgs-publications/OFR LA - English DB - GeoRef N1 - Conference title - Natural science and public health; prescription for a better environment N1 - Copyright - GeoRef, Copyright 2016, American Geosciences Institute. N1 - Date revised - 2003-01-01 N1 - PubXState - VA N1 - SuppNotes - Accessed on Sept. 3, 2003 N1 - Last updated - 2016-10-25 N1 - CODEN - XGROAG N1 - SubjectsTermNotLitGenreText - agriculture; agrochemicals; epidemiology; land use; NHANES III; pesticides; programs; public health; seasonal variations; spatial variations; United States; USGS ER - TY - JOUR T1 - Deriving crop maps from remotely sensed imagery to support agricultural chemical exposure research AN - 51943168; 2003-065891 JF - Open-File Report - U. S. Geological Survey AU - Maxwell, S K AU - Nuckols, J R AU - Ward, M H Y1 - 2003 PY - 2003 DA - 2003 SP - 28 PB - U. S. Geological Survey, Reston, VA SN - 0196-1497, 0196-1497 KW - imagery KW - medical geology KW - agriculture KW - mapping KW - epidemiology KW - geography KW - agrochemicals KW - risk assessment KW - USGS KW - land use KW - remote sensing KW - public health KW - 22:Environmental geology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/51943168?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ageorefmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Open-File+Report+-+U.+S.+Geological+Survey&rft.atitle=Deriving+crop+maps+from+remotely+sensed+imagery+to+support+agricultural+chemical+exposure+research&rft.au=Maxwell%2C+S+K%3BNuckols%2C+J+R%3BWard%2C+M+H&rft.aulast=Maxwell&rft.aufirst=S&rft.date=2003-01-01&rft.volume=&rft.issue=&rft.spage=28&rft.isbn=&rft.btitle=&rft.title=Open-File+Report+-+U.+S.+Geological+Survey&rft.issn=01961497&rft_id=info:doi/ L2 - http://pubs.usgs.gov/of/2003/of03-097/ https://pubs.er.usgs.gov/browse/usgs-publications/OFR LA - English DB - GeoRef N1 - Conference title - Natural science and public health; prescription for a better environment N1 - Copyright - GeoRef, Copyright 2016, American Geosciences Institute. N1 - Date revised - 2003-01-01 N1 - PubXState - VA N1 - SuppNotes - Accessed on Sept 3, 2003 N1 - Last updated - 2016-09-16 N1 - CODEN - XGROAG N1 - SubjectsTermNotLitGenreText - agriculture; agrochemicals; epidemiology; geography; imagery; land use; mapping; medical geology; public health; remote sensing; risk assessment; USGS ER - TY - JOUR T1 - Health risks from mercury exposure in Gorlovka, Ukraine AN - 51941463; 2003-065899 JF - Open-File Report - U. S. Geological Survey AU - Kolker, Allan AU - Panov, Boris AU - Kamel, Freya AU - Bunnell, Joseph E AU - Landa, Edward R AU - Korchemagin, Viktor AU - Panov, Yuriy AU - Conko, Kathryn M AU - Finkelman, Robert B Y1 - 2003 PY - 2003 DA - 2003 SP - 36 PB - U. S. Geological Survey, Reston, VA SN - 0196-1497, 0196-1497 KW - mines KW - concentration KW - Ukraine KW - pollution KW - Europe KW - bioavailability KW - sedimentary rocks KW - Commonwealth of Independent States KW - Gorlovka Ukraine KW - metals KW - coal KW - risk assessment KW - USGS KW - Donets Basin KW - abandoned mines KW - public health KW - mercury KW - 22:Environmental geology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/51941463?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ageorefmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Open-File+Report+-+U.+S.+Geological+Survey&rft.atitle=Health+risks+from+mercury+exposure+in+Gorlovka%2C+Ukraine&rft.au=Kolker%2C+Allan%3BPanov%2C+Boris%3BKamel%2C+Freya%3BBunnell%2C+Joseph+E%3BLanda%2C+Edward+R%3BKorchemagin%2C+Viktor%3BPanov%2C+Yuriy%3BConko%2C+Kathryn+M%3BFinkelman%2C+Robert+B&rft.aulast=Kolker&rft.aufirst=Allan&rft.date=2003-01-01&rft.volume=&rft.issue=&rft.spage=36&rft.isbn=&rft.btitle=&rft.title=Open-File+Report+-+U.+S.+Geological+Survey&rft.issn=01961497&rft_id=info:doi/ L2 - http://pubs.usgs.gov/of/2003/of03-097/ https://pubs.er.usgs.gov/browse/usgs-publications/OFR LA - English DB - GeoRef N1 - Conference title - Natural science and public health; prescription for a better environment N1 - Copyright - GeoRef, Copyright 2016, American Geosciences Institute. N1 - Date revised - 2003-01-01 N1 - PubXState - VA N1 - SuppNotes - Accessed on Sept. 3, 2003 N1 - Last updated - 2016-10-25 N1 - CODEN - XGROAG N1 - SubjectsTermNotLitGenreText - abandoned mines; bioavailability; coal; Commonwealth of Independent States; concentration; Donets Basin; Europe; Gorlovka Ukraine; mercury; metals; mines; pollution; public health; risk assessment; sedimentary rocks; Ukraine; USGS ER - TY - JOUR T1 - Importance sampling method of correction for multiple testing in affected sib-pair linkage analysis AN - 21311440; 11704817 AB - Using the Genetic Analysis Workshop 13 simulated data set, we compared the technique of importance sampling to several other methods designed to adjust p-values for multiple testing: the Bonferroni correction, the method proposed by Feingold et al., and naive Monte Carlo simulation. We performed affected sib-pair linkage analysis for each of the 100 replicates for each of five binary traits and adjusted the derived p-values using each of the correction methods. The type I error rates for each correction method and the ability of each of the methods to detect loci known to influence trait values were compared. All of the methods considered were conservative with respect to type I error, especially the Bonferroni method. The ability of these methods to detect trait loci was also low. However, this may be partially due to a limitation inherent in our binary trait definitions. JF - BMC Genetics AU - Klein, Alison P AU - Kovac, Ilija AU - Sorant, Alexa JM AU - Baffoe-Bonnie, Agnes AU - Doan, Betty Q AU - Ibay, Grace AU - Lockwood, Erica AU - Mandal, Diptasri AU - Santhosh, Lekshmi AU - Weissbecker, Karen AU - Woo, Jessica AU - Zambelli-Weiner, April AU - Zhang, Jie AU - Naiman, Daniel Q AU - Malley, James AU - Bailey-Wilson, Joan E AD - Inherited Disease Research Branch, NHGRI, NIH, Baltimore, Maryland, USA, jebw@nhgri.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - S73 PB - BioMed Central Ltd., Middlesex House London W1T 4LB UK VL - 4 IS - Suppl 1 KW - Genetics Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology KW - Monte Carlo simulation KW - Linkage analysis KW - Data processing KW - Conferences KW - Genetic analysis KW - Sampling KW - G 07880:Human Genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21311440?accountid=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=BMC+Genetics&rft.atitle=Importance+sampling+method+of+correction+for+multiple+testing+in+affected+sib-pair+linkage+analysis&rft.au=Klein%2C+Alison+P%3BKovac%2C+Ilija%3BSorant%2C+Alexa+JM%3BBaffoe-Bonnie%2C+Agnes%3BDoan%2C+Betty+Q%3BIbay%2C+Grace%3BLockwood%2C+Erica%3BMandal%2C+Diptasri%3BSanthosh%2C+Lekshmi%3BWeissbecker%2C+Karen%3BWoo%2C+Jessica%3BZambelli-Weiner%2C+April%3BZhang%2C+Jie%3BNaiman%2C+Daniel+Q%3BMalley%2C+James%3BBailey-Wilson%2C+Joan+E&rft.aulast=Klein&rft.aufirst=Alison&rft.date=2003-01-01&rft.volume=4&rft.issue=Suppl+1&rft.spage=S73&rft.isbn=&rft.btitle=&rft.title=BMC+Genetics&rft.issn=1471-2156&rft_id=info:doi/10.1186%2F1471-2156-4-S1-S73 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-01-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Monte Carlo simulation; Data processing; Linkage analysis; Conferences; Genetic analysis; Sampling DO - http://dx.doi.org/10.1186/1471-2156-4-S1-S73 ER - TY - JOUR T1 - Performance of high-throughput DNA quantification methods AN - 21232763; 7673537 AB - Background The accuracy and precision of estimates of DNA concentration are critical factors for efficient use of DNA samples in high-throughput genotype and sequence analyses. We evaluated the performance of spectrophotometric (OD) DNA quantification, and compared it to two fluorometric quantification methods, the PicoGreen super( registered )assay (PG), and a novel real-time quantitative genomic PCR assay (QG) specific to a region at the human BRCA1 locus. Twenty-Two lymphoblastoid cell line DNA samples with an initial concentration of ~350 ng/uL were diluted to 20 ng/uL. DNA concentration was estimated by OD and further diluted to 5 ng/uL. The concentrations of multiple aliquots of the final dilution were measured by the OD, QG and PG methods. The effects of manual and robotic laboratory sample handling procedures on the estimates of DNA concentration were assessed using variance components analyses. Results The OD method was the DNA quantification method most concordant with the reference sample among the three methods evaluated. A large fraction of the total variance for all three methods (36.0-95.7%) was explained by sample-to-sample variation, whereas the amount of variance attributable to sample handling was small (0.8-17.5%). Residual error (3.2-59.4%), corresponding to un-modelled factors, contributed a greater extent to the total variation than the sample handling procedures. Conclusion The application of a specific DNA quantification method to a particular molecular genetic laboratory protocol must take into account the accuracy and precision of the specific method, as well as the requirements of the experimental workflow with respect to sample volumes and throughput. While OD was the most concordant and precise DNA quantification method in this study, the information provided by the quantitative PCR assay regarding the suitability of DNA samples for PCR may be an essential factor for some protocols, despite the decreased concordance and precision of this method. JF - BMC Biotechnology AU - Haque, Kashif A AU - Pfeiffer, Ruth M AU - Beerman, Michael B AU - Struewing, Jeff P AU - Chanock, Stephen J AU - Bergen, Andrew W AD - 1 Core Genotyping Facility, SAIC-Frederick, Inc., National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA, haquek@mail.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 20 PB - BioMed Central Ltd., Middlesex House VL - 3 KW - Biotechnology and Bioengineering Abstracts KW - Lymphoblastoid cell lines KW - Nucleotide sequence KW - BRCA1 protein KW - Polymerase chain reaction KW - Spectrophotometry KW - robotics KW - Genotypes KW - genomics KW - W 30945:Fermentation & Cell Culture UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21232763?accountid=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=BMC+Biotechnology&rft.atitle=Performance+of+high-throughput+DNA+quantification+methods&rft.au=Haque%2C+Kashif+A%3BPfeiffer%2C+Ruth+M%3BBeerman%2C+Michael+B%3BStruewing%2C+Jeff+P%3BChanock%2C+Stephen+J%3BBergen%2C+Andrew+W&rft.aulast=Haque&rft.aufirst=Kashif&rft.date=2003-01-01&rft.volume=3&rft.issue=&rft.spage=20&rft.isbn=&rft.btitle=&rft.title=BMC+Biotechnology&rft.issn=1472-6750&rft_id=info:doi/10.1186%2F1472-6750-3-20 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-02-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Polymerase chain reaction; Nucleotide sequence; robotics; Spectrophotometry; genomics; Lymphoblastoid cell lines; BRCA1 protein; Genotypes DO - http://dx.doi.org/10.1186/1472-6750-3-20 ER - TY - JOUR T1 - Pharmacogenomics of Alcohol Response and Addiction AN - 20206367; 7473134 AB - Alcoholism is a complex psychiatric disorder that has high heritability (50-60%) and is relatively common; in the US the lifetime prevalence of alcohol dependence is 20% in men and 8% in women. Current psychosocial and pharmacological therapies have relatively modest effects. Treatment is complicated by the fact that alcoholism is often co-morbid with other disorders, including anxiety, depression, and antisocial personality disorder. Approximately 80% of alcoholics smoke cigarettes and there is considerable genetic overlap between nicotine and alcohol addiction. Convergent evidence supports the classification of alcoholics into two broad categories: type 1 - later onset with feelings of anxiety, guilt, and high harm avoidance; and type 2 - early age of onset, usually men, impulsive, antisocial, and with low levels of brain serotonin. The pharmacogenomics of alcohol response is well established; genetic variants for the principal enzymes of alcohol metabolism influence drinking behavior and protect against alcoholism. Vulnerability to alcoholism is likely to be due to multiple interacting genetic loci of small to modest effects. First-line therapeutic targets for alcoholism are neurotransmitter pathway genes implicated in alcohol use. Of particular interest are the `reward pathway (serotonin, dopamine, GABA, glutamate, and beta endorphin) and the behavioral stress response system (corticotrophin-releasing factor and neuropeptide Y). Common functional polymorphisms in these genes are likely to be predictive (although each with small effect) of individualized pharmacological responses. Genetic studies, including case- control association studies and genome wide linkage studies, have identified associations between alcoholism and common functional polymorphisms in several candidate genes. Meanwhile, the current pharmacological therapies for alcoholism are effective in some alcoholics but not all. Some progress has been made in elucidating the pharmacogenomic responses to these drugs, particularly in the context of the type 1/type 2 classification system for alcoholics. JF - American Journal of PharmacoGenomics AU - M-A, Enoch AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institute of Health, Bethesda, Maryland, USA Y1 - 2003 PY - 2003 DA - 2003 SP - 217 EP - 232 PB - Adis International Ltd., 41 Centorian Drive Private Bay 65901, Mairangi Bay Auckland 10 New Zealand, [mailto:sportsmed@adis.co.nz], [URL:http://www.adis.com] VL - 3 IS - 6 SN - 1175-2203, 1175-2203 KW - Genetics Abstracts; Biotechnology and Bioengineering Abstracts; CSA Neurosciences Abstracts KW - Classification systems KW - Cigarettes KW - Anxiety KW - Gene polymorphism KW - Neuropeptide Y KW - Personality KW - Drug abuse KW - Endorphins KW - Mental disorders KW - Dopamine KW - Classification KW - Reinforcement KW - Addiction KW - Neurotransmitters KW - Drug addiction KW - Ethanol KW - Depression KW - pharmacogenomics KW - gamma -Aminobutyric acid KW - Brain KW - Stress KW - Enzymes KW - Drug development KW - Alcoholics KW - Serotonin KW - Smoke KW - Drug dependence KW - Alcoholism KW - Social behavior KW - Drinking behavior KW - Heritability KW - Metabolism KW - G 07880:Human Genetics KW - N3 11001:Behavioral and Cognitive Neuroscience KW - W 30940:Products UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20206367?accountid=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+PharmacoGenomics&rft.atitle=Pharmacogenomics+of+Alcohol+Response+and+Addiction&rft.au=M-A%2C+Enoch&rft.aulast=M-A&rft.aufirst=Enoch&rft.date=2003-01-01&rft.volume=3&rft.issue=6&rft.spage=217&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+PharmacoGenomics&rft.issn=11752203&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-07-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Classification systems; Anxiety; Cigarettes; Neuropeptide Y; Gene polymorphism; Personality; Drug abuse; Endorphins; Mental disorders; Dopamine; Classification; Reinforcement; Neurotransmitters; Addiction; Drug addiction; Ethanol; Depression; pharmacogenomics; gamma -Aminobutyric acid; Brain; Enzymes; Stress; Drug development; Serotonin; Alcoholics; Smoke; Drug dependence; Alcoholism; Social behavior; Drinking behavior; Metabolism; Heritability ER - TY - JOUR T1 - Reduced COMT activity as a possible environmental risk factor for breast cancer. Opinion AN - 20181394; 10263053 AB - Recent genetic epidemiological studies implicate a low activity form of catechol-O-methyltransferase (COMT) with increased risk factor for breast cancer. Taking into account, the role of COMT in the metabolism of otherwise carcinogenic catecholestrogens, it is reasonable to propose that environmental or dietary products that inhibit COMT pose a risk for breast cancer. JF - Neurotoxicity Research AU - Creveling, C R AD - Laboratory of Chemistry, NIDDK, National Institutes of Health, 20814-4008 Bethesda, MD, USA, CrevelingB@extra.niddk.nih.gov Y1 - 2003/01// PY - 2003 DA - Jan 2003 SP - 473 EP - 474 PB - Taylor & Francis Group Ltd., 2 Park Square Milton Park, Abingdon Oxford OX14 4RN UK, [URL:http://www.taylorandfrancis.co.uk/] VL - 5 IS - 7 SN - 1029-8428, 1029-8428 KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - Catechol O-methyltransferase KW - Risk factors KW - Neurotoxicity KW - Breast cancer KW - Metabolism KW - N3 11028:Neuropharmacology & toxicology KW - X 24490:Other UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20181394?accountid=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=Neurotoxicity+Research&rft.atitle=Reduced+COMT+activity+as+a+possible+environmental+risk+factor+for+breast+cancer.+Opinion&rft.au=Creveling%2C+C+R&rft.aulast=Creveling&rft.aufirst=C&rft.date=2003-01-01&rft.volume=5&rft.issue=7&rft.spage=473&rft.isbn=&rft.btitle=&rft.title=Neurotoxicity+Research&rft.issn=10298428&rft_id=info:doi/10.1007%2FBF03033157 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-08-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Catechol O-methyltransferase; Risk factors; Neurotoxicity; Breast cancer; Metabolism DO - http://dx.doi.org/10.1007/BF03033157 ER - TY - JOUR T1 - Striatal glutamatergic mechanisms and extrapyramidal movement disorders AN - 20174871; 10263021 AB - The nonphysiologic stimulation of striatal dopaminergic receptors, as a result of disease- or drug-related denervation or intermittent excitation, triggers adaptive responses in the basal ganglia which contribute to the appearance of parkinsonian symptoms and later to the dyskinesias and other alterations in motor response associated with dopaminergic therapy. Current evidence suggests that these altered responses involve activation of signal transduction cascades in striatal medium spiny neurons linking dopaminergic to coexpressed ionotropic glutamatergic receptors of theN-methyl-d-aspartate (NMDA) and alpha -amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) classes. These intraneuronal signaling pathways appear capable of modifying the phosphorylation state of NMDA and AMPA receptor subunits; resultant sensitization enhances cortical glutamatergic input which in turn modifies striatal output in ways that compromise motor behavior. The regulation of these spiny neuron glutamate receptors can also be affected by the activation state of coexpressed nondopaminergic receptors as well as by changes associated with Huntington's disease. These observations lend new insight into molecular mechanisms contributing to the integration of synaptic inputs to spiny neurons. They also suggest novel approaches to the pharmacotherapy of extrapyramidal motor dysfunction. JF - Neurotoxicity Research AU - Chase, Thomas N AU - Bibbiani, Francesco AU - Oh, Justin D AD - National Institutes of Health, Experimental Therapeutics Branch, NINDS, NIH, Building 10, Room 5C103, Bethesda, MD, USA, chase@ninds.nih.gov Y1 - 2003/01// PY - 2003 DA - Jan 2003 SP - 139 EP - 145 PB - Taylor & Francis Group Ltd., 2 Park Square Milton Park, Abingdon Oxford OX14 4RN UK, [URL:http://www.taylorandfrancis.co.uk/] VL - 5 IS - 1-2 SN - 1029-8428, 1029-8428 KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - Molecular modelling KW - N-Methyl-D-aspartic acid receptors KW - Dyskinesia KW - Denervation KW - Dopamine receptors KW - Glutamic acid receptors KW - alpha -Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors KW - Glutamic acid receptors (ionotropic) KW - Huntington's disease KW - Integration KW - Movement disorders KW - Phosphorylation KW - spiny neurons KW - Neurotoxicity KW - Neostriatum KW - Central nervous system diseases KW - alpha -Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid KW - proprionic acid KW - Basal ganglia KW - Signal transduction KW - X 24500:Reviews, Legislation, Book & Conference Notices KW - N3 11007:Neurobiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20174871?accountid=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=Neurotoxicity+Research&rft.atitle=Striatal+glutamatergic+mechanisms+and+extrapyramidal+movement+disorders&rft.au=Chase%2C+Thomas+N%3BBibbiani%2C+Francesco%3BOh%2C+Justin+D&rft.aulast=Chase&rft.aufirst=Thomas&rft.date=2003-01-01&rft.volume=5&rft.issue=1-2&rft.spage=139&rft.isbn=&rft.btitle=&rft.title=Neurotoxicity+Research&rft.issn=10298428&rft_id=info:doi/10.1007%2FBF03033378 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-08-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Molecular modelling; N-Methyl-D-aspartic acid receptors; Dyskinesia; Dopamine receptors; Denervation; alpha -Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors; Glutamic acid receptors; Glutamic acid receptors (ionotropic); Huntington's disease; Integration; Movement disorders; spiny neurons; Phosphorylation; Central nervous system diseases; Neostriatum; Neurotoxicity; alpha -Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid; proprionic acid; Basal ganglia; Signal transduction DO - http://dx.doi.org/10.1007/BF03033378 ER - TY - JOUR T1 - Coupled reductions in brain oxidative phosphorylation and synaptic function can be quantified and staged in the course of Alzheimer disease AN - 20139157; 10263044 AB - In vivo, post-mortem and biopsy data suggest that coupled deelines occur in brain synaptic activity and brain energy consumption during the evolution of Alzheimer disease. In the first stage of these declines, changes in synaptic structure and function reduce neuronal energy demand and lead to potentially reversible downregulation of oxidative phosphorylation (OXPHOS) within neuronal mitochondria. At this stage, measuring brain glucose metabolism or brain blood flow in patients, using positron emission tomography (PET), shows that the brain can be almost normally activated in response to stimulation. Thus, therapy at this stage should be designed to re-establish synaptic integrity or prevent its further deterioration. As disease progresses, neurofibrillary tangles with abnormally phosphorylated tau protein accumulate within neuronal cytoplasm, to the point that they co-opt the nonphosphorylated tau necessary for axonal transport of mitochondria between the cell nucleus and the synapse. In this second stage, severe energy depletion and other pathological processes associated with irreversibly downregulated OXPHOS lead to cell death, and the brain cannot normally respond to functional stimulation. JF - Neurotoxicity Research AU - Rapoport, Stanley I AD - Brain Physiology and Metabolism Sections, National Institutes of Health, Bldg. 10, Rm. 6N202, National Institute on Aging, 20892 Bethesda, MD, USA, sir@helix.nih.gov Y1 - 2003/01// PY - 2003 DA - Jan 2003 SP - 385 EP - 397 PB - Taylor & Francis Group Ltd., 2 Park Square Milton Park, Abingdon Oxford OX14 4RN UK, [URL:http://www.taylorandfrancis.co.uk/] VL - 5 IS - 6 SN - 1029-8428, 1029-8428 KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - Axonal transport KW - Synapses KW - Data processing KW - Oxidative phosphorylation KW - Alzheimer's disease KW - Brain KW - Mitochondria KW - Biopsy KW - Glucose metabolism KW - Neurodegenerative diseases KW - Cell death KW - Structure-function relationships KW - Cytoplasm KW - Neurotoxicity KW - Tau protein KW - Positron emission tomography KW - Neurofibrillary tangles KW - Cerebral blood flow KW - Evolution KW - X 24310:Pharmaceuticals KW - N3 11028:Neuropharmacology & toxicology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20139157?accountid=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=Neurotoxicity+Research&rft.atitle=Coupled+reductions+in+brain+oxidative+phosphorylation+and+synaptic+function+can+be+quantified+and+staged+in+the+course+of+Alzheimer+disease&rft.au=Rapoport%2C+Stanley+I&rft.aulast=Rapoport&rft.aufirst=Stanley&rft.date=2003-01-01&rft.volume=5&rft.issue=6&rft.spage=385&rft.isbn=&rft.btitle=&rft.title=Neurotoxicity+Research&rft.issn=10298428&rft_id=info:doi/10.1007%2FBF03033167 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-08-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Axonal transport; Synapses; Data processing; Oxidative phosphorylation; Alzheimer's disease; Brain; Mitochondria; Biopsy; Glucose metabolism; Neurodegenerative diseases; Cell death; Structure-function relationships; Cytoplasm; Tau protein; Neurotoxicity; Positron emission tomography; Neurofibrillary tangles; Evolution; Cerebral blood flow DO - http://dx.doi.org/10.1007/BF03033167 ER - TY - JOUR T1 - Trimethyltin-induced neurogenesis in the murine hippocampus AN - 20136992; 10263068 AB - Neurogenesis continues to occur in the mature rodent brain with one of the most prominent sources for new neurons being the subgranular layer (SGL) of the dentate gyrus (DG) in the hippocampus. A number of factors can stimulate this process including synaptic activity and injury. To determine if this process would occur upon a direct injury to the dentate region, we exposed young, 21 day old male CD-1 mice to the hippocampal toxicant, trimethyltin (TMT). An acute i.p. injection of TMT (2 mg/kg) produced extensive damage and loss of dentate granule neurons within 72 h. This active period of degeneration was accompanied by an increase in the generation of progenitor cells within the SGL as identified by BrdU uptake and Ki-67 immunostaining. As additional markers for neurogenesis, both nestin and doublecortin showed increased staining patterns within the blades of the dentate. In these young weanling mice, the level of proliferation was sufficient to significantly repopulate the dentate region by 4 weeks post-TMT, suggesting a high level of regenerative potential. Our data indicate a significant level of neurogenesis occurring during the active process of degeneration and in an environment of microglia activation. The TMT-induced injury offers a model system for further examination of the process of neurogenesis, neural adaptation, and the influence of inflammatory factors and glia interactions. JF - Neurotoxicity Research AU - Harry, G Jean AU - McPherson, Christopher A AU - Wine, Robert N AU - Atkinson, Kelly AU - d'Hellencourt, Christian Lefebvre AD - Neurotoxicology Group, Laboratory of Molecular Toxicology, Department of Health and Human Services, National Institutes of Health, National Institute of Environmental Health Sciences, P.O. Box 12233, MD C1-04, 27709 Research Triangle Park, NC, USA, harry@niehs.nih.gov Y1 - 2003/01// PY - 2003 DA - Jan 2003 SP - 623 EP - 627 PB - Taylor & Francis Group Ltd., 2 Park Square Milton Park, Abingdon Oxford OX14 4RN UK, [URL:http://www.taylorandfrancis.co.uk/] VL - 5 IS - 8 SN - 1029-8428, 1029-8428 KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - Data processing KW - Adaptations KW - Toxicants KW - Injuries KW - Hippocampus KW - Brain KW - Animal models KW - Microglia KW - Neurodegeneration KW - Dentate gyrus KW - Inflammation KW - Granule cells KW - Neurogenesis KW - Stem cells KW - Neurotoxicity KW - Nestin KW - Trimethyltin KW - Doublecortin protein KW - N3 11028:Neuropharmacology & toxicology KW - X 24300:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20136992?accountid=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=Neurotoxicity+Research&rft.atitle=Trimethyltin-induced+neurogenesis+in+the+murine+hippocampus&rft.au=Harry%2C+G+Jean%3BMcPherson%2C+Christopher+A%3BWine%2C+Robert+N%3BAtkinson%2C+Kelly%3Bd%27Hellencourt%2C+Christian+Lefebvre&rft.aulast=Harry&rft.aufirst=G&rft.date=2003-01-01&rft.volume=5&rft.issue=8&rft.spage=623&rft.isbn=&rft.btitle=&rft.title=Neurotoxicity+Research&rft.issn=10298428&rft_id=info:doi/10.1007%2FBF03033182 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-08-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Adaptations; Data processing; Injuries; Toxicants; Hippocampus; Animal models; Brain; Microglia; Neurodegeneration; Dentate gyrus; Inflammation; Granule cells; Stem cells; Neurogenesis; Neurotoxicity; Trimethyltin; Nestin; Doublecortin protein DO - http://dx.doi.org/10.1007/BF03033182 ER - TY - JOUR T1 - Direct and indirect induction of apoptosis in human mesenchymal stem cells in response to titanium particles AN - 19927566; 5638938 AB - The most frequent complication of total joint arthroplasty is periprosthetic osteolysis initiated by an inflammatory response to orthopaedic wear debris, which if left untreated, can result in implant instability and failure, eventually requiring revision surgery. We have previously reported that osteogenic differentiation of human marrow stroma-derived mesenchymal stem cells (hMSCs) is suppressed upon exposure to titanium particles, accompanied by reduced bone sialoprotein (BSP) gene expression, diminished production of collagen type I and BSP, decreased cellular viability and proliferation, and inhibition of extracellular matrix mineralization. In this study, we have further investigated hMSC cytotoxicity upon exposure to submicron particles of commercially pure titanium (cpTi) and zirconium oxide (ZrO sub(2)). Our results showed that direct exposure to cpTi and ZrO sub(2) particles compromises cell viability through the induction of apoptosis, eliciting increased levels of the tumor suppressor proteins p53 and p73, in a manner dependent on material composition, particle dosage, and time. Additionally, conditioned medium collected from hMSCs exposed to cpTi particles, but not to ZrO sub(2) particles, is cytotoxic to hMSCs, inducing apoptosis in the absence of particles. These findings demonstrate that exposure to orthopaedically derived wear particles can compromise hMSC viability through the direct and indirect induction of apoptosis. Thus, prolonged in vivo exposure of marrow-derived hMSCs to implant- derived wear debris is likely to reduce the population of viable osteoprogenitor cells, and may contribute to poor periprosthetic bone quality and implant loosening. JF - Journal of Orthopaedic Research AU - Wang, M L AU - Tuli, R AU - Manner, P A AU - Sharkey, P F AU - Hall, D J AU - Tuan, R S AD - Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, PA 19107, USA, tuanr@mail.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 697 EP - 707 PB - Elsevier Science Ltd. VL - 21 IS - 4 SN - 0736-0266, 0736-0266 KW - Biotechnology and Bioengineering Abstracts KW - Mesenchymal stem cell KW - Apoptosis KW - Wear particles KW - Titanium KW - Zirconia KW - Osteolysis KW - Tumor suppressor genes KW - Particulate matter KW - Joint diseases KW - Mineralization KW - p53 protein KW - Inflammation KW - Gene expression KW - Differentiation KW - Stem cells KW - Cytotoxicity KW - Bone sialoprotein KW - Surgery KW - Extracellular matrix KW - Osteoprogenitor cells KW - oxides KW - Cell proliferation KW - Mesenchyme KW - Collagen (type I) KW - Arthroplasty KW - W 30920:Tissue Engineering UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19927566?accountid=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+Orthopaedic+Research&rft.atitle=Direct+and+indirect+induction+of+apoptosis+in+human+mesenchymal+stem+cells+in+response+to+titanium+particles&rft.au=Wang%2C+M+L%3BTuli%2C+R%3BManner%2C+P+A%3BSharkey%2C+P+F%3BHall%2C+D+J%3BTuan%2C+R+S&rft.aulast=Wang&rft.aufirst=M&rft.date=2003-01-01&rft.volume=21&rft.issue=4&rft.spage=697&rft.isbn=&rft.btitle=&rft.title=Journal+of+Orthopaedic+Research&rft.issn=07360266&rft_id=info:doi/10.1016%2FS0736-0266%2802%2900241-3 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-07-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Osteolysis; Tumor suppressor genes; Titanium; Apoptosis; Particulate matter; Joint diseases; Mineralization; Inflammation; p53 protein; Gene expression; Differentiation; Cytotoxicity; Stem cells; Bone sialoprotein; Extracellular matrix; Surgery; Osteoprogenitor cells; oxides; Mesenchyme; Cell proliferation; Collagen (type I); Arthroplasty DO - http://dx.doi.org/10.1016/S0736-0266(02)00241-3 ER - TY - JOUR T1 - No simple dependence between protein evolution rate and the number of protein-protein interactions: only the most prolific interactors tend to evolve slowly AN - 19826178; 6044797 AB - It has been suggested that rates of protein evolution are influenced, to a great extent, by the proportion of amino acid residues that are directly involved in protein function. In agreement with this hypothesis, recent work has shown a negative correlation between evolutionary rates and the number of protein- protein interactions. However, the extent to which the number of protein-protein interactions influences evolutionary rates remains unclear. Here, we address this question at several different levels of evolutionary relatedness. Manually curated data on the number of protein-protein interactions among Saccharomyces cerevisiae proteins was examined for possible correlation with evolutionary rates between S. cerevisiae and Schizosaccharomyces pombe orthologs. Only a very weak negative correlation between the number of interactions and evolutionary rate of a protein was observed. Furthermore, no relationship was found between a more general measure of the evolutionary conservation of S. cerevisiae proteins, based on the taxonomic distribution of their homologs, and the number of protein-protein interactions. However, when the proteins from yeast were assorted into discrete bins according to the number of interactions, it turned out that 6.5% of the proteins with the greatest number of interactions evolved, on average, significantly slower than the rest of the proteins. Comparisons were also performed using protein-protein interaction data obtained with high-throughput analysis of Helicobacter pylori proteins. No convincing relationship between the number of protein- protein interactions and evolutionary rates was detected, either for comparisons of orthologs from two completely sequenced H. pylori strains or for comparisons of H. pylori and Campylobacter jejuni orthologs, even when the proteins were classified into bins by the number of interactions. The currently available comparative-genomic data do not support the hypothesis that the evolutionary rates of the majority of proteins substantially depend on the number of protein-protein interactions they are involved in. However, a small fraction of yeast proteins with the largest number of interactions (the hubs of the interaction network) tend to evolve slower than the bulk of the proteins. JF - BMC Evolutionary Biology AU - Jordan, I King AU - Wolf, Yuri I AU - Koonin, Eugene V AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, jordan@ncbi.nlm.nih.gov Y1 - 2003 PY - 2003 DA - 2003 PB - BioMed Central Ltd., Middlesex House 34-42 Cleveland Street London W1T 4LB UK, [mailto:info@biomedcentral.com], [URL:http://www.biomedcentral.com] VL - 3 KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; Microbiology Abstracts B: Bacteriology KW - Helicobacter pylori KW - Evolutionary conservation KW - Amino acids KW - Data processing KW - Campylobacter jejuni KW - Protein interaction KW - Saccharomyces cerevisiae KW - Schizosaccharomyces pombe KW - J 02310:Genetics & Taxonomy KW - K 03310:Genetics & Taxonomy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19826178?accountid=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=BMC+Evolutionary+Biology&rft.atitle=No+simple+dependence+between+protein+evolution+rate+and+the+number+of+protein-protein+interactions%3A+only+the+most+prolific+interactors+tend+to+evolve+slowly&rft.au=Jordan%2C+I+King%3BWolf%2C+Yuri+I%3BKoonin%2C+Eugene+V&rft.aulast=Jordan&rft.aufirst=I&rft.date=2003-01-01&rft.volume=3&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=BMC+Evolutionary+Biology&rft.issn=1471-2148&rft_id=info:doi/10.1186%2F1471-2148-3-1 L2 - http://www.biomedcentral.com/content/pdf/1471-2148-3-1.pdf LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-07-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Evolutionary conservation; Data processing; Amino acids; Protein interaction; Helicobacter pylori; Campylobacter jejuni; Schizosaccharomyces pombe; Saccharomyces cerevisiae DO - http://dx.doi.org/10.1186/1471-2148-3-1 ER - TY - JOUR T1 - A model of tripeptidyl-peptidase I (CLN2), a ubiquitous and highly conserved member of the sedolisin family of serine-carboxyl peptidases AN - 19822271; 6059715 AB - Tripeptidyl-peptidase I, also known as CLN2, is a member of the family of sedolisins (serine-carboxyl peptidases). In humans, defects in expression of this enzyme lead to a fatal neurodegenerative disease, classical late-infantile neuronal ceroid lipofuscinosis. Similar enzymes have been found in the genomic sequences of several species, but neither systematic analyses of their distribution nor modeling of their structures have been previously attempted. We have analyzed the presence of orthologs of human CLN2 in the genomic sequences of a number of eukaryotic species. Enzymes with sequences sharing over 80% identity have been found in the genomes of macaque, mouse, rat, dog, and cow. Closely related, although clearly distinct, enzymes are present in fish (fugu and zebra), as well as in frogs (Xenopus tropicalis). A three-dimensional model of human CLN2 was built based mainly on the homology with Pseudomonas sp. 101 sedolisin. CLN2 is very highly conserved and widely distributed among higher organisms and may play an important role in their life cycles. The model presented here indicates a very open and accessible active site that is almost completely conserved among all known CLN2 enzymes. This result is somehow surprising for a tripeptidase where the presence of a more constrained binding pocket was anticipated. This structural model should be useful in the search for the physiological substrates of these enzymes and in the design of more specific inhibitors of CLN2. JF - BMC Structural Biology AU - Wlodawer, Alexander AU - Durell, Stewart R AU - Li, Mi AU - Oyama, Hiroshi AU - Oda, Kohei AU - Dunn, Ben M AD - Protein Structure Section, Macromolecular Crystallography Laboratory, National Cancer Institute at Frederick, Frederick, MD 21702, USA, wlodawer@ncifcrf.gov Y1 - 2003 PY - 2003 DA - 2003 PB - BioMed Central Ltd., Middlesex House 34-42 Cleveland Street London W1T 4LB UK, [mailto:info@biomedcentral.com], [URL:http://www.biomedcentral.com] VL - 3 KW - Microbiology Abstracts B: Bacteriology KW - Genomes KW - Macaca KW - Anura KW - Xenopus tropicalis KW - Animal models KW - Enzymes KW - Pseudomonas KW - Neuronal ceroid lipofuscinosis KW - peptidase KW - Fugu KW - CLN2 protein KW - Neurodegenerative diseases KW - Homology KW - genomics KW - J 02310:Genetics & Taxonomy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19822271?accountid=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=BMC+Structural+Biology&rft.atitle=A+model+of+tripeptidyl-peptidase+I+%28CLN2%29%2C+a+ubiquitous+and+highly+conserved+member+of+the+sedolisin+family+of+serine-carboxyl+peptidases&rft.au=Wlodawer%2C+Alexander%3BDurell%2C+Stewart+R%3BLi%2C+Mi%3BOyama%2C+Hiroshi%3BOda%2C+Kohei%3BDunn%2C+Ben+M&rft.aulast=Wlodawer&rft.aufirst=Alexander&rft.date=2003-01-01&rft.volume=3&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=BMC+Structural+Biology&rft.issn=1472-6807&rft_id=info:doi/10.1186%2F1472-6807-3-8 L2 - http://www.biomedcentral.com/content/pdf/1472-6807-3-8.pdf LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-05-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Genomes; Neurodegenerative diseases; CLN2 protein; Homology; Animal models; Enzymes; genomics; Neuronal ceroid lipofuscinosis; peptidase; Macaca; Xenopus tropicalis; Anura; Pseudomonas; Fugu DO - http://dx.doi.org/10.1186/1472-6807-3-8 ER - TY - JOUR T1 - Evolutionary connection between the catalytic subunits of DNA-dependent RNA polymerases and eukaryotic RNA-dependent RNA polymerases and the origin of RNA polymerases AN - 19813070; 6059726 AB - The eukaryotic RNA-dependent RNA polymerase (RDRP) is involved in the amplification of regulatory microRNAs during post-transcriptional gene silencing. This enzyme is highly conserved in most eukaryotes but is missing in archaea and bacteria. No evolutionary relationship between RDRP and other polymerases has been reported so far, hence the origin of this eukaryote- specific polymerase remains a mystery. Using extensive sequence profile searches, we identified bacteriophage homologs of the eukaryotic RDRP. The comparison of the eukaryotic RDRP and their homologs from bacteriophages led to the delineation of the conserved portion of these enzymes, which is predicted to harbor the catalytic site. Further, detailed sequence comparison, aided by examination of the crystal structure of the DNA- dependent RNA polymerase (DDRP), showed that the RDRP and the beta ' subunit of DDRP (and its orthologs in archaea and eukaryotes) contain a conserved double- psi beta -barrel (DPBB) domain. This DPBB domain contains the signature motif DbDGD (b is a bulky residue), which is conserved in all RDRPs and DDRPs and contributes to catalysis via a coordinated divalent cation. Apart from the DPBB domain, no similarity was detected between RDRP and DDRP, which leaves open two scenarios for the origin of RDRP: i) RDRP evolved at the onset of the evolution of eukaryotes via a duplication of the DDRP beta ' subunit followed by dramatic divergence that obliterated the sequence similarity outside the core catalytic domain and II) the primordial RDRP, which consisted primarily of the DPBB domain, evolved from a common ancestor with the DDRP at a very early stage of evolution, during the RNA world era. The latter hypothesis implies that RDRP had been subsequently eliminated from cellular life forms and might have been reintroduced into the eukaryotic genomes through a bacteriophage. Sequence and structure analysis of the DDRP led to further insights into the evolution of RNA polymerases. In addition to the beta ' subunit, beta subunit of DDRP also contains a DPBB domain, which is, however, distorted by large inserts and does not harbor a counterpart of the DbDGD motif. The DPBB domains of the two DDRP subunits together form the catalytic cleft, with the domain from the beta ' subunit supplying the metal-coordinating DbDGD motif and the one from the beta subunit providing two lysine residues involved in catalysis. Given that the two DPBB domains of DDRP contribute completely different sets of active residues to the catalytic center, it is hypothesized that the ultimate ancestor of RNA polymerases functioned as a homodimer of a generic, RNA-binding DPBB domain. This ancestral protein probably did not have catalytic activity and served as a cofactor for a ribozyme RNA polymerase. Subsequent evolution of DDRP and RDRP involved accretion of distinct sets of additional domains. In the DDRPs, these included a RNA-binding Zn-ribbon, an AT-hook-like module and a sandwich-barrel hybrid motif (SBHM) domain. Further, lineage-specific accretion of SBHM domains and other, DDRP-specific domains is observed in bacterial DDRPs. In contrast, the orthologs of the beta ' subunit in archaea and eukaryotes contains a four- stranded alpha + beta domain that is shared with the alpha -subunit of bacterial DDRP, eukaryotic DDRP subunit RBP11, translation factor eIF1 and type II topoisomerases. The additional domains of the RDRPs remain to be characterized. Eukaryotic RNA-dependent RNA polymerases share the catalytic double-psi beta - barrel domain, containing a signature metal-coordinating motif, with the universally conserved beta ' subunit of DNA-dependent RNA polymerases. Beyond this core catalytic domain, the two classes of RNA polymerases do not have common domains, suggesting early divergence from a common ancestor, with subsequent independent domain accretion. The beta -subunit of DDRP contains another, highly diverged DPBB domain. The presence of two distinct DPBB domains in two subunits of DDRP is compatible with the hypothesis that the ultimate ancestor of RNA polymerases was a RNA-binding DPBB domain that had no catalytic activity but rather functioned as a homodimeric cofactor for a ribozyme polymerase. JF - BMC Structural Biology AU - Iyer, Lakshminarayan M AU - Koonin, Eugene V AU - Aravind, L AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA, lakshmin@ncbi.nlm.nih.gov Y1 - 2003 PY - 2003 DA - 2003 PB - BioMed Central Ltd., Middlesex House 34-42 Cleveland Street London W1T 4LB UK, [mailto:info@biomedcentral.com], [URL:http://www.biomedcentral.com] VL - 3 KW - Microbiology Abstracts B: Bacteriology; Virology & AIDS Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Phages KW - Genomes KW - Archaea KW - Nucleotide sequence KW - miRNA KW - Leaves KW - Enzymes KW - Lysine KW - Catalytic subunits KW - Protein structure KW - DNA-directed RNA polymerase KW - Cofactors KW - Cations KW - RNA-directed RNA polymerase KW - Hybrids KW - Crystal structure KW - Conserved sequence KW - Active sites KW - Post-transcription KW - Ribozymes KW - Evolution KW - Gene silencing KW - Catalysis KW - V 22320:Replication KW - N 14830:RNA KW - J 02430:Symbiosis, Antibiosis & Phages UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19813070?accountid=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=BMC+Structural+Biology&rft.atitle=Evolutionary+connection+between+the+catalytic+subunits+of+DNA-dependent+RNA+polymerases+and+eukaryotic+RNA-dependent+RNA+polymerases+and+the+origin+of+RNA+polymerases&rft.au=Iyer%2C+Lakshminarayan+M%3BKoonin%2C+Eugene+V%3BAravind%2C+L&rft.aulast=Iyer&rft.aufirst=Lakshminarayan&rft.date=2003-01-01&rft.volume=8&rft.issue=1&rft.spage=95&rft.isbn=&rft.btitle=&rft.title=Journal+of+Business+Case+Studies+%28Online%29&rft.issn=&rft_id=info:doi/ L2 - http://www.biomedcentral.com/content/pdf/1472-6807-3-1.pdf LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-05-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Genomes; Phages; Nucleotide sequence; miRNA; Leaves; Catalytic subunits; Lysine; Enzymes; Protein structure; DNA-directed RNA polymerase; Cofactors; Cations; Hybrids; RNA-directed RNA polymerase; Crystal structure; Conserved sequence; Post-transcription; Active sites; Ribozymes; Evolution; Catalysis; Gene silencing; Archaea DO - http://dx.doi.org/10.1186/1472-6807-3-1 ER - TY - JOUR T1 - Filtering and selection of structural models: Combining docking and NMR AN - 19769577; 5715046 AB - It is generally accepted that protein structures are more conserved than protein sequences, and 3D structure determination by computer simulations have become an important necessity in the postgenomic area. Despite major successes no robust, fast, and automated ab initio prediction algorithms for deriving accurate folds of single polypeptide chains or structures of intermolecular complexes exist at present. Here we present a methodology that uses selection and filtering of structural models generated by docking of known substructures such as individual proteins or domains through easily obtainable experimental NMR constraints. In particular, residual dipolar couplings and chemical shift mapping are used. Heuristic inclusion of chemical or biochemical knowledge about point-to-point interactions is combined in our selection strategy with the NMR data and commonly used contact potentials. We demonstrate the approach for the determination of protein-protein complexes using the EIN/HPr complex as an example and for establishing the domain-domain orientation in a chimeric protein, the recently determined hybrid human-Escherichia. coli thioredoxin. Proteins 2003. JF - Proteins: Structure, Function & Genetics AU - Dobrodumov, A AU - Gronenborn, A M AD - Laboratory of Chemical Physics, Building 5, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, gronenborn@nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 18 EP - 32 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 53 IS - 1 SN - 0887-3585, 0887-3585 KW - Microbiology Abstracts B: Bacteriology KW - protein-protein complexes KW - domain interfaces KW - NMR KW - residual dipolar couplings KW - Protein structure KW - Thioredoxin KW - Data processing KW - Mathematical models KW - Hybrids KW - Algorithms KW - Problem solving KW - N.M.R. KW - Mapping KW - J 02330:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19769577?accountid=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+Business+Case+Studies+%28Online%29&rft.atitle=Largest+IM+Platform+In+China+-+Tecent%27s+QQ&rft.au=Wu%2C+Jane+Peihusn%3BFrantz%2C+Terrill+L.&rft.aulast=Wu&rft.aufirst=Jane&rft.date=2012-01-01&rft.volume=8&rft.issue=1&rft.spage=147&rft.isbn=&rft.btitle=&rft.title=Journal+of+Library+and+Information+Science+Research&rft.issn=19909128&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-05-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Thioredoxin; Protein structure; Mathematical models; Data processing; Hybrids; Algorithms; Problem solving; N.M.R.; Mapping DO - http://dx.doi.org/10.1002/prot.10439 ER - TY - JOUR T1 - Oxidative stress and hemorheological changes induced by acute treadmill exercise AN - 19620381; 8719087 AB - The present investigation was designed to evaluate the acute effect of aerobic exercise on oxidative stress and the flow properties of the blood. Fourteen clinically healthy subjects [lpar ]7 men and 7 women aged 56[plusmn]19 yr[rpar ] underwent maximal treadmill exercise with blood samples drawn prior to and immediately after exercise. Post-exercise significant increases were observed in plasma lipid hydroperoxides from 6.5[plusmn]2.0 [mu ]M to 7.9[plusmn]1.9 [mu ]M [lpar ]p[lt ]0.0001[rpar ] and the relative concentration of plasma fluorescent products associated with red cell peroxidation from 138[plusmn]28 RF to 220[plusmn]92 RF [lpar ]p[lt ]0.005[rpar ]. After exercise there was a rise in the hematocrit from 41.4[plusmn]3.7[percnt] to 44.4[plusmn]4.1[percnt] [lpar ]p[lt ]0.0001[rpar ], increases in whole blood viscosity at shear rates of 22.5[sol ]sec to 450[sol ]sec [lpar ]p[lt ]0.0005[rpar ], an increase in plasma viscosity from 1.27[plusmn]0.12 cP to 1.36[plusmn]0.11 cP [lpar ]p[lt ]0.01[rpar ], an increase in red cell rigidity from 2.44[plusmn]0.48 cP to 2.62[plusmn]0.42 cP [lpar ]p[lt ]0.001[rpar ] and a decrease in erythrocyte sedimentation rate from 26.9[plusmn]18.6 mm[sol ]h to 22.5[plusmn]15.9 mm[sol ]h [lpar ]p[lt ]0.01[rpar ]. The findings suggest that acute aerobic exercise induces oxidative damage to red blood cells and adversely affects rheological properties of the peripheral blood. JF - Clinical Hemorheology and Microcirculation AU - Ajmani, Ranjeet S AU - Fleg, Jerome L AU - Demehin, AAndrew AU - Wright, Jeanette G AU - O'Connor, Frances AU - Heim, Jane M AU - Tarien, Edward AU - Rifkind, Joseph M AD - National Institute on Aging, National Institutes of Health, Molecular Dynamics Section and the Laboratory of Cardiovascular Sciences, Baltimore, MD, USA Y1 - 2003 PY - 2003 DA - 2003 SP - 29 EP - 40 PB - I O S Press VL - 28 IS - 1 SN - 1386-0291, 1386-0291 KW - Physical Education Index KW - Blood KW - Exercise physiology KW - Aerobics KW - Lipids KW - Women KW - Stress KW - Hematocrit KW - Exercise (effects) KW - Treadmill ergometry KW - PE 090:Sports Medicine & Exercise Sport Science UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19620381?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Library+and+Information+Science+Research&rft.atitle=Understanding+the+Public+Library%27s+Internet+Services+for+Elderly%3A+The+Internet+Behavior+of+Baby+Boomers+in+Taiwan&rft.au=Hsu%2C+Yu-Chun%3BChang%2C+Shan-Ju+Lin&rft.aulast=Hsu&rft.aufirst=Yu-Chun&rft.date=2013-12-01&rft.volume=8&rft.issue=1&rft.spage=147&rft.isbn=&rft.btitle=&rft.title=Journal+of+Library+and+Information+Science+Research&rft.issn=19909128&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2009-02-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Blood; Exercise physiology; Aerobics; Lipids; Women; Hematocrit; Stress; Exercise (effects); Treadmill ergometry ER - TY - JOUR T1 - Late Effects of the Chernobyl Radiation Accident on T Cell-Mediated Immunity in Cleanup Workers AN - 19620103; 8693369 AB - Kuzmenok, O., Potapnev, M., Potapova, S., Smolnikova, V., Rzheutsky, V., Yarilin, A. A., Savino, W. and Belyakov, I. M. Late Effects of the Chernobyl Radiation Accident on T Cell-Mediated Immunity in Cleanup Workers. Radiat. Res. 159, 109-116 (2003). The main goal of this investigation was to evaluate the abnormal T-cell immunity in cleanup workers who took part in the cleanup after the Chernobyl accident in 1986. Peripheral blood mononuclear cells (MNCs) of apparently healthy cleanup workers (n = 134) were used to analyze the phenotype and proliferative response to mitogens in vitro. Evaluation of the MNC phenotype of cleanup workers did not reveal a significant disturbance in the T-cell subpopulation content except for an increase in CD3+CD16+56+ (NKT) cells. Immunophenotyping of phytohemagglutinin (PHA)-activated MNCs demonstrated suppression of CD4+ T-cell propagation and augmentation of CD8+ T-cell propagation in vitro compared to control individuals. DNA synthesis in the MNCs of cleanup workers was markedly inhibited after activation for 3 days with suboptimal concentrations of PHA, pokeweed mitogen and PMA. In contrast to control individuals, the monocytes of cleanup workers were able to stimulate the proliferation of T cells from healthy individuals but inhibited the proliferation of T cells from cleanup workers. This study affords a better understanding of the response of MNCs to stimulation with suboptimal concentrations of PHA and provides an approach to a more accurate analysis of the immunological disorders found after exposure to radiation from Chernobyl-related activities. JF - Radiation Research AU - Kuzmenok, Oleg AU - Potapnev, Michail AU - Potapova, Svetlana AU - Smolnikova, Victoria AU - Rzheutsky, Valeriy AU - Yarilin, Alexandr A AU - Savino, Wilson AU - Belyakov, Igor M AD - Laboratory on Thymus Research, Department of Immunology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Av. Brasil, 4365-Manguinhos 21045-900 Brazil, belyakov@box-b.nih.gov Y1 - 2003/01// PY - 2003 DA - Jan 2003 SP - 109 EP - 116 PB - Allen Press, Inc., 810 East Tenth St. VL - 159 IS - 1 SN - 0033-7587, 0033-7587 KW - Toxicology Abstracts; Immunology Abstracts KW - DNA biosynthesis KW - Phorbol esters KW - Pokeweed mitogen KW - Natural killer cells KW - CD8 antigen KW - phytohemagglutinins KW - Workers KW - Peripheral blood mononuclear cells KW - CD4 antigen KW - Accidents KW - Immunity (cell-mediated) KW - Radiation KW - Lymphocytes T KW - Mitogens KW - Monocytes KW - Cell proliferation KW - X 24390:Radioactive Materials KW - F 06965:Immune Cells UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19620103?accountid=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=Radiation+Research&rft.atitle=Late+Effects+of+the+Chernobyl+Radiation+Accident+on+T+Cell-Mediated+Immunity+in+Cleanup+Workers&rft.au=Kuzmenok%2C+Oleg%3BPotapnev%2C+Michail%3BPotapova%2C+Svetlana%3BSmolnikova%2C+Victoria%3BRzheutsky%2C+Valeriy%3BYarilin%2C+Alexandr+A%3BSavino%2C+Wilson%3BBelyakov%2C+Igor+M&rft.aulast=Kuzmenok&rft.aufirst=Oleg&rft.date=2003-01-01&rft.volume=159&rft.issue=1&rft.spage=109&rft.isbn=&rft.btitle=&rft.title=Radiation+Research&rft.issn=00337587&rft_id=info:doi/10.1667%2F0033-7587%282003%291592.0.CO%3B2 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-12-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - DNA biosynthesis; Phorbol esters; Pokeweed mitogen; Natural killer cells; CD8 antigen; phytohemagglutinins; Workers; Accidents; CD4 antigen; Peripheral blood mononuclear cells; Radiation; Immunity (cell-mediated); Lymphocytes T; Mitogens; Monocytes; Cell proliferation DO - http://dx.doi.org/10.1667/0033-7587(2003)159[0109:LEOTCR]2.0.CO;2 ER - TY - JOUR T1 - Zooprophylaxis or zoopotentiation: the outcome of introducing animals on vector transmission is highly dependent on the mosquito mortality while searching AN - 19504582; 7198337 AB - Background: Zooprophylaxis, the diversion of disease carrying insects from humans to animals, may reduce transmission of diseases such as malaria. However, as the number of animals increases, improved availability of blood meals may increase mosquito survival, thereby countering the impact of diverting feeds. Methods Computer simulation was used to examine the effects of animals on the transmission of human diseases by mosquitoes. Three scenarios were modelled: (1) endemic transmission, where the animals cannot be infected, eg. malaria; (2) epidemic transmission, where the animals cannot be infected but humans remain susceptible, e.g. malaria; (3) epidemic disease, where both humans and animals can be infected, but develop sterile immunity, eg. Japanese encephalitis B. For each, the passive impact of animals as well as the use of animals as bait to attract mosquitoes to insecticide was examined. The computer programmes are available from the author. A teaching model accompanies this article. Results For endemic and epidemic malaria with significant searching-associated vector mortality, changing animal numbers and accessibility had little impact. Changing the accessibility of the humans had a much greater effect. For diseases with an animal amplification cycle, the most critical factor was the proximity of the animals to the mosquito breeding sites. Conclusion Estimates of searching- associated vector mortality are essential before the effects of changing animal husbandry practices can be predicted. With realistic values of searching- associated vector mortality rates, zooprophylaxis may be ineffective. However, use of animals as bait to attract mosquitoes to insecticide is predicted to be a promising strategy. JF - Malaria Journal AU - Saul, Allan AD - Malaria Vaccine Development Unit, NIAID, NIH, Rockville MD 20852, USA Y1 - 2003///0, PY - 2003 DA - 0, 2003 PB - BioMed Central Ltd., Middlesex House 34-42 Cleveland Street London W1T 4LB UK, [mailto:info@biomedcentral.com] VL - 2 SN - 1475-2875, 1475-2875 KW - Virology & AIDS Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology; Entomology Abstracts; ASFA 3: Aquatic Pollution & Environmental Quality; ASFA 1: Biological Sciences & Living Resources KW - Article No. 32 KW - Human diseases KW - Survival KW - Malaria KW - Blood meals KW - Models KW - Public health KW - Disease transmission KW - Endemic species KW - Insecticides KW - Aquatic insects KW - Mortality KW - Mathematical models KW - Epidemics KW - Computers KW - Vectors KW - Culicidae KW - Pest control KW - Immunity KW - Encephalitis KW - Breeding sites KW - Husbandry KW - K 03400:Human Diseases KW - Z 05350:Medical, Veterinary, and Agricultural Entomology KW - Q1 08485:Species interactions: pests and control KW - Q5 08524:Public health, medicines, dangerous organisms KW - V 22400:Human Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19504582?accountid=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=Malaria+Journal&rft.atitle=Zooprophylaxis+or+zoopotentiation%3A+the+outcome+of+introducing+animals+on+vector+transmission+is+highly+dependent+on+the+mosquito+mortality+while+searching&rft.au=Saul%2C+Allan&rft.aulast=Saul&rft.aufirst=Allan&rft.date=2003-01-01&rft.volume=2&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Malaria+Journal&rft.issn=14752875&rft_id=info:doi/10.1186%2F1475-2875-2-32 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-01-01 N1 - Last updated - 2016-05-27 N1 - SubjectsTermNotLitGenreText - Endemic species; Human diseases; Insecticides; Epidemics; Malaria; Pest control; Aquatic insects; Disease transmission; Public health; Mortality; Mathematical models; Computers; Vectors; Survival; Blood meals; Immunity; Encephalitis; Models; Breeding sites; Husbandry; Culicidae DO - http://dx.doi.org/10.1186/1475-2875-2-32 ER - TY - JOUR T1 - Increase in Cardiovascular Pathology in Female Sprague-Dawley Rats Following Chronic Treatment with 2,3,7,8-Tetrachlorodibenzo-p-Dioxin and 3,3',4,4',5-Pentachlorobiphenyl AN - 19258446; 5824952 AB - The effects of chronic exposure to dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD]) and a dioxin-like compound (3,3',4,4',5-pentachlorobiphenyl [PCB126]) on the cardiovascular system were evaluated in female Harlan Sprague-Dawley rats as part of an ongoing National Toxicology Program investigation. The animals were gavage treated 5 d per week with up to 1000 ng of PCB126 per kilogram of body weight per day or up to 100 ng of TCDD per kilogram of body weight per day for up to 2 yr. The control animals received only a corn oil/acetone vehicle (99:1 mixture). The corresponding stop-study groups received the highest doses for 31 wk and then received only the vehicle for the remainder of the study. After a full necropsy of all animals, a complete set of tissues was examined microscopically. Administration of each compound was associated with treatment-related increases in the incidences of degenerative cardiovascular lesions. Cardiomyopathy and chronic active arteritis increased in a dose-related manner in all groups treated with PCB126 or with TCDD. Increased incidences were also observed in the stop-study groups, indicating that a shorter term exposure may produce some effects. The average severity of cardiomyopathy was minimal or slightly greater in all dose groups, including the controls. Chronic active arteritis occurred primarily in the mesentery and pancreas, although the rectum, liver, heart, ovary, uterus, and glandular stomach in the PCB126 study and the liver and ovary in the TCDD study were affected in a few of the dosed animals. The authors' investigations indicate that the rat cardiovascular system is a target for dioxin toxicity, which increases the incidence of spontaneous cardiomyopathy and arteritis. JF - Cardiovascular Toxicology AU - Jokinen, M P AU - Walker, N J AU - Brix, A E AU - Sells, D M AU - Haseman, J K AU - Nyska, A AD - Laboratory of Experimental Pathology, MD B3-06, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health, P.O. Box 12233, Research Triangle Park, NC 27709, USA, nyska@niehs.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 299 EP - 310 VL - 3 IS - 4 SN - 1530-7905, 1530-7905 KW - rats KW - females KW - pentachlorobiphenyl KW - Toxicology Abstracts KW - Heart KW - Cardiovascular system KW - TCDD KW - X 24152:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19258446?accountid=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=Cardiovascular+Toxicology&rft.atitle=Increase+in+Cardiovascular+Pathology+in+Female+Sprague-Dawley+Rats+Following+Chronic+Treatment+with+2%2C3%2C7%2C8-Tetrachlorodibenzo-p-Dioxin+and+3%2C3%27%2C4%2C4%27%2C5-Pentachlorobiphenyl&rft.au=Jokinen%2C+M+P%3BWalker%2C+N+J%3BBrix%2C+A+E%3BSells%2C+D+M%3BHaseman%2C+J+K%3BNyska%2C+A&rft.aulast=Jokinen&rft.aufirst=M&rft.date=2003-01-01&rft.volume=3&rft.issue=4&rft.spage=299&rft.isbn=&rft.btitle=&rft.title=Cardiovascular+Toxicology&rft.issn=15307905&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 - TCDD; Cardiovascular system; Heart ER - TY - JOUR T1 - Contribution of mitochondria to cardiac muscle water/macromolecule proton magnetization transfer AN - 19222028; 5764650 AB - The contribution of mitochondria to water-macromolecule proton magnetization transfer (MT) was evaluated in porcine heart tissue. An examination of isolated mitochondria in suspension, at the same concentration as found in heart tissue, revealed MT effects very similar in magnitude and bandwidth to those in intact heart tissue. Disruption of the gross structure of the mitochondria by freeze- thawing or with detergent resulted in only ~25% decreases in MT, which suggests that the structure of the mitochondria is not critical for these effects. The current data indicate that mitochondria macromolecules contribute significantly to MT in the intact heart. JF - Magnetic Resonance in Medicine AU - Ward, K AU - Schussheim, A E AU - Balaban, R S AD - Laboratory of Cardiac Energetics, National Heart Lung and Blood Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, rsb@nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 1312 EP - 1316 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 50 IS - 6 SN - 0740-3194, 0740-3194 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Heart KW - Magnetic fields KW - Magnetic resonance imaging KW - Cardiac muscle KW - Mitochondria KW - N.M.R. KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19222028?accountid=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=Magnetic+Resonance+in+Medicine&rft.atitle=Contribution+of+mitochondria+to+cardiac+muscle+water%2Fmacromolecule+proton+magnetization+transfer&rft.au=Ward%2C+K%3BSchussheim%2C+A+E%3BBalaban%2C+R+S&rft.aulast=Ward&rft.aufirst=K&rft.date=2003-01-01&rft.volume=50&rft.issue=6&rft.spage=1312&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.10625 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - N.M.R.; Magnetic resonance imaging; Heart; Mitochondria; Cardiac muscle; Magnetic fields DO - http://dx.doi.org/10.1002/mrm.10625 ER - TY - JOUR T1 - Combination of transfection agents and magnetic resonance contrast agents for cellular imaging: Relationship between relaxivities, electrostatic forces, and chemical composition AN - 19221516; 5764572 AB - The purpose of this study was to investigate the changes in electrostatic and magnetic resonance (MR) properties observed when MR contrast agents (CAs) (Feridex, MION-46L, or G5-dendrimer-DOTA-Gd) are combined with transfection agents (TAs) under various conditions for use as a CA-TA complex basis for cellular labeling and MRI. CAs were incubated with various classes of TAs for 0- 48 hr in solutions of varying concentrations and pH values. NMR relaxation rates (1/T sub(1), 1/T sub(2)), MRI and zeta potential (ZP) of CA-TA solutions were measured. TAs decreased the 1/T sub(1) and 1/T sub(2) of G5-DOTA-Gd, Feridex, and MION-46L by 0-95%. Altering the pH of G5-DOTA-Gd-TA decreased the T sub(1)- weighted signal intensity (SI) on MRI from 0 to 78%. Measured ZP values for G5- DOTA-Gd, Feridex, and MION-46L were-51,-41, and-2.0 mV, respectively. The TA LV had a negative ZP, while the other TAs had ZPs ranging from +20 to +65 mV. The alteration of the ZP and NMR relaxivities of the MR CAs, Feridex, MION-46L, and G5-DOTA-Gd by TAs has been demonstrated. These results enhance our understanding of the relationship between electrostatic and MR properties. JF - Magnetic Resonance in Medicine AU - Kalish, H AU - Arbab, A S AU - Miller, B R AU - Lewis, B K AU - Zywicke, HA AU - Bulte, JWM AU - Bryant, LH Jr AU - Frank, JA AD - Laboratory of Diagnostic Radiology Research (CC), National Institutes of Health, Bethesda, Maryland, hkalish@mail.cc.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 275 EP - 282 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 50 IS - 2 SN - 0740-3194, 0740-3194 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Chemical composition KW - Transfection KW - Magnetic resonance imaging KW - Electrostatic properties KW - N.M.R. KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19221516?accountid=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=Magnetic+Resonance+in+Medicine&rft.atitle=Combination+of+transfection+agents+and+magnetic+resonance+contrast+agents+for+cellular+imaging%3A+Relationship+between+relaxivities%2C+electrostatic+forces%2C+and+chemical+composition&rft.au=Kalish%2C+H%3BArbab%2C+A+S%3BMiller%2C+B+R%3BLewis%2C+B+K%3BZywicke%2C+HA%3BBulte%2C+JWM%3BBryant%2C+LH+Jr%3BFrank%2C+JA&rft.aulast=Kalish&rft.aufirst=H&rft.date=2003-01-01&rft.volume=50&rft.issue=2&rft.spage=275&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.10556 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Magnetic resonance imaging; N.M.R.; Electrostatic properties; Transfection; Chemical composition DO - http://dx.doi.org/10.1002/mrm.10556 ER - TY - JOUR T1 - DNA mismatch repair: Molecular mechanisms and biological function AN - 19210352; 5795891 AB - DNA mismatch repair (MMR) guards the integrity of the genome in virtually all cells. It contributes about 1000-fold to the overall fidelity of replication and targets mispaired bases that arise through replication errors, during homologous recombination, and as a result of DNA damage. Cells deficient in MMR have a mutator phenotype in which the rate of spontaneous mutation is greatly elevated, and they frequently exhibit microsatellite instability at mono- and dinucleotide repeats. The importance of MMR in mutation avoidance is highlighted by the finding that defects in MMR predispose individuals to hereditary nonpolyposis colorectal cancer. In addition to its role in postreplication repair, the MMR machinery serves to police homologous recombination events and acts as a barrier to genetic exchange between species. JF - Annual Review of Microbiology AU - Schofield, MJ AU - Hsieh, P AD - Genetics and Biochemistry Branch, National Institute of Diabetes, and Digestive and Kidney Diseases, Bethesda, MD 20892, USA, schofiel@helix.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 579 EP - 608 VL - 57 SN - 0066-4227, 0066-4227 KW - Microbiology Abstracts B: Bacteriology KW - Bacteria KW - Recombination KW - Exchange KW - DNA repair KW - Mutation KW - J 02725:DNA UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19210352?accountid=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=Annual+Review+of+Microbiology&rft.atitle=DNA+mismatch+repair%3A+Molecular+mechanisms+and+biological+function&rft.au=Schofield%2C+MJ%3BHsieh%2C+P&rft.aulast=Schofield&rft.aufirst=MJ&rft.date=2003-01-01&rft.volume=57&rft.issue=&rft.spage=579&rft.isbn=&rft.btitle=&rft.title=Annual+Review+of+Microbiology&rft.issn=00664227&rft_id=info:doi/10.1146%2Fannurev.micro.57.030502.090847 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - DNA repair; Recombination; Mutation; Exchange; Bacteria DO - http://dx.doi.org/10.1146/annurev.micro.57.030502.090847 ER - TY - JOUR T1 - Real-time volumetric flow measurements with complex-difference MRI AN - 19204959; 5764642 AB - Blood flow in large vessels can be noninvasively evaluated with phase- contrast (PC) MRI by encoding the spin velocity to the image phase. Conventional phase-difference processing of the flow-encoded image data yields velocity images. Complex-difference processing is an alternative to phase-difference methods, and has the advantage of eliminating signal from stationary spins. In this study, two acquisitions with differential flow encoding are subtracted to yield a single projection that contains signal from only those spins moving in the direction of the flow-encoding gradients. The increase in acquisition efficiency allows real-time flow imaging with a temporal window as short as two acquisition lengths (60 ms). Validation of the complex-difference method by comparison with conventional gated-segmented PC-MRI in a flow phantom yielded a correlation of r > 0.99. Peak arterial flow rates in the popliteal artery and desending aorta measured in vivo with the complex-difference method were 0.92 +/- 0.06 of the values measured with conventional PC imaging. Real-time in vivo volumetric flow imaging of transient flow events is also presented. JF - Magnetic Resonance in Medicine AU - Thompson, R B AU - McVeigh, E R AD - Laboratory of Cardiac Energetics, National Institutes of Health, Bethesda, Maryland, thompsor@nhlbi.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 1248 EP - 1255 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 50 IS - 6 SN - 0740-3194, 0740-3194 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Blood flow KW - Magnetic resonance imaging KW - Image processing KW - N.M.R. KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19204959?accountid=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=Magnetic+Resonance+in+Medicine&rft.atitle=Real-time+volumetric+flow+measurements+with+complex-difference+MRI&rft.au=Thompson%2C+R+B%3BMcVeigh%2C+E+R&rft.aulast=Thompson&rft.aufirst=R&rft.date=2003-01-01&rft.volume=50&rft.issue=6&rft.spage=1248&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.10637 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - N.M.R.; Magnetic resonance imaging; Blood flow; Image processing DO - http://dx.doi.org/10.1002/mrm.10637 ER - TY - JOUR T1 - Automatic in-plane rotation for doubly-oblique cardiac imaging AN - 19200638; 5748220 AB - To develop and test a method for automatically calculating the in-plane rotation for doubly-oblique slice geometry in order to minimize wrap artifacts for a given FOV. The equations for in-plane rotation were formulated for doubly- oblique imaging of a cylindrical body with elliptical cross-section. Based on this formulation, automatic in-plane rotation was implemented and tested on a commercial scanner using nominal values for ellipticity of the body. Short axis, doubly oblique, cardiac imaging were acquired with and without in-plane rotation. The desired in-plane rotation proved to be relatively insensitive to the ellipticity of the body, permitting an automatic solution based on a nominal value. In-plane rotation is desirable for doubly oblique imaging (e.g. cardiac applications), particularly for reduced-FOV accelerated imaging such as SENSE. The proposed method, which provides an approximate solution for automatic, in- plane rotation for doubly-oblique imaging, was demonstrated. JF - Journal of Magnetic Resonance Imaging AU - Kellman, P AU - Derbyshire, JA AU - McVeigh, E R AD - Laboratory of Cardiac Energetics, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, kellman@nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 612 EP - 615 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 18 IS - 5 SN - 1053-1807, 1053-1807 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Heart KW - Magnetic resonance imaging KW - Image processing KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19200638?accountid=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+Magnetic+Resonance+Imaging&rft.atitle=Automatic+in-plane+rotation+for+doubly-oblique+cardiac+imaging&rft.au=Kellman%2C+P%3BDerbyshire%2C+JA%3BMcVeigh%2C+E+R&rft.aulast=Kellman&rft.aufirst=P&rft.date=2003-01-01&rft.volume=18&rft.issue=5&rft.spage=612&rft.isbn=&rft.btitle=&rft.title=Journal+of+Magnetic+Resonance+Imaging&rft.issn=10531807&rft_id=info:doi/10.1002%2Fjmri.10398 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Magnetic resonance imaging; Image processing; Heart DO - http://dx.doi.org/10.1002/jmri.10398 ER - TY - JOUR T1 - caCORE: A common infrastructure for cancer informatics AN - 19200377; 5795253 AB - Motivation:Sites with substantive bioinformatics operations are challenged to build data processing and delivery infrastructure that provides reliable access and enables data integration. Locally generated data must be processed and stored such that relationships to external data sources can be presented. Consistency and comparability across data sets requires annotation with controlled vocabularies and, further, metadata standards for data representation. Programmatic access to the processed data should be supported to ensure the maximum possible value is extracted. Confronted with these challenges at the National Cancer Institute Center for Bioinformatics, we decided to develop a robust infrastructure for data management and integration that supports advanced biomedical applications. JF - Bioinformatics AU - Covitz, P A AU - Hartel, F AU - Schaefer, C AU - De Coronado, S AU - Fragoso, G AU - Sahni, H AU - Gustafson, S AU - Buetow, KH AD - National Cancer Institute Center for Bioinformatics, National Institutes of Health, U.S. Department of Health and Human Services, 6116 Executive Boulevard, Suite 403, Rockville MD 20852, USA Y1 - 2003 PY - 2003 DA - 2003 SP - 2404 EP - 2412 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 19 IS - 18 SN - 1367-4803, 1367-4803 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Data processing KW - Bioinformatics KW - Data acquisition KW - Cancer KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19200377?accountid=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=Bioinformatics&rft.atitle=caCORE%3A+A+common+infrastructure+for+cancer+informatics&rft.au=Covitz%2C+P+A%3BHartel%2C+F%3BSchaefer%2C+C%3BDe+Coronado%2C+S%3BFragoso%2C+G%3BSahni%2C+H%3BGustafson%2C+S%3BBuetow%2C+KH&rft.aulast=Covitz&rft.aufirst=P&rft.date=2003-01-01&rft.volume=19&rft.issue=18&rft.spage=2404&rft.isbn=&rft.btitle=&rft.title=Bioinformatics&rft.issn=13674803&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 - Bioinformatics; Cancer; Data processing; Data acquisition ER - TY - JOUR T1 - A random variance model for detection of differential gene expression in small microarray experiments AN - 19192316; 5795273 AB - Microarray techniques provide a valuable way of characterizing the molecular nature of disease. Unfortunately expense and limited specimen availability often lead to studies with small sample sizes. This makes accurate estimation of variability difficult, since variance estimates made on a gene by gene basis will have few degrees of freedom, and the assumption that all genes share equal variance is unlikely to be true. JF - Bioinformatics AU - Wright, G W AU - Simon, R M AD - National Cancer Institute Biometric Research Branch, 6130 Executive Blvd., MSC 7434, Bethesda, MD 20892-7434, USA Y1 - 2003 PY - 2003 DA - 2003 SP - 2448 EP - 2455 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 19 IS - 18 SN - 1367-4803, 1367-4803 KW - DNA microarrays KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Gene expression KW - Genetic variance KW - Bioinformatics KW - Sampling KW - N 14510:Occurrence, isolation & assay KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19192316?accountid=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=Bioinformatics&rft.atitle=A+random+variance+model+for+detection+of+differential+gene+expression+in+small+microarray+experiments&rft.au=Wright%2C+G+W%3BSimon%2C+R+M&rft.aulast=Wright&rft.aufirst=G&rft.date=2003-01-01&rft.volume=19&rft.issue=18&rft.spage=2448&rft.isbn=&rft.btitle=&rft.title=Bioinformatics&rft.issn=13674803&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Gene expression; Sampling; Bioinformatics; Genetic variance ER - TY - JOUR T1 - Real-time accelerated interactive MRI with adaptive TSENSE and UNFOLD AN - 19189810; 5764577 AB - Reduced field-of-view (FOV) acceleration using time-adaptive sensitivity encoding (TSENSE) or unaliasing by Fourier encoding the overlaps using the temporal dimension (UNFOLD) can improve the depiction of motion in real-time MRI. However, increased computational resources are required to maintain a high frame rate and low latency in image reconstruction and display. A high- performance software system has been implemented to perform TSENSE and UNFOLD reconstructions for real-time MRI with interactive, on-line display. Images were displayed in the scanner room to investigate image-guided procedures. Examples are shown for normal volunteers and cardiac interventional experiments in animals using a steady-state free precession (SSFP) sequence. In order to maintain adequate image quality for interventional procedures, the imaging rate was limited to seven frames per second after an acceleration factor of 2 with a voxel size of 1.8 X 3.5 X 8 mm. Initial experiences suggest that TSENSE and UNFOLD can each improve the compromise between spatial and temporal resolution in real-time imaging, and can function well in interactive imaging. UNFOLD places no additional constraints on receiver coils, and is therefore more flexible than SENSE methods; however, the temporal image filtering can blur motion and reduce the effective acceleration. Methods are proposed to overcome the challenges presented by the use of TSENSE in interactive imaging. TSENSE may be temporarily disabled after changing the imaging plane to avoid transient artifacts as the sensitivity coefficients adapt. For imaging with a combination of surface and interventional coils, a hybrid reconstruction approach is proposed whereby UNFOLD is used for the interventional coils, and TSENSE with or without UNFOLD is used for the surface coils. JF - Magnetic Resonance in Medicine AU - Guttman, MA AU - Kellman, P AU - Dick, A J AU - Lederman, R J AU - McVeigh, E R AD - Laboratory of Cardiac Energetics, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, mguttman@nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 315 EP - 321 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 50 IS - 2 SN - 0740-3194, 0740-3194 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Computer programs KW - Magnetic resonance imaging KW - Image processing KW - N.M.R. KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19189810?accountid=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=Magnetic+Resonance+in+Medicine&rft.atitle=Real-time+accelerated+interactive+MRI+with+adaptive+TSENSE+and+UNFOLD&rft.au=Guttman%2C+MA%3BKellman%2C+P%3BDick%2C+A+J%3BLederman%2C+R+J%3BMcVeigh%2C+E+R&rft.aulast=Guttman&rft.aufirst=MA&rft.date=2003-01-01&rft.volume=50&rft.issue=2&rft.spage=315&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.10504 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Magnetic resonance imaging; N.M.R.; Image processing; Computer programs DO - http://dx.doi.org/10.1002/mrm.10504 ER - TY - JOUR T1 - In vivo study of microcirculation in canine myocardium using the IVIM method AN - 19185118; 5764548 AB - The intravoxel incoherent motion (IVIM) method was implemented in closed- chest dogs to obtain measurements on microcirculation in the left ventricular wall in vivo. Specifically, it enabled us to measure the mean microflow velocity (400 +/- 40 mu m/s) and the vascular volume fraction (VVF) (11.1% +/- 2.2%), and observe the directional preference of capillary orientation. The apparent diffusion coefficients (ADCs) of water along and perpendicular to myofibers were also measured. With vasodilatation by adenosine infusion, a 25% increase in the VVF and a 7% increase in the mean microflow velocity were observed, while no change in the ADC was detected. A 28.5% decrease of the ADC was observed postmortem. JF - Magnetic Resonance in Medicine AU - Callot, V AU - Bennett, E AU - Decking, UKM AU - Balaban, R S AU - Wen, H AD - Laboratory of Cardiac Energetics, NHLBI, NIH, Bethesda, Maryland, wenh@nhlbi.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 531 EP - 540 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 50 IS - 3 SN - 0740-3194, 0740-3194 KW - dogs KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Autopsy KW - Ventricle KW - Magnetic resonance imaging KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19185118?accountid=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=Magnetic+Resonance+in+Medicine&rft.atitle=In+vivo+study+of+microcirculation+in+canine+myocardium+using+the+IVIM+method&rft.au=Callot%2C+V%3BBennett%2C+E%3BDecking%2C+UKM%3BBalaban%2C+R+S%3BWen%2C+H&rft.aulast=Callot&rft.aufirst=V&rft.date=2003-01-01&rft.volume=50&rft.issue=3&rft.spage=531&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.10568 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Magnetic resonance imaging; Autopsy; Ventricle DO - http://dx.doi.org/10.1002/mrm.10568 ER - TY - JOUR T1 - Application of support vector machines for T-cell epitopes prediction AN - 19163465; 5757932 AB - The T-cell receptor, a major histocompatibility complex (MHC) molecule, and a bound antigenic peptide, play major roles in the process of antigen-specific T-cell activation. T-cell recognition was long considered exquisitely specific. Recent data also indicate that it is highly flexible, and one receptor may recognize thousands of different peptides. Deciphering the patterns of peptides that elicit a MHC restricted T-cell response is critical for vaccine development. JF - Bioinformatics AU - Zhao, Y AU - Pinilla, C AU - Valmori, D AU - Martin, R AU - Simon, R AD - Biometric Research Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 2003 PY - 2003 DA - 2003 SP - 1978 EP - 1984 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 19 IS - 15 SN - 1367-4803, 1367-4803 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - ^AT-cell receptor KW - Lymphocytes T KW - Major histocompatibility complex KW - Vaccines KW - Bioinformatics KW - W4 140:Bioinformatics & Computers in Health & Medicine KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19163465?accountid=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=Bioinformatics&rft.atitle=Application+of+support+vector+machines+for+T-cell+epitopes+prediction&rft.au=Zhao%2C+Y%3BPinilla%2C+C%3BValmori%2C+D%3BMartin%2C+R%3BSimon%2C+R&rft.aulast=Zhao&rft.aufirst=Y&rft.date=2003-01-01&rft.volume=19&rft.issue=15&rft.spage=1978&rft.isbn=&rft.btitle=&rft.title=Bioinformatics&rft.issn=13674803&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 - Bioinformatics; Major histocompatibility complex; Lymphocytes T; ^AT-cell receptor; Vaccines ER - TY - JOUR T1 - Biological response of chondrocytes cultured in three-dimensional nanofibrous poly( epsilon -caprolactone) scaffolds AN - 19161837; 5752511 AB - Nanofibrous materials, by virtue of their morphological similarities to natural extracellular matrix, have been considered as candidate scaffolds for cell delivery in tissue-engineering applications. In this study, we have evaluated a novel, three-dimensional, nanofibrous poly( epsilon -caprolactone) (PCL) scaffold composed of electrospun nanofibers for its ability to maintain chondrocytes in a mature functional state. Fetal bovine chondrocytes (FBCs), maintained in vitro between passages 2 to 6, were seeded onto three-dimensional biodegradable PCL nanofibrous scaffolds or as monolayers on standard tissue culture polystyrene (TCPS) as a control substrate. Gene expression analysis by reverse transcription-polymerase chain reaction showed that chondrocytes seeded on the nanofibrous scaffold and maintained in serum-free medium supplemented with ITS+, ascorbate, and dexamethasone continuously maintained their chondrocytic phenotype by expressing cartilage-specific extracellular matrix genes, including collagen types II and IX, aggrecan, and cartilage oligomeric matrix protein. Specifically, expression of the collagen type IIB splice variant transcript, which is indicative of the mature chondrocyte phenotype, was up- regulated. FBCs exhibited either a spindle or round shape on the nanofibrous scaffolds, in contrast to a flat, well-spread morphology seen in monolayer cultures on TCPS. Organized actin stress fibers were only observed in the cytoplasm of cells cultured on TCPS. Histologically, nanofibrous cultures maintained in the supplemented serum-free medium produced more sulfated proteoglycan-rich, cartilaginous matrix than monolayer cultures. In addition to promoting phenotypic differentiation, the nanofibrous scaffold also supported cellular proliferation as evidenced by a 21-fold increase in cell growth over 21 days when the cultures were maintained in serum-containing medium. These results indicate that the biological activities of FBCs are crucially dependent on the architecture of the extracellular scaffolds as well as the composition of the culture medium, and that nanofibrous PCL acts as a biologically preferred scaffold/substrate for proliferation and maintenance of the chondrocytic phenotype. We propose that the PCL nanofibrous structure may be a suitable candidate scaffold for cartilage tissue engineering. JF - Journal of Biomedical Materials Research, Part A AU - Li, W-J AU - Danielson, K G AU - Alexander, P G AU - Tuan, R S AD - Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis, and Musculoskeletal and Skin Diseases, National Institutes of Health, Department of Health and Human Services, Building 50, Room 1503, MSC8022, Bethesda, Maryland 20892-8022, tuanr@mail.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 1105 EP - 1114 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 67A IS - 4 SN - 0021-9304, 0021-9304 KW - poly-^e-caprolactone KW - poly- epsilon -caprolactone KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Bioengineering Abstracts KW - Cartilage KW - Biomaterials KW - Chondrocytes KW - Cell culture KW - Tissue engineering KW - W 30965:Miscellaneous, Reviews KW - W3 33220:Cell culture KW - W4 110:Biomedical Materials & Tissue Engineering UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19161837?accountid=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+Biomedical+Materials+Research%2C+Part+A&rft.atitle=Biological+response+of+chondrocytes+cultured+in+three-dimensional+nanofibrous+poly%28+epsilon+-caprolactone%29+scaffolds&rft.au=Li%2C+W-J%3BDanielson%2C+K+G%3BAlexander%2C+P+G%3BTuan%2C+R+S&rft.aulast=Li&rft.aufirst=W-J&rft.date=2003-01-01&rft.volume=67A&rft.issue=4&rft.spage=1105&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biomedical+Materials+Research%2C+Part+A&rft.issn=00219304&rft_id=info:doi/10.1002%2Fjbm.a.10101 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Chondrocytes; Cell culture; Biomaterials; Cartilage; Tissue engineering DO - http://dx.doi.org/10.1002/jbm.a.10101 ER - TY - JOUR T1 - Pyruvate: An in vivo marker of cestodal infestation of the human brain on proton MR spectroscopy AN - 19161257; 5758494 AB - To study intracranial cestodal cysts using in vivo proton magnetic resonance spectroscopy ( super(1)H MRS) in an effort to identify metabolite(s) that may help in recognizing the parasitic etiology and, perhaps, viability of such tapeworm cysts. Cestodal infestations of the human central nervous system (CNS)- cysticercosis and hydatidosis-are not rare. Identification of a scolex is considered diagnostic of cysticercosis on imaging. In its absence, however, the features are non-specific. Three patients with intracranial hydatid cysts and 13 patients with intracranial cysticercal cysts (four intraventricular, seven parenchymal, and two subarachnoid racemose cysts) were studied on a 1.5-T MR system. In vivo super(1)H MRS was performed by multivoxel two-dimensional hybrid chemical shift imaging technique (TE = 135 msec). In vitro super(1)H NMR and mass spectroscopy (matrix assisted laser desorption/ionization [MALDI]) were performed on excised cysticercal and hydatid cyst fluid. MALDI spectra for pyruvate and succinate were also obtained. Alanine, pyruvate, and acetate were seen in all the three hydatid cysts. Lactate was seen in racemose cysticercal cysts. A large resonance at 2.4 ppm, confirmed as pyruvate at mass spectroscopy, was seen in 13 cestodal cysts. Pyruvate was not seen in one each of racemose, intraventricular, and parenchymal cysticercal cysts. Pyruvate is the predominant metabolite in cestodal cysts infesting the human CNS. It may be a marker of parasitic etiology and perhaps that of viability of such intracranial cysts. JF - Journal of Magnetic Resonance Imaging AU - Jayakumar, P N AU - Srikanth, S G AU - Chandrashekar, H S AU - Kovoor, JME AU - Shankar, S K AU - Anandh, B AD - Department of Neuroimaging and Interventional Radiology, National Institute of Mental Health and NeuroSciences, Bangalore, India, jayakumarpn@nimhans.kar.nic.in Y1 - 2003 PY - 2003 DA - 2003 SP - 675 EP - 680 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 18 IS - 6 SN - 1053-1807, 1053-1807 KW - man KW - cysticercosis KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Pyruvic acid KW - Central nervous system diseases KW - Magnetic resonance imaging KW - Brain KW - Image processing KW - Parasitic diseases KW - Cysts KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19161257?accountid=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+Magnetic+Resonance+Imaging&rft.atitle=Pyruvate%3A+An+in+vivo+marker+of+cestodal+infestation+of+the+human+brain+on+proton+MR+spectroscopy&rft.au=Jayakumar%2C+P+N%3BSrikanth%2C+S+G%3BChandrashekar%2C+H+S%3BKovoor%2C+JME%3BShankar%2C+S+K%3BAnandh%2C+B&rft.aulast=Jayakumar&rft.aufirst=P&rft.date=2003-01-01&rft.volume=18&rft.issue=6&rft.spage=675&rft.isbn=&rft.btitle=&rft.title=Journal+of+Magnetic+Resonance+Imaging&rft.issn=10531807&rft_id=info:doi/10.1002%2Fjmri.10409 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Magnetic resonance imaging; Cysts; Parasitic diseases; Brain; Central nervous system diseases; Pyruvic acid; Image processing DO - http://dx.doi.org/10.1002/jmri.10409 ER - TY - JOUR T1 - Simple stochastic birth and death models of genome evolution: was there enough time for us to evolve? AN - 19160763; 5757864 AB - The distributions of many genome-associated quantities, including the membership of paralogous gene families can be approximated with power laws. We are interested in developing mathematical models of genome evolution that adequately account for the shape of these distributions and describe the evolutionary dynamics of their formation. JF - Bioinformatics AU - Karev, G P AU - Wolf, YI AU - Koonin, E V AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA Y1 - 2003 PY - 2003 DA - 2003 SP - 1889 EP - 1900 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 19 IS - 15 SN - 1367-4803, 1367-4803 KW - mathematical models KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Birth KW - Genomes KW - Mortality KW - Evolution KW - N 14610:Occurrence, isolation & assay KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19160763?accountid=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=Bioinformatics&rft.atitle=Simple+stochastic+birth+and+death+models+of+genome+evolution%3A+was+there+enough+time+for+us+to+evolve%3F&rft.au=Karev%2C+G+P%3BWolf%2C+YI%3BKoonin%2C+E+V&rft.aulast=Karev&rft.aufirst=G&rft.date=2003-01-01&rft.volume=19&rft.issue=15&rft.spage=1889&rft.isbn=&rft.btitle=&rft.title=Bioinformatics&rft.issn=13674803&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 - Genomes; Evolution; Birth; Mortality ER - TY - JOUR T1 - Evaluation of gene expression measurements from commercial microarray platforms AN - 19152099; 5760041 AB - Multiple commercial microarrays for measuring genome-wide gene expression levels are currently available, including oligonucleotide and cDNA, single- and two-channel formats. This study reports on the results of gene expression measurements generated from identical RNA preparations that were obtained using three commercially available microarray platforms. RNA was collected from PANC-1 cells grown in serum-rich medium and at 24 h following the removal of serum. Three biological replicates were prepared for each condition, and three experimental replicates were produced for the first biological replicate. RNA was labeled and hybridized to microarrays from three major suppliers according to manufacturers' protocols, and gene expression measurements were obtained using each platform's standard software. For each platform, gene targets from a subset of 2009 common genes were compared. Correlations in gene expression levels and comparisons for significant gene expression changes in this subset were calculated, and showed considerable divergence across the different platforms, suggesting the need for establishing industrial manufacturing standards, and further independent and thorough validation of the technology. JF - Nucleic Acids Research AU - Tan, P K AU - Downey, T J AU - Spitznagel, EL Jr AU - Xu, P AU - Fu, D AU - Dimitrov, D S AU - Lempicki, R A AU - Raaka, B M AU - Cam, M C AD - Microarray Core Laboratory, National Institute of Diabetes and Digestive and Kidney Disorders, maggiec@intra.niddk.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 5676 EP - 5684 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 31 IS - 19 SN - 0305-1048, 0305-1048 KW - PANC-1 cells KW - DNA microarrays KW - Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Bioengineering Abstracts KW - Gene expression KW - Replication KW - Hybridization analysis KW - N 14510:Occurrence, isolation & assay KW - W4 130:General Biomedical Engineering: Tools & Techniques KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19152099?accountid=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=Evaluation+of+gene+expression+measurements+from+commercial+microarray+platforms&rft.au=Tan%2C+P+K%3BDowney%2C+T+J%3BSpitznagel%2C+EL+Jr%3BXu%2C+P%3BFu%2C+D%3BDimitrov%2C+D+S%3BLempicki%2C+R+A%3BRaaka%2C+B+M%3BCam%2C+M+C&rft.aulast=Tan&rft.aufirst=P&rft.date=2003-01-01&rft.volume=31&rft.issue=19&rft.spage=5676&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 - Replication; Hybridization analysis; Gene expression ER - TY - JOUR T1 - Binding of copper(II) ions to the polyproline II helices of PEVK modules of the giant elastic protein titin as revealed by ESI-MS, CD, and NMR AN - 19151780; 5748060 AB - Titin, a family of giant elastic proteins, constitutes an elastic sarcomere matrix in striated muscle. In the I-band region of the sarcomere, the titin PEVK segment acts as a molecular spring to generate elasticity as well as sites of adhesion with parallel thin filaments. Previously, we reported that PEVK consists of tandem repeats of 28 residue modules and that the "polyproline II- coil" motif is the fundamental conformational motif of the PEVK module. In order to characterize the factors that may affect and alter the PPII-coil conformational motifs, we have initiated a systematic study of the interaction with divalent cations (Cu super(2+), Ca super(2+), Zn super(2+), and Ni super(2+)) and a conformational profile of PEVK peptides (a representative 28-mer peptide PR: PEPPKEVVPEKKAPVAPPKKPEVPPVKV and its subfragments PR1: kvPEPPKEVVPE, PR2: VPEKKAPVAPPK, PR3: KPEVPPVKV). UV-Vis absorption difference spectra and CD spectra showed that Cu super(2+) bound to PR1 with high affinity (20 mu M), while its binding to PR2 and PR3 as well as the binding of other cations to all four peptides were of lower affinity (>100 mu M). Conformational studies by CD revealed that Cu super(2+) binding to PR1 resulted in a polyproline II to turn transition up to a 1:2 PR1/Cu super(2+) ratio and a coil to turn transition at higher Cu super(2+) concentration. ESI-MS provided the stoichiometry of PEVK peptide-Cu super(2+) complexes at both low and high ion strength, confirming the specific high affinity binding of Cu super(2+) to PR1 and PR. Furthermore, NMR and ESI-MS/MS fragmentation analysis elucidated the binding sites of the PEVK peptide-Cu super(2+) complexes at super(-2)KVPE super(2), super(8)VPE super(10), super(13)APV super(15), and super(22)EVP super(24). A potential application of Cu super(2+) binding in peptide sequencing by mass spectrometry was also revealed. We conclude that Cu super(2+) binds and bends PEVK peptides to a beta-turn-like structure at specific sites. The specific targeting of Cu super(2+) towards PPII is likely to be of significant value in elucidating the roles of PPII in titin elasticity as well as in interactions of proline-rich proteins. JF - Biopolymers AU - Ma, K AU - Wang, K AD - Muscle Proteomics and Nanotechnology Section, Laboratory of Muscle Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, wangk@exchange.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 297 EP - 309 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 70 IS - 3 SN - 0006-3525, 0006-3525 KW - copper KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - C.D. KW - Biopolymers KW - N.M.R. KW - Filaments KW - Elasticity KW - Mass spectroscopy KW - Cell adhesion KW - W4 330:Biopolymers & Food Biotechnology KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19151780?accountid=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=Biopolymers&rft.atitle=Binding+of+copper%28II%29+ions+to+the+polyproline+II+helices+of+PEVK+modules+of+the+giant+elastic+protein+titin+as+revealed+by+ESI-MS%2C+CD%2C+and+NMR&rft.au=Ma%2C+K%3BWang%2C+K&rft.aulast=Ma&rft.aufirst=K&rft.date=2003-01-01&rft.volume=70&rft.issue=3&rft.spage=297&rft.isbn=&rft.btitle=&rft.title=Biopolymers&rft.issn=00063525&rft_id=info:doi/10.1002%2Fbip.10477 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - N.M.R.; C.D.; Filaments; Cell adhesion; Mass spectroscopy; Biopolymers; Elasticity DO - http://dx.doi.org/10.1002/bip.10477 ER - TY - JOUR T1 - Application of continuous-wave EPR spectral-spatial image reconstruction techniques for in vivo oxymetry: Comparison of projection reconstruction and constant-time modalities AN - 18940582; 5727525 AB - In this study we report the application of continuous-wave (CW) electron paramagnetic resonance (EPR) constant-time spectral spatial imaging (CTSSI) for in vivo oxymetry. 2D and 3D SSI studies of a phantom and live mice were carried out using projection reconstruction (PR) and constant-time (CT) modalities using a CW-EPR spectrometer/imager operating at 300 MHz frequency. Distortion of line shape, which is inherent in the PR method, was minimized by the CTSSI modality. It was also found that CTSSI offers improved noise reduction, restores a smoother line shape, and gives high convergence of estimated values. Spatial resolution was also improved by CTSSI, although fundamental spectral line-width broadening was observed. Although additional corrections are required for accurate estimations of spectral line width, CTSSI was able to demonstrate distinct differences in oxygen tension between a tumor and the normal legs of a C3H mouse. The PR method, on the other hand, was unable to make such a distinction unequivocally with the triarylmethyl spin probes. CTSSI promises to be a more suitable method for quantitative in vivo oxymetric studies using radiofrequency EPR imaging (EPRI). JF - Magnetic Resonance in Medicine AU - Matsumoto, K-I AU - Chandrika, B AU - Lohman, JAB AU - Mitchell, J B AU - Krishna, M C AU - Subramanian, S AD - Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, murali@helix.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 865 EP - 874 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 50 IS - 4 SN - 0740-3194, 0740-3194 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - E.S.R. KW - Magnetic resonance imaging KW - Image processing KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18940582?accountid=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=Magnetic+Resonance+in+Medicine&rft.atitle=Application+of+continuous-wave+EPR+spectral-spatial+image+reconstruction+techniques+for+in+vivo+oxymetry%3A+Comparison+of+projection+reconstruction+and+constant-time+modalities&rft.au=Matsumoto%2C+K-I%3BChandrika%2C+B%3BLohman%2C+JAB%3BMitchell%2C+J+B%3BKrishna%2C+M+C%3BSubramanian%2C+S&rft.aulast=Matsumoto&rft.aufirst=K-I&rft.date=2003-01-01&rft.volume=50&rft.issue=4&rft.spage=865&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.10594 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Magnetic resonance imaging; E.S.R.; Image processing DO - http://dx.doi.org/10.1002/mrm.10594 ER - TY - JOUR T1 - Comparison of dendrimer-based macromolecular contrast agents for dynamic micro-magnetic resonance lymphangiography AN - 18938136; 5727513 AB - Few methods are currently available to visualize the entire lymphatic system. A method known as micro-magnetic resonance lymphangiography (MRL), which employs a dendrimer-based MRI contrast agent (PAMAM-G8) and a clinical-grade 1.5T MRI instrument, was recently developed for use in mice. In the present study, three dendrimer-based MRI contrast agents (PAMAM-G8, DAB-G5, and PAMAM- G4) with different pharmacokinetic characteristics were compared to determine the best reagent to visualize the lymphatic system under physiological or pathological conditions. In addition, two established MRI contrast agents (Gadomer-17 and Gd-[DTPA]-dimeglumine (Magnevist)) were used as control agents. In experiments with mice, most of the deep lymphatic system was visualized by micro-MRL with all agents except Gd-[DTPA]-dimeglumine. PAMAM-G8 was best for visualizing lymphatic vessels, whereas DAB-G5 was better for visualizing lymph nodes. PAMAM-G4 was intermediate in character between PAMAM-G8 and DAB-G5, except in exhibiting a low background signal (especially in the liver). The lymphatic system was not clearly visualized with Gd-[DTPA]-dimeglumine; however, the lymph nodes were visualized with Gadomer-17, although not as well as with dendrimer-based agents. In conclusion, DAB-G5 and PAMAM-G4 can be used to identify lymph nodes and lymphatic vessels, respectively. Their rapid excretion makes these compounds potentially attractive for human use. JF - Magnetic Resonance in Medicine AU - Kobayashi, H AU - Kawamoto, S AU - Choyke, P L AU - Sato, N AU - Knopp, M V AU - Star, R A AU - Waldmann, T A AU - Tagaya, Y AU - Brechbiel, M W AD - Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, Kobayash@mail.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 758 EP - 766 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 50 IS - 4 SN - 0740-3194, 0740-3194 KW - man KW - contrast agents KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Magnetic resonance imaging KW - Lymphatic system KW - Lymph nodes KW - Lymphangiography KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18938136?accountid=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=Magnetic+Resonance+in+Medicine&rft.atitle=Comparison+of+dendrimer-based+macromolecular+contrast+agents+for+dynamic+micro-magnetic+resonance+lymphangiography&rft.au=Kobayashi%2C+H%3BKawamoto%2C+S%3BChoyke%2C+P+L%3BSato%2C+N%3BKnopp%2C+M+V%3BStar%2C+R+A%3BWaldmann%2C+T+A%3BTagaya%2C+Y%3BBrechbiel%2C+M+W&rft.aulast=Kobayashi&rft.aufirst=H&rft.date=2003-01-01&rft.volume=50&rft.issue=4&rft.spage=758&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.10583 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Magnetic resonance imaging; Lymphangiography; Lymph nodes; Lymphatic system DO - http://dx.doi.org/10.1002/mrm.10583 ER - TY - JOUR T1 - Nonmyeloablative stem cell transplantation as immunotherapy for kidney cancer and other metastatic solid tumors AN - 18933303; 5691387 AB - Over the past few decades, great strides have been made to advance the field of allogeneic hematopoietic stem cell transplantation. The donor immune mediated graft-vs-tumor effect that follows the procedure is now widely accepted as the most effective form cancer immunotherapy available for patients with a variety of advanced hematological malignancies. Recognition that a transplanted immune system could cure patients with treatment refractory leukemia led to the development of `low-intensity' conditioning regimens, which have improved the safety of the procedure and broadened the application of allogeneic immunotherapy to a growing list of neoplastic diseases. Here we discuss the investigational use of allogeneic transplantation as immunotherapy for patients with metastatic, treatment-refractory solid tumors. JF - Cytotechnology AU - Carvallo, C AU - Childs, R AD - Urologic Oncology Branch, National Cancer Institute, Hematology Branch, National Heart Lung and Blood Institute, National Institutes for Health, Bethesda, MD, U.S.A., childsr@nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 197 EP - 206 PB - Kluwer Academic Publishers VL - 41 IS - 2-3 SN - 0920-9069, 0920-9069 KW - man KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Bioengineering Abstracts KW - Stem cells KW - Transplantation KW - Immunotherapy KW - Kidney KW - Tumors KW - Cancer KW - W4 130:General Biomedical Engineering: Tools & Techniques KW - W3 33170:Cellular based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18933303?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytotechnology&rft.atitle=Nonmyeloablative+stem+cell+transplantation+as+immunotherapy+for+kidney+cancer+and+other+metastatic+solid+tumors&rft.au=Carvallo%2C+C%3BChilds%2C+R&rft.aulast=Carvallo&rft.aufirst=C&rft.date=2003-01-01&rft.volume=41&rft.issue=2-3&rft.spage=197&rft.isbn=&rft.btitle=&rft.title=Cytotechnology&rft.issn=09209069&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Stem cells; Transplantation; Immunotherapy; Tumors; Cancer; Kidney ER - TY - JOUR T1 - Circular spectrum mapping for intravoxel fiber structures based on high angular resolution apparent diffusion coefficients AN - 18932855; 5675444 AB - A method is presented for mapping intravoxel fiber structures using spectral decomposition onto a circular distribution of measured apparent diffusion coefficients (ADCs). The zeroth-, second-, and fourth-order harmonic components of the ADC distribution on the circle spanned by the major and median eigenvectors of the diffusion tensor can be used to provide quantitative indices for isotropic, linear, and fiber-crossing diffusion, respectively. A diffusion- weighted MRI technique with 90 encoding orientations was implemented to estimate the circular ADC distribution and calculate the circular spectrum. A digital phantom was used to simulate various diffusion patterns. Comparisons were made between the circular spectrum and regular DTI-based index maps. The results indicated that the zeroth- and second-order circular spectrum maps exhibited a strong consistency with the DTI-based mean diffusivity and linear indices, respectively, and the fourth-order circular spectrum map was able to identify the fiber crossings. MRI experiments were performed on seven healthy human brains using a 3T scanner. The in vivo fourth-order maps showed significantly higher densities in several brain regions, including the corpus callosum, cingulum bundle, superior longitudinal fasciculus, corticospinal tract, and middle cerebellar peduncle, which indicated the existence of fiber crossings in these regions. JF - Magnetic Resonance in Medicine AU - Zhan, W AU - Gu, H AU - Xu, S AU - Silbersweig, DA AU - Stern, E AU - Yang, Y AD - MRI Physics Unit, Neuroimaging Research Branch, National Institute on Drug Abuse, NIH, 5500 Nathan Shock Drive, Rm. 383, Baltimore 21224, YiHongYang@intra.nida.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 1077 EP - 1088 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 49 IS - 6 SN - 0740-3194, 0740-3194 KW - man KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Fibers KW - Magnetic resonance imaging KW - Brain KW - N.M.R. KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18932855?accountid=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=Magnetic+Resonance+in+Medicine&rft.atitle=Circular+spectrum+mapping+for+intravoxel+fiber+structures+based+on+high+angular+resolution+apparent+diffusion+coefficients&rft.au=Zhan%2C+W%3BGu%2C+H%3BXu%2C+S%3BSilbersweig%2C+DA%3BStern%2C+E%3BYang%2C+Y&rft.aulast=Zhan&rft.aufirst=W&rft.date=2003-01-01&rft.volume=49&rft.issue=6&rft.spage=1077&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.10484 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - N.M.R.; Magnetic resonance imaging; Fibers; Brain DO - http://dx.doi.org/10.1002/mrm.10484 ER - TY - JOUR T1 - Fast measurement of intracardiac pressure differences with 2D breath-hold phase-contrast MRI AN - 18929589; 5675442 AB - Intracardiovascular blood pressure differences can be derived from velocity images acquired with phase-contrast (PC) MRI by evaluating the Navier-Stokes equations. Pressure differences within a slice of interest can be calculated using only the in-plane velocity components from that slice. This rapid exam is proposed as an alternative to the lengthy 3D velocity imaging exams. Despite their good spatial coverage, the 3D exams are prone to artifacts and errors from respiratory motion and insufficient temporal resolution, and are unattractive in the clinical setting due to their excessive scan times (>10 min of free breathing). The proposed single-slice approach requires only one or two breath- holds of acquisition time, and the velocity data can be processed for the calculation of pressure differences online with immediate feedback. The impact of reducing the pressure difference calculation to two dimensions is quantified by comparison with 3D data sets for the case of blood flow within the cardiac chambers. The calculated pressure differences are validated using high-fidelity pressure transducers both in a pulsatile flow phantom and in vivo in a dog model. There was excellent agreement between the transducer and PC-MRI results in all of the studies. JF - Magnetic Resonance in Medicine AU - Thompson, R B AU - McVeigh, E R AD - Laboratory of Cardiac Energetics, National Institutes of Health, 10 Center Drive, Bldg. 10, Rm. B1D 416, Bethesda 20892-1061, thompsor@nhlbi.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 1056 EP - 1066 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 49 IS - 6 SN - 0740-3194, 0740-3194 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Heart KW - Magnetic resonance imaging KW - Velocity KW - N.M.R. KW - Blood pressure KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18929589?accountid=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=Magnetic+Resonance+in+Medicine&rft.atitle=Fast+measurement+of+intracardiac+pressure+differences+with+2D+breath-hold+phase-contrast+MRI&rft.au=Thompson%2C+R+B%3BMcVeigh%2C+E+R&rft.aulast=Thompson&rft.aufirst=R&rft.date=2003-01-01&rft.volume=49&rft.issue=6&rft.spage=1056&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.10486 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - N.M.R.; Magnetic resonance imaging; Blood pressure; Velocity; Heart DO - http://dx.doi.org/10.1002/mrm.10486 ER - TY - JOUR T1 - Mice Lacking Myeloid Differentiation Factor 88 Display Profound Defects in Host Resistance and Immune Responses to Mycobacterium avium Infection Not Exhibited by Toll-Like Receptor 2 (TLR2)- and TLR4-Deficient Animals AN - 18899210; 5757418 AB - To assess the role of Toll-like receptor (TLR) signaling in host resistance to Mycobacterium avium infection, mice deficient in the TLR adaptor molecule myeloid differentiation factor 88 (MyD88), as well as TLR2 super(-/-) and TLR4 super(-/- ) animals, were infected with a virulent strain of M. avium, and bacterial burdens and immune responses were compared with those in wild-type (WT) animals. MyD88 super(-/-) mice failed to control acute and chronic M. avium growth and succumbed 9-14 wk postinfection. Infected TLR2 super(-/-) mice also showed increased susceptibility, but displayed longer survival and lower bacterial burdens than MyD88 super(-/-) animals, while TLR4 super(-/-) mice were indistinguishable from their WT counterparts. Histopathological examination of MyD88 super(-/-) mice revealed massive destruction of lung tissue not present in WT, TLR2 super(-/-), or TLR4 super(-/- ) mice. In addition, MyD88 super(-/-) and TLR2 super(-/-), but not TLR4 super(-/-), mice displayed marked reductions in hepatic neutrophil infiltration during the first 2 h of infection. Although both MyD88 super(-/-) and TLR2 super(-/-) macrophages showed profound defects in IL-6, TNF, and IL-12p40 responses to M. avium stimulation in vitro, in vivo TNF and IL-12p40 mRNA induction was impaired only in infected MyD88 super(-/-) mice. Similarly, MyD88 super(-/-) mice displayed a profound defect in IFN-[gamma] response that was not evident in TLR2 super(-/-) or TLR4 super(-/- ) mice or in animals deficient in IL-18. These findings indicate that resistance to mycobacterial infection is regulated by multiple MyD88-dependent signals in addition to those previously attributed to TLR2 or TLR4, and that these undefined elements play a major role in determining bacterial induced proinflammatory as well as IFN-[gamma] responses. JF - Journal of Immunology AU - Feng, C G AU - Scanga, CA AU - Collazo-Custodio, C M AU - Cheever, A W AU - Hieny, S AU - Caspar, P AU - Sher, A AD - Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 Y1 - 2003 PY - 2003 DA - 2003 SP - 4758 EP - 4764 PB - American Association of Immunologists, 9650 Rockville Pike Bethesda MD 20814-3998 USA, [URL:http://www.jimmunol.org/] VL - 171 IS - 9 SN - 0022-1767, 0022-1767 KW - MyD88 protein KW - TLR2 protein KW - TLR4 protein KW - Toll-like receptors KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - F 06801:Bacteria KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18899210?accountid=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=Mice+Lacking+Myeloid+Differentiation+Factor+88+Display+Profound+Defects+in+Host+Resistance+and+Immune+Responses+to+Mycobacterium+avium+Infection+Not+Exhibited+by+Toll-Like+Receptor+2+%28TLR2%29-+and+TLR4-Deficient+Animals&rft.au=Feng%2C+C+G%3BScanga%2C+CA%3BCollazo-Custodio%2C+C+M%3BCheever%2C+A+W%3BHieny%2C+S%3BCaspar%2C+P%3BSher%2C+A&rft.aulast=Feng&rft.aufirst=C&rft.date=2003-01-01&rft.volume=171&rft.issue=9&rft.spage=4758&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunology&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Studies of radon and lung cancer in North America and China AN - 18893250; 5761243 AB - Studies of radon-exposed underground miners indicate that residential radon is the second leading cause of lung cancer. Seven case-control studies of residential radon have been conducted in North America and two in China, and represent all studies in these areas which included 200 or more lung cancer cases and used long-term radon detectors. North American studies enrolled 4081 cases and 5281 controls, and Chinese studies enrolled 1076 cases and 2015 controls. Based on analyses of pooled data, odds ratios (ORs) and 95% confidence limits at 100 Bq m super(-3) were 1.106 (1.00,1.28) for the North American studies and 1.139 (1.01,1.37) for the Chinese studies. Tests of homogeneity of ORs within populations were not significant. Among subjects with complete dosimetry for the 5-30 y exposure period prior to interview, ORs at 100 Bq m super(-3) were 1.205 (1.03,1.50) for the North American studies and 1.279 (1.07,0.75) for the Chinese studies. Results are consistent with extrapolations from miners and indicate an excess lung cancer risk from residential radon. JF - Radiation Protection Dosimetry AU - Lubin, J H AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd, MSC-7244, Bethesda, MD 20892, USA, lubinj@mail.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 315 EP - 319 VL - 104 IS - 4 SN - 0144-8420, 0144-8420 KW - Health & Safety Science Abstracts; Pollution Abstracts; Risk Abstracts KW - R2 23030:Natural hazards KW - H 8000:Radiation Safety/Electrical Safety KW - P 8000:RADIATION UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18893250?accountid=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=Radiation+Protection+Dosimetry&rft.atitle=Studies+of+radon+and+lung+cancer+in+North+America+and+China&rft.au=Lubin%2C+J+H&rft.aulast=Lubin&rft.aufirst=J&rft.date=2003-01-01&rft.volume=104&rft.issue=4&rft.spage=315&rft.isbn=&rft.btitle=&rft.title=Radiation+Protection+Dosimetry&rft.issn=01448420&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 - Reannotation of Shewanella oneidensis Genome AN - 18864420; 5711269 AB - As more and more complete bacterial genome sequences become available, the genome annotation of previously sequenced genomes may become quickly outdated. This is primarily due to the discovery and functional characterization of new genes. We have reannotated the recently published genome of Shewanella oneidensis with the following results: 51 new genes have been identified, and functional annotation has been added to the 97 genes, including 15 new and 82 existing ones with previously unassigned function. The identification of new genes was achieved by predicting the protein coding regions using the HMM-based program GeneMark.hmm Subsequent comparison of the predicted gene products to the non-redundant protein database using BLAST and the COG (Clusters of Orthologous Groups) database using COGNITOR provided for the functional annotation. JF - OMICS: A Journal of Integrative Biology AU - Daraselia, N AU - Dernovoy, D AU - Tian, Y AU - Borodovsky, M AU - Tatusov, R AU - Tatusova, T AD - National Center for Biotechnology Information, National Library of Medicine, Building 45, Room 6As.55, Bethesda MD 20894, USA, Tatiana@ncbi.nlm.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 171 EP - 176 VL - 7 IS - 2 SN - 1536-2310, 1536-2310 KW - annotation KW - databases KW - gene identification KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18864420?accountid=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=OMICS%3A+A+Journal+of+Integrative+Biology&rft.atitle=Reannotation+of+Shewanella+oneidensis+Genome&rft.au=Daraselia%2C+N%3BDernovoy%2C+D%3BTian%2C+Y%3BBorodovsky%2C+M%3BTatusov%2C+R%3BTatusova%2C+T&rft.aulast=Daraselia&rft.aufirst=N&rft.date=2003-01-01&rft.volume=7&rft.issue=2&rft.spage=171&rft.isbn=&rft.btitle=&rft.title=OMICS%3A+A+Journal+of+Integrative+Biology&rft.issn=15362310&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 - Computation method to identify differential allelic gene expression and novel imprinted genes AN - 18825921; 5713177 AB - Genomic imprinting plays an important role in both normal development and diseases. Abnormal imprinting is strongly associated with several human diseases including cancers. Most of the imprinted genes were discovered in the neighborhood of the known imprinted genes. This approach is difficult to extend to analyze the whole genome. We have decided to take a computational approach to systematically search the whole genome for the presence of mono-allelic expressed genes and imprinted genes in human genome. JF - Bioinformatics AU - Yang, H H AU - Hu, Y AU - Edmonson, M AU - Buetow, K AU - Lee, M P AD - Laboratory of Population Genetics, National Cancer Institute, Gaithersburg, MD 20877, USA Y1 - 2003 PY - 2003 DA - 2003 SP - 952 EP - 955 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 19 IS - 8 SN - 1367-4803, 1367-4803 KW - man KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Genetics Abstracts KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics KW - G 07300:Theoretical genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18825921?accountid=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=Bioinformatics&rft.atitle=Computation+method+to+identify+differential+allelic+gene+expression+and+novel+imprinted+genes&rft.au=Yang%2C+H+H%3BHu%2C+Y%3BEdmonson%2C+M%3BBuetow%2C+K%3BLee%2C+M+P&rft.aulast=Yang&rft.aufirst=H&rft.date=2003-01-01&rft.volume=19&rft.issue=8&rft.spage=952&rft.isbn=&rft.btitle=&rft.title=Bioinformatics&rft.issn=13674803&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Development of a biologically-based controlled growth and differentiation model for developmental toxicology AN - 18824738; 5719039 AB - A mathematical model is developed with a highly controlled birth and death process for precursor cells. This model is both biologically- and statistically-based. The controlled growth and differentiation (CGD) model limits the number of replications allowed in the development of a tissue or organ and thus, more closely reflects the presence of a true stem cell population. Leroux et al. (1996) presented a biologically-based dose-response model for developmental toxicology that was derived from a partial differential equation for the generating function. This formulation limits further expansion into more realistic models of mammalian development. The same formulae for the probability of a defect (a system of ordinary differential equations) can be derived through the Kolmogorov forward equations due to the nature of this Markov process. This modified approach is easily amenable to the expansion of more complicated models of the developmental process such as the one presented here. Comparisons between the Leroux et al. (1996) model and the controlled growth and differentiation (CGD) model as developed in this paper are also discussed. JF - Journal of Mathematical Biology AU - Whitaker, SY AU - Tran, H T AU - Portier, C J AD - Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, 111 T. W. Alexander Drive, Bldg. 101, MD A3-06, Research Triangle Park, NC 27709, USA, whitake2@niehs.nih.gov Y1 - 2003/01// PY - 2003 DA - Jan 2003 SP - 1 EP - 16 VL - 46 IS - 1 SN - 0303-6812, 0303-6812 KW - development KW - Toxicology Abstracts KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18824738?accountid=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+Mathematical+Biology&rft.atitle=Development+of+a+biologically-based+controlled+growth+and+differentiation+model+for+developmental+toxicology&rft.au=Whitaker%2C+SY%3BTran%2C+H+T%3BPortier%2C+C+J&rft.aulast=Whitaker&rft.aufirst=SY&rft.date=2003-01-01&rft.volume=46&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Journal+of+Mathematical+Biology&rft.issn=03036812&rft_id=info:doi/10.1007%2Fs00285-002-0164-8 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1007/s00285-002-0164-8 ER - TY - JOUR T1 - A simple two-step, 'hit and fix' method to generate subtle mutations in BACs using short denatured PCR fragments AN - 18811010; 5683642 AB - The bacteriophage lambda recombination system has proven to be a valuable tool for engineering bacterial artificial chromosomes (BAC). Due to its high efficiency, subtle alterations in the BACs can be generated using oligonucleotides as targeting vectors. Since no selection marker is used, recombinant clones are identified utilizing a selective PCR screening method. However, occasionally the selective PCR screening is not feasible. We describe here a two-step 'hit and fix' method that can be reliably used for generating any subtle alteration in BACs using short denatured PCR fragments as targeting vectors. In the first step of this method, 6-20 nucleotides are changed around the base where the mutation has to be generated. In the second step, these altered nucleotides are reverted to the original sequence and simultaneously a subtle alteration is introduced. Since in each step several nucleotides are changed, PCR primers specific for such alterations can be designed. This two- step method provides a simple and efficient tool for generating subtle alterations in BACs that can be very valuable for functional analysis of genes. JF - Nucleic Acids Research AU - Yang, Y AU - Sharan, S K AD - Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute at Frederick, 1050 Boyles Street, Frederick, MD 21702, USA, ssharan@mail.ncifcrf.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 1 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 31 IS - 15 SN - 0305-1048, 0305-1048 KW - hit and fix method KW - nucleotides KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - N 14610:Occurrence, isolation & assay KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18811010?accountid=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+simple+two-step%2C+%27hit+and+fix%27+method+to+generate+subtle+mutations+in+BACs+using+short+denatured+PCR+fragments&rft.au=Yang%2C+Y%3BSharan%2C+S+K&rft.aulast=Yang&rft.aufirst=Y&rft.date=2003-01-01&rft.volume=31&rft.issue=15&rft.spage=e80&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Binge eating disorder and obesity in 2003: Could treating an eating disorder have a positive effect on the obesity epidemic? AN - 18806455; 5678668 AB - The purpose of this paper is to explore the relationship between binge eating disorder (BED) and obesity. Recent literature relating to the etiology, risk factors, pathophysiology, and treatment of binge eating disorder was reviewed. The data suggest that binge eating may be a contributor to the development of obesity in susceptible individuals. Although eating disorders treatment in the absence of obesity treatment does not result in large weight losses, amelioration of binge eating does result in small weight losses and decreased weight regain over time. Our challenge in the future is to understand better the ways in which BED and obesity co-exist, and to find treatment strategies that will relieve the distress and dysfunction due to this disordered eating while enhancing appropriate weight loss or preventing further weight gain. Published 2003 by Wiley Periodicals, Inc. super([dagger]) Int J Eat Disord 34: S117-S120, 2003. JF - International Journal of Eating Disorders AU - Yanovski, S Z AD - National Institute of Diabetes and Digestive and Kidney Diseases, 6707 Democracy Blvd, Room 665, Bethesda, MD 20892-5450, sy29f@nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - S117 EP - S120 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 34 SN - 0276-3478, 0276-3478 KW - Physical Education Index KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18806455?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Eating+Disorders&rft.atitle=Binge+eating+disorder+and+obesity+in+2003%3A+Could+treating+an+eating+disorder+have+a+positive+effect+on+the+obesity+epidemic%3F&rft.au=Yanovski%2C+S+Z&rft.aulast=Yanovski&rft.aufirst=S&rft.date=2003-01-01&rft.volume=34&rft.issue=&rft.spage=S117&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Eating+Disorders&rft.issn=02763478&rft_id=info:doi/10.1002%2Feat.10211 LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1002/eat.10211 ER - TY - JOUR T1 - Trafficking of NMDA receptors AN - 18801530; 5661489 AB - The NMDA receptor (NMDAR) plays a central role in the function of excitatory synapses. Recent studies have provided interesting insights into several aspects of the trafficking of this receptor in neurons. The NMDAR is not a static resident of the synapse. Rather, the number and composition of synaptic NMDARs can be modulated by several factors. The interaction of PDZ proteins, generally thought to occur at the synapse, appears to occur early in the secretory pathway; this interaction may play a role in the assembly of the receptor complex and its exit from the endoplasmic reticulum. This review addresses recent advances in our understanding of NMDAR trafficking and its synaptic delivery and maintenance. JF - Annual Review of Pharmacology and Toxicology AU - Wenthold, R J AU - Prybylowski, K AU - Standley, S AU - Sans, N AU - Petralia, R S AD - Laboratory of Neurochemistry, NIDCD, NIH, Bethesda, MD 20892, USA, wenthold@nidcd.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 335 EP - 358 VL - 43 SN - 0362-1642, 0362-1642 KW - NMDA receptors KW - trafficking KW - CSA Neurosciences Abstracts; Toxicology Abstracts KW - X 24250:Reviews KW - N3 11091:Vertebrate Nervous Systems: General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18801530?accountid=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=Annual+Review+of+Pharmacology+and+Toxicology&rft.atitle=Trafficking+of+NMDA+receptors&rft.au=Wenthold%2C+R+J%3BPrybylowski%2C+K%3BStandley%2C+S%3BSans%2C+N%3BPetralia%2C+R+S&rft.aulast=Wenthold&rft.aufirst=R&rft.date=2003-01-01&rft.volume=43&rft.issue=&rft.spage=335&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - A NIEHS-Oriented Perspective on Hormesis AN - 18784351; 5655262 JF - Critical Reviews in Toxicology AU - Fouts, J R AD - NIEHS Y1 - 2003 PY - 2003 DA - 2003 SP - 425 EP - 429 VL - 33 IS - 3-4 SN - 1040-8444, 1040-8444 KW - NIEHS KW - hormesis KW - Toxicology Abstracts KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18784351?accountid=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=Critical+Reviews+in+Toxicology&rft.atitle=A+NIEHS-Oriented+Perspective+on+Hormesis&rft.au=Fouts%2C+J+R&rft.aulast=Fouts&rft.aufirst=J&rft.date=2003-01-01&rft.volume=33&rft.issue=3-4&rft.spage=425&rft.isbn=&rft.btitle=&rft.title=Critical+Reviews+in+Toxicology&rft.issn=10408444&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Special Issue: Hormesis: Environmental and Biomedical Perspectives. N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Mutagenesis and DNA adduct formation in the mouse mammary gland exposed to 2-hydroxyamino-1-methyl-6-phenylimidazo-[4,5-b]pyridine in whole organ culture AN - 18775657; 5644895 AB - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mutagen and rodent mammary gland carcinogen found in the human diet. 2-Hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-hydroxy-PhIP) is the proximate reactive metabolite of PhIP associated with PhIP-DNA adduct formation and mutagenesis. In the current study, whole mammary glands obtained from transgenic C57B1/6 mice carrying the plasmid-lacZ mutational reporter gene were cultured in defined medium and exposed to various concentrations of N-hydroxy-PhIP for 24 h. At various times after N-hydroxy-PhIP exposure, PhIP-DNA adduct levels were determined by the super(32)P-post-labeling assay and the lacZ super(-) mutant frequency determined by the positive selection system. Glands were cultured in either medium containing insulin (I medium), necessary for maintenance of the gland, or I medium containing prolactin, aldosterone and hydrocortisone (IPAH medium) to induce lobuloalveolar development. At 3 and 7 days after exposure to 10 mu M N-hydroxy-PhIP, mutant frequency was upwards of 9-fold higher in glands incubated in IPAH medium than in I medium (15.2 plus or minus 1.9 and 1.6 plus or minus 0.7x10 super(-3), respectively, 3 day time point). PhIP-DNA adduct levels were 1.7-fold higher in glands cultivated in IPAH medium than in I medium immediately after exposure to 10 mu M N-hydroxy-PhIP. A statistically significant reduction in PhIP-DNA adduct levels occurred with time in glands cultivated in IPAH medium but not I medium (one-way analysis of variance, P < 0.05). By 7 days after exposure, PhIP-DNA adduct levels were similar in glands cultured in I and IPAH medium (3.2 plus or minus 0.2 and 2.8 plus or minus 0.29 adducts/10 super(7) nucleotides, respectively). DNA synthesis as measured by [ super(3)H]thymidine labeling was similar to 2-fold higher in glands cultured in IPAH medium than in I medium. The higher mutant frequency in glands cultivated in IPAH medium versus I medium appeared to be due to a combination of higher initial PhIP-DNA adduct levels and a greater fixation of mutations that occurred at higher proliferation rates. The findings indicate that mammotrophic hormones influence the mutagenicity of PhIP in the mammary gland in vitro and emphasize the importance of hormonal milieu on carcinogen-DNA adduct-induced mutations in this organ. JF - Mutagenesis AU - Snyderwine, E G AU - Yoon, H-S AU - Knight-Jones, L P AU - Tran, M AU - Schut, HAJ AU - Yu, M AD - Chemical Carcinogenesis Section, Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, Building 37, Room 3C28, 37 Convent Drive, MSC 4258, Bethesda, MD 20892-4258, USA, elizabeth_snyderwine@nih.gov Y1 - 2003/01// PY - 2003 DA - Jan 2003 SP - 7 EP - 12 VL - 18 IS - 1 SN - 0267-8357, 0267-8357 KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - Biochemistry Abstracts 2: Nucleic Acids; Toxicology Abstracts 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/18775657?accountid=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=Mutagenesis&rft.atitle=Mutagenesis+and+DNA+adduct+formation+in+the+mouse+mammary+gland+exposed+to+2-hydroxyamino-1-methyl-6-phenylimidazo-%5B4%2C5-b%5Dpyridine+in+whole+organ+culture&rft.au=Snyderwine%2C+E+G%3BYoon%2C+H-S%3BKnight-Jones%2C+L+P%3BTran%2C+M%3BSchut%2C+HAJ%3BYu%2C+M&rft.aulast=Snyderwine&rft.aufirst=E&rft.date=2003-01-01&rft.volume=18&rft.issue=1&rft.spage=7&rft.isbn=&rft.btitle=&rft.title=Mutagenesis&rft.issn=02678357&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Mouse Bone Marrow Micronucleus Test Results Do Not Predict the Germ Cell Mutagenicity of N-Hydroxymethylacrylamide in the Mouse Dominant Lethal Assay AN - 18773091; 5640292 AB - N-Hydroxymethylacrylamide (NHMA), a mouse carcinogen inactive in the Salmonella assay and mouse micronucleus (MN) assay, was tested for reproductive effects in a mouse continuous breeding study. In that study, increased embryonic deaths were observed after 13 weeks exposure of parental animals to NHMA via drinking water (highest dose, 360 ppm); the results indicated the possible induction of chromosome damage in germ cells of treated males. An additional mouse MN test was conducted using a 31-day treatment period to better match the dosing regimen used in the breeding study; the results were negative. Additional studies were conducted to explore the germ cell activity of NHMA. A male mouse dominant lethal study was conducted using a single intraperitoneal injection of 150 mg/kg NHMA; the results were negative. A follow-up study was conducted using fractionated dosing, 50 mg/kg/day for 5 days; again, no increase in dominant lethal mutations was observed. NHMA (180-720 ppm) was then administered to male mice in drinking water for 13 weeks, during which three sets of matings occurred. Two weeks after mating, females were killed and the uterine contents were analyzed. Large, dose-related increases in dominant lethal mutations were observed with increasing length of exposure. The magnitude of the increases stabilized after 8 weeks of treatment. However, the frequency of micronucleated peripheral blood erythrocytes was not elevated in mice treated for 13 weeks with NHMA in drinking water. Thus, NHMA appears to be unique in inducing genetic damage in germ cells but not somatic cells of male mice. JF - Environmental and Molecular Mutagenesis AU - Witt, K L AU - Hughes, LA AU - Burka, L T AU - McFee, A F AU - Mathews, J M AU - Black, S L AU - Bishop, J B AD - NIEHS MD B3-05, PO Box 12233, Research Triangle Park, NC 27709, USA, bishop@niehs.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 111 EP - 120 VL - 41 IS - 2 SN - 0893-6692, 0893-6692 KW - N-Hydroxymethylacrylamide KW - mice KW - mouse dominant lethal assay KW - Toxicology Abstracts KW - X 24155:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18773091?accountid=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=Mouse+Bone+Marrow+Micronucleus+Test+Results+Do+Not+Predict+the+Germ+Cell+Mutagenicity+of+N-Hydroxymethylacrylamide+in+the+Mouse+Dominant+Lethal+Assay&rft.au=Witt%2C+K+L%3BHughes%2C+LA%3BBurka%2C+L+T%3BMcFee%2C+A+F%3BMathews%2C+J+M%3BBlack%2C+S+L%3BBishop%2C+J+B&rft.aulast=Witt&rft.aufirst=K&rft.date=2003-01-01&rft.volume=41&rft.issue=2&rft.spage=111&rft.isbn=&rft.btitle=&rft.title=Environmental+and+Molecular+Mutagenesis&rft.issn=08936692&rft_id=info:doi/10.1002%2Fem.10139 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1002/em.10139 ER - TY - JOUR T1 - The Conscious Perception of the Sensation of Fatigue AN - 18761206; 5633881 AB - In this review, fatigue is described as a conscious sensation rather than a physiological occurrence. We suggest that the sensation of fatigue is the conscious awareness of changes in subconscious homeostatic control systems, and is derived from a temporal difference between subconscious representations of these homeostatic control systems in neural networks that are induced by changes in the level of activity. These mismatches are perceived by consciousness-producing structures in the brain as the sensation of fatigue. In this model, fatigue is a complex emotion affected by factors such as motivation and drive, other emotions such as anger and fear, and memory of prior activity. It is not clear whether the origin of the conscious sensation of fatigue is associated with particular localised brain structures, or is the result of electrophysiological synchronisation of entire brain activity. JF - Sports Medicine AU - Gibson, AStC AU - Baden, DA AU - Lambert, MI AU - Lambert, E V AU - Harley, YXR AU - Hampson, D AU - Russell, V A AU - Noakes, T D AD - Human Motor Control Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA Y1 - 2003 PY - 2003 DA - 2003 SP - 167 EP - 176 VL - 33 IS - 3 SN - 0112-1642, 0112-1642 KW - Physical Education Index KW - PE 090:Sports Medicine & Exercise Sport Science UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18761206?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Sports+Medicine&rft.atitle=The+Conscious+Perception+of+the+Sensation+of+Fatigue&rft.au=Gibson%2C+AStC%3BBaden%2C+DA%3BLambert%2C+MI%3BLambert%2C+E+V%3BHarley%2C+YXR%3BHampson%2C+D%3BRussell%2C+V+A%3BNoakes%2C+T+D&rft.aulast=Gibson&rft.aufirst=AStC&rft.date=2003-01-01&rft.volume=33&rft.issue=3&rft.spage=167&rft.isbn=&rft.btitle=&rft.title=Sports+Medicine&rft.issn=01121642&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Current Situation and Countermeasures for Urban Community Sport Development in Nei-mongol of China AN - 18751068; 5624798 AB - By applying questionnaire investigation and literature consultation, the current situation of the urban community sport development in Nei-mogol was analyzed comprehensively. Based on the current situation and characteristics of the Nei-mongol urban community sport development, the social and economical development situation in Nei-mongol as well as the chief target of the "National Fitness Program", suggestions and countermeasures were advanced for urban community sport development in Nei-mongol. JF - Journal of Beijing University of Physical Education AU - Li, F-X AU - Bu, H-J AD - Inst. of PE, Nei-mongol Normal University, Hohhot 010022, Nei - mongol, China Y1 - 2003/01// PY - 2003 DA - Jan 2003 SP - 15 EP - 16 VL - 26 IS - 1 SN - 1007-3612, 1007-3612 KW - Physical Education Index KW - PE 120:Sport: Psychology, Sociology & History UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18751068?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Beijing+University+of+Physical+Education&rft.atitle=Current+Situation+and+Countermeasures+for+Urban+Community+Sport+Development+in+Nei-mongol+of+China&rft.au=Li%2C+F-X%3BBu%2C+H-J&rft.aulast=Li&rft.aufirst=F-X&rft.date=2003-01-01&rft.volume=26&rft.issue=1&rft.spage=15&rft.isbn=&rft.btitle=&rft.title=Journal+of+Beijing+University+of+Physical+Education&rft.issn=10073612&rft_id=info:doi/ LA - Chinese DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Ex vivo magnetic resonance microscopy of an osteochondral transfer TT - This article is a US Government work and, as such, is in the public domain in the United States of America. AN - 18735960; 5611518 AB - A 49-year-old woman with right knee pain and a chondral defect on the medial femoral condyle underwent an osteochondral transfer. The patient initially had pain relief, but then sustained a twisting injury and had progressive chondromalacia and pain on the affected side. She subsequently underwent a total knee replacement, and the tissue from the osteochondral transfer (OATS) site was harvested for analysis. In vitro MR microimaging of the excised joint segment revealed undamaged, full-thickness cartilage on the OATS plug, intact cartilage on the posterior condyle, and severely thinned and damaged cartilage on the anterior condyle. Alcian blue-stained sections revealed that proteoglycans were present throughout the OATS core but were nearly absent in the native cartilage. Quantitative T sub(1) data acquired after equilibration with Gd-DTPA indicated a distribution of matrix fixed charge in the OATS plug and anterior tissue that agreed well with histology and literature observations, while the posterior native cartilage appeared to have fixed charge similar to that of the OATS tissue. Histology revealed poor graft integration between OATS and native cartilage, with a distinct layer of fibrous tissue at the posterior interface. MRI images, by comparison, showed a hypointense feature at the posterior interface but uniform intensity across the anterior interface. Quantitative T sub(2), magnetization transfer and T sub(1) data acquired with and without gadolinium contrast showed dependences on depth, location, and pathology that were consistent with measurements reported in the literature for articular cartilage. JF - Journal of Magnetic Resonance Imaging AU - Petersen, E F AU - Fishbein, K W AU - Laouar, L AU - Spencer, RGS AU - Wenz, J F AD - NIH/National Institute on Aging, Gerontology Research Center, Room 4D-06, 5600 Nathan Shock Drive, Baltimore 21224, spencer@helix.nih.gov spencer@helix.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 603 EP - 608 VL - 17 IS - 5 SN - 1053-1807, 1053-1807 KW - man KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18735960?accountid=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+Magnetic+Resonance+Imaging&rft.atitle=Ex+vivo+magnetic+resonance+microscopy+of+an+osteochondral+transfer&rft.au=Petersen%2C+E+F%3BFishbein%2C+K+W%3BLaouar%2C+L%3BSpencer%2C+RGS%3BWenz%2C+J+F&rft.aulast=Petersen&rft.aufirst=E&rft.date=2003-01-01&rft.volume=17&rft.issue=5&rft.spage=603&rft.isbn=&rft.btitle=&rft.title=Journal+of+Magnetic+Resonance+Imaging&rft.issn=10531807&rft_id=info:doi/10.1002%2Fjmri.10305 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1002/jmri.10305 ER - TY - JOUR T1 - Functional tumor imaging with dynamic contrast-enhanced magnetic resonance imaging TT - This article is a US Government work and, as such, is in the public domain in the United States of America. AN - 18734068; 5611507 AB - Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is the acquisition of serial MRI images before, during, and after the administration of an MR contrast agent. Unlike conventional enhanced MRI, which simply provides a snapshot of enhancement at one point in time, DCE-MRI permits a fuller depiction of the wash-in and wash-out contrast kinetics within tumors, and thus provides insight into the nature of the bulk tissue properties. Such data is readily amenable to two-compartment pharmacokinetic modeling from which parameters based on the rates of exchange between the compartments can be generated. These parameters can be used to generate color-encoded images that aid in the visual assessment of tumors. DCE-MRI is used currently to characterize masses, stage tumors, and noninvasively monitor therapy. While DCE-MRI is in clinical use, there are also a number of limitations, including overlap between malignant and benign inflammatory tissue, failure to resolve microscopic disease, and the inconsistent predictive value of enhancement pattern with regard to clinical outcome. Current research focuses on improving understanding of the meaning of DCE-MRI at a molecular level, evaluating macromolecular and targeted contrast agents, and combining DCE-MRI with other physiologic imaging techniques such as positron emission tomography. Efforts to standardize DCE-MRI acquisition, analysis, and reporting methods will allow wider dissemination of this useful functional imaging technique. JF - Journal of Magnetic Resonance Imaging AU - Choyke, P L AU - Dwyer, A J AU - Knopp, M V AD - Department of Radiology, NIH, Building 10, Room 1C660, Bethesda 20892-1162, pchoyke@nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 509 EP - 520 VL - 17 IS - 5 SN - 1053-1807, 1053-1807 KW - pharmacokinetics KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18734068?accountid=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+Magnetic+Resonance+Imaging&rft.atitle=Functional+tumor+imaging+with+dynamic+contrast-enhanced+magnetic+resonance+imaging&rft.au=Choyke%2C+P+L%3BDwyer%2C+A+J%3BKnopp%2C+M+V&rft.aulast=Choyke&rft.aufirst=P&rft.date=2003-01-01&rft.volume=17&rft.issue=5&rft.spage=509&rft.isbn=&rft.btitle=&rft.title=Journal+of+Magnetic+Resonance+Imaging&rft.issn=10531807&rft_id=info:doi/10.1002%2Fjmri.10304 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1002/jmri.10304 ER - TY - JOUR T1 - Defense against filoviruses used as biological weapons AN - 18733382; 5613305 AB - The filoviruses, Marburg and Ebola, are classified as Category A biowarfare agents by the Centers for Disease Control. Most known human infections with these viruses have been fatal, and no vaccines or effective therapies are currently available. Filoviruses are highly infectious by the airborne route in the laboratory, but investigations of African outbreaks have shown that person-to-person spread requires direct contact with virus-containing material. In consequence, filovirus epidemics can be halted by isolating patients and instituting standard infection control and barrier nursing procedures. The filovirus disease syndrome resembles that caused by other hemorrhagic fever viruses, necessitating studies in a biocontainment laboratory to confirm the diagnosis. Some progress has been made in developing vaccines and antiviral drugs, but efforts are hindered by the limited number of maximum containment laboratories. Terrorists might have great difficulty acquiring a filovirus for use as a weapon, but my attempt to do so because of the agents' ability to inspire fear. Accurate information is the best tool to prevent panic in the event of an attack. JF - Antiviral Research AU - Bray, M AD - Medical Officer, Biodefense Clinical Research Branch, OCR/OD/NIAID/NIH, 6700A Rockledge Drive, Room 5132, Bethesda, MD 20892, USA Y1 - 2003/01// PY - 2003 DA - Jan 2003 SP - 53 EP - 60 PB - Elsevier Science VL - 57 IS - 1-2 SN - 0166-3542, 0166-3542 KW - biological warfare agents KW - man KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Virology & AIDS Abstracts KW - W4 240:Bioterrorism & Biological Warfare KW - V 22124:Prophylaxis & control KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18733382?accountid=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=Antiviral+Research&rft.atitle=Defense+against+filoviruses+used+as+biological+weapons&rft.au=Bray%2C+M&rft.aulast=Bray&rft.aufirst=M&rft.date=2003-01-01&rft.volume=57&rft.issue=1-2&rft.spage=53&rft.isbn=&rft.btitle=&rft.title=Antiviral+Research&rft.issn=01663542&rft_id=info:doi/10.1016%2FS0166-3542%2802%2900200-0 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0166-3542(02)00200-0 ER - TY - JOUR T1 - IR spectra of cytochrome c denatured with deuterated guanidine hydrochloride show increase in beta sheet AN - 18732102; 5611543 AB - Attenuated total reflectance Fourier transform IR (ATR-FTIR) spectra are obtained for horse heart ferricytochrome c in solutions of 0-7M guanidine hydrochloride and deuterated guanidine hydrochloride. Substitutions of deuterium for hydrogen in both the denaturant and protein provide resolvable amide I spectra over a wide range of denaturant concentrations. Deuteration enhances the ability to measure the true protein IR spectrum in the amide I region in which the secondary structure can be deduced, because spectra in D sub(2)O are less prone to spectral distortion upon background denaturant subtraction than spectra in H sub(2)O. Other investigators studying equilibrium unfolded cytochrome c were limited to guanidine concentrations below 3.0M because of detector saturation. Detector saturation is avoided with the use of ATR-FTIR spectroscopy, allowing one to obtain protein spectra at high denaturant concentrations. Second derivative spectra of samples show reductions in alpha helix and increases in beta sheet at high denaturant concentrations, contrary to expectations of finding primarily a random coil secondary structure. Using this new technique, the protein was estimated to consist of 51% beta sheet and only 15% random coil in the presence of 6.6M deuterated guanidine hydrochloride. JF - Biopolymers AU - Speare, JO AU - Rush, TS III AD - Department of Chemistry, University of Montana, Missoula, Montana 59812, jspeare@niaid.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 193 EP - 204 VL - 72 IS - 3 SN - 0006-3525, 0006-3525 KW - cytochrome c KW - guanidine hydrochloride KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W4 330:Biopolymers & Food Biotechnology KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18732102?accountid=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=Biopolymers&rft.atitle=IR+spectra+of+cytochrome+c+denatured+with+deuterated+guanidine+hydrochloride+show+increase+in+beta+sheet&rft.au=Speare%2C+JO%3BRush%2C+TS+III&rft.aulast=Speare&rft.aufirst=JO&rft.date=2003-01-01&rft.volume=72&rft.issue=3&rft.spage=193&rft.isbn=&rft.btitle=&rft.title=Biopolymers&rft.issn=00063525&rft_id=info:doi/10.1002%2Fbip.10337 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1002/bip.10337 ER - TY - JOUR T1 - Analysis of intracellular regulatory proteins by immunoaffinity capillary electrophoresis coupled with laser-induced fluorescence detection AN - 18722342; 5608349 AB - Measurement of intracellular regulatory proteins is of great importance in many areas of biomedical research. In this communication we describe an antibody-based capillary electrophoresis system equipped with an on-line laser- induced fluorescence detector capable of measuring intracellular proteins in cultures as low as 100 cells. The system demonstrated a high degree of precision and accuracy, being capable of detecting the fluorochrome-labeled analytes of interest at concentration of approximately 0.5 pg. We have used this instrument to study concentrations of the intracellular regulatory proteins STAT-1 and STAT-3, following stimulation of lymphocyte cultures with the inflammatory cytokine, IL-6. Using a combination of four antibodies specific for either STAT- 1 or STAT-3 in both their nonphosphorylated and phosphorylated forms, we were able to demonstrate the differential expression of these proteins over time. Copyright 2003 John Wiley & Sons, Ltd. JF - Biomedical Chromatography AU - Phillips, T M AU - Smith, P AD - UAIR, DBEPS, ORS, National Institutes of Health, 13/3E42, 9000 Rockville Pike, Bethesda, MD 20892, USA, phillipt@ors.od.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 182 EP - 187 VL - 17 IS - 2-3 SN - 0269-3879, 0269-3879 KW - capillary electrophoresis KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W4 130:General Biomedical Engineering: Tools & Techniques KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18722342?accountid=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=Biomedical+Chromatography&rft.atitle=Analysis+of+intracellular+regulatory+proteins+by+immunoaffinity+capillary+electrophoresis+coupled+with+laser-induced+fluorescence+detection&rft.au=Phillips%2C+T+M%3BSmith%2C+P&rft.aulast=Phillips&rft.aufirst=T&rft.date=2003-01-01&rft.volume=17&rft.issue=2-3&rft.spage=182&rft.isbn=&rft.btitle=&rft.title=Biomedical+Chromatography&rft.issn=02693879&rft_id=info:doi/10.1002%2Fbmc.240 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1002/bmc.240 ER - TY - JOUR T1 - A Simple, High-Yield Method for Obtaining Multipotential Mesenchymal Progenitor Cells from Trabecular Bone AN - 18686423; 5574624 AB - In vitro cultures of primary, human trabecular bone-derived cells represent a useful system for investigation of the biology of osteoblasts. Our recent discovery of the multilineage mesenchymal differentiation potential of trabecular bone-derived cells suggests the potential application of these cells as mesenchymal progenitors for tissue repair and regeneration. Such applications are crucially dependent on efficient cell-isolation protocols to yield cells that optimally proliferate and differentiate. In this study, we describe a simple, high-yield procedure, requiring minimal culture expansion, for the isolation of mesenchymal progenitor cells from human trabecular bone. Moreover, these cells retain their ability to differentiate along multiple mesenchymal lineages through successive subculturing. Cell populations isolated and cultured as described here allow the efficient acquisition of a clinically significant number of cells, which may be used as the cell source for tissue-engineering applications. JF - Molecular Biotechnology AU - Tuli, R AU - Seghatoleslami, M R AU - Tuli, S AU - Wang, M L AU - Hozack, W J AU - Manner, P A AU - Danielson, K G AU - Tuan, R S AD - Cartilage Biology and Orthopedics Branch, 50 South Drive, Rm 1503, MSC 8022, National Institute of Arthritis, and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA, tuanr@mail.nih.gov Y1 - 2003/01// PY - 2003 DA - Jan 2003 SP - 37 EP - 49 VL - 23 IS - 1 SN - 1073-6085, 1073-6085 KW - man KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W 30965:Miscellaneous, Reviews KW - W3 33220:Cell culture KW - W4 110:Biomedical Materials & Tissue Engineering UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18686423?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Biotechnology&rft.atitle=A+Simple%2C+High-Yield+Method+for+Obtaining+Multipotential+Mesenchymal+Progenitor+Cells+from+Trabecular+Bone&rft.au=Tuli%2C+R%3BSeghatoleslami%2C+M+R%3BTuli%2C+S%3BWang%2C+M+L%3BHozack%2C+W+J%3BManner%2C+P+A%3BDanielson%2C+K+G%3BTuan%2C+R+S&rft.aulast=Tuli&rft.aufirst=R&rft.date=2003-01-01&rft.volume=23&rft.issue=1&rft.spage=37&rft.isbn=&rft.btitle=&rft.title=Molecular+Biotechnology&rft.issn=10736085&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 - Large-Scale Production of Pseudotyped Lentiviral Vectors Using Baculovirus GP64 AN - 18680608; 5574596 AB - Unlike oncoretroviruses, lentiviral vectors can insert large genes and can target both dividing and nondividing cells; thus they hold unique promise as gene transfer agents. To enhance target range, the native lentiviral envelope glycoprotein is replaced (pseudotyped) with vesicular stomatitis virus G (VSVG), and the genes of interest are packaged in nonreplicating vectors by transient transfection with three plasmids. However, because of cytotoxic effects of VSVG expression in producer cells (293T cells) it has been difficult to generate a packaging cell line, required for even modest scale-up of vector production. Here we introduce a pseudotyped lentivirus vector using the baculovirus GP64 envelope glycoprotein. Compared with VSVG, GP64 vectors exhibited a similar broad tropism and similar native titers. GP64-pseudotyped vectors were usually highly concentrated without much loss of titer. Because, unlike VSVG, GP64 expression does not kill cells, we generated 293T-based cell lines constitutively expressing GP64. Our results demonstrate that the baculovirus GP64 protein is an attractive alternative to VSVG for viral vectors used in the large-scale production of high-titer virus required for clinical and commercial applications. JF - Human Gene Therapy AU - Kumar, M AU - Bradow, B P AU - Zimmerberg, J AD - Room 10D14, Building 10, NICHD, NIH, Bethesda, MD 20892-1855, USA, joshz@helix.nih.gov Y1 - 2003/01/01/ PY - 2003 DA - 2003 Jan 01 SP - 67 EP - 77 VL - 14 IS - 1 SN - 1043-0342, 1043-0342 KW - glycoprotein gp64 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews KW - W4 120:Genetic Engineering in Medicine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18680608?accountid=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=Large-Scale+Production+of+Pseudotyped+Lentiviral+Vectors+Using+Baculovirus+GP64&rft.au=Kumar%2C+M%3BBradow%2C+B+P%3BZimmerberg%2C+J&rft.aulast=Kumar&rft.aufirst=M&rft.date=2003-01-01&rft.volume=14&rft.issue=1&rft.spage=67&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - CDD: a curated Entrez database of conserved domain alignments AN - 18665433; 5561687 AB - The Conserved Domain Database (CDD) is now indexed as a separate database within the Entrez system and linked to other Entrez databases such as MEDLINE registered . This allows users to search for domain types by name, for example, or to view the domain architecture of any protein in Entrez's sequence database. CDD can be accessed on the WorldWideWeb at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=cdd. Users may also employ the CD-Search service to identify conserved domains in new sequences, at http://www.ncbi.nlm.nih.gov/Structure/cdd/wrpsb.cgi. CD-Search results, and pre-computed links from Entrez's protein database, are calculated using the RPS-BLAST algorithm and Position Specific Score Matrices (PSSMs) derived from CDD alignments. CD-Searches are also run by default for protein-protein queries submitted to BLAST registered at http://www.ncbi.nlm.nih.gov/BLAST. CDD mirrors the publicly available domain alignment collections SMART and PFAM, and now also contains alignment models curated at NCBI. Structure information is used to identify the core substructure likely to be present in all family members, and to produce sequence alignments consistent with structure conservation. This alignment model allows NCBI curators to annotate `columns' corresponding to functional sites conserved among family members. JF - Nucleic Acids Research AU - Marchler-Bauer, A AU - Anderson, J B AU - DeWeese-Scott, C AU - Fedorova, N D AU - Geer, L Y AU - He, S AU - Hurwitz, DI AU - Jackson, J D AU - Jacobs, A R AU - Lanczycki, C J AU - Liebert, CA AU - Liu, C AU - Madej, T AU - Marchler, G H AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Building 38A, Room 8N805, 8600 Rockville Pike, Bethesda, MD 20894, USA, bauer@ncbi.nlm.nih.gov Y1 - 2003/01/01/ PY - 2003 DA - 2003 Jan 01 SP - 383 EP - 387 VL - 31 IS - 1 SN - 0305-1048, 0305-1048 KW - Entrez database KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - N 14100:Reviews KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18665433?accountid=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=CDD%3A+a+curated+Entrez+database+of+conserved+domain+alignments&rft.au=Marchler-Bauer%2C+A%3BAnderson%2C+J+B%3BDeWeese-Scott%2C+C%3BFedorova%2C+N+D%3BGeer%2C+L+Y%3BHe%2C+S%3BHurwitz%2C+DI%3BJackson%2C+J+D%3BJacobs%2C+A+R%3BLanczycki%2C+C+J%3BLiebert%2C+CA%3BLiu%2C+C%3BMadej%2C+T%3BMarchler%2C+G+H&rft.aulast=Marchler-Bauer&rft.aufirst=A&rft.date=2003-01-01&rft.volume=31&rft.issue=1&rft.spage=383&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Beyond six colors: A new era in flow cytometry AN - 18660474; 5567750 AB - More than 100 functionally distinct populations of lymphocytes can be identified in the peripheral blood of humans; each of these cell types undoubtedly has a unique role in the organization and effectiveness of an immune response. To distinguish specifically among these cells, however, it is necessary to measure simultaneously at least six to eight different T-cell surface antigens; additional functional correlations require even greater detection capability. For this purpose, flow cytometers capable of independently detecting as many as 12 different molecules now exist. Here we review the history and applications of this technology and discuss future directions. JF - Nature Medicine AU - De Rosa, SC AU - Brenchley, J M AU - Roederer, M AD - Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA, roederer@nih.gov Y1 - 2003/01// PY - 2003 DA - Jan 2003 SP - 112 EP - 117 VL - 9 IS - 1 SN - 1078-8956, 1078-8956 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews KW - W3 33250:Methods: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18660474?accountid=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=Beyond+six+colors%3A+A+new+era+in+flow+cytometry&rft.au=De+Rosa%2C+SC%3BBrenchley%2C+J+M%3BRoederer%2C+M&rft.aulast=De+Rosa&rft.aufirst=SC&rft.date=2003-01-01&rft.volume=9&rft.issue=1&rft.spage=112&rft.isbn=&rft.btitle=&rft.title=Nature+Medicine&rft.issn=10788956&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - The Homeodomain Resource: 2003 update AN - 18659929; 5561667 AB - The Homeodomain Resource is a searchable, curated collection of information for the homeodomain protein family. The resource is organized in a compact form and provides user-friendly interfaces for both querying the component databases and assembling customized datasets. The current release (version 5.0, October 2002) contains 1056 full-length homeodomain-containing sequences, 37 experimentally-derived structures, 81 homeodomain interactions, 84 homeodomain DNA-binding sites and 114 homeodomain proteins implicated in human genetic disorders. A new feature of this new release is the inclusion of experimentally-derived protein-protein interaction data for homeodomain family members. All entries are cross-linked for easy retrieval of the original records from source databases. The Homeodomain Resource is freely available through the World Wide Web at http://research.nhgri.nih.gov/homeodomain/. JF - Nucleic Acids Research AU - Banerjee-Basu, S AU - Moreland, T AU - Hsu, B J AU - Trout, K L AU - Baxevanis, AD AD - Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA, andy@nhgri.nih.gov Y1 - 2003/01/01/ PY - 2003 DA - 2003 Jan 01 SP - 304 EP - 306 VL - 31 IS - 1 SN - 0305-1048, 0305-1048 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - N 14100:Reviews KW - W4 140:Bioinformatics & Computers in Health & Medicine KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18659929?accountid=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=The+Homeodomain+Resource%3A+2003+update&rft.au=Banerjee-Basu%2C+S%3BMoreland%2C+T%3BHsu%2C+B+J%3BTrout%2C+K+L%3BBaxevanis%2C+AD&rft.aulast=Banerjee-Basu&rft.aufirst=S&rft.date=2003-01-01&rft.volume=31&rft.issue=1&rft.spage=304&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - NCBI Reference Sequence Project: update and current status AN - 18656144; 5561601 AB - The goal of the NCBI Reference Sequence (RefSeq) project is to provide the single best non-redundant and comprehensive collection of naturally occurring biological molecules, representing the central dogma. Nucleotide and protein sequences are explicitly linked on a residue-by-residue basis in this collection. Ideally all molecule types will be available for each well-studied organism, but the initial database collection pragmatically includes only those molecules and organisms that are most readily identified. Thus different amounts of information are available for different organisms at any given time. Furthermore, for some organisms additional intermediate records are provided when the genome sequence is not yet finished. The collection is supplied by NCBI through three distinct pipelines in addition to collaborations with community groups. The collection is curated on an ongoing basis. Additional information about the NCBI RefSeq project is available at http://www.ncbi.nih.gov/RefSeq/. JF - Nucleic Acids Research AU - Pruitt, K D AU - Tatusova, T AU - Maglott AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Building 38A Room 6N605, 8600 Rockville Pike, Bethesda, MD 20894, USA, pruitt@ncbi.nlm.nih.gov Y1 - 2003/01/01/ PY - 2003 DA - 2003 Jan 01 SP - 34 EP - 37 VL - 31 IS - 1 SN - 0305-1048, 0305-1048 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - N 14100:Reviews KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18656144?accountid=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=NCBI+Reference+Sequence+Project%3A+update+and+current+status&rft.au=Pruitt%2C+K+D%3BTatusova%2C+T%3BMaglott&rft.aulast=Pruitt&rft.aufirst=K&rft.date=2003-01-01&rft.volume=31&rft.issue=1&rft.spage=34&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - MMDB: Entrez's 3D-structure database AN - 18656096; 5561714 AB - Three-dimensional structures are now known within most protein families and it is likely, when searching a sequence database, that one will identify a homolog of known structure. The goal of Entrez's 3D-structure database is to make structure information and the functional annotation it can provide easily accessible to molecular biologists. To this end, Entrez's search engine provides several powerful features: (i) links between databases, for example between a protein's sequence and structure; (ii) pre-computed sequence and structure neighbors; and (iii) structure and sequence/structure alignment visualization. Here, we focus on a new feature of Entrez's Molecular Modeling Database (MMDB): Graphical summaries of the biological annotation available for each 3D structure, based on the results of automated comparative analysis. MMDB is available at: http://www.ncbi.nlm.nih.gov/Entrez/structure.html. JF - Nucleic Acids Research AU - Chen, J AU - Anderson, J B AU - DeWeese-Scott, C AU - Fedorova, N D AU - Geer, L Y AU - He, S AU - Hurwitz, DI AU - Jackson, J D AU - Jacobs, A R AU - Lanczycki, C J AU - Liebert, CA AU - Liu, C AU - Madej, T AU - Bryant, SH AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA, bryant@ncbi.nlm.nih.gov Y1 - 2003/01/01/ PY - 2003 DA - 2003 Jan 01 SP - 474 EP - 477 VL - 31 IS - 1 SN - 0305-1048, 0305-1048 KW - MMDB KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - N 14100:Reviews KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18656096?accountid=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=MMDB%3A+Entrez%27s+3D-structure+database&rft.au=Chen%2C+J%3BAnderson%2C+J+B%3BDeWeese-Scott%2C+C%3BFedorova%2C+N+D%3BGeer%2C+L+Y%3BHe%2C+S%3BHurwitz%2C+DI%3BJackson%2C+J+D%3BJacobs%2C+A+R%3BLanczycki%2C+C+J%3BLiebert%2C+CA%3BLiu%2C+C%3BMadej%2C+T%3BBryant%2C+SH&rft.aulast=Chen&rft.aufirst=J&rft.date=2003-01-01&rft.volume=31&rft.issue=1&rft.spage=474&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Database resources of the National Center for Biotechnology AN - 18655756; 5561600 AB - In addition to maintaining the GenBank(R) nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides data analysis and retrieval resources for the data in GenBank and other biological data made available through NCBI's Web site. NCBI resources include Entrez, PubMed, PubMed Central (PMC), LocusLink, the NCBITaxonomy Browser, BLAST, BLAST Link (BLink), Electronic PCR (e-PCR), Open Reading Frame (ORF) Finder, References Sequence (RefSeq), UniGene, HomoloGene, ProtEST, Database of Single Nucleotide Polymorphisms (dbSNP), Human/Mouse Homology Map, Cancer Chromosome Aberration Project (CCAP), Entrez Genomes and related tools, the Map Viewer, Model Maker (MM), Evidence Viewer (EV), Clusters of Orthologous Groups (COGs) database, Retroviral Genotyping Tools, SAGEmap, Gene Expression Omnibus (GEO), Online Mendelian Inheritance in Man (OMIM), the Molecular Modeling Database (MMDB), the Conserved Domain Database (CDD), and the Conserved Domain Architecture Retrieval Tool (CDART). Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized data sets. All of the resources can be accessed through the NCBI home page at: http://www.ncbi.nlm.nih.gov. JF - Nucleic Acids Research AU - Wheeler, D L AU - Church, D M AU - Federhen, S AU - Lash, A E AU - Madden, T L AU - Pontius, JU AU - Schuler, G D AU - Schriml, L M AU - Sequeira, E AU - Tatusova, T A AU - Wagner, L AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Building 38A, 8600 Rockville Pike, Bethesda, MD 20894, USA, wheeler@ncbi.nlm.nih.gov Y1 - 2003/01/01/ PY - 2003 DA - 2003 Jan 01 SP - 28 EP - 33 VL - 31 IS - 1 SN - 0305-1048, 0305-1048 KW - NBCI KW - National Center for Biotechnology Information KW - OMIM KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - N 14100:Reviews KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18655756?accountid=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=Database+resources+of+the+National+Center+for+Biotechnology&rft.au=Wheeler%2C+D+L%3BChurch%2C+D+M%3BFederhen%2C+S%3BLash%2C+A+E%3BMadden%2C+T+L%3BPontius%2C+JU%3BSchuler%2C+G+D%3BSchriml%2C+L+M%3BSequeira%2C+E%3BTatusova%2C+T+A%3BWagner%2C+L&rft.aulast=Wheeler&rft.aufirst=D&rft.date=2003-01-01&rft.volume=31&rft.issue=1&rft.spage=28&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Brief Assessment of Motor Function: Reliability and Concurrent Validity of the Gross Motor Scale AN - 18654543; 5559146 AB - The Brief Assessment of Motor Function (BAMF) is a series of 10-point ordinal scales developed for rapid description of gross motor, fine motor, and oral motor performance. We examined interrater and intrarater reliability and concurrent validity of the BAMF Gross Motor Scale. This validation study included 48 children (age, 5 mo to 17 yr) with a wide range of gross motor capability. Ten children with varied diagnoses participated in the reliability study. For concurrent validity, the BAMF performance of 38 children with osteogenesis imperfecta was compared with scores on the Peabody Developmental Motor Scales, laboratory gait analysis, and manual muscle testing. Reliability values for intraclass correlations were 0.996 (interrater) and 1.00 (intrarater). Significant relationships were identified between the BAMF and gait speed (r = 0.68, P < 0.0001), stride length (r = 0.71, P < 0.0001), duration of double-limb support (r = -0.40, P < 0.03), number of weak muscles (r = -0.74, P < 0.0001), and the Peabody Developmental Motor Scales (r = 0.95, P < 0.0001). Number of weak muscles was the strongest predictor of BAMF score (R super(2) = 0.5080, F = 24.77, P < 0.0001). The BAMF demonstrates good reliability for children with a range of diagnoses and acceptable concurrent validity with gross motor development, muscle strength, and formal gait assessment in children with osteogenesis imperfecta. JF - American Journal of Physical Medicine and Rehabilitation AU - Cintas, H L AU - Siegel, K L AU - Furst, G P AU - Gerber, L H AD - Physical Therapy Rehabilitation Medicine Department, National Institutes of Health, Building 10, Room 6 South 235, Bethesda, MD 20892-1604, USA Y1 - 2003/01// PY - 2003 DA - Jan 2003 SP - 33 EP - 41 VL - 82 IS - 1 SN - 0894-9115, 0894-9115 KW - Physical Education Index KW - PE 100:Kinesiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18654543?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Physical+Medicine+and+Rehabilitation&rft.atitle=Brief+Assessment+of+Motor+Function%3A+Reliability+and+Concurrent+Validity+of+the+Gross+Motor+Scale&rft.au=Cintas%2C+H+L%3BSiegel%2C+K+L%3BFurst%2C+G+P%3BGerber%2C+L+H&rft.aulast=Cintas&rft.aufirst=H&rft.date=2003-01-01&rft.volume=82&rft.issue=1&rft.spage=33&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Physical+Medicine+and+Rehabilitation&rft.issn=08949115&rft_id=info:doi/10.1097%2F01.PHM.0000043767.35490.42 LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1097/01.PHM.0000043767.35490.42 ER - TY - JOUR T1 - Activation of the rainbow trout metallothionein-A promoter by silver and zinc AN - 18640543; 5549664 AB - In fish, the synthesis of metallothionein (MT) is increased by a number of heavy metals. The rainbow trout MT-A gene promoter region contains six known metal responsive elements (MREs), that mediate promoter activation by metals. In the present study, two fish cell lines differing in their ability to produce MT, RTG-2 (produce MT protein) and CHSE-214 (produce no detectable MT protein), were used to help elucidate the roles of Zn, Ag and MT in the activation of the MT promoter. The hypothesis tested was that Ag activates the MT-A promoter indirectly by displacing Zn from pre-existing Zn-MT and that this liberated Zn subsequently induces MT synthesis. Both cell lines were transfected with a luciferase reporter gene construct containing the rainbow trout MT-A promoter, exposed to various concentrations of Zn or Ag, and assayed for luciferase activity. CHSE-214 cells showed five times greater production of luciferase than RTG-2 cells when exposed to identical concentrations of Ag. Thus, Ag can likely induce MT transcription without displacing Zn from pre-existing Zn-MT. Furthermore, Ag activated the MT promoter at concentrations 100-fold lower than those required for Zn to initiate transcription, suggesting that zinc displaced from other sites by such low concentrations of Ag would not be sufficient to initiate MT transcription. This interpretation was further supported by radiotracer studies indicating that Ag did not cause a redistribution of super(65)Zn within either of the two cell types. These combined results indicate that Ag may be a direct inducer of MT. JF - Comparative Biochemistry and Physiology, Part B: Biochemistry and Molecular Biology AU - Mayer, G D AU - Leach, A AU - Kling, P AU - Olsson, P-E AU - Hogstrand, C AD - University of Miami, NIEHS Marine and Freshwater Biomedical Sciences Center, Rosenstiel School of Marine and Atmospheric Sciences, 4600 Rickenbacker Causeway, Miami, FL 33149-1098, USA, gmayer@rsmas.miami.edu Y1 - 2003/01// PY - 2003 DA - Jan 2003 SP - 181 EP - 188 VL - 134 IS - 1 SN - 1096-4959, 1096-4959 KW - Gene regulation KW - Promoters KW - Rainbow trout KW - gene regulation KW - metallothionein-A KW - ASFA 1: Biological Sciences & Living Resources; ASFA 3: Aquatic Pollution & Environmental Quality; Oceanic Abstracts; ASFA Marine Biotechnology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Marine KW - Regulatory sequences KW - Brackish KW - Transcription KW - Pollution effects KW - Oncorhynchus mykiss KW - Freshwater KW - Gene expression KW - Metallothioneins KW - Zinc KW - Silver KW - O 4020:Pollution - Organisms/Ecology/Toxicology KW - Q1 08346:Physiology, biochemistry, biophysics KW - Q5 08504:Effects on organisms KW - O 1050:Vertebrates, Urochordates and Cephalochordates KW - Q4 27210:Fish KW - N 14662:Gene regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18640543?accountid=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=Comparative+Biochemistry+and+Physiology%2C+Part+B%3A+Biochemistry+and+Molecular+Biology&rft.atitle=Activation+of+the+rainbow+trout+metallothionein-A+promoter+by+silver+and+zinc&rft.au=Mayer%2C+G+D%3BLeach%2C+A%3BKling%2C+P%3BOlsson%2C+P-E%3BHogstrand%2C+C&rft.aulast=Mayer&rft.aufirst=G&rft.date=2003-01-01&rft.volume=134&rft.issue=1&rft.spage=181&rft.isbn=&rft.btitle=&rft.title=Comparative+Biochemistry+and+Physiology%2C+Part+B%3A+Biochemistry+and+Molecular+Biology&rft.issn=10964959&rft_id=info:doi/10.1016%2FS1096-4959%2802%2900248-8 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2014-05-07 N1 - SubjectsTermNotLitGenreText - Gene expression; Metallothioneins; Zinc; Pollution effects; Transcription; Silver; Promoters; Regulatory sequences; Gene regulation; Oncorhynchus mykiss; Freshwater; Brackish; Marine DO - http://dx.doi.org/10.1016/S1096-4959(02)00248-8 ER - TY - JOUR T1 - Phagocyte NADPH Oxidase, but Not Inducible Nitric Oxide Synthase, Is Essential for Early Control of Burkholderia cepacia and Chromobacterium violaceum Infection in Mice AN - 18626646; 5532511 AB - Reactive oxygen and nitrogen intermediates have critical, partially overlapping roles in host defense against a variety of pathogens. Using mice deficient in generating phagocyte superoxide (p47phox super(-/-)) and mice deficient in generating inducible nitric oxide synthase (iNOS super(-/-)), we examined the roles of these reactive species in host defense against Burkholderia cepacia and Chromobacterium violaceum, organisms known to have unusual virulence in chronic granulomatous disease. Intraperitoneal B. cepacia challenge (4.0 x 10 to 4.0 x 10 organisms/mouse) resulted in mortality in all p47phox super(-/-) mice, with the survival interval being inversely proportionate to the amount of inoculum. Pretreatment with gamma interferon did not affect survival. C. violaceum was strikingly virulent in p47phoxu super(-/-) mice (the 50% lethal dose (LD sub(50)) was <13 organisms). iNOS super(-/-) and wild-type mice were resistant to B. cepacia challenges of at least 10 organisms per mouse, and the LD sub(50) of C. violaceum was between 10 and 10 organisms per mouse. Consistent with the survival data, numbers of organisms in cultures of B. cepacia from multiple sites were higher for p47phox super(-/-) mice than for iNOS super(-/-) and wild-type mice at day 4 after challenge, but numbers of organisms for different B. cepacia strains varied. The recovery of C. violaceum was strikingly greater at 18 h after challenge for p47phox super(-/-) mice than for iNOS super(-/-) and wild- type mice, in which the organism burdens were virtually nil. In vitro, both B. cepacia and C. violaceum were sensitive to H sub(2)O sub(2) and to reactive nitrogen intermediates but the sensitivities of different strains varied significantly. Host defense against B. cepacia and C. violaceum is critically dependent in vivo on reactive oxygen intermediates, and these species are model organisms to further dissect host and pathogen interactions related to the generation and scavenging of microbicidal reactive intermediates. JF - Infection and Immunity AU - Segal, B H AU - Ding, L AU - Holland, S M AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Dr., MSC 1886, Bethesda, MD 20892, smh@nih.gov Y1 - 2003/01// PY - 2003 DA - Jan 2003 SP - 205 EP - 210 VL - 71 IS - 1 SN - 0019-9567, 0019-9567 KW - NADPH oxidase KW - mice KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - G 07240:Immunogenetics KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18626646?accountid=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=Phagocyte+NADPH+Oxidase%2C+but+Not+Inducible+Nitric+Oxide+Synthase%2C+Is+Essential+for+Early+Control+of+Burkholderia+cepacia+and+Chromobacterium+violaceum+Infection+in+Mice&rft.au=Segal%2C+B+H%3BDing%2C+L%3BHolland%2C+S+M&rft.aulast=Segal&rft.aufirst=B&rft.date=2003-01-01&rft.volume=71&rft.issue=1&rft.spage=205&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.71.1.205-210.2003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/IAI.71.1.205-210.2003 ER - TY - JOUR T1 - Enhanced Immunogenicity to Mycobacterium tuberculosis by Vaccination with an Alphavirus Plasmid Replicon Expressing Antigen 85A AN - 18623117; 5532548 AB - The immunogenicity of a plasmid DNA vaccine incorporating Sindbis virus RNA replicase functions (pSINCP) and expressing antigen 85A (Ag85A) from Mycobacterium tuberculosis was compared with a conventional plasmid DNA vector encoding Ag85A. pSINCP-85A was highly immunogenic in mice and gave enhanced long-term protection against M. tuberculosis compared with the conventional vector. JF - Infection and Immunity AU - Kirman, J R AU - Turon, T AU - Su, H AU - Li, A AU - Kraus, C AU - Polo, J M AU - Belisle, J AU - Morris, S AU - Seder, R A AD - Vaccine Research Center, 40 Convent Dr., Room 40/3512, NIH, Bethesda, MD 20892-3005, RSEDER@MAIL.NIH.GOV Y1 - 2003/01// PY - 2003 DA - Jan 2003 SP - 575 EP - 579 VL - 71 IS - 1 SN - 0019-9567, 0019-9567 KW - RNA replicase KW - antigen 85A KW - mice KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - J 02834:Vaccination and immunization KW - F 06807:Active immunization KW - N 14800:Immunological aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18623117?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Enhanced+Immunogenicity+to+Mycobacterium+tuberculosis+by+Vaccination+with+an+Alphavirus+Plasmid+Replicon+Expressing+Antigen+85A&rft.au=Kirman%2C+J+R%3BTuron%2C+T%3BSu%2C+H%3BLi%2C+A%3BKraus%2C+C%3BPolo%2C+J+M%3BBelisle%2C+J%3BMorris%2C+S%3BSeder%2C+R+A&rft.aulast=Kirman&rft.aufirst=J&rft.date=2003-01-01&rft.volume=71&rft.issue=1&rft.spage=575&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.71.1.575-579.2003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/IAI.71.1.575-579.2003 ER - TY - JOUR T1 - Nonsteroidal Anti-Inflammatory Drug Use and the Risk for Alzheimer's Disease: Dissecting the Epidemiological Evidence AN - 17964959; 5907082 AB - Inflammation is hypothesised to contribute to the genesis of pathology causing or contributing to Alzheimer's disease (AD). As a part of the immune response in the brain, the prostaglandin pathway is induced; this pathway is the target for NSAIDs, the most widely used anti-inflammatory medication. There are many epidemiological studies, which are reviewed here, suggesting NSAIDs reduce the risk for AD. The most recent of these studies suggest NSAIDs should be taken for at least 2 years. There are little data in humans about whether one type of NSAID is more effective than another. To date, randomised, double-blind, clinical trials in patients with AD have been negative. There is one prevention trial that will yield valuable information about the efficacy of NSAIDs in slowing down the progression of, or preventing, AD. At present, no recommendations can be made concerning the when, what, who and for how long a person should take an NSAID to reduce his or her risk for AD. JF - Drugs AU - Launer, L J AD - Laboratory for Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, MD, USA Y1 - 2003 PY - 2003 DA - 2003 SP - 731 EP - 739 VL - 63 IS - 8 SN - 0012-6667, 0012-6667 KW - Health & Safety Science Abstracts; Risk Abstracts KW - Alzheimer's disease KW - antiinflammatory agents KW - Side effects KW - R2 23060:Medical and environmental health KW - H 4000:Food and Drugs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17964959?accountid=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=Drugs&rft.atitle=Nonsteroidal+Anti-Inflammatory+Drug+Use+and+the+Risk+for+Alzheimer%27s+Disease%3A+Dissecting+the+Epidemiological+Evidence&rft.au=Launer%2C+L+J&rft.aulast=Launer&rft.aufirst=L&rft.date=2003-01-01&rft.volume=63&rft.issue=8&rft.spage=731&rft.isbn=&rft.btitle=&rft.title=Drugs&rft.issn=00126667&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; Alzheimer's disease; antiinflammatory agents ER - TY - JOUR T1 - Dmt and opioid peptides: A potent alliance AN - 17878067; 5907917 AB - The introduction of the Dmt (2',6'-dimethyl-L-tyrosine)-Tic pharmacophore into the design of opioid ligands produced an extraordinary family of potent delta -opioid receptor antagonists and heralded a new phase in opioid research. First reviewed extensively in 1998, the incorporation of Dmt into a diverse group of opioid molecules stimulated the opioid field leading to the development of unique analogues with remarkable properties. This overview will document the crucial role played by this residue in the proliferation of opioid peptides with high receptor affinity (K sub(i) equal to or less than 1 nM) and potent bioactivity. The discussion will include the metamorphosis between delta - opioid receptor antagonists to delta -agonists based solely on subtle structural changes at the C-terminal region of the Dmt-Tic pharmacophore as well as their behavior in vivo. Dmt may be considered promiscuous due to the acquisition of potent mu -agonism by dermorphin and endomorphin derivatives as well as by a unique class of opioidmimetics containing two Dmt residues separated by alkyl or pyrazinone linkers. Structural studies on the Dmt-Tic compounds were enhanced tremendously by x-ray diffraction data for three potent and biologically diverse Dmt-Tic opioidmimetics that led to the development of pharmacophores for both delta -opioid receptor agonists and antagonists. Molecular modeling studies of other unique Dmt opioid analogues illuminated structural differences between delta - and mu -receptor ligand interactions. The future of these compounds as therapeutic applications for various medical syndromes including the control of cancer-associated pain is only a matter of time and perseverance. JF - Biopolymers (Peptide Science) AU - Bryant, Sharon D AU - Jinsmaa, Yunden AU - Salvadori, Severo AU - Okada, Yoshio AU - Lazarus, Lawrence H AD - Peptide Neurochemistry, LCBRA, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 USA, bryant2@niehs.nih.gov Y1 - 2003 PY - 2003 DA - 2003 SP - 86 EP - 102 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 71 IS - 2 SN - 0006-3525, 0006-3525 KW - 2',6'-dimethyl-L-tyrosine KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Opioid receptors KW - opioid peptides KW - Endomorphin KW - Opioid receptors (type ^d) KW - Reviews KW - Therapeutic applications KW - Pain KW - Metamorphosis KW - X-ray diffraction KW - Antagonists KW - pharmacophores KW - W4 130:General Biomedical Engineering: Tools & Techniques KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17878067?accountid=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=Biopolymers+%28Peptide+Science%29&rft.atitle=Dmt+and+opioid+peptides%3A+A+potent+alliance&rft.au=Bryant%2C+Sharon+D%3BJinsmaa%2C+Yunden%3BSalvadori%2C+Severo%3BOkada%2C+Yoshio%3BLazarus%2C+Lawrence+H&rft.aulast=Bryant&rft.aufirst=Sharon&rft.date=2003-01-01&rft.volume=71&rft.issue=2&rft.spage=86&rft.isbn=&rft.btitle=&rft.title=Biopolymers+%28Peptide+Science%29&rft.issn=00063525&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 - pharmacophores; Antagonists; Reviews; Opioid receptors (type ^d); opioid peptides; X-ray diffraction; Opioid receptors; Endomorphin; Therapeutic applications; Metamorphosis; Pain ER - TY - JOUR T1 - Photocarcinogenesis in the Tg.AC Mouse: Lomefloxacin and 8-Methoxypsoralen AN - 17858349; 5973416 AB - The Tg.AC mouse is a good predictor of carcinogenic potential when the test article is administered by dorsal painting (Tennant et al. (1995) Environ. Health Perspect. 103, 942). We have used lomefloxacin (LOME) and 8-methoxypsoralen (8-MOP) in combination with UVA to determine whether the Tg.AC transgenic mouse also responds to parenterally administered photocarcinogens. Female Tg.AC mice were given LOME (25 mg/kg intraperitoneal in normal saline) followed by UVA (25 J/cm2) 1-2 h later, five times every 2 weeks on a repetitive schedule. Other groups received LOME, UVA or vehicle alone. After 16 weeks, the mean numbers of papillomas/mouse +/- SD (% responding) were: saline, 0.3 +/- 0.5 (33%); UVA + saline, 1.3 +/- 0.6 (100%); LOME, 1.9 +/- 1.6 (86%) and LOME-UVA, 1.5 +/- 1.9 (64%). Only the 100% incidence of tumors in the UVA group and the maximum tumor yields in the LOME and UVA groups are significant (P < 0.05) when compared with the control. In a second study, Tg.AC mice were administered the classical photocarcinogen 8-MOP (8 mg/kg intragastric in corn oil) followed by 2 J/cm2 UVA 1-2 h later, five times every 2 weeks on a repetitive schedule. The second group received 8-MOP, whereas the third was exposed to UVA alone. Papillomas began to appear at 2 weeks in the 8-MOP-UVA group, and after 17 weeks the mean numbers of papillomas/mouse +/- SD (% responding) were: 8-MOP-UVA, 6.9 +/- 8.6 (93%); UVA + corn oil, 1.1 +/- 1.2 (69%) and 8-MOP, 1.1 +/- 1.6 (50%). The maximum tumor yield in the 8-MOP-UVA group was significantly higher (P < 0.01) than that in the other two groups. Our findings suggest that more studies need to be done before the Tg.AC mouse can be used with confidence to identify parenterally administered photocarcinogens. JF - Photochemistry and Photobiology AU - Chignell, C F AU - Haseman, J K AU - Sik, R H AU - Tennant, R W AU - Trempus, C S AD - Laboratory of Pharmacology and Chemistry, ETP, NIEHS, NIH, Research Triangle Park, NC Y1 - 2003/01// PY - 2003 DA - Jan 2003 SP - 77 EP - 80 PB - American Society for Photobiology VL - 77 IS - 1 SN - 0031-8655, 0031-8655 KW - 8-Methoxypsoralen KW - Toxicology Abstracts KW - Photochemistry KW - Oil KW - saline KW - Lomefloxacin KW - Transgenic mice KW - Papilloma KW - X 24210:Radiation & radioactive materials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17858349?accountid=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=Photochemistry+and+Photobiology&rft.atitle=Photocarcinogenesis+in+the+Tg.AC+Mouse%3A+Lomefloxacin+and+8-Methoxypsoralen&rft.au=Chignell%2C+C+F%3BHaseman%2C+J+K%3BSik%2C+R+H%3BTennant%2C+R+W%3BTrempus%2C+C+S&rft.aulast=Chignell&rft.aufirst=C&rft.date=2003-01-01&rft.volume=77&rft.issue=1&rft.spage=77&rft.isbn=&rft.btitle=&rft.title=Photochemistry+and+Photobiology&rft.issn=00318655&rft_id=info:doi/10.1562%2F0031-8655%282003%290772.0.CO%3B2 L2 - http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0031-8655&volume=77&page=77 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Papilloma; saline; Lomefloxacin; Oil; Transgenic mice; Photochemistry DO - http://dx.doi.org/10.1562/0031-8655(2003)077<0077:PITTAM>2.0.CO;2 ER - TY - JOUR T1 - The COG database: an updated version includes eukaryotes AN - 17531407; 6234072 AB - Background: The availability of multiple, essentially complete genome sequences of prokaryotes and eukaryotes spurred both the demand and the opportunity for the construction of an evolutionary classification of genes from these genomes. Such a classification system based on orthologous relationships between genes appears to be a natural framework for comparative genomics and should facilitate both functional annotation of genomes and large-scale evolutionary studies. Results: We describe here a major update of the previously developed system for delineation of Clusters of Orthologous Groups of proteins (COGs) from the sequenced genomes of prokaryotes and unicellular eukaryotes and the construction of clusters of predicted orthologs for 7 eukaryotic genomes, which we named KOGs after eukaryotic orthologous groups. The COG collection currently consists of 138,458 proteins, which form 4873 COGs and comprise 75% of the 185,505 (predicted) proteins encoded in 66 genomes of unicellular organisms. The eukaryotic orthologous groups (KOGs) include proteins from 7 eukaryotic genomes: three animals (the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster and Homo sapiens), one plant, Arabidopsis thaliana, two fungi (Saccharomyces cerevisiae and Schizosaccharomyces pombe), and the intracellular microsporidian parasite Encephalitozoon cuniculi. The current KOG set consists of 4852 clusters of orthologs, which include 59,838 proteins, or ~54% of the analyzed eukaryotic 110,655 gene products. Compared to the coverage of the prokaryotic genomes with COGs, a considerably smaller fraction of eukaryotic genes could be included into the KOGs; addition of new eukaryotic genomes is expected to result in substantial increase in the coverage of eukaryotic genomes with KOGs. Examination of the phyletic patterns of KOGs reveals a conserved core represented in all analyzed species and consisting of ~20% of the KOG set. This conserved portion of the KOG set is much greater than the ubiquitous portion of the COG set (~1% of the COGs). In part, this difference is probably due to the small number of included eukaryotic genomes, but it could also reflect the relative compactness of eukaryotes as a clade and the greater evolutionary stability of eukaryotic genomes. Conclusions: The updated collection of orthologous protein sets for prokaryotes and eukaryotes is expected to be a useful platform for functional annotation of newly sequenced genomes, including those of complex eukaryotes, and genome-wide evolutionary studies. JF - BMC Bioinformatics AU - Tatusov, Roman L AU - Fedorova, Natalie D AU - Jackson, John D AU - Jacobs, Aviva R AU - Kiryutin, Boris AU - Koonin, Eugene V AU - Krylov, Dmitri M AU - Mazumder, Raja AU - Mekhedov, Sergei L AU - Nikolskaya, Anastasia N AU - Rao, BSridhar AU - Smirnov, Sergei AU - Sverdlov, Alexander V AU - Vasudevan, Sona AU - Wolf, Yuri I AU - Yin, Jodie J AU - Natale, Darren A AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda MD, USA, tatusov@ncbi.nlm.nih.gov Y1 - 2003 PY - 2003 DA - 2003 PB - BioMed Central Ltd., Middlesex House 34-42 Cleveland Street London W1T 4LB UK, [mailto:info@biomedcentral.com], [URL:http://www.biomedcentral.com] VL - 4 KW - budding yeast KW - Nematodes KW - fission yeast KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Classification systems KW - Genomes KW - Parasites KW - Fungi KW - Saccharomyces cerevisiae KW - Eukaryotes KW - Databases KW - Arabidopsis thaliana KW - Caenorhabditis elegans KW - Drosophila melanogaster KW - genomics KW - Bioinformatics KW - Prokaryotes KW - Encephalitozoon cuniculi KW - Evolution KW - Nematoda KW - Schizosaccharomyces pombe KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17531407?accountid=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=BMC+Bioinformatics&rft.atitle=The+COG+database%3A+an+updated+version+includes+eukaryotes&rft.au=Tatusov%2C+Roman+L%3BFedorova%2C+Natalie+D%3BJackson%2C+John+D%3BJacobs%2C+Aviva+R%3BKiryutin%2C+Boris%3BKoonin%2C+Eugene+V%3BKrylov%2C+Dmitri+M%3BMazumder%2C+Raja%3BMekhedov%2C+Sergei+L%3BNikolskaya%2C+Anastasia+N%3BRao%2C+BSridhar%3BSmirnov%2C+Sergei%3BSverdlov%2C+Alexander+V%3BVasudevan%2C+Sona%3BWolf%2C+Yuri+I%3BYin%2C+Jodie+J%3BNatale%2C+Darren+A&rft.aulast=Tatusov&rft.aufirst=Roman&rft.date=2003-01-01&rft.volume=4&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=BMC+Bioinformatics&rft.issn=1471-2105&rft_id=info:doi/10.1186%2F1471-2105-4-41 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Saccharomyces cerevisiae; Drosophila melanogaster; Nematoda; Encephalitozoon cuniculi; Schizosaccharomyces pombe; Arabidopsis thaliana; Caenorhabditis elegans; Eukaryotes; Genomes; Prokaryotes; Evolution; Bioinformatics; genomics; Parasites; Classification systems; Databases; Fungi DO - http://dx.doi.org/10.1186/1471-2105-4-41 ER - TY - JOUR T1 - PubMatrix: a tool for multiplex literature mining AN - 17527931; 6234094 AB - Background: Molecular experiments using multiplex strategies such as cDNA microarrays or proteomic approaches generate large datasets requiring biological interpretation. Text based data mining tools have recently been developed to query large biological datasets of this type of data. PubMatrix is a web-based tool that allows simple text based mining of the NCBI literature search service PubMed using any two lists of keywords terms, resulting in a frequency matrix of term co-occurrence. Results: For example, a simple term selection procedure allows automatic pair-wise comparisons of approximately 1-100 search terms versus approximately 1-10 modifier terms, resulting in up to 1,000 pair wise comparisons. The matrix table of pair-wise comparisons can then be surveyed, queried individually, and archived. Lists of keywords can include any terms currently capable of being searched in PubMed. In the context of cDNA microarray studies, this may be used for the annotation of gene lists from clusters of genes that are expressed coordinately. An associated PubMatrix public archive provides previous searches using common useful lists of keyword terms. Conclusions: In this way, lists of terms, such as gene names, or functional assignments can be assigned genetic, biological, or clinical relevance in a rapid flexible systematic fashion. http://pubmatrix.grc.nia.nih.gov/ JF - BMC Bioinformatics AU - Becker, Kevin G AU - Hosack, Douglas A AU - Dennis, Glynn AU - Lempicki, Richard A AU - Bright, Tiffani J AU - Cheadle, Chris AU - Engel, Jim AD - Gene Expression and Genomics Unit, National Institutes of Health, Baltimore, MD, USA, beckerk@grc.nia.nih.gov Y1 - 2003 PY - 2003 DA - 2003 PB - BioMed Central Ltd., Middlesex House 34-42 Cleveland Street London W1T 4LB UK, [mailto:info@biomedcentral.com], [URL:http://www.biomedcentral.com] VL - 4 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Data processing KW - Bioinformatics KW - proteomics KW - DNA microarrays KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17527931?accountid=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=BMC+Bioinformatics&rft.atitle=PubMatrix%3A+a+tool+for+multiplex+literature+mining&rft.au=Becker%2C+Kevin+G%3BHosack%2C+Douglas+A%3BDennis%2C+Glynn%3BLempicki%2C+Richard+A%3BBright%2C+Tiffani+J%3BCheadle%2C+Chris%3BEngel%2C+Jim&rft.aulast=Becker&rft.aufirst=Kevin&rft.date=2003-01-01&rft.volume=4&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=BMC+Bioinformatics&rft.issn=1471-2105&rft_id=info:doi/10.1186%2F1471-2105-4-61 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - DNA microarrays; Data processing; proteomics; Bioinformatics DO - http://dx.doi.org/10.1186/1471-2105-4-61 ER - TY - JOUR T1 - A tool for sharing annotated research data: the "Category 0" UMLS (Unified Medical Language System) vocabularies AN - 17516398; 6060634 AB - Large biomedical data sets have become increasingly important resources for medical researchers. Modern biomedical data sets are annotated with standard terms to describe the data and to support data linking between databases. The largest curated listing of biomedical terms is the the National Library of Medicine's Unified Medical Language System (UMLS). The UMLS contains more than 2 million biomedical terms collected from nearly 100 medical vocabularies. Many of the vocabularies contained in the UMLS carry restrictions on their use, making it impossible to share or distribute UMLS-annotated research data. However, a subset of the UMLS vocabularies, designated Category 0 by UMLS, can be used to annotate and share data sets without violating the UMLS License Agreement. The UMLS Category 0 vocabularies can be extracted from the parent UMLS metathesaurus using a Perl script supplied with this article. There are 43 Category 0 vocabularies that can be used freely for research purposes without violating the UMLS License Agreement. Among the Category 0 vocabularies are: MESH (Medical Subject Headings), NCBI (National Center for Bioinformatics) Taxonomy and ICD-9-CM (International Classification of Diseases-9-Clinical Modifiers). The extraction file containing all Category 0 terms and concepts is 72,581,138 bytes in length and contains 1,029,161 terms. The UMLS Metathesaurus MRCON file (January, 2003) is 151,048,493 bytes in length and contains 2,146,899 terms. Therefore the Category 0 vocabularies, in aggregate, are about half the size of the UMLS metathesaurus. A large publicly available listing of 567,921 different medical phrases were automatically coded using the full UMLS metatathesaurus and the Category 0 vocabularies. There were 545,321 phrases with one or more matches against UMLS terms while 468,785 phrases had one or more matches against the Category 0 terms. This indicates that when the two vocabularies are evaluated by their fitness to find at least one term for a medical phrase, the Category 0 vocabularies performed 86% as well as the complete UMLS metathesaurus. The Category 0 vocabularies of UMLS constitute a large nomenclature that can be used by biomedical researchers to annotate biomedical data. These annotated data sets can be distributed for research purposes without violating the UMLS License Agreement. These vocabularies may be of particular importance for sharing heterogeneous data from diverse biomedical data sets. The software tools to extract the Category 0 vocabularies are freely available Perl scripts entered into the public domain and distributed with this article. JF - BMC Medical Informatics and Decision Making AU - Berman, Jules J AD - Cancer Diagnosis Program, National Cancer Institute, NIH, Rockville, MD, USA, bermanj@mail.nih.gov Y1 - 2003 PY - 2003 DA - 2003 PB - BioMed Central Ltd., Middlesex House 34-42 Cleveland Street London W1T 4LB UK, [mailto:info@biomedcentral.com], [URL:http://www.biomedcentral.com] VL - 3 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Databases KW - Computer programs KW - software KW - Taxonomy KW - Language KW - Bioinformatics KW - W4 140:Bioinformatics & Computers in Health & Medicine KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17516398?accountid=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=BMC+Medical+Informatics+and+Decision+Making&rft.atitle=A+tool+for+sharing+annotated+research+data%3A+the+%22Category+0%22+UMLS+%28Unified+Medical+Language+System%29+vocabularies&rft.au=Berman%2C+Jules+J&rft.aulast=Berman&rft.aufirst=Jules&rft.date=2003-01-01&rft.volume=3&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=BMC+Medical+Informatics+and+Decision+Making&rft.issn=1472-6947&rft_id=info:doi/10.1186%2F1472-6947-3-6 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Language; Bioinformatics; Computer programs; Databases; software; Taxonomy DO - http://dx.doi.org/10.1186/1472-6947-3-6 ER - TY - JOUR T1 - The tissue microarray data exchange specification: A community-based, open source tool for sharing tissue microarray data AN - 17515272; 6060671 AB - Tissue Microarrays (TMAs) allow researchers to examine hundreds of small tissue samples on a single glass slide. The information held in a single TMA slide may easily involve Gigabytes of data. To benefit from TMA technology, the scientific community needs an open source TMA data exchange specification that will convey all of the data in a TMA experiment in a format that is understandable to both humans and computers. A data exchange specification for TMAs allows researchers to submit their data to journals and to public data repositories and to share or merge data from different laboratories. In May 2001, the Association of Pathology Informatics (API) hosted the first in a series of four workshops, co- sponsored by the National Cancer Institute, to develop an open, community- supported TMA data exchange specification. A draft tissue microarray data exchange specification was developed through workshop meetings. The first workshop confirmed community support for the effort and urged the creation of an open XML-based specification. This was to evolve in steps with approval for each step coming from the stakeholders in the user community during open workshops. By the fourth workshop, held October, 2002, a set of Common Data Elements (CDEs) was established as well as a basic strategy for organizing TMA data in self-describing XML documents. The TMA data exchange specification is a well-formed XML document with four required sections: 1) Header, containing the specification Dublin Core identifiers, 2) Block, describing the paraffin-embedded array of tissues, 3)Slide, describing the glass slides produced from the Block, and 4) Core, containing all data related to the individual tissue samples contained in the array. Eighty CDEs, conforming to the ISO-11179 specification for data elements constitute XML tags used in the TMA data exchange specification. A set of six simple semantic rules describe the complete data exchange specification. Anyone using the data exchange specification can validate their TMA files using a software implementation written in Perl and distributed as a supplemental file with this publication. The TMA data exchange specification is now available in a draft form with community-approved Common Data Elements and a community-approved general file format and data structure. The specification can be freely used by the scientific community. Efforts sponsored by the Association for Pathology Informatics to refine the draft TMA data exchange specification are expected to continue for at least two more years. The interested public is invited to participate in these open efforts. Information on future workshops will be posted at http://www.pathologyinformatics.org (API we site). JF - BMC Medical Informatics and Decision Making AU - Berman, Jules J AU - Edgerton, Mary E AU - Friedman, Bruce A AD - Cancer Diagnosis Program, National Cancer Institute, Bethesda, MD, USA, bermanj@mail.nih.gov Y1 - 2003 PY - 2003 DA - 2003 PB - BioMed Central Ltd., Middlesex House 34-42 Cleveland Street London W1T 4LB UK, [mailto:info@biomedcentral.com], [URL:http://www.biomedcentral.com] VL - 3 KW - tissue microarrays KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Decision making KW - Computer programs KW - software KW - Computers KW - Cancer KW - W4 140:Bioinformatics & Computers in Health & Medicine KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17515272?accountid=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=BMC+Medical+Informatics+and+Decision+Making&rft.atitle=The+tissue+microarray+data+exchange+specification%3A+A+community-based%2C+open+source+tool+for+sharing+tissue+microarray+data&rft.au=Berman%2C+Jules+J%3BEdgerton%2C+Mary+E%3BFriedman%2C+Bruce+A&rft.aulast=Berman&rft.aufirst=Jules&rft.date=2003-01-01&rft.volume=3&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=BMC+Medical+Informatics+and+Decision+Making&rft.issn=1472-6947&rft_id=info:doi/10.1186%2F1472-6947-3-5 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - software; Computer programs; Cancer; Computers; Decision making DO - http://dx.doi.org/10.1186/1472-6947-3-5 ER - TY - JOUR T1 - Validation of the Eulerian pollution transport model PolTran on the Kincaid data set AN - 16175400; 5967600 AB - The study represents the first performance of the model PolTran on the Kincaid data set. PolTran is a typical representative of the Eulerian models: two dimensional Eulerian advection scheme and numerical calculation of the vertical diffusion. The meteorological pre-processor uses the Kincaid measurements of wind and temperature at 10, 50 and 100 m and provides the dispersion model with wind and turbulence exchange profiles. The model performance is comparable to other models applied to the Model Validation Kit, that could be considered as a good result for a local scale application of a model of Eulerian type. JF - International Journal of Environment and Pollution AU - Atanassov, D AD - National Institute of Meteorology and Hydrology (NIMH), 66, Tsarigradsko chaussee, 1784 Sofia, Bulgaria, Dimiter.Atanassov@meteo.bg Y1 - 2003 PY - 2003 DA - 2003 SP - 105 EP - 113 VL - 20 IS - 1-6 SN - 0957-4352, 0957-4352 KW - PolTran KW - Pollution Abstracts KW - Air pollution KW - Mathematical models KW - Pollution dispersion KW - Diffusion KW - Meteorology KW - Turbulence KW - Wind KW - P 0000:AIR POLLUTION UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16175400?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Apollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Environment+and+Pollution&rft.atitle=Validation+of+the+Eulerian+pollution+transport+model+PolTran+on+the+Kincaid+data+set&rft.au=Atanassov%2C+D&rft.aulast=Atanassov&rft.aufirst=D&rft.date=2003-01-01&rft.volume=20&rft.issue=1-6&rft.spage=105&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Environment+and+Pollution&rft.issn=09574352&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2004-09-01 N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Air pollution; Mathematical models; Pollution dispersion; Meteorology; Diffusion; Turbulence; Wind ER - TY - JOUR T1 - Gene expression profiling: methodological challenges, results, and prospects for addiction research. AN - 72807004; 12505704 AB - This review describes the current methods used to profile gene expression. These methods include microarrays, spotted arrays, serial analysis of gene expression (SAGE), and massive parallel signature sequencing (MPSS). Methodological and statistical problems in interpreting microarray and spotted array experiments are also discussed. Methods and formats such as minimum information about microarray experiments (MIAME) needed to share gene expression data are described. The last part of the review provides an overview of the application of gene-expression profiling technology to substance abuse research and discusses future directions. JF - Chemistry and physics of lipids AU - Pollock, Jonathan D AD - Genetics and Molecular Neurobiology Research Branch, National Institute on Drug Abuse, 6001 Executive Blvd, Rockville, MD 20850, USA. jp183r@nih.gov Y1 - 2002/12/31/ PY - 2002 DA - 2002 Dec 31 SP - 241 EP - 256 VL - 121 IS - 1-2 SN - 0009-3084, 0009-3084 KW - Index Medicus KW - Signal Transduction -- physiology KW - Animals KW - Humans KW - Oligonucleotide Array Sequence Analysis -- methods KW - Data Interpretation, Statistical KW - Research -- trends KW - Substance-Related Disorders -- metabolism KW - Substance-Related Disorders -- genetics KW - Gene Expression Profiling -- methods KW - Gene Expression Profiling -- standards UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72807004?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemistry+and+physics+of+lipids&rft.atitle=Gene+expression+profiling%3A+methodological+challenges%2C+results%2C+and+prospects+for+addiction+research.&rft.au=Pollock%2C+Jonathan+D&rft.aulast=Pollock&rft.aufirst=Jonathan&rft.date=2002-12-31&rft.volume=121&rft.issue=1-2&rft.spage=241&rft.isbn=&rft.btitle=&rft.title=Chemistry+and+physics+of+lipids&rft.issn=00093084&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-22 N1 - Date created - 2002-12-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Addictive potential of cannabinoids: the underlying neurobiology. AN - 72806894; 12505706 AB - Drugs that are addictive in humans have a number of commonalities in animal model systems-(1). they enhance electrical brain-stimulation reward in the core meso-accumbens reward circuitry of the brain, a circuit encompassing that portion of the medial forebrain bundle (MFB) which links the ventral tegmental area (VTA) of the mesencephalic midbrain with the nucleus accumbens (Acb) of the ventral limbic forebrain; (2). they enhance neural firing of a core dopamine (DA) component of this meso-accumbens reward circuit; (3). they enhance DA tone in this reward-relevant meso-accumbens DA circuit, with resultant enhancement of extracellular Acb DA; (4). they produce conditioned place preference (CPP), a behavioral model of incentive motivation; (5). they are self-administered; and (6). they trigger reinstatement of drug-seeking behavior in animals behaviorally extinguished from intravenous drug self-administration behavior and, perforce, pharmacologically detoxified from their self-administered drug. Cannabinoids were long considered 'anomalous', in that they were believed to not interact with these brain reward processes or support drug-seeking and drug-taking behavior in these animal model systems. However, it is now clear-from the published data of several research groups over the last 15 years-that this view of cannabinoid action on brain reward processes and reward-related behaviors is untenable. This paper reviews those data, and concludes that cannabinoids act on brain reward processes and reward-related behaviors in strikingly similar fashion to other addictive drugs. JF - Chemistry and physics of lipids AU - Gardner, Eliot L AD - National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Building C, Room 272, 5500 Nathan Shock Drive, Baltimore, MD 20850, USA. egardner@intra.nida.nih.gov Y1 - 2002/12/31/ PY - 2002 DA - 2002 Dec 31 SP - 267 EP - 290 VL - 121 IS - 1-2 SN - 0009-3084, 0009-3084 KW - Cannabinoids KW - 0 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Behavior, Addictive KW - Reward KW - Humans KW - Dopamine -- physiology KW - Nucleus Accumbens -- metabolism KW - Ventral Tegmental Area -- metabolism KW - Substance-Related Disorders -- physiopathology KW - Cannabinoids -- adverse effects KW - Brain -- drug effects KW - Substance-Related Disorders -- etiology KW - Cannabinoids -- pharmacology KW - Brain -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72806894?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemistry+and+physics+of+lipids&rft.atitle=Addictive+potential+of+cannabinoids%3A+the+underlying+neurobiology.&rft.au=Gardner%2C+Eliot+L&rft.aulast=Gardner&rft.aufirst=Eliot&rft.date=2002-12-31&rft.volume=121&rft.issue=1-2&rft.spage=267&rft.isbn=&rft.btitle=&rft.title=Chemistry+and+physics+of+lipids&rft.issn=00093084&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-22 N1 - Date created - 2002-12-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - pol iota -dependent lesion bypass in vitro AN - 19815772; 5514703 AB - Based upon phylogenetic relationships, the broad Y-family of DNA polymerases can be divided into various subfamilies consisting of UmuC (polV)-like; DinB (polIV/pol Kappa )-like; Rev1-like, Rad30A (pol eta )-like and Rad30B (pol iota )-like polymerases. The polIV /pol Kappa -like polymerases are most ubiquitous, having been identified in bacteria, archaea and eukaryotes. In contrast, the polV-like polymerases appear restricted to bacteria (both Gram positive and Gram negative). Rev1 and pol eta -like polymerases are found exclusively in eukaryotes, and to date, pol iota -like polymerases have only been identified in higher eukaryotes. In general, the in vitro properties of polymerases characterized within each sub-family are quite similar. An exception to this rule occurs with the pol iota -like polymerases, where the enzymatic properties of Drosophila melanogaster pol iota are more similar to that of Saccharomyces cerevisiae and human pol eta than to the related human pol iota . For example, like pol eta , Drosophila pol iota can bypass a cis-syn thymine-thymine dimer both accurately and efficiently, while human pol iota bypasses the same lesion inefficiently and with low-fidelity. Even in cases where human pol iota can efficiently insert a base opposite a lesion (such as a synthetic abasic site, the 3T of a 6-4-thymine-thymine pyrimidine-pyrimidone photoproduct or opposite benzo[a]pyrene diol epoxide deoxyadenosine adducts), further extension is often limited. Thus, although pol iota most likely arose from a genetic duplication of pol eta millions of years ago as eukaryotes evolved, it would appear that pol iota from humans (and possibly all mammals) has been further subjected to evolutionary pressures that have 'tailored' its enzymatic properties away from lesion bypass and towards other function(s) specific for higher eukaryotes. The identification of such functions and the role that mammalian pol iota plays in lesion bypass in vivo, should hopefully be forthcoming with the construction of human cell lines deleted for pol iota and the identification of mice deficient in pol iota . JF - Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis AU - Vaisman, A AU - Frank, E G AU - McDonald, J P AU - Tissier, A AU - Woodgate, R AD - Section on DNA Replication, Repair and Mutagenesis, National Institute of Child Health and Human Development, National Institutes of Health, Building 6, Room 1A13, 9000 Rockville Pike, Bethesda, MD 20892-2725, USA, woodgate@helix.nih.gov Y1 - 2002/12/29/ PY - 2002 DA - 2002 Dec 29 SP - 9 EP - 22 PB - Elsevier Science VL - 510 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; Microbiology Abstracts B: Bacteriology; Genetics Abstracts; Entomology Abstracts KW - Phylogeny KW - Molecular modelling KW - Epoxides KW - Archaea KW - Adducts KW - deoxyadenosine KW - Saccharomyces cerevisiae KW - Mutagenesis KW - DNA-directed DNA polymerase KW - Drosophila melanogaster KW - Benzo(a)pyrene KW - Pressure KW - Evolution KW - Z 05300:General KW - J 02400:Human Diseases KW - K 03310:Genetics & Taxonomy KW - G 07770:Bacteria UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19815772?accountid=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=Mutation+Research-Fundamental+and+Molecular+Mechanisms+of+Mutagenesis&rft.atitle=pol+iota+-dependent+lesion+bypass+in+vitro&rft.au=Vaisman%2C+A%3BFrank%2C+E+G%3BMcDonald%2C+J+P%3BTissier%2C+A%3BWoodgate%2C+R&rft.aulast=Vaisman&rft.aufirst=A&rft.date=2002-12-29&rft.volume=510&rft.issue=1-2&rft.spage=9&rft.isbn=&rft.btitle=&rft.title=Mutation+Research-Fundamental+and+Molecular+Mechanisms+of+Mutagenesis&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-06-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Phylogeny; Molecular modelling; Epoxides; Adducts; DNA-directed DNA polymerase; deoxyadenosine; Benzo(a)pyrene; Pressure; Evolution; Mutagenesis; Archaea; Drosophila melanogaster; Saccharomyces cerevisiae ER - TY - JOUR T1 - Disposition of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5h)-furanone (mx) in b6c3f1 mice and f344 rats. AN - 72808142; 12515589 AB - 3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) is a mutagenic by-product of chlorination of drinking water, particularly where the water contains humic matter. MX has been estimated to account for 50% of the mutagenic activity in some drinking water. A bioassay in rats demonstrated an increased tumor incidence, primarily in liver and thyroid glands. This study was designed to provide disposition/metabolism information in mice to evaluate the necessity of a National Toxicology Program chronic bioassay and to provide data for female rats. Radioactivity was rapidly absorbed and excreted near equally in urine (42-54%) and feces (40-51%) 72 h following oral administration of (14)C-labeled MX at single doses from 0.2 to 20 mg/kg to male and female mice and female rats. A larger percentage (71-73%) of MX-derived radioactivity was excreted in urine after an iv dose (0.2 mg/kg) in both female rats and male mice. Most MX-derived radioactivity was excreted within the first 24 h postdosing. MX was transformed to urinary and biliary metabolites. A major extremely polar urinary metabolite was tentatively identified as 1-hydroxy-1,2,2-ethanetricarboxylic acid. This metabolite is likely transformed from the MX degradation product 2-hydroxy-3-formyl-4-oxo-2-butenoic acid. Oral administration produced highest tissue/blood ratios in the following order: forestomach (>100), glandular stomach, intestine, and kidney. Intravenous administration resulted in high, prolonged levels of radioactivity in blood compared to oral dosing. Therefore, MX disposition appears to be dominated by its chemical reactivity with highest concentrations of radioactivity being found at the site of administration. JF - Journal of toxicology and environmental health. Part A AU - Lebetkin, Edward H AU - Chen, Ling-Jen AU - Burka, Leo T AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2002/12/27/ PY - 2002 DA - 2002 Dec 27 SP - 2101 EP - 2118 VL - 65 IS - 24 SN - 1528-7394, 1528-7394 KW - Carcinogens KW - 0 KW - Furans KW - Water Pollutants, Chemical KW - 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone KW - 77439-76-0 KW - Index Medicus KW - Spectrometry, Mass, Electrospray Ionization KW - Animals KW - Hydrogen-Ion Concentration KW - Spectrophotometry, Ultraviolet KW - Bile -- metabolism KW - Mice KW - Tissue Distribution KW - Feces -- chemistry KW - Chromatography, High Pressure Liquid KW - Magnetic Resonance Spectroscopy KW - Rats KW - Mice, Inbred Strains KW - Rats, Inbred F344 KW - Biotransformation KW - Female KW - Male KW - Furans -- pharmacokinetics KW - Carcinogens -- pharmacokinetics KW - Water Pollutants, Chemical -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72808142?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+toxicology+and+environmental+health.+Part+A&rft.atitle=Disposition+of+3-chloro-4-%28dichloromethyl%29-5-hydroxy-2%285h%29-furanone+%28mx%29+in+b6c3f1+mice+and+f344+rats.&rft.au=Lebetkin%2C+Edward+H%3BChen%2C+Ling-Jen%3BBurka%2C+Leo+T&rft.aulast=Lebetkin&rft.aufirst=Edward&rft.date=2002-12-27&rft.volume=65&rft.issue=24&rft.spage=2101&rft.isbn=&rft.btitle=&rft.title=Journal+of+toxicology+and+environmental+health.+Part+A&rft.issn=15287394&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-01-21 N1 - Date created - 2003-01-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genomic interrogation of mechanism(s) underlying cellular responses to toxicants. AN - 72802845; 12505366 AB - Assessment of the impact of xenobiotic exposure on human health and disease progression is complex. Knowledge of mode(s) of action, including mechanism(s) contributing to toxicity and disease progression, is valuable for evaluating compounds. Toxicogenomics, the subdiscipline which merges genomics with toxicology, holds the promise to contributing significantly toward the goal of elucidating mechanism(s) by studying genome-wide effects of xenobiotics. Global gene expression profiling, revolutionized by microarray technology and a crucial aspect of a toxicogenomic study, allows measuring transcriptional modulation of thousands of genes following exposure to a xenobiotic. We use our results from previous studies on compounds representing two different classes of xenobiotics (barbiturate and peroxisome proliferator) to discuss the application of computational approaches for analyzing microarray data to elucidate mechanism(s) underlying cellular responses to toxicants. In particular, our laboratory demonstrated that chemical-specific patterns of gene expression can be revealed using cDNA microarrays. Transcript profiling provides discrimination between classes of toxicants, as well as, genome-wide insight into mechanism(s) of toxicity and disease progression. Ultimately, the expectation is that novel approaches for predicting xenobiotic toxicity in humans will emerge from such information. JF - Toxicology AU - Amin, Rupesh P AU - Hamadeh, Hisham K AU - Bushel, Pierre R AU - Bennett, Lee AU - Afshari, Cynthia A AU - Paules, Richard S AD - National Institute of Environmental Health Sciences, National Institutes of Health, P.O. Box 12233, Mail Drop F1-05, Research Triangle Park, NC 27709, USA. Y1 - 2002/12/27/ PY - 2002 DA - 2002 Dec 27 SP - 555 EP - 563 VL - 181-182 SN - 0300-483X, 0300-483X KW - Xenobiotics KW - 0 KW - Index Medicus KW - United States KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - National Institutes of Health (U.S.) KW - Gene Expression Regulation -- drug effects KW - Computational Biology KW - Xenobiotics -- toxicity KW - Pharmacogenetics -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72802845?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Genomic+interrogation+of+mechanism%28s%29+underlying+cellular+responses+to+toxicants.&rft.au=Amin%2C+Rupesh+P%3BHamadeh%2C+Hisham+K%3BBushel%2C+Pierre+R%3BBennett%2C+Lee%3BAfshari%2C+Cynthia+A%3BPaules%2C+Richard+S&rft.aulast=Amin&rft.aufirst=Rupesh&rft.date=2002-12-27&rft.volume=181-182&rft.issue=&rft.spage=555&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-28 N1 - Date created - 2002-12-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transgenic models in xenobiotic metabolism and toxicology. AN - 72799013; 12505317 AB - There exist in animals a large number of enzymes that primarily metabolize xenobiotics including drugs, toxins and carcinogens. While these enzymes are known to activate or inactivate toxins and carcinogens in vitro, it had not been demonstrated until recently whether they are responsible for the biological effects of these chemicals in intact animal models. In order to determine the biological affects of xenobiotic-metabolizing enzymes, gene knockout mice were made that lack expression of certain P450s (CYP1A1, CYP1A2, CYP1B1 and CYP2E1), microsomal and cytosolic epoxide hydrolases, and NADPH:quinone oxidoreductase. These mice have no deleterious phenotypes indicating that xenobiotic-metabolizing enzymes have no direct role in mammalian development and physiological homeostasis even though all the genes and enzymes examined are conserved in mammals. However, in many cases, mice lacking certain xenobiotic-metabolizing enzymes confer resistance to acute toxicities and chemical carcinogenesis thus demonstrating that these enzymes mediate the deleterious effects of chemicals. The use of xenobiotic metabolism null animal models to study the mechanisms of actions of toxins and carcinogens will be reviewed. JF - Toxicology AU - Gonzalez, Frank J AD - National Cancer Institute, National Institutes of Health, Building 37, Room 3E-24, Bethesda, MD 20892, USA. fjgonz@helix.nih.gov Y1 - 2002/12/27/ PY - 2002 DA - 2002 Dec 27 SP - 237 EP - 239 VL - 181-182 SN - 0300-483X, 0300-483X KW - Carcinogens KW - 0 KW - Xenobiotics KW - Index Medicus KW - Animals KW - Carcinogens -- toxicity KW - Mice KW - Mice, Transgenic KW - Models, Biological KW - Mice, Knockout KW - Xenobiotics -- metabolism KW - Toxicology -- trends KW - Xenobiotics -- toxicity KW - Animals, Genetically Modified -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72799013?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Transgenic+models+in+xenobiotic+metabolism+and+toxicology.&rft.au=Gonzalez%2C+Frank+J&rft.aulast=Gonzalez&rft.aufirst=Frank&rft.date=2002-12-27&rft.volume=181-182&rft.issue=&rft.spage=237&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-28 N1 - Date created - 2002-12-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Processing of Escherichia coli alkaline phosphatase. Sequence requirements and possible conformations of the -6 to -4 region of the signal peptide. AN - 72789450; 12393890 AB - Analysis of the precursors of bacterial exported proteins revealed that those having bulky hydrophobic residues at position -5 have a high incidence of Pro residues at positions -6 and -4, Val at position -3, and Ser at positions -4 and -2. This led to a hypothesis that the previously observed inhibition of processing by bulky residues at position -5 can be suppressed by introduction of Pro, Ser, or Val in the corresponding nearby positions. Subsequent mutational analysis of Escherichia coli alkaline phosphatase showed that, as it was predicted, Pro on either side of bulky hydrophobic -5 Leu, Ile, or Tyr completely restores efficiency of the maturation. Introduction of Val at position -3 also partially suppresses the inhibition imposed by -5 Leu, while a Ser residue at position -4 or -2 does not restore processing. In addition, effective maturation of a mutant with Pro residues at positions from -6 throughout -4 proved that polyproline conformation of this region is permissive for processing. To understand the effects of the mutations, we modeled a peptide substrate into the active site of the signal peptidase using the known position of the beta-lactam inhibitor. The inhibitory effect of the -5 residue and its suppression by either Pro -6 or Pro -4 can be explained if we assume that Pro-containing -6 to -4 regions adopt a polyproline conformation whereas the region without Pro residues has a beta-conformation. These results permit us to specify sequence requirements at -6, -5, and -4 positions for efficient processing and to improve the prediction of yet unknown cleavage sites. JF - The Journal of biological chemistry AU - Kajava, Andrey V AU - Zolov, Sergey N AU - Pyatkov, Konstantin I AU - Kalinin, Andrey E AU - Nesmeyanova, Marina A AD - Center for Molecular Modeling, CIT, National Institutes of Health, Bethesda, Maryland 20892, USA. kajava@crbm.cnrs-mop.fr Y1 - 2002/12/27/ PY - 2002 DA - 2002 Dec 27 SP - 50396 EP - 50402 VL - 277 IS - 52 SN - 0021-9258, 0021-9258 KW - Isoenzymes KW - 0 KW - Recombinant Proteins KW - Alkaline Phosphatase KW - EC 3.1.3.1 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Isoenzymes -- chemistry KW - Base Sequence KW - Recombinant Proteins -- metabolism KW - Models, Molecular KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Recombinant Proteins -- chemistry KW - Isoenzymes -- metabolism KW - Protein Conformation KW - Alkaline Phosphatase -- chemistry KW - Escherichia coli -- enzymology KW - Alkaline Phosphatase -- metabolism KW - Alkaline Phosphatase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72789450?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Processing+of+Escherichia+coli+alkaline+phosphatase.+Sequence+requirements+and+possible+conformations+of+the+-6+to+-4+region+of+the+signal+peptide.&rft.au=Kajava%2C+Andrey+V%3BZolov%2C+Sergey+N%3BPyatkov%2C+Konstantin+I%3BKalinin%2C+Andrey+E%3BNesmeyanova%2C+Marina+A&rft.aulast=Kajava&rft.aufirst=Andrey&rft.date=2002-12-27&rft.volume=277&rft.issue=52&rft.spage=50396&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 - 2003-02-27 N1 - Date created - 2002-12-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structural basis for the substrate specificity of tobacco etch virus protease. AN - 72786140; 12377789 AB - Because of its stringent sequence specificity, the 3C-type protease from tobacco etch virus (TEV) is frequently used to remove affinity tags from recombinant proteins. It is unclear, however, exactly how TEV protease recognizes its substrates with such high selectivity. The crystal structures of two TEV protease mutants, inactive C151A and autolysis-resistant S219D, have now been solved at 2.2- and 1.8-A resolution as complexes with a substrate and product peptide, respectively. The enzyme does not appear to have been perturbed by the mutations in either structure, and the modes of binding of the product and substrate are virtually identical. Analysis of the protein-ligand interactions helps to delineate the structural determinants of substrate specificity and provides guidance for reengineering the enzyme to further improve its utility for biotechnological applications. JF - The Journal of biological chemistry AU - Phan, Jason AU - Zdanov, Alexander AU - Evdokimov, Artem G AU - Tropea, Joseph E AU - Peters, Howard K AU - Kapust, Rachel B AU - Li, Mi AU - Wlodawer, Alexander AU - Waugh, David S AD - Macromolecular Crystallography Laboratory, Center for Cancer Research, NCI-Frederick, National Institutes of Health, Frederick, Maryland 21702-1201, USA. Y1 - 2002/12/27/ PY - 2002 DA - 2002 Dec 27 SP - 50564 EP - 50572 VL - 277 IS - 52 SN - 0021-9258, 0021-9258 KW - Recombinant Proteins KW - 0 KW - Endopeptidases KW - EC 3.4.- KW - TEV protease KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Sequence Alignment KW - Tobacco -- virology KW - Recombinant Proteins -- metabolism KW - Models, Molecular KW - Protein Folding KW - Molecular Sequence Data KW - Crystallography, X-Ray KW - Amino Acid Sequence KW - Substrate Specificity KW - Recombinant Proteins -- chemistry KW - Sequence Homology, Amino Acid KW - Endopeptidases -- metabolism KW - Potyvirus -- enzymology KW - Endopeptidases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72786140?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Structural+basis+for+the+substrate+specificity+of+tobacco+etch+virus+protease.&rft.au=Phan%2C+Jason%3BZdanov%2C+Alexander%3BEvdokimov%2C+Artem+G%3BTropea%2C+Joseph+E%3BPeters%2C+Howard+K%3BKapust%2C+Rachel+B%3BLi%2C+Mi%3BWlodawer%2C+Alexander%3BWaugh%2C+David+S&rft.aulast=Phan&rft.aufirst=Jason&rft.date=2002-12-27&rft.volume=277&rft.issue=52&rft.spage=50564&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 - 2003-02-27 N1 - Date created - 2002-12-23 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 1LVB; PDB; 1LVM N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Environmental epidemiology Basics and proof of cause-effect AN - 18672183; 5567663 AB - Bringing epidemiology and toxicology together to better understand cause and effect relationships requires attention to several interconnected problems: problems of commitment, complexity, and of communication. The most fundamental of these is commitment as it is reflected in the basic purpose of environmental epidemiology. The purpose of epidemiology is not to prove cause-effect relationships, and not only because scientific proof is elusive. The purpose of epidemiology is to acquire knowledge about the determinants and distributions of disease and to apply that knowledge to improve public health. A key problem, therefore, is how much and what kinds of evidence are sufficient to warrant public health (typically preventive) actions? The assessment of available evidence lays the foundation for the problem of complexity: relevant evidence arrives from toxicologic and epidemiological investigations, and reflects the acquisition of knowledge from many levels of scientific understanding: molecular, cellular, tissue, organ systems, complete organisms (man and mouse), relationships between individuals, and on to social and political processes that may impact human health. How to combine evidence from several levels of understanding will require the effective communication of current methodological practices. The practice of causal inference in contemporary environmental epidemiology, for example, relies upon three largely qualitative methods: systematic narrative reviews, criteria-based inference methods, and (increasingly) meta-analysis. These methods are described as they are currently used in practice and several key problems in that practice are highlighted including the relevance to public health practice of toxicological evidence. JF - Toxicology AU - Weed, D L AD - Office of Preventive Oncology, Division of Cancer Prevention, National Cancer Institute, EPS T-41, 6130 Executive Blvd. Suite 3109, Bethesda, MD 20892-7105, USA, dw102i@nih.gov Y1 - 2002/12/27/ PY - 2002 DA - 2002 Dec 27 SP - 399 EP - 403 VL - 181-182 SN - 0300-483X, 0300-483X KW - environmental epidemiology KW - Toxicology Abstracts KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18672183?accountid=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=Environmental+epidemiology+Basics+and+proof+of+cause-effect&rft.au=Weed%2C+D+L&rft.aulast=Weed&rft.aufirst=D&rft.date=2002-12-27&rft.volume=181-182&rft.issue=&rft.spage=399&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Molecular pathogenesis of human hepatocellular carcinoma AN - 18664899; 5567604 AB - Primary hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. However, the viral-chemical etiology as well as molecular mechanisms of HCC pathogenesis remains largely unknown. Recent studies in our laboratory have identified several potential factors that may contribute to the pathogenesis of HCC. Oxidative stress and chronic inflammation have been linked to an increased risk of liver cancer. For example, oxyradical overload diseases such as Wilson disease and hemochromatosis result in the generation of oxygen/nitrogen species that can cause mutations in the p53 tumor suppressor gene. The Hepatitis B virus X gene (HBx), a viral transactivator with oncogenic potentials, has been shown to bind to and inactivate p53-mediated apoptosis. HBx mutants derived from HCC have a diminished ability to act as a transctivator. However, they still retain the ability to bind to and abrogate p53-mediated apoptosis. The comparison of gene expression profiles between HBx-expressing primary human hepatocytes and HBV-infected liver samples by cDNA microarrays indicate a unique alteration of a subset of oncogenes and tumor suppressor genes including p53. Our studies implicate both viral and endogenous chemical processes in the etiology of HCC, and p53 may be a common target for the inactivation during liver carcinogenesis. JF - Toxicology AU - Wang, X W AU - Hussain, S P AU - Huo, T-I AU - Wu, C-G AU - Forgues, M AU - Hofseth, L J AU - Brechot, C AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA, xin_wei_wang@nih.gov Y1 - 2002/12/27/ PY - 2002 DA - 2002 Dec 27 SP - 43 EP - 47 VL - 181-182 SN - 0300-483X, 0300-483X KW - DNA microarrays KW - double prime X gene KW - hepatitis B virus KW - man KW - Toxicology Abstracts; Genetics Abstracts KW - X 24240:Miscellaneous KW - G 07470:Cytogenetics & general UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18664899?accountid=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=Molecular+pathogenesis+of+human+hepatocellular+carcinoma&rft.au=Wang%2C+X+W%3BHussain%2C+S+P%3BHuo%2C+T-I%3BWu%2C+C-G%3BForgues%2C+M%3BHofseth%2C+L+J%3BBrechot%2C+C%3BHarris%2C+C+C&rft.aulast=Wang&rft.aufirst=X&rft.date=2002-12-27&rft.volume=181-182&rft.issue=&rft.spage=43&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - DnaK Promotes the Selective Export of Outer Membrane Protein Precursors in SecA-deficient Escherichia coli AN - 18616067; 5532706 AB - Consistent with many other results indicating that SecA plays an essential role in the translocation of presecretory proteins across the Escherichia coli inner membrane, we previously found that a 95% depletion of SecA completely blocks the export of periplasmic proteins in vivo. Surprisingly, we found that about 25% of the outer membrane protein (OMP) OmpA synthesized after SecA depletion was gradually translocated across the inner membrane. In this study we analyzed the export of several other OMPs after SecA depletion. We found that 25-50% of each OMP as well as an OmpA-alkaline phosphatase fusion protein was exported from SecA-deficient cells. This partial export was completely abolished by the SecA inhibitor sodium azide and therefore still required the participation of SecA. Examination of a variety of OmpA derivatives, however, ruled out the possibility that OMPs are selectively translocated in SecA-deficient cells because SecA binds to their N termini with unusually high affinity. Export after SecA depletion was observed in cells that lack SecB, the primary targeting factor for OMPs, but was abolished by partial inactivation of DnaK. Furthermore, OmpA could be isolated in a stable complex with DnaK. The data strongly suggest that OMPs require only a relatively low level of translocase activity to cross the inner membrane because they can be preserved in a prolonged export-competent state by DnaK. Recent studies have demonstrated that fatty acids induce insulin resistance in skeletal muscle by blocking insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase (PI3-kinase). To examine the mechanism by which fatty acids mediate this effect, rats were infused with either a lipid emulsion (consisting mostly of 18:2 fatty acids) or glycerol. Intracellular C18:2 CoA increased in a time-dependent fashion, reaching an 6-fold elevation by 5 h, whereas there was no change in the concentration of any other fatty acyl-CoAs. Diacylglycerol (DAG) also increased transiently after 3-4 h of lipid infusion. In contrast there was no increase in intracellular ceramide or triglyceride concentrations during the lipid infusion. Increases in intracellular C18:2 CoA and DAG concentration were associated with protein kinase C (PKC)-[theta] activation and a reduction in both insulin- stimulated IRS-1 tyrosine phosphorylation and IRS-1 associated PI3-kinase activity, which were associated with an increase in IRS-1 Ser super(307) phosphorylation. These data support the hypothesis that an increase in plasma fatty acid concentration results in an increase in intracellular fatty acyl-CoA and DAG concentrations, which results in activation of PKC-[theta] leading to increased IRS-1 Ser super(307) phosphorylation. This in turn leads to decreased IRS-1 tyrosine phosphorylation and decreased activation of IRS-1-associated PI3-kinase activity resulting in decreased insulin-stimulated glucose transport activity. JF - Journal of Biological Chemistry AU - Qi, H AU - Hyndman, J B AU - Bernstein, H D AU - Yu, C AU - Chen, Y AU - Cline, G W AU - Zhang, D AU - Zong, H AU - Wang, Y AU - Bergeron, R AU - Kim, J-K AU - Cushman, S W AU - Cooney, G J AU - Atcheson, B AU - White, M F AU - Kraegen, E W AU - Shulman, GI AD - Genetics and Biochemistry Branch, NIDDK, National Institutes of Health, Bethesda, Maryland, harris_bernstein@nih.gov. Y1 - 2002/12/27/ PY - 2002 DA - 2002 Dec 27 SP - 51077 EP - 51083 VL - 277 IS - 52 SN - 0021-9258, 0021-9258 KW - DnaK protein KW - SecA protein KW - insulin receptor substrate 1 KW - insulin resistance KW - outer membrane proteins KW - rats KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - G 07320:Bacterial genetics KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18616067?accountid=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=DnaK+Promotes+the+Selective+Export+of+Outer+Membrane+Protein+Precursors+in+SecA-deficient+Escherichia+coli&rft.au=Qi%2C+H%3BHyndman%2C+J+B%3BBernstein%2C+H+D%3BYu%2C+C%3BChen%2C+Y%3BCline%2C+G+W%3BZhang%2C+D%3BZong%2C+H%3BWang%2C+Y%3BBergeron%2C+R%3BKim%2C+J-K%3BCushman%2C+S+W%3BCooney%2C+G+J%3BAtcheson%2C+B%3BWhite%2C+M+F%3BKraegen%2C+E+W%3BShulman%2C+GI&rft.aulast=Qi&rft.aufirst=H&rft.date=2002-12-27&rft.volume=277&rft.issue=52&rft.spage=51077&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 - POTE, a highly homologous gene family located on numerous chromosomes and expressed in prostate, ovary, testis, placenta, and prostate cancer. AN - 72794115; 12475935 AB - We have identified a gene located on chromosomes 21 that is expressed in normal and neoplastic prostate, and in normal testis, ovary, and placenta. We name this gene POTE (expressed in prostate, ovary, testis, and placenta). The POTE gene has 11 exons and 10 introns and spans approximately equal 32 kb of chromosome 21q11.2 region. The 1.83-kb mRNA of POTE encodes a protein of 66 kDa. Ten paralogs of the gene have been found dispersed among eight different chromosomes (2, 8, 13, 14, 15, 18, 21, and 22) with preservation of ORFs and splice junctions. The synonymous:nonsynonymous ratio indicates that the genes were duplicated rather recently but are diverging at a rate faster than the average for other paralogous genes. In prostate and in testis, at least five different paralogs are expressed. In situ hybridization shows that POTE is expressed in basal and terminal cells of normal prostate epithelium. It is also expressed in some prostate cancers and in the LnCAP prostate cancer cell line. The POTE protein contains seven ankyrin repeats between amino acids 140 and 380. Expression of POTE in prostate cancer and its undetectable expression in normal essential tissues make POTE a candidate for the immunotherapy of prostate cancer. The existence of a large number of closely related but rapidly diverging members, their location on multiple chromosomes and their limited expression pattern suggest an important role for the POTE gene family in reproductive processes. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Bera, Tapan K AU - Zimonjic, Drazen B AU - Popescu, Nicholas C AU - Sathyanarayana, Bangalore K AU - Kumar, Vasantha AU - Lee, Byungkook AU - Pastan, Ira AD - Laboratories of Molecular Biology and Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4264, USA. Y1 - 2002/12/24/ PY - 2002 DA - 2002 Dec 24 SP - 16975 EP - 16980 VL - 99 IS - 26 SN - 0027-8424, 0027-8424 KW - RNA, Messenger KW - 0 KW - Index Medicus KW - Gene Duplication KW - Genome, Human KW - Multigene Family KW - Humans KW - RNA, Messenger -- analysis KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Male KW - Female KW - Cloning, Molecular KW - Ovary -- metabolism KW - Testis -- metabolism KW - Genes KW - Prostate -- metabolism KW - Prostatic Neoplasms -- genetics KW - Placenta -- metabolism KW - Chromosome Mapping UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72794115?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=POTE%2C+a+highly+homologous+gene+family+located+on+numerous+chromosomes+and+expressed+in+prostate%2C+ovary%2C+testis%2C+placenta%2C+and+prostate+cancer.&rft.au=Bera%2C+Tapan+K%3BZimonjic%2C+Drazen+B%3BPopescu%2C+Nicholas+C%3BSathyanarayana%2C+Bangalore+K%3BKumar%2C+Vasantha%3BLee%2C+Byungkook%3BPastan%2C+Ira&rft.aulast=Bera&rft.aufirst=Tapan&rft.date=2002-12-24&rft.volume=99&rft.issue=26&rft.spage=16975&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 - 2003-01-21 N1 - Date created - 2002-12-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9051-5 [1924367] Chromosoma. 1988;96(6):443-53 [3219915] Science. 1992 Aug 14;257(5072):967-71 [1354393] Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8611-5 [1528869] J Mol Evol. 1993 Jan;36(1):96-9 [8433381] Hum Genet. 1993 Feb;90(6):577-83 [8444464] Mol Biol Evol. 1993 Mar;10(2):271-81 [8487630] Blood. 1994 Jul 1;84(1):189-99 [8018917] Insect Mol Biol. 1994 Feb;3(1):41-7 [8069415] Comput Appl Biosci. 1994 Dec;10(6):685-6 [7704669] J Mol Biol. 1995 Apr 7;247(4):536-40 [7723011] Cancer Genet Cytogenet. 1995 Apr;80(2):100-2 [7736422] Science. 1995 Oct 20;270(5235):467-70 [7569999] Science. 1997 May 23;276(5316):1268-72 [9157888] Nucleic Acids Res. 1997 Sep 1;25(17):3389-402 [9254694] Protein Eng. 1997 Jun;10(6):673-6 [9278280] Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11461-5 [9326632] Proc Natl Acad Sci U S A. 1998 Jan 6;95(1):300-4 [9419370] Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10757-62 [9724777] J Mol Biol. 1999 Apr 9;287(4):797-815 [10191147] Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9287-92 [10430935] Genomics. 1991 Sep;11(1):15-23 [1765373] J Mol Biol. 2000 Jun 2;299(2):499-520 [10860755] Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9437-42 [10931945] Hepatology. 2000 Nov;32(5):1060-8 [11050057] Science. 2000 Nov 10;290(5494):1151-5 [11073452] Nature. 2001 Feb 15;409(6822):860-921 [11237011] Gene. 2001 Mar 7;265(1-2):55-60 [11255007] Prostate. 2001 Sep 15;48(4):231-41 [11536302] Leukemia. 2001 Oct;15(10):1582-8 [11587216] Trends Genet. 2001 Nov;17(11):661-9 [11672867] Nucleic Acids Res. 2002 Jan 1;30(1):276-80 [11752314] Nat Rev Genet. 2002 Jan;3(1):65-72 [11823792] Genome Biol. 2002;3(2):RESEARCH0008 [11864370] Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):3058-63 [11880645] Genome Res. 2002 Apr;12(4):656-64 [11932250] Genome Res. 2002 Jun;12(6):996-1006 [12045153] Science. 2002 Aug 9;297(5583):1003-7 [12169732] Erratum In: Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1462 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - New associations of human papillomavirus, Simian virus 40, and Epstein-Barr virus with human cancer. AN - 72776435; 12488476 JF - Journal of the National Cancer Institute AU - Wong, May AU - Pagano, Joseph S AU - Schiller, John T AU - Tevethia, Satvir S AU - Raab-Traub, Nancy AU - Gruber, Jack AD - Biological Carcinogenesis Branch, National Cancer Institute, Bethesda, MD 20892, USA. mw132k@nih.gov Y1 - 2002/12/18/ PY - 2002 DA - 2002 Dec 18 SP - 1832 EP - 1836 VL - 94 IS - 24 SN - 0027-8874, 0027-8874 KW - Index Medicus KW - Polyomavirus Infections -- complications KW - Papillomavirus Infections -- complications KW - Humans KW - Head and Neck Neoplasms -- virology KW - Epstein-Barr Virus Infections -- complications KW - Carcinoma, Squamous Cell -- virology KW - Neoplasms -- virology KW - Tumor Virus Infections -- virology KW - Simian virus 40 -- isolation & purification KW - Papillomaviridae -- isolation & purification KW - Tumor Virus Infections -- complications KW - Herpesvirus 4, Human -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72776435?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=New+associations+of+human+papillomavirus%2C+Simian+virus+40%2C+and+Epstein-Barr+virus+with+human+cancer.&rft.au=Wong%2C+May%3BPagano%2C+Joseph+S%3BSchiller%2C+John+T%3BTevethia%2C+Satvir+S%3BRaab-Traub%2C+Nancy%3BGruber%2C+Jack&rft.aulast=Wong&rft.aufirst=May&rft.date=2002-12-18&rft.volume=94&rft.issue=24&rft.spage=1832&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 - 2003-01-16 N1 - Date created - 2002-12-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inorganic Arsenite-Induced Malignant Transformation of Human Prostate Epithelial Cells AN - 18659321; 5560444 AB - Although several epidemiologic studies show an association between arsenic exposure and prostate cancer, it is still unknown whether human prostate epithelial cells are directly susceptible to arsenic-induced transformation. This study was designed to determine whether the nontumorigenic human prostate epithelial cell line RWPE-1 could be malignantly transformed in vitro by arsenite. RWPE-1 cells were continuously exposed to 5 mu M arsenite and monitored for signs of transformation, assessed as changes in matrix metalloproteinase-9 levels. After 29 weeks of exposure, the arsenite-exposed RWPE-1 cells (referred to as CAsE-PE) showed a marked increase in matrix metalloproteinase-9 secretion, a common finding in prostate malignancies. Malignant transformation was confirmed when CAsE-PE cells produced aggressive undifferentiated malignant epithelial tumors in nude mice. The tumors stained positive for human prostate-specific antigen, confirming their origin. These results are the first report of arsenite-induced malignant transformation of a human epithelial cell line and provide an important in vitro model for studying the mechanisms underlying arsenic-induced carcinogenesis in humans. JF - Journal of the National Cancer Institute AU - Achanzar, W E AU - Brambila, E M AU - Diwan, BA AU - Webber, M M AU - Waalkes, M P AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at National Institute of Environmental Health Sciences, MD F0-09, 111 Alexander Dr., Research Triangle Park, NC 27709, USA, waalkes@niehs.nih.gov Y1 - 2002/12/18/ PY - 2002 DA - 2002 Dec 18 SP - 1888 EP - 1891 VL - 94 IS - 24 SN - 0027-8874, 0027-8874 KW - RWPE-1 cells KW - man KW - Toxicology Abstracts KW - X 24162:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18659321?accountid=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+the+National+Cancer+Institute&rft.atitle=Inorganic+Arsenite-Induced+Malignant+Transformation+of+Human+Prostate+Epithelial+Cells&rft.au=Achanzar%2C+W+E%3BBrambila%2C+E+M%3BDiwan%2C+BA%3BWebber%2C+M+M%3BWaalkes%2C+M+P&rft.aulast=Achanzar&rft.aufirst=W&rft.date=2002-12-18&rft.volume=94&rft.issue=24&rft.spage=1888&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Biological functions of the ISWI chromatin remodeling complex NURF. AN - 72802103; 12502740 AB - The nucleosome remodeling factor (NURF) is one of several ISWI-containing protein complexes that catalyze ATP-dependent nucleosome sliding and facilitate transcription of chromatin in vitro. To establish the physiological requirements of NURF, and to distinguish NURF genetically from other ISWI-containing complexes, we isolated mutations in the gene encoding the large NURF subunit, nurf301. We confirm that NURF is required for transcription activation in vivo. In animals lacking NURF301, heat-shock transcription factor binding to and transcription of the hsp70 and hsp26 genes are impaired. Additionally, we show that NURF is required for homeotic gene expression. Consistent with this, nurf301 mutants recapitulate the phenotypes of Enhancer of bithorax, a positive regulator of the Bithorax-Complex previously localized to the same genetic interval. Finally, mutants in NURF subunits exhibit neoplastic transformation of larval blood cells that causes melanotic tumors to form. JF - Genes & development AU - Badenhorst, Paul AU - Voas, Matthew AU - Rebay, Ilaria AU - Wu, Carl AD - Laboratory of Molecular Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda Maryland 20892-4255, USA. Y1 - 2002/12/15/ PY - 2002 DA - 2002 Dec 15 SP - 3186 EP - 3198 VL - 16 IS - 24 SN - 0890-9369, 0890-9369 KW - Chromatin KW - 0 KW - Chromosomal Proteins, Non-Histone KW - DNA-Binding Proteins KW - Drosophila Proteins KW - HSP70 Heat-Shock Proteins KW - Homeodomain Proteins KW - Hsf protein, Drosophila KW - ISWI protein KW - Insect Proteins KW - Nucleosomes KW - Transcription Factors KW - Ubx protein, Drosophila KW - enhancer of bithorax protein, Drosophila KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - Index Medicus KW - Sex Chromosome Aberrations KW - Animals KW - HSP70 Heat-Shock Proteins -- metabolism KW - Neuroectodermal Tumor, Melanotic -- genetics KW - Nucleosomes -- physiology KW - Larva -- metabolism KW - Animals, Genetically Modified KW - Mutagenesis, Site-Directed KW - Gene Expression Regulation -- physiology KW - X Chromosome -- genetics KW - Gene Expression Regulation -- drug effects KW - Drosophila Proteins -- metabolism KW - Genes, Homeobox -- genetics KW - Larva -- growth & development KW - Neuroectodermal Tumor, Melanotic -- metabolism KW - DNA-Binding Proteins -- metabolism KW - Drosophila melanogaster -- embryology KW - Hematopoiesis -- physiology KW - Transcription Factors -- physiology KW - Chromatin -- metabolism KW - Insect Proteins -- genetics KW - Drosophila melanogaster -- genetics KW - Insect Proteins -- physiology KW - Transcriptional Activation -- drug effects KW - Adenosine Triphosphatases -- physiology KW - Drosophila melanogaster -- metabolism KW - Transcriptional Activation -- physiology KW - Insect Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72802103?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Biological+functions+of+the+ISWI+chromatin+remodeling+complex+NURF.&rft.au=Badenhorst%2C+Paul%3BVoas%2C+Matthew%3BRebay%2C+Ilaria%3BWu%2C+Carl&rft.aulast=Badenhorst&rft.aufirst=Paul&rft.date=2002-12-15&rft.volume=16&rft.issue=24&rft.spage=3186&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 - 2003-01-23 N1 - Date created - 2002-12-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Dev Biol. 1981 Sep;86(2):409-18 [6793431] Differentiation. 1979;12(3):167-78 [111992] Nature. 1991 Oct 31;353(6347):822-7 [1944557] Cell. 1992 Feb 7;68(3):561-72 [1346755] Mol Gen Genet. 1993 Apr;238(1-2):33-7 [8479437] Mol Cell Biol. 1993 Dec;13(12):7961-70 [7504178] Nature. 1994 Feb 10;367(6463):525-32 [8107823] Nature. 1994 Oct 27;371(6500):806-8 [7935842] Methods Cell Biol. 1994;44:565-73 [7535884] Development. 1995 Feb;121(2):463-75 [7768187] EMBO J. 1995 Jun 15;14(12):2857-65 [7796812] Genes Dev. 1995 Nov 15;9(22):2756-69 [7590251] Cell. 1995 Dec 15;83(6):1011-20 [8521501] Cell. 1995 Dec 15;83(6):1021-6 [8521502] Cell. 1996 Feb 9;84(3):411-9 [8608595] Development. 1996 Apr;122(4):1113-24 [8620838] Cell. 1999 Jun 25;97(7):843-52 [10399913] Chromosoma. 1996 Sep;105(3):158-71 [8781184] Annu Rev Genet. 1995;29:289-303 [8825476] Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12418-22 [8901596] Cell. 1997 Jul 11;90(1):145-55 [9230310] Nature. 1997 Aug 7;388(6642):598-602 [9252192] Genes Dev. 1997 Dec 1;11(23):3254-64 [9389656] Proc Natl Acad Sci U S A. 1998 Jan 6;95(1):132-7 [9419341] Development. 1998 May;125(10):1909-20 [9550723] Mol Cell. 1997 Dec;1(1):141-50 [9659911] Genes Dev. 1998 Oct 15;12(20):3206-16 [9784495] Mol Cell. 1999 Feb;3(2):239-45 [10078206] Genes Dev. 1999 Jun 15;13(12):1529-39 [10385622] EMBO J. 1999 Jul 1;18(13):3724-35 [10393187] Cell. 1999 Jun 25;97(7):833-42 [10399912] Mol Cell. 2000 Feb;5(2):355-65 [10882076] Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11427-32 [11027343] Cell. 2000 Oct 27;103(3):423-33 [11081629] EMBO J. 2001 Feb 1;20(3):499-509 [11157756] Genes Dev. 2001 Mar 1;15(5):619-26 [11238381] Development. 2001 Apr;128(8):1429-41 [11262242] EMBO J. 2001 May 1;20(9):2236-45 [11331589] Genes Dev. 2001 Jun 1;15(11):1334-48 [11390354] Science. 2001 Aug 10;293(5532):1083-5 [11498577] Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9563-8 [11504941] Mol Cell. 2001 Sep;8(3):531-43 [11583616] Bioessays. 2001 Dec;23(12):1138-47 [11746233] Genes Dev. 2002 Feb 1;16(3):388-98 [11825879] Curr Opin Microbiol. 2002 Feb;5(1):102-10 [11834378] Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2895-900 [11854460] EMBO Rep. 2002 Mar;3(3):242-7 [11882543] EMBO J. 2002 Mar 15;21(6):1406-13 [11889046] EMBO J. 2002 May 1;21(9):2231-41 [11980720] Oncogene. 2002 Jul 18;21(31):4812-21 [12101419] Science. 1978 Jun 30;200(4349):1448-59 [96525] Nature. 1978 Dec 7;276(5688):565-70 [103000] Genetics. 1991 Mar;127(3):515-24 [1849859] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gadd45a protects against UV irradiation-induced skin tumors, and promotes apoptosis and stress signaling via MAPK and p53. AN - 72800218; 12499274 AB - Skin cancer is the most frequent form of malignancy in the world, and UV radiation is the primary environmental carcinogen responsible for its development. Herein we demonstrate that Gadd45a is a critical factor protecting the epidermis against UV radiation-induced tumorigenesis by promoting damaged keratinocytes to undergo apoptosis and/or cell cycle arrest, two crucial events that prevent the expansion of mutant or deregulated cells. Whereas Gadd45a has been implicated in cell cycle arrest, apoptosis, and DNA repair, to determine the physiological function of endogenous Gadd45a after genotoxic stress, the skin of Gadd45a-null mice was targeted with UV radiation. We report that Gadd45a induces apoptosis and cell cycle arrest by maintaining p38 and c-JNK MAPK activation in keratinocytes. The absence of Gadd45a results in loss of sustained p38/JNK MAPK activity beyond 15-30 min after UV radiation that leads to inadequate p53 activation and loss of normal activation of G(1) and G(2) checkpoints. Moreover, loss of Gadd45a dramatically reduces UV-induced apoptotic keratinocytes, "sunburn cells." Consequently, Gadd45a-null mice are more prone to tumors relative to wild-type mice. Therefore, we conclude that Gadd45a, like p53, is a key component protecting skin against UV-induced tumors. JF - Cancer research AU - Hildesheim, Jeffrey AU - Bulavin, Dmitry V AU - Anver, Miriam R AU - Alvord, W Gregory AU - Hollander, M Christine AU - Vardanian, Lilit AU - Fornace, Albert J AD - Gene Response Section, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 2002/12/15/ PY - 2002 DA - 2002 Dec 15 SP - 7305 EP - 7315 VL - 62 IS - 24 SN - 0008-5472, 0008-5472 KW - Cell Cycle Proteins KW - 0 KW - Gadd45a protein, mouse KW - Nuclear Proteins KW - Tumor Suppressor Protein p53 KW - JNK Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinases KW - p38 Mitogen-Activated Protein Kinases KW - Index Medicus KW - Keratinocytes -- radiation effects KW - Animals KW - Transcriptional Activation -- radiation effects KW - Mitogen-Activated Protein Kinases -- metabolism KW - Enzyme Activation KW - Cell Cycle -- physiology KW - Mice KW - Mice, Knockout KW - Keratinocytes -- physiology KW - Skin -- radiation effects KW - Mice, Inbred C57BL KW - Skin -- cytology KW - Keratinocytes -- cytology KW - Cell Cycle -- genetics KW - Cell Cycle -- radiation effects KW - Tumor Suppressor Protein p53 -- biosynthesis KW - Tumor Suppressor Protein p53 -- physiology KW - MAP Kinase Signaling System -- physiology KW - Nuclear Proteins -- genetics KW - Apoptosis -- physiology KW - Skin Neoplasms -- etiology KW - Apoptosis -- radiation effects KW - Skin Neoplasms -- pathology KW - Skin Neoplasms -- prevention & control KW - Skin Neoplasms -- genetics KW - Apoptosis -- genetics KW - MAP Kinase Signaling System -- radiation effects KW - Ultraviolet Rays -- adverse effects KW - Tumor Suppressor Protein p53 -- genetics KW - Nuclear Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72800218?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Gadd45a+protects+against+UV+irradiation-induced+skin+tumors%2C+and+promotes+apoptosis+and+stress+signaling+via+MAPK+and+p53.&rft.au=Hildesheim%2C+Jeffrey%3BBulavin%2C+Dmitry+V%3BAnver%2C+Miriam+R%3BAlvord%2C+W+Gregory%3BHollander%2C+M+Christine%3BVardanian%2C+Lilit%3BFornace%2C+Albert+J&rft.aulast=Hildesheim&rft.aufirst=Jeffrey&rft.date=2002-12-15&rft.volume=62&rft.issue=24&rft.spage=7305&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 - 2003-01-28 N1 - Date created - 2002-12-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pentagastrin-induced sleep panic attacks: panic in the absence of elevated baseline arousal. AN - 72777386; 12488064 AB - It has been suggested that pharmacological challenges that induce panic attacks are confounded by effects of environmental stress, elevated baseline arousal, and expectancy bias. To control for effects of arousal and cognition on the panicogenic effects of pentagastrin, pharmacological challenges were conducted during sleep in seven patients with panic disorder or social phobia. All patients had previously experienced pentagastrin-induced panic while awake. Infusions of normal saline and pentagastrin (0.6 microg/kg) were administered in fixed order and timed so that pentagastrin infusions took place during the transition from Stage 2 to Stage 3 sleep. Long intravenous lines were placed for remote blood sampling and subsequent analysis of plasma adrenocorticotropic hormone and cortisol. Measures of anxiety and panic were obtained at baseline and upon awakening after pharmacological challenge. All seven subjects awoke within seconds following pentagastrin infusion. Four patients reported symptoms that met criteria for panic. Neither baseline anxiety nor neuroendocrine measures were predictive of panic. These data demonstrate the ability to induce panic during a period of diminishing arousal and indicate that panic attacks can occur in the absence of elevated arousal and environmental stress. JF - Biological psychiatry AU - Geraci, Marilla AU - Anderson, Todd S AU - Slate-Cothren, Shiyoko AU - Post, Robert M AU - McCann, Una D AD - Clinical Center Nursing Department, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2002/12/15/ PY - 2002 DA - 2002 Dec 15 SP - 1183 EP - 1189 VL - 52 IS - 12 SN - 0006-3223, 0006-3223 KW - Gastrointestinal Agents KW - 0 KW - Pentagastrin KW - EF0NX91490 KW - Index Medicus KW - Hemodynamics -- drug effects KW - Behavior -- drug effects KW - Arousal KW - Humans KW - Male KW - Female KW - Panic Disorder -- chemically induced KW - Sleep -- drug effects KW - Panic Disorder -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72777386?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Pentagastrin-induced+sleep+panic+attacks%3A+panic+in+the+absence+of+elevated+baseline+arousal.&rft.au=Geraci%2C+Marilla%3BAnderson%2C+Todd+S%3BSlate-Cothren%2C+Shiyoko%3BPost%2C+Robert+M%3BMcCann%2C+Una+D&rft.aulast=Geraci&rft.aufirst=Marilla&rft.date=2002-12-15&rft.volume=52&rft.issue=12&rft.spage=1183&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 - 2003-04-10 N1 - Date created - 2002-12-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cross-regulation of T cell growth factor expression by p53 and the Tax oncogene. AN - 72761712; 12471108 AB - In this study, we demonstrate that p53 directly inhibits expression of the T cell growth factor (IL-2) in activated T cells. This repression is independent of the intrinsic transcriptional activity of p53 and is mediated by the Tax-responsive CD28RE-3'-12-O-tetradecanoylphorbol-13-acetate response element (AP1) element of the IL-2 promoter. Coexpression of the Tax oncogene causes full reversal of this repression through coordinate targeting of p300, CREB, and the NF-kappaB pathways. Paradoxically, IL-2 repression by p53 is not reversed by mdm2. Instead, mdm2 represses the IL-2 promoter by a mechanism that is synergistic with p53 and resistant to Tax reversal. The p300 structure-function studies show that these effects are linked to competitive associations among p53, Tax, and mdm2 with multiple domains of p300. The functional outcome of these antagonistic associations is revealed further by the observation that Tax and p53 induce apoptosis in activated T cells through separate and mutually exclusive pathways. Interestingly, both pathways are abrogated by mdm2. These results provide evidence that a dynamic interplay, between Tax and specific elements of the p53 network, mediates growth factor expression and programmed cell death in activated T cells. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Chaudhry, Sohail AU - Freebern, Wendy J AU - Smith, James L AU - Butscher, Wayne G AU - Haggerty, Cynthia M AU - Gardner, Kevin AD - Laboratory of Receptor Biology and Gene Expression, Advanced Technology Center, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4605, USA. Y1 - 2002/12/15/ PY - 2002 DA - 2002 Dec 15 SP - 6767 EP - 6778 VL - 169 IS - 12 SN - 0022-1767, 0022-1767 KW - Antigens, CD28 KW - 0 KW - Cyclic AMP Response Element-Binding Protein KW - Interleukin-2 KW - NF-kappa B KW - Nuclear Proteins KW - Proto-Oncogene Proteins KW - Trans-Activators KW - Transcription Factor AP-1 KW - Tumor Suppressor Protein p53 KW - MDM2 protein, human KW - EC 2.3.2.27 KW - Proto-Oncogene Proteins c-mdm2 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Abridged Index Medicus KW - Index Medicus KW - Promoter Regions, Genetic -- immunology KW - Humans KW - Protein Processing, Post-Translational -- immunology KW - Jurkat Cells KW - Response Elements -- immunology KW - Transcription Factor AP-1 -- physiology KW - Lymphocyte Activation -- genetics KW - Cyclic AMP Response Element-Binding Protein -- metabolism KW - Apoptosis -- genetics KW - Cyclic AMP Response Element-Binding Protein -- genetics KW - Signal Transduction -- immunology KW - Response Elements -- drug effects KW - Trans-Activators -- antagonists & inhibitors KW - Drug Synergism KW - Apoptosis -- immunology KW - Transcription, Genetic -- immunology KW - NF-kappa B -- genetics KW - Proto-Oncogene Proteins -- physiology KW - Nuclear Proteins -- antagonists & inhibitors KW - Antigens, CD28 -- genetics KW - Tetradecanoylphorbol Acetate -- metabolism KW - Dose-Response Relationship, Immunologic KW - Signal Transduction -- genetics KW - Trans-Activators -- physiology KW - Nuclear Proteins -- physiology KW - NF-kappa B -- metabolism KW - Interleukin-2 -- antagonists & inhibitors KW - Tumor Suppressor Protein p53 -- physiology KW - Tumor Suppressor Protein p53 -- antagonists & inhibitors KW - Gene Expression Regulation -- immunology KW - Interleukin-2 -- biosynthesis KW - Interleukin-2 -- genetics KW - Genes, pX -- physiology KW - Interleukin-2 -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72761712?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Cross-regulation+of+T+cell+growth+factor+expression+by+p53+and+the+Tax+oncogene.&rft.au=Chaudhry%2C+Sohail%3BFreebern%2C+Wendy+J%3BSmith%2C+James+L%3BButscher%2C+Wayne+G%3BHaggerty%2C+Cynthia+M%3BGardner%2C+Kevin&rft.aulast=Chaudhry&rft.aufirst=Sohail&rft.date=2002-12-15&rft.volume=169&rft.issue=12&rft.spage=6767&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 - 2003-01-23 N1 - Date created - 2002-12-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prevalence of hepatitis C virus infection and risk for hepatocellular carcinoma and non-Hodgkin lymphoma in AIDS. AN - 72747998; 12473843 AB - Hepatitis C virus (HCV) infection is highly prevalent in some subpopulations with AIDS. HCV is linked to hepatocellular carcinoma (HCC) and possibly non-Hodgkin lymphoma (NHL), but the impact of AIDS on these associations is uncertain. We used U.S. registry data to study HCC and NHL risk in 304,411 adults with AIDS, comparing cohort subgroups with high prevalence (hemophiliacs and injection drug users) or low prevalence (homosexual men, heterosexuals, and others) of HCV infection. The ratio of observed to expected cancer cases (standardized incidence ratio [SIR]) measured risk relative to the general population. Sixty-one HCC cases were observed (SIR, 7.5; 95% confidence interval, 5.7-9.6). Risk for HCC was higher in subgroups with high prevalence of HCV infection than in subgroups with low prevalence of HCV infection (SIR: 11.4 versus 5.5, respectively; p =.004). Subjects developed the following NHL grades: low, 35 cases; intermediate, 1035 cases; high, 784 cases; and unspecified, 1395 cases. For each NHL grade, SIRs were highest in subgroups with low prevalence of HCV infection. These data suggest an effect of HCV infection on HCC risk among adults with AIDS. On the other hand, NHL risk was not higher for groups in whom HCV infection was prevalent. JF - Journal of acquired immune deficiency syndromes (1999) AU - Engels, Eric A AU - Frisch, Morten AU - Lubin, Jay H AU - Gail, Mitchell H AU - Biggar, Robert J AU - Goedert, James J AD - Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute/NIH, 6120 Executive Boulevard, EPS 8010, Rockville, MD 20892, USA. engelse@exchange.nih.gov Y1 - 2002/12/15/ PY - 2002 DA - 2002 Dec 15 SP - 536 EP - 541 VL - 31 IS - 5 SN - 1525-4135, 1525-4135 KW - Index Medicus KW - AIDS/HIV KW - Homosexuality, Male KW - Risk KW - AIDS-Related Opportunistic Infections -- complications KW - Humans KW - Adult KW - Middle Aged KW - Hemophilia A -- complications KW - Substance Abuse, Intravenous -- complications KW - Male KW - Female KW - Prevalence KW - Acquired Immunodeficiency Syndrome -- complications KW - Carcinoma, Hepatocellular -- complications KW - Disease Susceptibility KW - Hepatitis C -- complications KW - Lymphoma, Non-Hodgkin -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72747998?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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+%281999%29&rft.atitle=Prevalence+of+hepatitis+C+virus+infection+and+risk+for+hepatocellular+carcinoma+and+non-Hodgkin+lymphoma+in+AIDS.&rft.au=Engels%2C+Eric+A%3BFrisch%2C+Morten%3BLubin%2C+Jay+H%3BGail%2C+Mitchell+H%3BBiggar%2C+Robert+J%3BGoedert%2C+James+J&rft.aulast=Engels&rft.aufirst=Eric&rft.date=2002-12-15&rft.volume=31&rft.issue=5&rft.spage=536&rft.isbn=&rft.btitle=&rft.title=Journal+of+acquired+immune+deficiency+syndromes+%281999%29&rft.issn=15254135&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-01-07 N1 - Date created - 2002-12-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Late complications following treatment for severe aplastic anemia (SAA) with high-dose cyclophosphamide (Cy): follow-up of a randomized trial. AN - 72719848; 12393567 AB - High-dose cyclophosphamide (Cy) has been promoted as curative therapy for severe aplastic anemia (SAA). However, our randomized trial comparing antithymocyte globulin (ATG) and Cy was terminated early because of excess morbidity/early mortality in the Cy arm. We now report analysis of secondary endpoints at a median of 38 months. Relapse occurred in 6 (46%) of 13 responders in the ATG arm versus 2 (25%) of 8 in the Cy arm (P =.38). Five (31%) of 16 patients in the ATG arm and 4 (27%) of 15 patients in the Cy arm had evidence of paroxysmal nocturnal hemoglobinuria (PNH) at diagnosis, with no substantial change in the overall percentage of glycophosphatidyl inositol (GPI)-anchored protein-deficient neutrophils over extended follow-up in individual patients in either arm. Bone marrow cytogenetic abnormalities have been observed among surviving patients in both arms (2 of 14 ATG versus 1 of 12 Cy, P =.70). High-dose Cy does not prevent relapse or clonal evolution in SAA. JF - Blood AU - Tisdale, John F AU - Maciejewski, Jaroslaw P AU - Nuñez, Olga AU - Rosenfeld, Stephen J AU - Young, Neal S AD - Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. johntis@intra.niddk.nih.gov Y1 - 2002/12/15/ PY - 2002 DA - 2002 Dec 15 SP - 4668 EP - 4670 VL - 100 IS - 13 SN - 0006-4971, 0006-4971 KW - Antilymphocyte Serum KW - 0 KW - Glycosylphosphatidylinositols KW - Immunosuppressive Agents KW - Cyclophosphamide KW - 8N3DW7272P KW - Abridged Index Medicus KW - Index Medicus KW - Clone Cells -- pathology KW - Disease-Free Survival KW - Myelodysplastic Syndromes -- prevention & control KW - Humans KW - Disease Progression KW - Recurrence KW - Antilymphocyte Serum -- therapeutic use KW - Hemoglobinuria, Paroxysmal -- etiology KW - Hemoglobinuria, Paroxysmal -- epidemiology KW - Neutrophils -- chemistry KW - Treatment Outcome KW - Chromosome Aberrations KW - Follow-Up Studies KW - Bone Marrow Cells -- ultrastructure KW - Glycosylphosphatidylinositols -- blood KW - T-Lymphocytes KW - Cyclophosphamide -- administration & dosage KW - Cyclophosphamide -- therapeutic use KW - Anemia, Aplastic -- mortality KW - Anemia, Aplastic -- drug therapy KW - Immunosuppressive Agents -- therapeutic use KW - Immunosuppressive Agents -- adverse effects KW - Immunosuppressive Agents -- administration & dosage KW - Cyclophosphamide -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72719848?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Late+complications+following+treatment+for+severe+aplastic+anemia+%28SAA%29+with+high-dose+cyclophosphamide+%28Cy%29%3A+follow-up+of+a+randomized+trial.&rft.au=Tisdale%2C+John+F%3BMaciejewski%2C+Jaroslaw+P%3BNu%C3%B1ez%2C+Olga%3BRosenfeld%2C+Stephen+J%3BYoung%2C+Neal+S&rft.aulast=Tisdale&rft.aufirst=John&rft.date=2002-12-15&rft.volume=100&rft.issue=13&rft.spage=4668&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-01-28 N1 - Date created - 2002-11-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of apoptosis in human cancer cell lines by diospyrin, a plant-derived bisnaphthoquinonoid, and its synthetic derivatives. AN - 72647530; 12406552 AB - Diospyrin, a bisnaphthoquinonoid natural product, and three synthetic derivatives have been tested for their action in four human cancer cell lines: acute myeloblastic leukemia (HL-60), chronic myelogenic leukemia (K-562), breast adenocarcinoma (MCF-7) and cervical epithelial carcinoma (HeLa). In cells grown in appropriate media several derivatives elicited cytotoxicity as assessed by Trypan Blue dye exclusion, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide reduction and DNA synthesis. Diethyl ether derivative (D7) was most effective in this regard while the parent compound diospyrin (D1) was least active (D7>D3>D2>D1). D7 was not cytotoxic toward normal human lymphocytes, suggesting its action is specific for tumor cells. On microscopic examination D7-treated cells exhibited characteristic morphological features of apoptosis, such as cell shrinkage and formation of apoptotic bodies. Fluorescent staining with propidium iodide revealed distinct chromatin condensation and nuclear fragmentation. The apoptotic index paralleled cytotoxic parameters, and fragmented DNA extracted free of genomic DNA displayed on gel electrophoresis a typical ladder pattern. D7-induced apoptosis was mediated via activation of caspase 3 and caspase 8. JF - Cancer letters AU - Chakrabarty, Sutapa AU - Roy, Madhumita AU - Hazra, Banasri AU - Bhattacharya, R K AD - Department of Environmental Carcinogenesis and Toxicology, Chittaranjan National Cancer Institute, 700 026, Kolkata, India. Y1 - 2002/12/15/ PY - 2002 DA - 2002 Dec 15 SP - 85 EP - 93 VL - 188 IS - 1-2 SN - 0304-3835, 0304-3835 KW - Antineoplastic Agents KW - 0 KW - Naphthoquinones KW - CASP3 protein, human KW - EC 3.4.22.- KW - CASP8 protein, human KW - CASP9 protein, human KW - Caspase 3 KW - Caspase 8 KW - Caspase 9 KW - Caspases KW - diospyrin KW - O0IQZ8B2R7 KW - Index Medicus KW - Microscopy, Fluorescence KW - Humans KW - Cell Division -- drug effects KW - Diospyros -- chemistry KW - Plant Bark -- chemistry KW - Caspases -- metabolism KW - Neoplasms -- drug therapy KW - Tumor Cells, Cultured -- metabolism KW - Tumor Cells, Cultured -- drug effects KW - Naphthoquinones -- pharmacology KW - Apoptosis -- drug effects KW - Tumor Cells, Cultured -- pathology KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72647530?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Induction+of+apoptosis+in+human+cancer+cell+lines+by+diospyrin%2C+a+plant-derived+bisnaphthoquinonoid%2C+and+its+synthetic+derivatives.&rft.au=Chakrabarty%2C+Sutapa%3BRoy%2C+Madhumita%3BHazra%2C+Banasri%3BBhattacharya%2C+R+K&rft.aulast=Chakrabarty&rft.aufirst=Sutapa&rft.date=2002-12-15&rft.volume=188&rft.issue=1-2&rft.spage=85&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 - 2003-01-13 N1 - Date created - 2002-10-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutations in the VHL gene from potassium bromate-induced rat clear cell renal tumors. AN - 72137722; 12359370 AB - Potassium bromate (KBrO(3)) is a rat renal carcinogen and a major drinking water disinfection by-product in water disinfected with ozone. Clear cell renal tumors, the most common form of human renal epithelial neoplasm, are rare in animals but are inducible by KBrO(3) in F344 rats. Detection of cytoplasmic periodic acid-Schiff-positive granules in clear cell tumors, indicative of glycogen accumulation, provides evidence of their biochemical similarity to human counterparts. Mutation in the coding region of the von Hippel-Lindau (VHL) gene is frequently detected in human clear cell renal carcinomas. Detection of VHL mutations in KBrO(3)-induced rat renal tumors could enhance the relevancy of these rat renal tumors for human health risk assessment. Formalin-fixed paraffin-embedded control tissues and renal tumors from male F344 rats exposed to KBrO(3) in the drinking water for 2 years were examined microscopically and were microdissected for DNA extraction. The coding sequence and a promoter region of the VHL gene were examined by polymerase chain reaction-single strand conformation polymorphism and/or DNA sequencing. Two of nine clear cell renal tumors carried the same C to T mutation at the core region of the Sp1 transcription factor binding motif in the VHL promoter and one of four untreated animals had C to T mutation outside the highly conserved core region. Mutation in the VHL coding sequence was only detected in one tumor. No VHL mutations were observed in three chromophilic tumors. KBrO(3)-induced rat renal tumors are morphologically similar to their human counterpart but the genetic basis of tumorigenesis is different. JF - Cancer letters AU - Shiao, Yih-Horng AU - Kamata, Sonie I AU - Li, Leeanne M AU - Hooth, Michelle J AU - DeAngelo, Anthony B AU - Anderson, Lucy M AU - Wolf, Douglas C AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, National Institutes of Health, Frederick, MD, USA. Y1 - 2002/12/10/ PY - 2002 DA - 2002 Dec 10 SP - 207 EP - 214 VL - 187 IS - 1-2 SN - 0304-3835, 0304-3835 KW - Bromates KW - 0 KW - DNA Primers KW - DNA, Neoplasm KW - Tumor Suppressor Proteins KW - potassium bromate KW - 04MB35W6ZA KW - Ubiquitin-Protein Ligases KW - EC 2.3.2.27 KW - Von Hippel-Lindau Tumor Suppressor Protein KW - Ligases KW - EC 6.- KW - Index Medicus KW - Rats KW - Polymerase Chain Reaction KW - Animals KW - DNA Mutational Analysis KW - Rats, Wistar KW - Promoter Regions, Genetic -- genetics KW - DNA, Neoplasm -- analysis KW - Open Reading Frames -- genetics KW - Polymorphism, Single-Stranded Conformational KW - Male KW - Ligases -- genetics KW - Kidney Neoplasms -- genetics KW - Adenocarcinoma, Clear Cell -- genetics KW - Kidney Neoplasms -- pathology KW - Kidney Neoplasms -- chemically induced KW - Adenocarcinoma, Clear Cell -- chemically induced KW - Bromates -- toxicity KW - Mutation KW - Adenocarcinoma, Clear Cell -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72137722?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutations+in+the+VHL+gene+from+potassium+bromate-induced+rat+clear+cell+renal+tumors.&rft.au=Shiao%2C+Yih-Horng%3BKamata%2C+Sonie+I%3BLi%2C+Leeanne+M%3BHooth%2C+Michelle+J%3BDeAngelo%2C+Anthony+B%3BAnderson%2C+Lucy+M%3BWolf%2C+Douglas+C&rft.aulast=Shiao&rft.aufirst=Yih-Horng&rft.date=2002-12-10&rft.volume=187&rft.issue=1-2&rft.spage=207&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 - 2003-01-06 N1 - Date created - 2002-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Respiratory symptoms and occupation: a cross-sectional study of the general population. AN - 72936521; 12537592 AB - This study focused on respiratory symptoms due to occupational exposures in a contemporary general population cohort. Subjects were from the Dutch Monitoring Project on Risk Factors for Chronic Diseases (MORGEN). The composition of this population enabled estimation of respiratory risks due to occupation from the recent past for both men and women. The study subjects (aged 20-59) were all inhabitants of Doetinchem, a small industrial town, and came from a survey of a random sample of 1104 persons conducted in 1993. A total of 274 cases with respiratory symptoms (subdivided in asthma and bronchitis symptoms) and 274 controls without symptoms were matched for age and sex. Relations between industry and occupation and respiratory symptoms were explored and adjusted for smoking habits and social economic status. Employment in the 'construction' (OR = 3.38; 95%CI 1.02 - 11.27), 'metal' (OR = 3.17; 95%CI 0. 98 - 10.28), 'rubber, plastics and synthetics' (OR = 6.52; 95%CI 1.26 - 53.80), and 'printing' industry (OR = 3.96; 95%CI 0.85 - 18.48) were positively associated with chronic bronchitis symptoms. In addition, the 'metal' industry was found to be weakly associated with asthma symptoms (OR = 2.59; 95%CI 0.87 - 7.69). Duration of employment within these industries was also positively associated with respiratory symptoms. Respiratory symptoms in the general population are traceable to employment in particular industries even in a contemporary cohort with relatively young individuals. JF - Environmental health : a global access science source AU - Vermeulen, Roel AU - Heederik, Dick AU - Kromhout, Hans AU - Smit, Henriëtte A AD - Environmental and Occupational Health Division, Institute for Risk Assessment Sciences, University Utrecht, Utrecht, PO Box 80176, 3503 TD Utrecht, The Netherlands. vermeulr@mail.nih.gov Y1 - 2002/12/09/ PY - 2002 DA - 2002 Dec 09 SP - 5 VL - 1 IS - 1 KW - Index Medicus KW - Respiratory Function Tests KW - Netherlands -- epidemiology KW - Asthma -- epidemiology KW - Age Factors KW - Analysis of Variance KW - Humans KW - Smoking KW - Cross-Sectional Studies KW - Bronchitis -- epidemiology KW - Construction Materials -- adverse effects KW - Logistic Models KW - Adult KW - Middle Aged KW - Chronic Disease KW - Radiography KW - Time Factors KW - Female KW - Male KW - Prevalence KW - Respiratory Tract Diseases -- diagnostic imaging KW - Respiratory Tract Diseases -- epidemiology KW - Occupational Exposure -- adverse effects KW - Respiratory Tract Diseases -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72936521?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+%3A+a+global+access+science+source&rft.atitle=Respiratory+symptoms+and+occupation%3A+a+cross-sectional+study+of+the+general+population.&rft.au=Vermeulen%2C+Roel%3BHeederik%2C+Dick%3BKromhout%2C+Hans%3BSmit%2C+Henri%C3%ABtte+A&rft.aulast=Vermeulen&rft.aufirst=Roel&rft.date=2002-12-09&rft.volume=1&rft.issue=1&rft.spage=5&rft.isbn=&rft.btitle=&rft.title=Environmental+health+%3A+a+global+access+science+source&rft.issn=1476-069X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-08-23 N1 - Date created - 2004-11-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am Rev Respir Dis. 1991 Mar;143(3):510-5 [2001059] Eur Respir J. 1991 Mar;4(3):273-8 [1864342] Am Rev Respir Dis. 1992 May;145(5):1098-102 [1586053] Am Rev Respir Dis. 1992 Aug;146(2):413-8 [1489133] Ann Occup Hyg. 1994 Feb;38(1):3-22 [8161092] Eur Respir J. 1994 Jun;7(6):1032-4 [7925869] Am J Respir Crit Care Med. 1996 Jul;154(1):137-43 [8680669] Occup Environ Med. 1997 May;54(5):301-6 [9196450] Am J Ind Med. 1998 Jan;33(1):16-23 [9408525] Am J Respir Crit Care Med. 1998 Feb;157(2):512-7 [9476866] Lancet. 1999 May 22;353(9166):1750-4 [10347988] Scand J Work Environ Health. 2001 Feb;27(1):76-81 [11266151] Am J Respir Crit Care Med. 2001 Jun;163(7):1572-7 [11401876] J Egypt Public Health Assoc. 1972;47(5):290-311 [4670666] Arch Environ Health. 1976 Jan-Feb;31(1):10-4 [1244803] Environ Res. 1977 Aug;14(1):59-67 [891505] Int J Epidemiol. 1979 Sep;8(3):201-12 [536090] J Occup Med. 1980 Nov;22(11):722-6 [7441390] Br J Ind Med. 1982 Feb;39(1):70-5 [7066223] J Occup Med. 1982 Sep;24(9):690-5 [7131111] Thorax. 1983 Feb;38(2):119-28 [6857569] Am Rev Respir Dis. 1983 Aug;128(2):226-30 [6881681] Arch Environ Health. 1986 Mar-Apr;41(2):85-9 [3718007] Br J Ind Med. 1986 Jul;43(7):474-85 [3718895] Am Rev Respir Dis. 1986 Nov;134(5):1011-9 [3777663] Am Rev Respir Dis. 1987 Aug;136(2):298-304 [3497594] J Allergy Clin Immunol. 1988 Jul;82(1):55-61 [3392370] Br J Ind Med. 1988 Nov;45(11):747-54 [3203079] Int J Epidemiol. 1989 Jun;18(2):382-9 [2767852] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Cleavage of the Urokinase Receptor Regulates Its Multiple Functions AN - 21339971; 5523680 AB - The urokinase-type plasminogen activator (uPA) is able to cleave its cell surface receptor (uPAR) anchored to the cell membrane through a glycophosphatidylinositol tail. The cleavage leads to the formation of cell surface truncated forms, devoid of the N-terminal domain 1 (D1) and unmasks or disrupts, depending on the cleavage site, a sequence in the D1-D2 linker region (residues 88-92), which in the soluble form is a potent chemoattractant for monocyte-like cells. To investigate the possible role(s) of the cleaved forms of cell surface glycophosphatidylinositol-anchored uPAR, uPAR-negative human embrional kidney 293 cells were transfected with the cDNA of intact uPAR (uPAR-293) or with cDNAs corresponding to the truncated forms of uPAR exposing (D2D3-293) or lacking (D2D3wc-293) the peptide 88-92 (P88-92). Cell adhesion assays and co-immunoprecipitation experiments indicated that the removal of D1, independently of the presence of P88-92, abolished the lateral interaction of uPAR with integrins and its capability to regulate integrin adhesive functions. The expression of intact uPAR induced also a moderate increase in 293 cell proliferation, which was accompanied by the activation of ERK. Also this effect was abolished by D1 removal, independently of the presence of P88-92. The expression of intact and truncated uPARs regulated cell directional migration toward uPA, the specific uPAR ligand, and toward fMLP, a bacterial chemotactic peptide. In fact, the uPA-dependent cell migration required the expression of intact uPAR, including D1, whereas the fMLP-dependent cell migration required the expression of a P88-92 containing uPAR and was independent of the presence of D1. Together these observations indicate that uPA-mediated uPAR cleavage and D1 removal, occurring on the cell surface of several cell types, can play a fundamental role in the regulation of multiple uPAR functions. JF - Journal of Biological Chemistry AU - Montuori, N AU - Carriero, M V AU - Salzano, S AU - Rossi, G AU - Ragno, P AD - Istituto di Endocrinologia ed Oncologia Sperimentale, Consiglio Nazionale delle Ricerche, via Pansini 5, I-80131, Naples, Italy, the National Cancer Institute, Via M. Semmola, I-80131, Naples, Italy, ragno@unina.it. Y1 - 2002/12/06/ PY - 2002 DA - 2002 Dec 06 SP - 46932 EP - 46939 VL - 277 IS - 49 SN - 0021-9258, 0021-9258 KW - Microbiology Abstracts B: Bacteriology KW - Cell surface KW - formyl peptides KW - Tails KW - Cell adhesion KW - Leukocyte migration KW - Extracellular signal-regulated kinase KW - Cell membranes KW - Integrins KW - Chemotactic factors KW - Kidney KW - Cell migration KW - u-Plasminogen activator KW - Cell proliferation KW - J 02320:Cell Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21339971?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=The+Cleavage+of+the+Urokinase+Receptor+Regulates+Its+Multiple+Functions&rft.au=Montuori%2C+N%3BCarriero%2C+M+V%3BSalzano%2C+S%3BRossi%2C+G%3BRagno%2C+P&rft.aulast=Montuori&rft.aufirst=N&rft.date=2002-12-06&rft.volume=277&rft.issue=49&rft.spage=46932&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 - 2010-02-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Cell surface; Tails; formyl peptides; Cell adhesion; Leukocyte migration; Extracellular signal-regulated kinase; Cell membranes; Integrins; Chemotactic factors; Kidney; u-Plasminogen activator; Cell migration; Cell proliferation ER - TY - JOUR T1 - Transmission of human herpesvirus 8 by sexual activity among adults in Lagos, Nigeria AN - 18654906; 5551350 AB - Background: Human herpesvirus 8 (HHV-8) infection is common in Africa, but prevalence varies geographically. Studies in Europe and America suggest spread through homosexual contact, but evidence of heterosexual spread is inconsistent. We examined the association between HHV-8 and markers of risky sexual activity in Nigeria. Methods: The study subjects included an adult referent population at relatively low risk of HIV infection, patients attending a sexually transmitted disease (STD) clinic, and female commercial sex workers (CSW). Sera were collected between 1991 and 1994 to study the epidemiology of retroviruses and STD in Lagos, Nigeria. Residual samples were tested for HHV-8 antibodies using a K8.1 enzyme immunoassay and for antibodies to syphilis, chancroid, herpes simplex virus 2, HIV-1/2, and HTLV-1. Associations were sought using chi square tests and logistic regression. Results: Overall, HHV-8 prevalence was 26.5% in 2002 study subjects, being higher among CSW and STD patients (31% in each) than in the referent population (19%). HHV-8 prevalence in women was approximately half that in men in both the referent and the STD populations. Increasing age and STD were each associated with HHV-8-seropositivity in men and women, and among women being a CSW was also a risk factor. HHV-8 antibodies were more frequently detected in those with laboratory evidence of STD in each group. Having at least one STD was associated with having HHV-8 antibodies. Conclusion: The higher prevalence of HHV-8 antibody in groups with multiple sexual partners and the association with STD among individuals both support the sexual transmission of HHV-8 in African adults. JF - AIDS AU - Eltom, MA AU - Mbulaiteye, S M AU - Dada, A J AU - Whitby, D AU - Biggar, R J AD - 6120 Executive Boulevard EPS Room 8014, Rockville, MD 20852 MSC 7248, USA, eltomm@mail.nih.gov Y1 - 2002/12/06/ PY - 2002 DA - 2002 Dec 06 SP - 2473 EP - 2478 VL - 16 IS - 18 SN - 0269-9370, 0269-9370 KW - HSV KW - disease transmission KW - man KW - prostitution KW - sexually transmitted diseases KW - Risk Abstracts; Health & Safety Science Abstracts; Virology & AIDS Abstracts KW - H 11000:Diseases/Injuries/Trauma KW - V 22123:Epidemiology KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18654906?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS&rft.atitle=Transmission+of+human+herpesvirus+8+by+sexual+activity+among+adults+in+Lagos%2C+Nigeria&rft.au=Eltom%2C+MA%3BMbulaiteye%2C+S+M%3BDada%2C+A+J%3BWhitby%2C+D%3BBiggar%2C+R+J&rft.aulast=Eltom&rft.aufirst=MA&rft.date=2002-12-06&rft.volume=16&rft.issue=18&rft.spage=2473&rft.isbn=&rft.btitle=&rft.title=AIDS&rft.issn=02699370&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Differential phosphorylation of SNAP-25 in vivo by protein kinase C and protein kinase A. AN - 72739490; 12459461 AB - SNAP-25 is a key protein required for the fusion of synaptic vesicles with the plasma membrane during exocytosis. This study establishes that SNAP-25 is differentially phosphorylated by protein kinase C and protein kinase A in neuroendocrine PC12 cells. Using phosphopeptide mapping and site-directed mutagenesis we identified both Thr138 and Ser187 as the targets of SNAP-25 phosphorylation by protein kinase C and Thr138 as the exclusive site of SNAP-25 phosphorylation by protein kinase A in vivo. Finally, despite published data to the contrary, we demonstrate that stimulation of regulated exocytosis under physiological conditions is independent of a measurable increase in SNAP-25 phosphorylation in PC12 cells. JF - FEBS letters AU - Hepp, Régine AU - Cabaniols, Jean-Pierre AU - Roche, Paul A AD - Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bldg. 10, Room 4B36, Bethesda, MD 20892, USA. Y1 - 2002/12/04/ PY - 2002 DA - 2002 Dec 04 SP - 52 EP - 56 VL - 532 IS - 1-2 SN - 0014-5793, 0014-5793 KW - Membrane Proteins KW - 0 KW - Nerve Tissue Proteins KW - SNAP25 protein, human KW - Snap25 protein, rat KW - Synaptosomal-Associated Protein 25 KW - Threonine KW - 2ZD004190S KW - Serine KW - 452VLY9402 KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Rats KW - Animals KW - Threonine -- metabolism KW - Phosphorylation KW - HeLa Cells KW - Norepinephrine -- metabolism KW - Kinetics KW - Humans KW - Serine -- metabolism KW - PC12 Cells KW - Protein Kinase C -- metabolism KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Membrane Proteins -- chemistry KW - Membrane Proteins -- metabolism KW - Nerve Tissue Proteins -- metabolism KW - Nerve Tissue Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72739490?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FEBS+letters&rft.atitle=Differential+phosphorylation+of+SNAP-25+in+vivo+by+protein+kinase+C+and+protein+kinase+A.&rft.au=Hepp%2C+R%C3%A9gine%3BCabaniols%2C+Jean-Pierre%3BRoche%2C+Paul+A&rft.aulast=Hepp&rft.aufirst=R%C3%A9gine&rft.date=2002-12-04&rft.volume=532&rft.issue=1-2&rft.spage=52&rft.isbn=&rft.btitle=&rft.title=FEBS+letters&rft.issn=00145793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-01-13 N1 - Date created - 2002-12-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A heterodimerizing leucine zipper coiled coil system for examining the specificity of a position interactions: amino acids I, V, L, N, A, and K. AN - 72732677; 12450375 AB - We use a heterodimerizing leucine zipper system to examine the contribution of the interhelical a-a' interaction to dimer stability for six amino acids (A, V, L, I, K, and N). Circular dichroism (CD) spectroscopy monitored the thermal denaturation of 36 heterodimers that generate six homotypic and 30 heterotypic a-a' interactions. Isoleucine (I-I) is the most stable homotypic a-a' interaction, being 9.2 kcal/mol per dimer more stable than the A-A interaction and 4.0 kcal/mol per dimer more stable than either the L-L or V-V interaction, and 7.0 kcal/mol per dimer more stable than the N-N interaction. Only lysine was less stable than alanine. An alanine-based double-mutant thermodynamic cycle calculated coupling energies between the a and a' positions in the heterodimer. The aliphatic amino acids L, V, and I prefer to form homotypic interactions with coupling energies of -0.6 to -0.9 kcal/mol per dimer, but the heterotypic aliphatic interactions have positive coupling energies of <1.0 kcal/mol per dimer. The asparagine homotypic interaction has a coupling energy of -0.5 kcal/mol per dimer, while heterotypic interactions with the aliphatic amino acids produce coupling energies ranging from 2.6 to 4.9 kcal/mol per dimer. The homotypic K-K interaction is 2.9 kcal/mol per dimer less stable than the A-A interaction, but the coupling energy is only 0.3 kcal/mol per dimer. Heterotypic interactions with lysine and either asparagine or aliphatic amino acids produce similar coupling energies ranging from -0.2 to -0.7 kcal/mol per dimer. Thus, of the amino acids that were examined, asparagine contributes the most to dimerization specificity because of the large positive coupling energies in heterotypic interactions with the aliphatic amino acids which results in the N-N homotypic interaction. JF - Biochemistry AU - Acharya, Asha AU - Ruvinov, Sergei B AU - Gal, Jozsef AU - Moll, Jonathan R AU - Vinson, Charles AD - Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/12/03/ PY - 2002 DA - 2002 Dec 03 SP - 14122 EP - 14131 VL - 41 IS - 48 SN - 0006-2960, 0006-2960 KW - Amino Acids KW - 0 KW - Avian Proteins KW - Basic-Leucine Zipper Transcription Factors KW - Carrier Proteins KW - Transcription Factors KW - Isoleucine KW - 04Y7590D77 KW - Asparagine KW - 7006-34-0 KW - Leucine KW - GMW67QNF9C KW - Valine KW - HG18B9YRS7 KW - Lysine KW - K3Z4F929H6 KW - Alanine KW - OF5P57N2ZX KW - Index Medicus KW - Animals KW - Carrier Proteins -- chemistry KW - Carrier Proteins -- genetics KW - Leucine -- chemistry KW - Valine -- genetics KW - Lysine -- genetics KW - Mutagenesis, Site-Directed KW - Protein Structure, Tertiary -- genetics KW - Amino Acid Substitution -- genetics KW - Asparagine -- genetics KW - Transcription Factors -- chemistry KW - Molecular Sequence Data KW - Alanine -- genetics KW - Valine -- chemistry KW - Lysine -- chemistry KW - Thermodynamics KW - Dimerization KW - Leucine -- genetics KW - Circular Dichroism KW - Amino Acid Sequence KW - Alanine -- chemistry KW - Ultracentrifugation KW - Transcription Factors -- genetics KW - Isoleucine -- genetics KW - Chickens KW - Protein Structure, Secondary -- genetics KW - Asparagine -- chemistry KW - Isoleucine -- chemistry KW - Leucine Zippers -- genetics KW - Amino Acids -- chemistry KW - Amino Acids -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72732677?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+heterodimerizing+leucine+zipper+coiled+coil+system+for+examining+the+specificity+of+a+position+interactions%3A+amino+acids+I%2C+V%2C+L%2C+N%2C+A%2C+and+K.&rft.au=Acharya%2C+Asha%3BRuvinov%2C+Sergei+B%3BGal%2C+Jozsef%3BMoll%2C+Jonathan+R%3BVinson%2C+Charles&rft.aulast=Acharya&rft.aufirst=Asha&rft.date=2002-12-03&rft.volume=41&rft.issue=48&rft.spage=14122&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-01-10 N1 - Date created - 2002-11-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dopamine in the nucleus accumbens: cellular actions, drug- and behavior-associated fluctuations, and a possible role in an organism's adaptive activity. AN - 72718944; 12445714 AB - This review expounds the idea that the analysis of dopamine (DA) action on target cells under behaviorally relevant conditions and behavior-related changes in DA activity can offer new information to clarify the functional significance of mesocorticolimbic DA. In contrast to the traditional association of DA with certain behavioral processes and mechanisms (activation, arousal, conditioning, motivation, reinforcement, sensorimotor integration, etc.), evaluation of DA activity during well-controlled behaviors established by different reinforcers can provide important clues for determining the role of DA in the development and regulation of goal-directed behavior. This review summarizes the results of our microiontophoretic studies of striatal neurons in awake, unrestrained rats, particularly the action of DA on spontaneously active and glutamate (GLU)-stimulated cells, the pattern of DA-GLU interaction, and the role of tonic DA release in regulating the activity and afferent responsiveness of these units. We present the results of our iontophoretic studies of ventral tegmental area (VTA) neurons in freely moving animals suggesting the complexity and limitations in their identification as DA- and non-DA cells under behaviorally relevant conditions. We also consider technical and methodological problems related to electrophysiological and electrochemical evaluation of DA transmission in behaving animals. Finally, we discuss parallels and differences in the activity of presumed DA VTA neurons and changes of nucleus accumbens DA-dependent electrochemical signal during heroin self-administration (SA) behavior. JF - Behavioural brain research AU - Kiyatkin, Eugene A AD - Behavioral Neuroscience Branch, National Institute on Drug Abuse-Intramural Research Program, 5500 Nathan Shock Drive, Baltimore, MD 21224 USA. ekiyatki@intra.nida.gov Y1 - 2002/12/02/ PY - 2002 DA - 2002 Dec 02 SP - 27 EP - 46 VL - 137 IS - 1-2 SN - 0166-4328, 0166-4328 KW - Glutamic Acid KW - 3KX376GY7L KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Nerve Net -- physiopathology KW - Limbic System -- physiopathology KW - Animals KW - Brain Mapping KW - Neurons -- physiology KW - Synaptic Transmission -- physiology KW - Glutamic Acid -- physiology KW - Ventral Tegmental Area -- physiopathology KW - Cerebral Cortex -- physiopathology KW - Heroin Dependence -- physiopathology KW - Dopamine -- physiology KW - Nucleus Accumbens -- physiopathology KW - Appetitive Behavior -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72718944?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dopamine+in+the+nucleus+accumbens%3A+cellular+actions%2C+drug-+and+behavior-associated+fluctuations%2C+and+a+possible+role+in+an+organism%27s+adaptive+activity.&rft.au=Kiyatkin%2C+Eugene+A&rft.aulast=Kiyatkin&rft.aufirst=Eugene&rft.date=2002-12-02&rft.volume=137&rft.issue=1-2&rft.spage=27&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 - 2003-03-03 N1 - Date created - 2002-11-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Post-analysis follow-up and validation of microarray experiments AN - 864951560; 13746526 AB - Measurement of gene-expression profiles using microarray technology is becoming increasingly popular among the biomedical research community. Although there has been great progress in this field, investigators are still confronted with a difficult question after completing their experiments: how to validate the large data sets that are generated? This review summarizes current approaches to verifying global expression results, discusses the caveats that must be considered, and describes some methods that are being developed to address outstanding problems. JF - Nature Genetics AU - Chuaqui, Rodrigo F AU - Bonner, Robert F AU - Best, Carolyn JM AU - Gillespie, John W AU - Flaig, Michael J AU - Hewitt, Stephen M AU - Phillips, John L AU - Krizman, David B AU - Tangrea, Michael A AU - Ahram, Mamoun AU - Linehan, WMarston AU - Knezevic, Vladimir AU - Emmert-Buck, Michael R AD - Pathogenetics Unit, Laboratory of Pathology and Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 509 EP - 514 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 32 Suppl 2 IS - Supp SN - 1061-4036, 1061-4036 KW - Genetics Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Biotechnology and Bioengineering Abstracts KW - Gene expression KW - Data processing KW - DNA microarrays KW - N 14810:Methods KW - W 30900:Methods KW - G 07700:Molecular Genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/864951560?accountid=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=Post-analysis+follow-up+and+validation+of+microarray+experiments&rft.au=Chuaqui%2C+Rodrigo+F%3BBonner%2C+Robert+F%3BBest%2C+Carolyn+JM%3BGillespie%2C+John+W%3BFlaig%2C+Michael+J%3BHewitt%2C+Stephen+M%3BPhillips%2C+John+L%3BKrizman%2C+David+B%3BTangrea%2C+Michael+A%3BAhram%2C+Mamoun%3BLinehan%2C+WMarston%3BKnezevic%2C+Vladimir%3BEmmert-Buck%2C+Michael+R&rft.aulast=Chuaqui&rft.aufirst=Rodrigo&rft.date=2002-12-01&rft.volume=32+Suppl+2&rft.issue=Supp&rft.spage=509&rft.isbn=&rft.btitle=&rft.title=Nature+Genetics&rft.issn=10614036&rft_id=info:doi/10.1038%2Fng1034 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2011-05-01 N1 - Last updated - 2016-02-04 N1 - SubjectsTermNotLitGenreText - Gene expression; Data processing; DNA microarrays DO - http://dx.doi.org/10.1038/ng1034 ER - TY - JOUR T1 - Clinical evaluation of patients with temporomandibular joint implants. AN - 85364583; pmid-12464999 AB - An undetermined number of patients with temporomandibular joint (TMJ) symptoms have been treated with intra-articular disc implants composed of Teflon ethylene/propylene or Teflon polytetrafluoroethylene and aluminum oxide (Proplast-Teflon; Vitek, Houston, TX). These implants have shown the potential to fragment in situ resulting in nonbiodegradable particles that stimulate a giant cell reaction and lead to degeneration of local structures, pain, and limitation of mandibular opening. We examined the possible relationship between TMJ implants and persistent pain, responses to sensory stimuli, quality of life, and systemic immune dysfunction.This case series (32 patients) were referred from university-based orofacial pain centers and private practices from across the United States. Laboratory and clinical assessments evaluated orofacial pain symptoms, neurologic function, clinical signs and symptoms of rheumatologic disease, physical function, systemic measures of immune function, and behavioral measures.We found that TMJ implant patients appeared to have altered sensitivity to sensory stimuli, a higher number of tender points with a diagnosis of fibromyalgia, increased self-report of chemical sensitivity, higher psychologic distress and significantly lower functional ability. Systemic illness or autoimmune disease was not evident in this series of TMJ implant patients.Significant problems were noted on clinical assessment of TMJ implant patients. This is a US government work. There are no restrictions on its use. JF - Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons AU - Ta, Lauren E AU - Phero, James C AU - Pillemer, Stanley R AU - Hale-Donze, Hollie AU - McCartney-Francis, Nancy AU - Kingman, Albert AU - Max, Mitchell B AU - Gordon, Sharon M AU - Wahl, Sharon M AU - Dionne, Raymond A AD - Postdoctoral Fellow, Pain and Neurosensory Mechanisms Branch, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2002/12// PY - 2002 DA - Dec 2002 SP - 1389 EP - 1399 VL - 60 IS - 12 SN - 0278-2391, 0278-2391 KW - National Library of Medicine KW - Adult KW - Analysis of Variance KW - *Arthroplasty, Replacement: adverse effects KW - Arthroplasty, Replacement: psychology KW - Autoimmune Diseases: etiology KW - Environmental Exposure KW - *Facial Pain: etiology KW - Female KW - Fibromyalgia: etiology KW - Humans KW - Immunophenotyping KW - *Joint Prosthesis: adverse effects KW - Joint Prosthesis: psychology KW - Male KW - Middle Aged KW - Pain Measurement KW - Polytetrafluoroethylene: adverse effects KW - Proplast: adverse effects KW - *Quality of Life KW - Range of Motion, Articular KW - Statistics, Nonparametric KW - Temporomandibular Joint: immunology KW - Temporomandibular Joint: physiology KW - *Temporomandibular Joint: surgery KW - Temporomandibular Joint Disorders: psychology KW - *Temporomandibular Joint Disorders: surgery UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85364583?accountid=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+oral+and+maxillofacial+surgery+%3A+official+journal+of+the+American+Association+of+Oral+and+Maxillofacial+Surgeons&rft.atitle=Clinical+evaluation+of+patients+with+temporomandibular+joint+implants.&rft.au=Ta%2C+Lauren+E%3BPhero%2C+James+C%3BPillemer%2C+Stanley+R%3BHale-Donze%2C+Hollie%3BMcCartney-Francis%2C+Nancy%3BKingman%2C+Albert%3BMax%2C+Mitchell+B%3BGordon%2C+Sharon+M%3BWahl%2C+Sharon+M%3BDionne%2C+Raymond+A&rft.aulast=Ta&rft.aufirst=Lauren&rft.date=2002-12-01&rft.volume=60&rft.issue=12&rft.spage=1389&rft.isbn=&rft.btitle=&rft.title=Journal+of+oral+and+maxillofacial+surgery+%3A+official+journal+of+the+American+Association+of+Oral+and+Maxillofacial+Surgeons&rft.issn=02782391&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Phased array ghost elimination (PAGE) for segmented SSFP imaging with interrupted steady-state. AN - 85276622; pmid-12465121 AB - Steady-state free precession (SSFP) has recently proven to be valuable for cardiac imaging due to its high signal-to-noise ratio and blood-myocardium contrast. Data acquired using ECG-triggered, segmented sequences during the approach to steady-state, or return to steady-state after interruption, may have ghost artifacts due to periodic k-space distortion. Schemes involving several preparatory RF pulses have been proposed to restore steady-state, but these consume imaging time during early systole. Alternatively, the phased-array ghost elimination (PAGE) method may be used to remove ghost artifacts from the first several frames. PAGE was demonstrated for cardiac cine SSFP imaging with interrupted steady-state using a simple alpha/2 magnetization preparation and storage scheme and a spatial tagging preparation. Magn Reson Med 48:1076-1080, 2002. Published 2002 Wiley-Liss, Inc. JF - Magnetic Resonance in Medicine AU - Kellman, Peter AU - Guttman, Michael A AU - Herzka, Daniel A AU - McVeigh, Elliot R AD - Laboratory of Cardiac Energetics, National Institutes of Health, National Heart, Lung and Blood Institute, Bethesda, Maryland. PY - 2002 SP - 1076 EP - 1080 VL - 48 IS - 6 SN - 0740-3194, 0740-3194 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85276622?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Magnetic+Resonance+in+Medicine&rft.atitle=Phased+array+ghost+elimination+%28PAGE%29+for+segmented+SSFP+imaging+with+interrupted+steady-state.&rft.au=Kellman%2C+Peter%3BGuttman%2C+Michael+A%3BHerzka%2C+Daniel+A%3BMcVeigh%2C+Elliot+R&rft.aulast=Kellman&rft.aufirst=Peter&rft.date=2002-12-01&rft.volume=48&rft.issue=6&rft.spage=1076&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Application of sensitivity-encoded echo-planar imaging for blood oxygen level-dependent functional brain imaging dagger. AN - 85273627; pmid-12465111 AB - The benefits of sensitivity-encoded (SENSE) echo-planar imaging (EPI) for functional MRI (fMRI) based on blood oxygen level-dependent (BOLD) contrast were quantitatively investigated at 1.5 T. For experiments with 3.4 x 3.4 x 4.0 mm(3) resolution, SENSE allowed the single-shot EPI image acquisition duration to be shortened from 24.1 to 12.4 ms, resulting in a reduced sensitivity to geometric distortions and T(*) (2) blurring. Finger-tapping fMRI experiments, performed on eight normal volunteers, showed an overall 18% loss in t-score in the activated area, which was substantially smaller than expected based on the image signal-to-noise ratio (SNR) and g-factor, but similar to the loss predicted by a model that takes physiologic noise into account. Magn Reson Med 48:1011-1020, 2002. Published 2002 Wiley-Liss, Inc. JF - Magnetic Resonance in Medicine AU - De Zwart Jacco A AU - Van Gelderen Peter AU - Kellman, Peter AU - Duyn, Jeff H AD - Advanced MRI, Laboratory of Functional and Molecular Imaging, NINDS, National Institutes of Health, Bethesda, Maryland. PY - 2002 SP - 1011 EP - 1020 VL - 48 IS - 6 SN - 0740-3194, 0740-3194 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85273627?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Magnetic+Resonance+in+Medicine&rft.atitle=Application+of+sensitivity-encoded+echo-planar+imaging+for+blood+oxygen+level-dependent+functional+brain+imaging+dagger.&rft.au=De+Zwart+Jacco+A%3BVan+Gelderen+Peter%3BKellman%2C+Peter%3BDuyn%2C+Jeff+H&rft.aulast=De+Zwart+Jacco+A&rft.aufirst=&rft.date=2002-12-01&rft.volume=48&rft.issue=6&rft.spage=1011&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Use of the best case series to evaluate complementary and alternative therapies for cancer: A systematic review. AN - 85268309; pmid-12516038 AB - The best case series (BCS) is a retrospective chart review that describes a series of patients who all appear to have benefitted from the treatment under study. The BCS has been advocated as the first research step for evaluating complementary and alternative medicine (CAM) treatments for cancer. However, the research value of the BCS has not been assessed. To address this deficiency, the present study evaluates the primary characteristics of the BCS process through a systematic review of the English language scientific literature. Twenty-four individual BCS investigating 16 unique CAM treatments for cancer were identified. About half of the BCS reported evidence of tumor regression in association with a particular CAM treatment, but only six contained documentation adequate for publication in peer-reviewed journals. For these six BCS the number of responders per BCS ranged from 2 to 12 (median, 3.5), the proportion of responders in the total number of evaluated cases varied from 6% to 100% (median, 40%), and the proportion of evaluated cases to identified cases ranged from 18% to 53% (median, 29%). The primary factors confounding the identified BCS were lack of documentation of disease and/or the use of concurrent or recent conventional treatment. Despite these general deficiencies, four BCS (antineoplastons, hydrazine sulfate, laetrile, and Kelly-Gonzalez) were sufficiently convincing to warrant follow-up clinical trials. These data suggest that while well-documented BCS do have an impact on the research agenda, in general, additional rigor is needed during their compilation. Semin Oncol 29:552-562. This is a US government work. There are no restrictions on its use. JF - Seminars in Oncology AU - Nahin, Richard L AD - National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, MD. PY - 2002 SP - 552 EP - 562 VL - 29 IS - 6 SN - 0093-7754, 0093-7754 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85268309?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Seminars+in+Oncology&rft.atitle=Use+of+the+best+case+series+to+evaluate+complementary+and+alternative+therapies+for+cancer%3A+A+systematic+review.&rft.au=Nahin%2C+Richard+L&rft.aulast=Nahin&rft.aufirst=Richard&rft.date=2002-12-01&rft.volume=29&rft.issue=6&rft.spage=552&rft.isbn=&rft.btitle=&rft.title=Seminars+in+Oncology&rft.issn=00937754&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - GNE mutations in an American family with quadriceps-sparing IBM and lack of mutations in s-IBM. AN - 85249272; pmid-12473769 AB - Analysis for GNE mutations was performed in an American, non-Iranian Jewish, family with quadriceps-sparing inclusion body myopathy (QS-IBM) and in 11 patients with sporadic IBM (s-IBM). Two novel nonallosteric site missense mutations were found in the QS-IBM kinship. No mutations were identified in s-IBM patients. After 8 years of follow-up and severe disease progression, the quadriceps muscle in the QS-IBM patient remains strong despite subclinical involvement documented with repeat MRI and muscle biopsy. JF - Neurology AU - Vasconcelos, Olavo M AU - Raghavan, Raju AU - Dalakas, Marinos C AD - Neuromuscular Diseases Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. PY - 2002 SP - 1776 EP - 1779 VL - 59 IS - 11 SN - 0028-3878, 0028-3878 KW - Pedigree KW - Magnetic Resonance Imaging KW - Exons KW - Human KW - Carbohydrate Epimerases KW - Disease Progression KW - Myositis, Inclusion Body KW - Reverse Transcriptase Polymerase Chain Reaction KW - Muscle Weakness KW - Polymorphism, Single-Stranded Conformational KW - Muscle, Skeletal KW - Cloning, Molecular KW - Genotype KW - RNA KW - Adult KW - Follow-Up Studies KW - Case Report KW - Mutation KW - Female UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85249272?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurology&rft.atitle=GNE+mutations+in+an+American+family+with+quadriceps-sparing+IBM+and+lack+of+mutations+in+s-IBM.&rft.au=Vasconcelos%2C+Olavo+M%3BRaghavan%2C+Raju%3BDalakas%2C+Marinos+C&rft.aulast=Vasconcelos&rft.aufirst=Olavo&rft.date=2002-12-01&rft.volume=59&rft.issue=11&rft.spage=1776&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Developmental changes in short-term synaptic depression in the neonatal mouse spinal cord. AN - 85235822; pmid-12466442 AB - We examined age-dependent changes in short-term synaptic depression of monosynaptic excitatory postsynaptic potentials (EPSPs) recorded in lumbar motoneurons in hemisected spinal cords of neonatal Swiss-Webster mice between postnatal day 2 (P2) and 12 (P12). We used four paradigms that sample the input-output dependence on stimulation history in different but complementary ways: 1) paired-pulse depression; 2) steady-state depression during constant frequency trains; 3) modulation during irregular stimulation sequences; and 4) recovery after high-frequency conditioning trains. Paired-pulse synaptic depression declined more than steady-state depression during 10-pulse trains at frequencies from 0.125 to 8 Hz in this age range. Depression during sequences of irregular stimulations that more closely mimic physiological activation also declined with postnatal age. On the other hand, the overall rate of synaptic recovery after a 4-Hz conditioning train exhibited surprisingly little change between P2 and P12. Control experiments indicated that these observations depend primarily, if not exclusively, on changes in presynaptic transmitter release. The data were examined using quantitative models that incorporate factors that have been suggested to exist at more specialized central synapses. The model that best predicted the observations included two presynaptic compartments that are depleted during activation, plus two superimposed processes that enhance transmitter release by different mechanisms. One of the latter produced rapidly-decaying enhancement of transmitter release fraction. The other mechanism indirectly enhanced the rate of renewal of one of the depleted presynaptic compartments. This model successfully predicted the constant frequency and irregular sequence data from all age groups, as well as the recovery curves following short, high-frequency tetani. The results suggest that a reduction in release fraction accounts for much of the decline in synaptic depression during early postnatal development, although changes in both enhancement processes also contribute. The time constants of resource renewal showed surprisingly little change through the first 12 days of postnatal life. JF - Journal of Neurophysiology AU - Li, Yan AU - Burke, R E AD - Laboratory of Neural Control, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-4455, USA. PY - 2002 SP - 3218 EP - 3231 VL - 88 IS - 6 SN - 0022-3077, 0022-3077 KW - Osmolar Concentration KW - Spinal Nerve Roots KW - Spinal Cord KW - Calcium KW - In Vitro KW - Random Allocation KW - Aging KW - Presynaptic Terminals KW - Animal KW - Mice KW - Neural Inhibition KW - Electric Stimulation KW - Animals, Newborn KW - gamma-Aminobutyric Acid KW - Excitatory Postsynaptic Potentials KW - Models, Neurological KW - Time Factors KW - Synaptic Transmission UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85235822?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Neurophysiology&rft.atitle=Developmental+changes+in+short-term+synaptic+depression+in+the+neonatal+mouse+spinal+cord.&rft.au=Li%2C+Yan%3BBurke%2C+R+E&rft.aulast=Li&rft.aufirst=Yan&rft.date=2002-12-01&rft.volume=88&rft.issue=6&rft.spage=3218&rft.isbn=&rft.btitle=&rft.title=Journal+of+Neurophysiology&rft.issn=00223077&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Movement rate effect on activation and functional coupling of motor cortical areas. AN - 85233769; pmid-12466454 AB - We investigated changes in the activation and functional coupling of bilateral primary sensorimotor (SM1) and supplementary motor (SMA) areas with different movement rates in eight normal volunteers. An auditory-cued repetitive right-thumb movement was performed at rates of 0.5, 0.75, 1, 2, 3, and 4 Hz. As a control condition, subjects listened to pacing tones with no movements. Electroencephalogram (EEG) was recorded from 28 scalp electrodes and electromyogram was obtained from the hand muscles. The event-related changes in EEG band-power (ERpow: activation of each area) and correlation (ERcor: functional coupling between each pair of cortical areas) were computed every 32 ms. Modulations of ERpow and ERcor were inspected in alpha (8-12 Hz) and beta (16-20 Hz) bands. Motor cortical activation and coupling was greater for faster movements. With increasing movement rate, the timing relationship between movement and tone switched from synchronization (for 0.5-1 Hz) to syncopation (for 3-4 Hz). The results suggested that for slow repetitive movements (0.5-1 Hz), each individual movement is separately controlled, and EEG activation and coupling of the motor cortical areas were immediately followed by transient deactivation and decoupling, having clear temporal modulation locked to each movement. In contrast, for fast repetitive movements (3-4 Hz), it appears that the rhythm is controlled and the motor cortices showed sustained EEG activation and continuous coupling. JF - Journal of Neurophysiology AU - Toma Keiichiro AU - Mima Tatsuya AU - Matsuoka Takahiro AU - Gerloff, Christian AU - Ohnishi Tatsuhito AU - Koshy, Benjamin AU - Andres, Frank AU - Hallett, Mark AD - Human Motor Control Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1428, USA. PY - 2002 SP - 3377 EP - 3385 VL - 88 IS - 6 SN - 0022-3077, 0022-3077 KW - Human KW - Electroencephalography KW - Electromyography KW - Movement KW - Alpha Rhythm KW - Motor Cortex KW - Behavior KW - Adult KW - Beta Rhythm KW - Middle Age KW - Support, Non-U.S. Gov't KW - Time Factors KW - Male KW - Female UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85233769?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Neurophysiology&rft.atitle=Movement+rate+effect+on+activation+and+functional+coupling+of+motor+cortical+areas.&rft.au=Toma+Keiichiro%3BMima+Tatsuya%3BMatsuoka+Takahiro%3BGerloff%2C+Christian%3BOhnishi+Tatsuhito%3BKoshy%2C+Benjamin%3BAndres%2C+Frank%3BHallett%2C+Mark&rft.aulast=Toma+Keiichiro&rft.aufirst=&rft.date=2002-12-01&rft.volume=88&rft.issue=6&rft.spage=3377&rft.isbn=&rft.btitle=&rft.title=Journal+of+Neurophysiology&rft.issn=00223077&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - HIV-1 evades antibody-mediated neutralization through conformational masking of receptor-binding sites. AN - 85227810; pmid-12478295 AB - The ability of human immunodeficiency virus (HIV-1) to persist and cause AIDS is dependent on its avoidance of antibody-mediated neutralization. The virus elicits abundant, envelope-directed antibodies that have little neutralization capacity. This lack of neutralization is paradoxical, given the functional conservation and exposure of receptor-binding sites on the gp120 envelope glycoprotein, which are larger than the typical antibody footprint and should therefore be accessible for antibody binding. Because gp120-receptor interactions involve conformational reorganization, we measured the entropies of binding for 20 gp120-reactive antibodies. Here we show that recognition by receptor-binding-site antibodies induces conformational change. Correlation with neutralization potency and analysis of receptor-antibody thermodynamic cycles suggested a receptor-binding-site 'conformational masking' mechanism of neutralization escape. To understand how such an escape mechanism would be compatible with virus-receptor interactions, we tested a soluble dodecameric receptor molecule and found that it neutralized primary HIV-1 isolates with great potency, showing that simultaneous binding of viral envelope glycoproteins by multiple receptors creates sufficient avidity to compensate for such masking. Because this solution is available for cell-surface receptors but not for most antibodies, conformational masking enables HIV-1 to maintain receptor binding and simultaneously to resist neutralization. JF - Nature AU - Kwong, Peter D AU - Doyle, Michael L AU - Casper, David J AU - Cicala, Claudia AU - Leavitt, Stephanie A AU - Majeed Shahzad AU - Steenbeke, Tavis D AU - Venturi Miro AU - Chaiken Irwin AU - Fung, Michael AU - Katinger Hermann AU - Parren Paul W I H AU - Robinson, James AU - Van Ryk Donald AU - Wang, Liping AU - Burton, Dennis R AU - Freire, Ernesto AU - Wyatt, Richard AU - Sodroski, Joseph AU - Hendrickson, Wayne A AU - Arthos, James AD - [1] Vaccine Research Center, National Institutes of Health, Bethesda, Maryland 20892, USA [2] Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA. PY - 2002 SP - 678 EP - 682 VL - 420 IS - 6916 SN - 0028-0836, 0028-0836 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85227810?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=HIV-1+evades+antibody-mediated+neutralization+through+conformational+masking+of+receptor-binding+sites.&rft.au=Kwong%2C+Peter+D%3BDoyle%2C+Michael+L%3BCasper%2C+David+J%3BCicala%2C+Claudia%3BLeavitt%2C+Stephanie+A%3BMajeed+Shahzad%3BSteenbeke%2C+Tavis+D%3BVenturi+Miro%3BChaiken+Irwin%3BFung%2C+Michael%3BKatinger+Hermann%3BParren+Paul+W+I+H%3BRobinson%2C+James%3BVan+Ryk+Donald%3BWang%2C+Liping%3BBurton%2C+Dennis+R%3BFreire%2C+Ernesto%3BWyatt%2C+Richard%3BSodroski%2C+Joseph%3BHendrickson%2C+Wayne+A%3BArthos%2C+James&rft.aulast=Kwong&rft.aufirst=Peter&rft.date=2002-12-01&rft.volume=420&rft.issue=6916&rft.spage=678&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Effect of Dopamine Receptor Antagonists on Renewal of Cocaine Seeking by Reexposure to Drug-associated Contextual Cues AN - 762277799; 13698419 AB - We recently found that in rats trained to self-administer a heroin-cocaine mixture, exposure to the drug self-administration environment, after extinction of the drug-reinforced behavior in a different context, leads to renewal of drug seeking. Here we further explored the role of contextual stimuli in drug seeking by characterizing the effect of drug-associated environmental stimuli on renewal of cocaine seeking. We also investigated whether activation of dopamine receptors contributes to context-induced renewal of cocaine seeking by testing the effects of selective D1-like (SCH 23390) and D2-like (raclopride) receptor antagonists. Rats were trained for 10 days to self-administer cocaine by pressing a lever. Next, lever pressing was extinguished in the presence of the discrete cues associated with cocaine infusions for 10 days in a context that was distinctively different from the drug-taking context. On the test days, rats were pretreated with SCH 23390 (0, 5 or 10 kg/kg) or raclopride (0, 50 or 100 kg/kg) and non-reinforced lever-pressing behavior was determined either in the extinction context (Control group) or the cocaine-associated context (Renewal group). Consistent with our previous report, cocaine seeking was renewed when rats were exposed to the drug-associated context after extinction in a different context. Furthermore, pretreatment with the D1-like or the D2-like receptor antagonists attenuated context-induced renewal of cocaine seeking. These data suggest that activation of dopamine receptors is involved in reinstatement of cocaine seeking induced by exposure to the drug self-administration context.Neuropsychopharmacology (2002) 27 1006-1015.10.1016/S0893-133X(02)00356-1 JF - Neuropsychopharmacology AU - Crombag, Hans S AU - Grimm, Jeffrey W AU - Shaham, Yavin AD - 1 Behavioral Neuroscience Branch, The National Institute on Drug Abuse, Intramural Research Program, Baltimore, MD USA Y1 - 2002/12// PY - 2002 DA - Dec 2002 SP - 1006 EP - 1015 PB - Nature Publishing Group, The Macmillan Building London N1 9XW UK VL - 27 IS - 6 SN - 0893-133X, 0893-133X KW - CSA Neurosciences Abstracts; Toxicology Abstracts KW - Data processing KW - Extinction KW - raclopride KW - Environmental effects KW - Cocaine KW - Dopamine receptors KW - Drug addiction KW - Drug abuse KW - Reinstatement KW - Antagonists KW - Drug self-administration KW - X 24380:Social Poisons & Drug Abuse KW - N3 11028:Neuropharmacology & toxicology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/762277799?accountid=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=Neuropsychopharmacology&rft.atitle=Effect+of+Dopamine+Receptor+Antagonists+on+Renewal+of+Cocaine+Seeking+by+Reexposure+to+Drug-associated+Contextual+Cues&rft.au=Crombag%2C+Hans+S%3BGrimm%2C+Jeffrey+W%3BShaham%2C+Yavin&rft.aulast=Crombag&rft.aufirst=Hans&rft.date=2002-12-01&rft.volume=27&rft.issue=6&rft.spage=1006&rft.isbn=&rft.btitle=&rft.title=Neuropsychopharmacology&rft.issn=0893133X&rft_id=info:doi/10.1016%2FS0893-133X%2802%2900356-1 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-10-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Data processing; raclopride; Extinction; Environmental effects; Drug abuse; Drug addiction; Dopamine receptors; Cocaine; Reinstatement; Antagonists; Drug self-administration DO - http://dx.doi.org/10.1016/S0893-133X(02)00356-1 ER - TY - JOUR T1 - Improving the use of 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PPIX) for the gastrointestinal tract by esterification--an in vitro study. AN - 72875981; 12699251 AB - Possible approaches to improve the diagnostic and therapeutic effects of 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PPIX) are the esterification of ALA for enhanced uptake and the choice of wavelength for irradiation. The human colonic cell lines HT29 [G2] and CCD18 (fibroblasts) were incubated with 0.6 mM ALA, ALA-hexylester or -benzylester respectively, and for further assays with hypotaurine, in addition. PPIX-accumulation was analyzed by flow cytometry and fluorescence spectroscopy. PPIX formation kinetics were continuously recorded. Incubated cells were irradiated with an incoherent light source lambda = 400-700 nm or lambda = 590-700 nm, respectively. After PDT treatment, clonogenicity assays were performed to determine cell viability. Esterification leads to increased PPIX-accumulation, decreased time for production of detectable amounts of PPIX as well as increased response to PDT. Tumor specificity is always maintained or exceeds values for ALA alone. ALA enters the cells via beta transporter whereas esters by passive diffusion. Altering irradiation wavelengths showed the independence of wavelength rather than light dose. Results emphasize the role of heme metabolism for generating tumor specificity rather than the process of ALA-uptake, an important detail for future clinical application. JF - Cellular and molecular biology (Noisy-le-Grand, France) AU - Krieg, R C AU - Uihlein, D AU - Murthum, T AU - Endlicher, E AU - Hausmann, F AU - Messmann, H AU - Knuechel, R AD - National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. krieg@cber.fda.gov Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 917 EP - 923 VL - 48 IS - 8 SN - 0145-5680, 0145-5680 KW - Protoporphyrins KW - 0 KW - Aminolevulinic Acid KW - 88755TAZ87 KW - protoporphyrin IX KW - C2K325S808 KW - Index Medicus KW - Tumor Cells, Cultured KW - Spectrometry, Fluorescence KW - Dose-Response Relationship, Drug KW - Kinetics KW - Humans KW - Colon -- drug effects KW - Light KW - Flow Cytometry KW - Dose-Response Relationship, Radiation KW - Photochemotherapy -- methods KW - Time Factors KW - Cell Line KW - Aminolevulinic Acid -- therapeutic use KW - Digestive System -- drug effects KW - Protoporphyrins -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72875981?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+biology+%28Noisy-le-Grand%2C+France%29&rft.atitle=Improving+the+use+of+5-aminolevulinic+acid+%28ALA%29-induced+protoporphyrin+IX+%28PPIX%29+for+the+gastrointestinal+tract+by+esterification--an+in+vitro+study.&rft.au=Krieg%2C+R+C%3BUihlein%2C+D%3BMurthum%2C+T%3BEndlicher%2C+E%3BHausmann%2C+F%3BMessmann%2C+H%3BKnuechel%2C+R&rft.aulast=Krieg&rft.aufirst=R&rft.date=2002-12-01&rft.volume=48&rft.issue=8&rft.spage=917&rft.isbn=&rft.btitle=&rft.title=Cellular+and+molecular+biology+%28Noisy-le-Grand%2C+France%29&rft.issn=01455680&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-26 N1 - Date created - 2003-04-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Uncertain science and a failure of trust. The NIH radioepidemiologic tables and compensation for radiation-induced cancer. AN - 72861706; 12664791 AB - In the late 1970s, the U.S. Congress was debating a number of different proposals to provide monetary compensation to residents of Utah and Nevada who had been exposed to radioactive fallout from government nuclear weapons testing in the 1950s. Yet scientists and government officials expressed concern that such a program would end up compensating many people for cancers that were not caused by the fallout. Thus, after much debate, Congress directed the National Institutes of Health to produce a set of statistical tables--the radioepidemiologic tables--to target compensation awards to "deserving" individuals. Advocates of the tables, notably Senator Orrin Hatch, argued that reliance on scientific data would provide compensation decisions with predictability and evenhandedness. Yet in the end, the effort to employ the tables failed. The substantial scientific uncertainties in the tables and in their application to individual claims failed to deliver the authority they promised. Additionally, the goal of fairness and objectivity could not be convincingly met because of persistent controversy and mistrust surrounding the government's role in the study of health effects of low-level radiation. JF - Isis; an international review devoted to the history of science and its cultural influences AU - Parascandola, Mark AD - National Cancer Institute, Cancer Prevention Fellowship Program, 6130 Executive Boulevard, Suite 3109, Bethesda, Maryland 20892, USA. Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 559 EP - 584 VL - 93 IS - 4 SN - 0021-1753, 0021-1753 KW - Radioactive Fallout KW - 0 KW - Index Medicus KW - History of medicine KW - History, 20th Century KW - Government Programs -- standards KW - Humans KW - Nuclear Warfare -- history KW - Government Programs -- history KW - United States -- epidemiology KW - Population Surveillance -- methods KW - Radioactive Fallout -- statistics & numerical data KW - Compensation and Redress -- legislation & jurisprudence KW - Neoplasms, Radiation-Induced -- economics KW - Compensation and Redress -- history KW - Epidemiologic Methods KW - Neoplasms, Radiation-Induced -- epidemiology KW - Radioactive Fallout -- history KW - Radioactive Fallout -- legislation & jurisprudence KW - National Institutes of Health (U.S.) -- history UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72861706?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Isis%3B+an+international+review+devoted+to+the+history+of+science+and+its+cultural+influences&rft.atitle=Uncertain+science+and+a+failure+of+trust.+The+NIH+radioepidemiologic+tables+and+compensation+for+radiation-induced+cancer.&rft.au=Parascandola%2C+Mark&rft.aulast=Parascandola&rft.aufirst=Mark&rft.date=2002-12-01&rft.volume=93&rft.issue=4&rft.spage=559&rft.isbn=&rft.btitle=&rft.title=Isis%3B+an+international+review+devoted+to+the+history+of+science+and+its+cultural+influences&rft.issn=00211753&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-01 N1 - Date created - 2003-03-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carcinogenicity and mechanistic insights on the behavior of epoxides and epoxide-forming chemicals. AN - 72839699; 12562636 AB - Many epoxides and their precursors are high production volume chemicals that have major uses in the polymer industry and as intermediates in the manufacture of other chemicals. Several of these chemicals were demonstrated to be carcinogenic in laboratory animal studies conducted by the Ramazzini Foundation (e.g., vinyl chloride, acrylonitrile, styrene, styrene oxide, and benzene) and by the National Toxicology Program (e.g., ethylene oxide, 1,3-butadiene, isoprene, chloroprene, acrylonitrile, glycidol, and benzene). The most common sites of tumor induction were lung, liver, harderian gland, and circulatory system in mice; Zymbal's gland and brain in rats; and mammary gland and forestomach in both species. Differences in cancer outcome among studies of epoxide chemicals may be related to differences in study design (e.g., dose, duration, and route of exposure; observation period; animal strains), as well as biological factors affecting target organ dosimetry of the DNA-reactive epoxide (toxicokinetics) and tissue response (toxicodynamics). N7-Alkylguanine, N1-alkyladenine, and cyclic etheno adducts, as well as K-ras and p53 mutations, have been detected in animals and/or workers exposed to several of these chemicals. The classifications of these chemical carcinogens by IARC and NTP are based on animal and human data and results of mechanistic studies. Reducing occupational and environmental exposures to these chemicals will certainly reduce human cancer risks. JF - Annals of the New York Academy of Sciences AU - Melnick, Ronald L AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. melnickr@niehs.nih.gov Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 177 EP - 189 VL - 982 SN - 0077-8923, 0077-8923 KW - Carcinogens KW - 0 KW - DNA Adducts KW - Epoxy Compounds KW - Mutagens KW - Vinyl Compounds KW - Index Medicus KW - United States KW - Vinyl Compounds -- toxicity KW - Animals KW - DNA Adducts -- analysis KW - Humans KW - Neoplasms -- chemically induced KW - Neoplasms -- epidemiology KW - Disease Models, Animal KW - Neoplasms -- genetics KW - Carcinogens -- toxicity KW - Mutagens -- toxicity KW - Epoxy Compounds -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72839699?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Carcinogenicity+and+mechanistic+insights+on+the+behavior+of+epoxides+and+epoxide-forming+chemicals.&rft.au=Melnick%2C+Ronald+L&rft.aulast=Melnick&rft.aufirst=Ronald&rft.date=2002-12-01&rft.volume=982&rft.issue=&rft.spage=177&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 - 2003-04-02 N1 - Date created - 2003-02-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The National Toxicology Program rodent bioassay: designs, interpretations, and scientific contributions. AN - 72835754; 12562638 AB - The National Toxicology Program rodent cancer bioassay program design evolved from that of the National Cancer Institute in the 1970s. Groups of 50 or more mice are assigned to control or treatment groups. Test substances are given at three dose levels by intubation, dietary or drinking water consumption, or dermal or inhalation exposure. Dosing starts at age 5-6 weeks and lasts for 2 years, when surviving animals receive a complete histopathologic examination. Statistical approaches accommodate survival differences and no longer require differentiation between fatal and incidental tumors. Photocarcinogenicity studies, employing SKH-1 hairless mice, evaluate onset of skin papillomas and incidences at 1 year. Top doses are chosen to expose animals to a minimally toxic challenge and lower doses to operate within the linear range of kinetics. This dosing allows comparison of results across studies. Bioassay and ancillary studies successfully identify tumor-causing agents in rodents, provide information on dose-response, and characterize other chemical-related toxicities. NTP and Ramazzini Foundation bioassay designs differ in several aspects, but bioassays at both institutions provide chemical-specific information for predicting human carcinogens, thus providing for protection of public health. Bioassays constitute an essential information reference set for new assay development and further investigations into mechanisms of action. The scientific community and the public owe a huge debt of gratitude to Dr. Cesare Maltoni of the European Foundation of Oncology and Environmental Sciences and to Dr. David P. Rall of the National Institute of Environmental Health Sciences for their foresight and wisdom in creating and nurturing these bioassay programs. JF - Annals of the New York Academy of Sciences AU - Bucher, John R AD - National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 22709, USA. bucher@niehs.nih.gov Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 198 EP - 207 VL - 982 SN - 0077-8923, 0077-8923 KW - Carcinogens KW - 0 KW - Index Medicus KW - Animals KW - Neoplasms, Experimental -- chemically induced KW - Rodentia KW - Neoplasms, Experimental -- pathology KW - Research Design KW - Biological Assay -- methods KW - Carcinogens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72835754?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+National+Toxicology+Program+rodent+bioassay%3A+designs%2C+interpretations%2C+and+scientific+contributions.&rft.au=Bucher%2C+John+R&rft.aulast=Bucher&rft.aufirst=John&rft.date=2002-12-01&rft.volume=982&rft.issue=&rft.spage=198&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 - 2003-04-02 N1 - Date created - 2003-02-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemicals studied and evaluated in long-term carcinogenesis bioassays by both the Ramazzini Foundation and the National Toxicology Program: in tribute to Cesare Maltoni and David Rall. AN - 72835592; 12562639 AB - The Ramazzini Foundation (RF) in Bentivoglio, Italy and the National Toxicology Program (NTP) in Research Triangle Park, North Carolina have carried out several hundred chemical carcinogenesis bioassays: 200 by RF and 500 by NTP. Of these, 21 have been evaluated by both laboratories. The 14 chemicals for which both laboratories have designed, conducted, and reported bioassay results are: acrylonitrile, benzene, chlorine, diesel fuel, ethylbenzene, methylene chloride (dichloromethane), propylene, styrene, styrene oxide, toluene, trichloroethylene, trichlorofluoromethane, vinylidene chloride, and xylenes. The other seven chemicals (two are fibers) were evaluated by both laboratories, but results have not yet been published. Results of these 14 interlaboratory studies were compared both to explore consistency of carcinogenic responses and to identify possible factors that may reveal reasons for any differences observed. Individual carcinogenesis results from each laboratory were duplicated and complementary. Of the 14 chemicals compared, 11 (80%) were either carcinogenic (9 chemicals) or noncarcinogenic (2 chemicals) in both studies. Eight of the paired chemicals had at least one carcinogenic target site in common. The other three were carcinogenic in one laboratory but not in the other. Possible explanations for these differences include dose, method of administration, duration of follow-up, and whether or not total tumors are counted. The collaboration between these two pioneering bioassay laboratory programs contributes greatly to our understanding of chemical carcinogenesis and results in better protection of workers and the general population from chemical diseases, especially cancers. JF - Annals of the New York Academy of Sciences AU - Huff, James AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. huff1@niehs.nih.gov Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 208 EP - 230 VL - 982 SN - 0077-8923, 0077-8923 KW - Carcinogens KW - 0 KW - Index Medicus KW - United States KW - Animals KW - Humans KW - Mice KW - Research Design KW - Italy KW - Biological Assay -- methods KW - Rats KW - Rats, Inbred Strains KW - Mice, Inbred Strains KW - Foundations KW - Time Factors KW - Species Specificity KW - Female KW - Male KW - Carcinogens -- administration & dosage KW - Neoplasms, Experimental -- chemically induced KW - Neoplasms -- chemically induced KW - Carcinogens -- toxicity KW - Neoplasms -- prevention & control KW - Neoplasms, Experimental -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72835592?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chemicals+studied+and+evaluated+in+long-term+carcinogenesis+bioassays+by+both+the+Ramazzini+Foundation+and+the+National+Toxicology+Program%3A+in+tribute+to+Cesare+Maltoni+and+David+Rall.&rft.au=Huff%2C+James&rft.aulast=Huff&rft.aufirst=James&rft.date=2002-12-01&rft.volume=982&rft.issue=&rft.spage=208&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 - 2003-04-02 N1 - Date created - 2003-02-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chipping away at breast cancer: insights from microarray studies of human and mouse mammary cancer. AN - 72830480; 12542399 AB - Breast cancer is the most prevalent tumor in American woman. Multiple factors, including age, diet, genetics, environment, geographic location, parity, as well as race, influence the development of this heterogeneous disease. As the process of oncogenesis involves the disruption of diverse cellular pathways including cell cycle, growth, survival, and apoptosis, the high throughput technique of microarray analyses provides a powerful insight into multiple cellular processes. These techniques have identified particular expression patterns that can classify tumors into new groups and aid in the prediction of the natural history of the disease and the therapeutic response. This wealth of information may also form the basis for the development of new types of targeted therapies. Studies to identify the earliest molecular events in oncogenesis and progressive changes in the human disease have been difficult to perform within the same patient. The use of transgenic mouse mammary cancer models provides an opportunity to decipher molecular changes that occur at progressive stages of tumor development. This paper reviews microarray technology, and the insights gained from published breast cancer microarray analyses, and considers the contribution of microarray studies in identifying mouse cancer models that may be appropriate for answering particular experimental questions. JF - Endocrine-related cancer AU - Desai, K V AU - Kavanaugh, C J AU - Calvo, A AU - Green, J E AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, NIH, Building 41, Room C629, 41 Library Dr., Bethesda, Maryland 20892, USA. Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 207 EP - 220 VL - 9 IS - 4 SN - 1351-0088, 1351-0088 KW - Neoplasm Proteins KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Neoplasm Proteins -- genetics KW - Disease Progression KW - Mice KW - Female KW - Breast Neoplasms -- genetics KW - Gene Expression Profiling KW - Breast Neoplasms -- pathology KW - Oligonucleotide Array Sequence Analysis -- methods KW - Mammary Neoplasms, Experimental -- genetics KW - Mammary Neoplasms, Experimental -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72830480?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Endocrine-related+cancer&rft.atitle=Chipping+away+at+breast+cancer%3A+insights+from+microarray+studies+of+human+and+mouse+mammary+cancer.&rft.au=Desai%2C+K+V%3BKavanaugh%2C+C+J%3BCalvo%2C+A%3BGreen%2C+J+E&rft.aulast=Desai&rft.aufirst=K&rft.date=2002-12-01&rft.volume=9&rft.issue=4&rft.spage=207&rft.isbn=&rft.btitle=&rft.title=Endocrine-related+cancer&rft.issn=13510088&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-27 N1 - Date created - 2003-01-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Single or group housing altered hormonal physiology and affected pituitary and interstitial cell kinetics. AN - 72821997; 12533915 AB - A significant negative correlation between testicular interstitial cell tumors and pituitary tumors in control male F344 rats has been reported associated with the number of animals per cage. Change in numbers of animals per cage may cause stress and increased serum corticosteroids that can impair testosterone synthesis by interstitial cells. Eventual atrophy of interstitial cells may result in pituitary hyperfunction and tumor development. For relevant risk assessments, understanding the effect husbandry has on cellular processes is necessary. Twenty-four 6-week-old male F344 rats were housed individually, as pairs, or as trios for 13 weeks. Measured parameters included feed consumption, body and organ weights, hemograms, hormonal levels, histopathology, and cellular kinetics in the pituitary and testicle. Several caging-related differences occurred, that, although not statistically different, could be biologically significant; these included increased serum levels of estradiol, progesterone, and corticosterone; increased spermatogonial proliferation; decreased apoptosis within seminiferous tubules; and increased BrdU immunoreactivity of the interstitial cells. The statistically significant decrease in lymphocyte numbers correlated with the associated increase in corticosterone levels. This study indicates that the number of animals in a cage is associated with hormonal and cellular kinetic changes in the pituitary and testes, which could influence the incidence of tumors in these organs. JF - The Journal of toxicological sciences AU - Nyska, Abraham AU - Hester, Susan D AU - Cooper, Ralph L AU - Goldman, Jerome M AU - Stoker, Tammy E AU - House, Dennis AU - Wolf, Douglas C AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 449 EP - 457 VL - 27 IS - 5 SN - 0388-1350, 0388-1350 KW - Antimetabolites KW - 0 KW - Hormones KW - Progesterone KW - 4G7DS2Q64Y KW - Estradiol KW - 4TI98Z838E KW - Bromodeoxyuridine KW - G34N38R2N1 KW - Corticosterone KW - W980KJ009P KW - Index Medicus KW - Pituitary Neoplasms -- epidemiology KW - Animals KW - Eating -- physiology KW - Body Weight -- physiology KW - Cell Division -- physiology KW - Rats KW - Rats, Inbred F344 KW - Estradiol -- blood KW - Corticosterone -- blood KW - Pituitary Neoplasms -- pathology KW - Testicular Neoplasms -- pathology KW - Kinetics KW - Progesterone -- blood KW - Testicular Neoplasms -- epidemiology KW - Male KW - Hormones -- physiology KW - Lung -- cytology KW - Housing, Animal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72821997?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+toxicological+sciences&rft.atitle=Single+or+group+housing+altered+hormonal+physiology+and+affected+pituitary+and+interstitial+cell+kinetics.&rft.au=Nyska%2C+Abraham%3BHester%2C+Susan+D%3BCooper%2C+Ralph+L%3BGoldman%2C+Jerome+M%3BStoker%2C+Tammy+E%3BHouse%2C+Dennis%3BWolf%2C+Douglas+C&rft.aulast=Nyska&rft.aufirst=Abraham&rft.date=2002-12-01&rft.volume=27&rft.issue=5&rft.spage=449&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+toxicological+sciences&rft.issn=03881350&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-10 N1 - Date created - 2003-01-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Matrix metalloproteinase(s) mediate(s) NO-induced dissociation of beta-catenin from membrane bound E-cadherin and formation of nuclear beta-catenin/LEF-1 complex. AN - 72817273; 12507936 AB - Modulation of the adenomatous polyposis coli (APC)-beta-catenin pathway by inflammatory mediators and extracellular matrix may be important in colon carcinogenesis. We have recently shown that nitric oxide (NO) induces the accumulation of cytosolic beta-catenin and subsequent formation of the nuclear beta-catenin/lymphocyte enhancing factor (LEF)-1 complex in conditionally immortalized young mouse colonic epithelial (YAMC) cells. In the present study, we explored the mechanism(s) through which NO exerts its effect on cytosolic beta-catenin accumulation and nuclear beta-catenin/LEF-1 complex formation. We found that NO-induced degradation of the membrane bound E-cadherin at tight junctions. Using an anti-E-cadherin antibody specific for its extracellular domain, we detected a 50kDa degradation fragment of E-cadherin (120 kDa) from the culture medium conditioned by YAMC cells exposed to the NO-releasing drug, NOR-1, for 4 and 24 h. As beta-catenin is normally bound to transmembrane E-cadherin and thus anchored to the cytoskeleton structure, the degradation of E-cadherin induced by NO may cause dissociation of beta-catenin from membrane bound E-cadherin. This was demonstrated by the detection of beta-catenin accumulation in the soluble cytosolic fractions in YAMC after exposure to NO-releasing drugs. Furthermore, the degradation of E-cadherin and the release of beta-catenin to cytosol were accompanied by the formation of nuclear beta-catenin/LEF-1 complex, demonstrating the dissociation of beta-catenin from E-cadherin may be responsible for the activation of beta-catenin/LEF-1 transcription complex. Co-treatment with NO donors and broad-spectrum matrix metalloproteinase (MMP) inhibitors TIMP-1 (100 ng/ml), GM6001 (10 micro M) and GM1489 (10 micro M) abolished the degradation of E-cadherin induced by NO as demonstrated by western blot analysis. These MMP inhibitors also blocked the cytosolic accumulation of beta-catenin and nuclear formation of beta-catenin/LEF-1 complex. The sum effect of MMP inhibitors demonstrated that NO-induced activation of MMP may cause the degradation of E-cadherin and the subsequent dissociation of beta-catenin, thereby contributing to the cytosolic accumulation of beta-catenin and nuclear formation of beta-catenin/LEF-1 complex. JF - Carcinogenesis AU - Mei, Jay M AU - Borchert, Gregory L AU - Donald, Steven P AU - Phang, James M AD - Metabolism and Cancer Susceptibility Section, Basic Research Laboratory, Center for Cancer Research, NCI-Frederick, MD, USA. Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 2119 EP - 2122 VL - 23 IS - 12 SN - 0143-3334, 0143-3334 KW - CTNNB1 protein, mouse KW - 0 KW - Cadherins KW - Cytoskeletal Proteins KW - DNA-Binding Proteins KW - Dipeptides KW - Enzyme Inhibitors KW - Lef1 protein, mouse KW - Lymphoid Enhancer-Binding Factor 1 KW - N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide KW - Tissue Inhibitor of Metalloproteinase-1 KW - Trans-Activators KW - Transcription Factors KW - beta Catenin KW - Nitric Oxide KW - 31C4KY9ESH KW - Matrix Metalloproteinases KW - EC 3.4.24.- KW - Index Medicus KW - Animals KW - Cytosol -- metabolism KW - Cell Nucleus -- metabolism KW - Tissue Inhibitor of Metalloproteinase-1 -- pharmacology KW - Mice KW - Blotting, Western KW - Cells, Cultured KW - Enzyme Inhibitors -- pharmacology KW - Cell Membrane -- metabolism KW - Time Factors KW - Dipeptides -- pharmacology KW - Signal Transduction KW - Trans-Activators -- metabolism KW - Cadherins -- metabolism KW - Transcription Factors -- metabolism KW - Nitric Oxide -- metabolism KW - Matrix Metalloproteinases -- metabolism KW - Cytoskeletal Proteins -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72817273?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Matrix+metalloproteinase%28s%29+mediate%28s%29+NO-induced+dissociation+of+beta-catenin+from+membrane+bound+E-cadherin+and+formation+of+nuclear+beta-catenin%2FLEF-1+complex.&rft.au=Mei%2C+Jay+M%3BBorchert%2C+Gregory+L%3BDonald%2C+Steven+P%3BPhang%2C+James+M&rft.aulast=Mei&rft.aufirst=Jay&rft.date=2002-12-01&rft.volume=23&rft.issue=12&rft.spage=2119&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-10 N1 - Date created - 2002-12-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombinant fusion toxins for cancer treatment. AN - 72816402; 12517258 JF - Expert opinion on biological therapy AU - Kreitman, Robert J AD - Clinical Immunotherapy Section, Laboratory of Molecular Biology, Division of Cancer Biology, National Cancer Institute/National Institutes of Health, 9000 Rockville Pike, Building 37, Room 5124b, Bethesda, MD 20892-4255, USA. kreitmar@mail.nih.gov Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 785 EP - 791 VL - 2 IS - 8 SN - 1471-2598, 1471-2598 KW - Antineoplastic Agents KW - 0 KW - Immunotoxins KW - Recombinant Fusion Proteins KW - Index Medicus KW - Animals KW - Humans KW - Immunotoxins -- therapeutic use KW - Neoplasms -- drug therapy KW - Antineoplastic Agents -- therapeutic use KW - Recombinant Fusion Proteins -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72816402?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Expert+opinion+on+biological+therapy&rft.atitle=Recombinant+fusion+toxins+for+cancer+treatment.&rft.au=Kreitman%2C+Robert+J&rft.aulast=Kreitman&rft.aufirst=Robert&rft.date=2002-12-01&rft.volume=2&rft.issue=8&rft.spage=785&rft.isbn=&rft.btitle=&rft.title=Expert+opinion+on+biological+therapy&rft.issn=14712598&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-19 N1 - Date created - 2003-01-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Highly sensitive chemiluminescence immunoassay for benzo[a]pyrene-DNA adducts: validation by comparison with other methods, and use in human biomonitoring. AN - 72812776; 12507927 AB - A chemiluminescence immunoassay (CIA) utilizing antiserum elicited against DNA modified with (+/-)-7beta, 8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]- pyrene (BPDE) has been developed and validated to study the formation of polycyclic aromatic hydrocarbon (PAH)-DNA adducts in human tissues. Advantages include a low limit of detection for 10b-(deoxyguanosin-N(2)-yl)-7beta,8alpha,9alpha-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPdG, approximately 1.5 adducts/10(9) nucleotides using 20 micro g DNA) and a high signal-to-noise ratio (> or =100). The CIA BPDE-DNA standard curve gave 50% inhibition at 0.60 +/- 0.08 fmol BPdG (mean +/- SE, n = 30), which was a 10-fold increase in sensitivity compared with the dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA). Calf thymus DNA modified with [1,3-(3)H]BPDE was assayed by radiolabeling, (32)P-postlabeling, DELFIA and CIA, and all assays gave similar values. Liver DNAs from mice exposed to 0.5 and 1.0 mg [7,8-(3)H]benzo[a]pyrene (BP) were assayed by the same four assays and a dose-response was obtained with all assays. The BPDE-DNA CIA was further validated in MCL-5 cells exposed to 4 micro M BP for 24 h, where nuclear and mitochondrial DNA adduct levels were associated with an increase in DNA tail length measured by the Comet assay. Human peripheral blood cell (buffy coat) DNA samples (n = 43) obtained from 25 individuals who were either colorectal adenocarcinoma patients or controls were assayed by BPDE-DNA CIA. Three samples (7%) were non-detectable, and the remaining 40 samples had values between 0.71 and 2.21 PAH-DNA adducts/10(8) nucleotides. The intra-assay coefficient of variation (CV), for four wells on the same microtiter plate, was 1.85%. Sufficient DNA for two assays, on separate plates, was available for 38 of the 43 samples, and the PAH-DNA adduct values obtained were highly correlated (r(2) = 0.95). Coded duplicate DNA samples from 15 individuals were assayed four times gave an inter-assay CV of 13.8%. JF - Carcinogenesis AU - Divi, Rao L AU - Beland, Frederick A AU - Fu, Peter P AU - Von Tungeln, Linda S AU - Schoket, Bernadette AU - Camara, Johanna Eltz AU - Ghei, Monica AU - Rothman, Nathaniel AU - Sinha, Rashmi AU - Poirier, Miriam C AD - National Cancer Institute, NIH, Bethesda, MD 20892-4255, USA. Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 2043 EP - 2049 VL - 23 IS - 12 SN - 0143-3334, 0143-3334 KW - DNA Adducts KW - 0 KW - Benzo(a)pyrene KW - 3417WMA06D KW - Index Medicus KW - Animals KW - Comet Assay KW - Adenocarcinoma -- blood KW - Reproducibility of Results KW - Dose-Response Relationship, Drug KW - Humans KW - Thymus Gland -- metabolism KW - Liver -- metabolism KW - Mice KW - Colorectal Neoplasms -- drug therapy KW - Chromatography, High Pressure Liquid KW - Cattle KW - Tumor Cells, Cultured KW - Liver -- drug effects KW - Mitochondria -- metabolism KW - Colorectal Neoplasms -- blood KW - Adenocarcinoma -- drug therapy KW - Time Factors KW - Lymphocytes -- drug effects KW - Male KW - Immunoassay -- methods KW - DNA Adducts -- analysis KW - Luminescent Measurements KW - Benzo(a)pyrene -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72812776?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Highly+sensitive+chemiluminescence+immunoassay+for+benzo%5Ba%5Dpyrene-DNA+adducts%3A+validation+by+comparison+with+other+methods%2C+and+use+in+human+biomonitoring.&rft.au=Divi%2C+Rao+L%3BBeland%2C+Frederick+A%3BFu%2C+Peter+P%3BVon+Tungeln%2C+Linda+S%3BSchoket%2C+Bernadette%3BCamara%2C+Johanna+Eltz%3BGhei%2C+Monica%3BRothman%2C+Nathaniel%3BSinha%2C+Rashmi%3BPoirier%2C+Miriam+C&rft.aulast=Divi&rft.aufirst=Rao&rft.date=2002-12-01&rft.volume=23&rft.issue=12&rft.spage=2043&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-10 N1 - Date created - 2002-12-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mistletoe and cancer: controversies and perspectives. AN - 72811832; 12516042 AB - Extracts and preparations from the tree parasitic plant mistletoe (Viscum album L.) have been used in the treatment of cancer for decades. Numerous preclinical and in vitro studies have reported immunostimulatory, cytotoxic, and proapoptotic effects. Translation of these effects into clinical response continues to pose a problem. While a number of clinical studies have found improvement in quality of life (QOL), data on the efficacy of mistletoe to prolong survival are conflicting and of variable quality. Clinical trial data regarding the toxicity and pharmacokinetics of mistletoe components with known in vitro or preclinical activity are lacking. Mistletoe is a widely used form of complementary and alternative medicine (CAM) for cancer treatment, and research into its use poses the challenges of translation of preclinical data into demonstrable clinical efficacy and investigating CAM approaches as a component of complex cancer treatment systems. JF - Seminars in oncology AU - Mansky, Patrick J AD - Laboratory of Clinical Investigation, National Center for Complementary and Alternative Medicine, National Institutes of Health, 8 West Drive, Quarters 15-B1, MSC 2669, Bethesda, MD 20892, USA. Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 589 EP - 594 VL - 29 IS - 6 SN - 0093-7754, 0093-7754 KW - Antineoplastic Agents KW - 0 KW - Plant Extracts KW - Index Medicus KW - Animals KW - Drug Interactions KW - Humans KW - Treatment Outcome KW - Clinical Trials as Topic KW - Quality of Life KW - Research KW - Survival Analysis KW - Plant Extracts -- pharmacology KW - Neoplasms -- drug therapy KW - Plant Extracts -- therapeutic use KW - Mistletoe KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72811832?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mistletoe+and+cancer%3A+controversies+and+perspectives.&rft.au=Mansky%2C+Patrick+J&rft.aulast=Mansky&rft.aufirst=Patrick&rft.date=2002-12-01&rft.volume=29&rft.issue=6&rft.spage=589&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 - 2003-01-23 N1 - Date created - 2003-01-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Validation of transgenic mammary cancer models: goals of the NCI Mouse Models of Human Cancer Consortium and the mammary cancer CD-ROM. AN - 72810291; 12509138 JF - Transgenic research AU - Green, Jeffrey E AU - Cardiff, Robert AU - Hennighausen, Lothar AU - Wakefield, Lalage AU - Wagner, Ulrike AU - Lee, Eva AU - Rosen, Jeffrey AU - Medina, Daniel AU - Nitkin, Alexander AU - Liu, Edison AD - Laboratory of Cellular Regulation and Carcinogenesis, National Cancer Institute, Building 41, Bethesda, MD 20892, USA. JEGreen@nih.gov Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 635 EP - 636 VL - 11 IS - 6 SN - 0962-8819, 0962-8819 KW - Index Medicus KW - Animals KW - Information Dissemination KW - Research -- standards KW - Mice KW - Mice, Transgenic KW - Mammary Neoplasms, Experimental UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72810291?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Transgenic+research&rft.atitle=Validation+of+transgenic+mammary+cancer+models%3A+goals+of+the+NCI+Mouse+Models+of+Human+Cancer+Consortium+and+the+mammary+cancer+CD-ROM.&rft.au=Green%2C+Jeffrey+E%3BCardiff%2C+Robert%3BHennighausen%2C+Lothar%3BWakefield%2C+Lalage%3BWagner%2C+Ulrike%3BLee%2C+Eva%3BRosen%2C+Jeffrey%3BMedina%2C+Daniel%3BNitkin%2C+Alexander%3BLiu%2C+Edison&rft.aulast=Green&rft.aufirst=Jeffrey&rft.date=2002-12-01&rft.volume=11&rft.issue=6&rft.spage=635&rft.isbn=&rft.btitle=&rft.title=Transgenic+research&rft.issn=09628819&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-31 N1 - Date created - 2003-01-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of glioblastoma multiforme in nonhuman primates after therapeutic doses of fractionated whole-brain radiation therapy. AN - 72806184; 12507137 AB - To determine the acute and long-term effects of a therapeutic dose of brain radiation in a primate model, the authors studied the clinical, laboratory, neuroimaging, molecular, and histological outcomes in rhesus monkeys that had received fractionated whole-brain radiation therapy (WBRT). Twelve 3-year-old male primates (Macaca mulatta) underwent fractionated WBRT (350 cGy for 5 days/week for 2 weeks, total dose 3500 cGy). Animals were followed clinically and with laboratory studies and serial magnetic resonance (MR) imaging. They were killed when they developed medical problems or neurological symptoms, lesions appeared on MR imaging, or at study completion. Gross, histological, and molecular analyses were then performed. Nine (82%) of 11 animals that underwent long-term follow up (> 2.5 years) developed neurological symptoms and/or enhancing lesions on MR imaging, which were defined as glioblastoma multiforme (GBM), 2.9 to 8.3 years after radiation therapy. The GBMs were categorized as either unifocal (three) or multifocal (six), and were located in the supratentorial (six), infratentorial (two), or both (one) cranial regions. Histological examination revealed distant, noncontiguous tumor invasion within the white matter of all nine animals harboring GBMs. Novel interspecies comparative genomic hybridization (three animals) uniformly showed deletions in the GBMs that corresponded to chromosome 9 in humans. The high rate of GBM formation (82%) following a therapeutic dose of WBRT in nonhuman primates indicates that radioinduction of these neoplasms as a late complication of this therapy may occur more frequently than is currently recognized in human patients. The development of these tumors while monitoring the monkeys' conditions with clinical and serial MR imaging studies, and access to the tumor and the entire brain for histological and molecular analyses offers an opportunity to gather unique insights into the nature and development of GBMs. JF - Journal of neurosurgery AU - Lonser, Russell R AU - Walbridge, Stuart AU - Vortmeyer, Alexander O AU - Pack, Svetlana D AU - Nguyen, Tung T AU - Gogate, Nitin AU - Olson, Jeffery J AU - Akbasak, Aytac AU - Bobo, R Hunt AU - Goffman, Thomas AU - Zhuang, Zhengping AU - Oldfield, Edward H AD - Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke National Institutes of Health, Bethesda, Maryland 20892-1414, USA. Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 1378 EP - 1389 VL - 97 IS - 6 SN - 0022-3085, 0022-3085 KW - DNA, Neoplasm KW - 0 KW - Interleukin-5 KW - Interleukin-6 KW - Tumor Suppressor Protein p53 KW - Epidermal Growth Factor KW - 62229-50-9 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Interleukin-5 -- genetics KW - Interleukin-6 -- genetics KW - Epidermal Growth Factor -- genetics KW - Macaca mulatta KW - DNA, Neoplasm -- analysis KW - Nucleic Acid Hybridization KW - Dose-Response Relationship, Radiation KW - Tumor Suppressor Protein p53 -- genetics KW - Male KW - Brain Neoplasms -- pathology KW - Neoplasms, Radiation-Induced -- etiology KW - Glioblastoma -- radiotherapy KW - Neoplasms, Radiation-Induced -- pathology KW - Glioblastoma -- pathology KW - Glioblastoma -- etiology KW - Brain Neoplasms -- radiotherapy KW - Neoplasms, Radiation-Induced -- genetics KW - Brain Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72806184?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Induction+of+glioblastoma+multiforme+in+nonhuman+primates+after+therapeutic+doses+of+fractionated+whole-brain+radiation+therapy.&rft.au=Lonser%2C+Russell+R%3BWalbridge%2C+Stuart%3BVortmeyer%2C+Alexander+O%3BPack%2C+Svetlana+D%3BNguyen%2C+Tung+T%3BGogate%2C+Nitin%3BOlson%2C+Jeffery+J%3BAkbasak%2C+Aytac%3BBobo%2C+R+Hunt%3BGoffman%2C+Thomas%3BZhuang%2C+Zhengping%3BOldfield%2C+Edward+H&rft.aulast=Lonser&rft.aufirst=Russell&rft.date=2002-12-01&rft.volume=97&rft.issue=6&rft.spage=1378&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 - 2003-01-16 N1 - Date created - 2002-12-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pre-clinical applications of transgenic mouse mammary cancer models. AN - 72803818; 12509137 AB - Breast cancer is a leading cause of cancer morbidity and mortality. Given that the majority of human breast cancers appear to be due to non-genetic factors, identifying agents and mechanisms of prevention is key to lowering the incidence of cancer. Genetically engineered mouse models of mammary cancer have been important in elucidating molecular pathways and signaling events associated with the initiation, promotion, and the progression of cancer. Since several transgenic mammary models of human breast cancer progress through well-defined cancer stages, they are useful pre-clinical systems to test the efficacy of chemopreventive and chemotherapeutic agents. This review outlines several oncogenic pathways through which mammary cancer can be induced in transgenic models and describes several types of preventive and therapeutic agents that have been tested in transgenic models of mammary cancer. The effectiveness of farnesyl inhibitors, aromatase inhibitors, differentiating agents, polyamine inhibitors, anti-angiogenic inhibitors, and immunotherapeutic compounds including vaccines have been evaluated in reducing mammary cancer and tumor progression in transgenic models. JF - Transgenic research AU - Kavanaugh, C J AU - Desai, K V AU - Calvo, A AU - Brown, P H AU - Couldrey, C AU - Lubet, R AU - Green, J E AD - Laboratory of Cellular Regulation and Carcinogenesis, National Cancer Institute, Building 41, Bethesda, MD 20892, USA. Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 617 EP - 633 VL - 11 IS - 6 SN - 0962-8819, 0962-8819 KW - Angiogenesis Inhibitors KW - 0 KW - Antineoplastic Agents KW - Index Medicus KW - Animals KW - Immunotherapy KW - Signal Transduction -- drug effects KW - Mice KW - Mice, Transgenic KW - Drug Evaluation, Preclinical -- methods KW - Cell Differentiation -- drug effects KW - Female KW - Cell Cycle -- drug effects KW - Mammary Neoplasms, Experimental -- drug therapy KW - Mammary Neoplasms, Experimental -- etiology KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72803818?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Transgenic+research&rft.atitle=Pre-clinical+applications+of+transgenic+mouse+mammary+cancer+models.&rft.au=Kavanaugh%2C+C+J%3BDesai%2C+K+V%3BCalvo%2C+A%3BBrown%2C+P+H%3BCouldrey%2C+C%3BLubet%2C+R%3BGreen%2C+J+E&rft.aulast=Kavanaugh&rft.aufirst=C&rft.date=2002-12-01&rft.volume=11&rft.issue=6&rft.spage=617&rft.isbn=&rft.btitle=&rft.title=Transgenic+research&rft.issn=09628819&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-31 N1 - Date created - 2003-01-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Transgenic Res. 2002 Dec;11(6):615 [12509136] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM): a review of the ICCVAM test method evaluation process and current international collaborations with the European Centre for the Validation of Alternative Methods (ECVAM). AN - 72803554; 12513648 AB - Over the last decade, national authorities in the USA and Europe have launched initiatives to validate new and improved toxicological test methods. In the USA, the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and its supporting National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) were established by the Federal Government to work with test developers and Federal agencies to facilitate the validation, review, and adoption of new scientifically sound test methods, including alternatives that can refine, reduce, and replace animal use. In Europe, the European Centre for the Validation of Alternative Methods (ECVAM) was established to conduct validation studies on alternative test methods. Despite differences in organisational structure and processes, both organisations seek to achieve the adoption and use of alternative test methods. Accordingly, both have adopted similar validation and regulatory acceptance criteria. Collaborations and processes have also evolved to facilitate the international adoption of new test methods recommended by ECVAM and ICCVAM. These collaborations involve the sharing of expertise and data for test-method workshops and independent scientific peer reviews, and the adoption of processes to expedite the consideration of test methods already reviewed by the other organisation. More recently, NICEATM and ECVAM initiated a joint international validation study on in vitro methods for assessing acute systemic toxicity. These collaborations are expected to contribute to accelerated international adoption of harmonised new test methods that will support improved public health and provide for reduced and more-humane use of laboratory animals. JF - Alternatives to laboratory animals : ATLA AU - Stokes, William S AU - Schechtman, Leonard M AU - Hill, Richard N AD - National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods, Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 23 EP - 32 VL - 30 Suppl 2 SN - 0261-1929, 0261-1929 KW - Index Medicus KW - United States KW - Animals KW - European Union KW - Reproducibility of Results KW - In Vitro Techniques KW - Toxicity Tests KW - Animal Welfare -- legislation & jurisprudence KW - Program Evaluation KW - Animal Welfare -- ethics KW - Evaluation Studies as Topic KW - International Cooperation KW - Government Agencies KW - Animal Testing Alternatives -- methods KW - Predictive Value of Tests UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72803554?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alternatives+to+laboratory+animals+%3A+ATLA&rft.atitle=The+Interagency+Coordinating+Committee+on+the+Validation+of+Alternative+Methods+%28ICCVAM%29%3A+a+review+of+the+ICCVAM+test+method+evaluation+process+and+current+international+collaborations+with+the+European+Centre+for+the+Validation+of+Alternative+Methods+%28ECVAM%29.&rft.au=Stokes%2C+William+S%3BSchechtman%2C+Leonard+M%3BHill%2C+Richard+N&rft.aulast=Stokes&rft.aufirst=William&rft.date=2002-12-01&rft.volume=30+Suppl+2&rft.issue=&rft.spage=23&rft.isbn=&rft.btitle=&rft.title=Alternatives+to+laboratory+animals+%3A+ATLA&rft.issn=02611929&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-09 N1 - Date created - 2003-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Seizures and tissue injury induce telomerase in hippocampal microglial cells. AN - 72802664; 12504888 AB - Telomerase is a reverse transcriptase that adds repeats of a six-base DNA sequence to chromosome ends and thereby prevents their shortening during successive cell divisions. Telomerase activity and expression of the catalytic subunit of telomerase (TERT) are high in brain cells during embryonic development, but are undetectable in the adult. We now report that telomerase activity and expression of TERT are induced in the hippocampus of adult mice after administration of the seizure-inducing excitotoxin kainate. Telomerase activity is present at 24 h and 7 days after kainate administration, but is no longer detectable at 4 weeks. Because the time course of telomerase induction was similar to the time course of microglial activation, we performed studies to determine whether microglia were the source of the telomerase activity. Examination of brain sections immunostained with a TERT antibody and an antibody against a microglia-specific antigen revealed that TERT was not detectable in the uninjured brain, and was present in microglia 24 h and 7 days after kainate administration. This is the first evidence that telomerase can be induced by brain injury and the first evidence that TERT can be expressed in microglia, suggesting roles for telomerase in microglial responses to brain injury. JF - Experimental neurology AU - Fu, Weiming AU - Lee, Jaewon AU - Guo, Zhihong AU - Mattson, Mark P AD - Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, Baltimore, Maryland 21224, USA. Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 294 EP - 300 VL - 178 IS - 2 SN - 0014-4886, 0014-4886 KW - Telomerase KW - EC 2.7.7.49 KW - Index Medicus KW - Up-Regulation -- physiology KW - Animals KW - Mice, Inbred C57BL KW - Mice KW - Male KW - Seizures -- chemically induced KW - Seizures -- enzymology KW - Microglia -- enzymology KW - Telomerase -- biosynthesis KW - Hippocampus -- enzymology KW - Hippocampus -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72802664?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Seizures+and+tissue+injury+induce+telomerase+in+hippocampal+microglial+cells.&rft.au=Fu%2C+Weiming%3BLee%2C+Jaewon%3BGuo%2C+Zhihong%3BMattson%2C+Mark+P&rft.aulast=Fu&rft.aufirst=Weiming&rft.date=2002-12-01&rft.volume=178&rft.issue=2&rft.spage=294&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 - 2003-01-21 N1 - Date created - 2002-12-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intraarticular gene transfer of TNFR:Fc suppresses experimental arthritis with reduced systemic distribution of the gene product. AN - 72793057; 12498769 AB - Tumor necrosis factor alpha (TNFalpha) plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA). Blockage of TNFalpha actions by systemic administration of TNF antagonists has recently been shown to ameliorate joint symptoms in RA patients. In the present study, a streptococcal cell wall (SCW)-induced rat arthritis model was used to evaluate the effect of different gene transfer routes of a TNF antagonist on the development and severity of arthritis. Successful delivery of a plasmid DNA encoding a rat TNF receptor-immunoglobulin Fc (TNFR:Fc) fusion gene prompted the subsequent administration of a recombinant adeno-associated virus (rAAV) vector encoding the antagonist, either locally (intraarticular) or systemically (intramuscular). The TNFR:Fc gene, delivered by either route, resulted in profound suppression of the arthritis as reflected in decreased inflammatory cell infiltration, pannus formation, cartilage and bone destruction, and mRNA expression of joint proinflammatory cytokines. Increased bioactive serum TNFR levels were detected as a result of rAAV-ratTNFR:Fc administration, concomitant with a decrease in circulating TNFalpha. Administration of the rAAV-ratTNFR:Fc vector to one joint also suppressed arthritis in the contralateral joint. Importantly, intraarticular administration resulted in significantly lower systemic distribution of the gene product. Hence, the use of rAAV as the delivery vector for TNFR:Fc effectively suppressed SCW-induced arthritis and may provide an approach for local delivery of antiarthritic therapy. JF - Molecular therapy : the journal of the American Society of Gene Therapy AU - Chan, James M K AU - Villarreal, Gilda AU - Jin, Wen Wen AU - Stepan, Tony AU - Burstein, Haim AU - Wahl, Sharon M AD - Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 727 EP - 736 VL - 6 IS - 6 SN - 1525-0016, 1525-0016 KW - Cytokines KW - 0 KW - Immunoglobulin Fc Fragments KW - Immunoglobulin G KW - Receptors, Tumor Necrosis Factor KW - Recombinant Fusion Proteins KW - Tumor Necrosis Factor-alpha KW - Index Medicus KW - Animals KW - Injections, Intra-Articular KW - Rats, Inbred Lew KW - Plasmids -- genetics KW - Injections, Intramuscular KW - Cartilage -- pathology KW - Ankle -- pathology KW - Cytokines -- metabolism KW - Rats KW - Tumor Necrosis Factor-alpha -- analysis KW - Recombinant Fusion Proteins -- genetics KW - Genetic Vectors -- genetics KW - Immunoglobulin G -- metabolism KW - Time Factors KW - Recombinant Fusion Proteins -- therapeutic use KW - Female KW - Arthritis, Rheumatoid -- genetics KW - Arthritis, Rheumatoid -- chemically induced KW - Arthritis, Rheumatoid -- therapy KW - Receptors, Tumor Necrosis Factor -- therapeutic use KW - Receptors, Tumor Necrosis Factor -- analysis KW - Immunoglobulin Fc Fragments -- metabolism KW - Genetic Therapy -- methods KW - Immunoglobulin Fc Fragments -- genetics KW - Receptors, Tumor Necrosis Factor -- genetics KW - Receptors, Tumor Necrosis Factor -- blood KW - Arthritis, Rheumatoid -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72793057?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+therapy+%3A+the+journal+of+the+American+Society+of+Gene+Therapy&rft.atitle=Intraarticular+gene+transfer+of+TNFR%3AFc+suppresses+experimental+arthritis+with+reduced+systemic+distribution+of+the+gene+product.&rft.au=Chan%2C+James+M+K%3BVillarreal%2C+Gilda%3BJin%2C+Wen+Wen%3BStepan%2C+Tony%3BBurstein%2C+Haim%3BWahl%2C+Sharon+M&rft.aulast=Chan&rft.aufirst=James+M&rft.date=2002-12-01&rft.volume=6&rft.issue=6&rft.spage=727&rft.isbn=&rft.btitle=&rft.title=Molecular+therapy+%3A+the+journal+of+the+American+Society+of+Gene+Therapy&rft.issn=15250016&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-18 N1 - Date created - 2002-12-24 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 ER - TY - JOUR T1 - Semiquantitation of polycyclic aromatic hydrocarbon-DNA adducts in human esophagus by immunohistochemistry and the automated cellular imaging system. AN - 72791947; 12496053 AB - It has been suggested that ingestion of polycyclic aromatic hydrocarbons (PAHs) may contribute to the high incidence and mortality of esophageal cancer in Linxian, China. To explore this relationship a semiquantitative immunohistochemical staining method was developed for localization of PAH-DNA adducts. Nuclear color intensity (bright field average pink intensity per nucleus for >1000 cells) was measured using the ChromaVision Automated Cellular Imaging System (ACIS). Paraffin-embedded sections of cultured human keratinocytes exposed to increasing concentrations of 7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydro-benzo[a]pyrene (BPDE) were incubated with BPDE-DNA antiserum and served as an internal positive control (standard curve). Values for nuclear staining intensity correlated directly with BPDE exposure concentration (r(2) = 0.99) and were reproducible. DNA adduct levels determined by BPDE-DNA chemiluminescence immunoassay in DNA from BPDE-exposed keratinocytes, correlated with BPDE exposure concentrations (r(2) = 0.99), showing that nuclear staining intensity determined by ACIS correlated directly with BPDE-DNA adduct levels determined by chemiluminescence immunoassay. The ACIS methodology was applied to 5 human samples from Linxian, and significantly positive nuclear PAH-DNA adduct staining was observed in this group when compared with esophageal tissue from 4 laboratory-housed monkey controls and 6 samples obtained at autopsy from smokers and nonsmokers in the United States. Nuclear PAH-DNA staining was absent from Linxian samples when serial sections were incubated with normal rabbit serum (negative control) and was significantly reduced on incubation with BPDE-DNA antiserum absorbed previously with the immunogen BPDE-DNA. These results appear to support the hypothesis that high PAH exposure levels may be etiologically associated with the development of esophageal cancer in Linxian. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - van Gijssel, Hilde E AU - Divi, Rao L AU - Olivero, Ofelia A AU - Roth, Mark J AU - Wang, Guo-Qing AU - Dawsey, Sanford M AU - Albert, Paul S AU - Qiao, You-Lin AU - Taylor, Philip R AU - Dong, Zhi-Wei AU - Schrager, Jeffrey A AU - Kleiner, David E AU - Poirier, Miriam C AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 1622 EP - 1629 VL - 11 IS - 12 SN - 1055-9965, 1055-9965 KW - Culture Media KW - 0 KW - DNA Adducts KW - Polycyclic Aromatic Hydrocarbons KW - benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA KW - polycyclic aromatic hydrocarbons-DNA adduct KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide KW - 55097-80-8 KW - Index Medicus KW - Sensitivity and Specificity KW - Animals KW - Reference Values KW - Culture Techniques KW - Reproducibility of Results KW - Esophagectomy KW - Humans KW - China -- epidemiology KW - Sampling Studies KW - Automation KW - Rabbits KW - Immunohistochemistry KW - Carcinoma, Squamous Cell -- epidemiology KW - DNA Adducts -- pharmacology KW - Keratinocytes -- drug effects KW - Esophageal Neoplasms -- surgery KW - DNA Adducts -- metabolism KW - Diagnostic Imaging -- methods KW - Esophageal Neoplasms -- epidemiology KW - Esophageal Neoplasms -- pathology KW - Carcinoma, Squamous Cell -- surgery KW - DNA Adducts -- analysis KW - Carcinoma, Squamous Cell -- pathology KW - Polycyclic Aromatic Hydrocarbons -- analysis KW - Keratinocytes -- pathology KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- pharmacology KW - Polycyclic Aromatic Hydrocarbons -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72791947?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Semiquantitation+of+polycyclic+aromatic+hydrocarbon-DNA+adducts+in+human+esophagus+by+immunohistochemistry+and+the+automated+cellular+imaging+system.&rft.au=van+Gijssel%2C+Hilde+E%3BDivi%2C+Rao+L%3BOlivero%2C+Ofelia+A%3BRoth%2C+Mark+J%3BWang%2C+Guo-Qing%3BDawsey%2C+Sanford+M%3BAlbert%2C+Paul+S%3BQiao%2C+You-Lin%3BTaylor%2C+Philip+R%3BDong%2C+Zhi-Wei%3BSchrager%2C+Jeffrey+A%3BKleiner%2C+David+E%3BPoirier%2C+Miriam+C&rft.aulast=van+Gijssel&rft.aufirst=Hilde&rft.date=2002-12-01&rft.volume=11&rft.issue=12&rft.spage=1622&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 - 2003-04-04 N1 - Date created - 2002-12-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oxidant-induced cell death in respiratory epithelial cells is due to DNA damage and loss of ATP. AN - 72786740; 12490035 AB - Oxidative stress is considered to be an important pathogenic event in ischemia-reperfusion injury, leading to apoptosis or necrosis. We show acute cytotoxicity upon exposure to hydrogen peroxide (H(2)O(2)) in BEAS-2B cells and A549 cells. Single-cell gel electrophoresis showed formation of large comet tails from DNA upon oxidant exposure suggestive of DNA damage. The ATP content of the cells decreased upon exposure to H(2)O(2). Preincubation with 3-aminobenzamide (3-ABA), an inhibitor of poly (ADP-ribosyl) polymerase (PARP), prevented the cytotoxicity. The decrease in the ATP content of the cells was also prevented by 3-ABA. Increase in PARP activity was further confirmed by measuring incorporation of [(32)P]-NAD into nuclear proteins in presence of the cell extracts. Markers of apoptosis were not seen in cells treated with H(2)O(2) with or without 3-ABA pretreatment. These studies suggest that DNA damage is one of the primary reasons for oxidant-induced cell death and that PARP plays an important role in cell death due to its consumption of ATP. Further elaboration of this and other pathways that consume ATP may help prevent oxidant-mediated acute lung injury. JF - Experimental lung research AU - Nanavaty, Uday B AU - Pawliczak, Rafal AU - Doniger, Jeremy AU - Gladwin, Mark T AU - Cowan, Mark J AU - Logun, Carolea AU - Shelhamer, James H AD - Critical Care Medicine Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 591 EP - 607 VL - 28 IS - 8 SN - 0190-2148, 0190-2148 KW - Oxidants KW - 0 KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Hydrogen Peroxide KW - BBX060AN9V KW - Poly(ADP-ribose) Polymerases KW - EC 2.4.2.30 KW - Index Medicus KW - Epithelial Cells -- metabolism KW - Comet Assay KW - Epithelial Cells -- cytology KW - Epithelial Cells -- drug effects KW - Cell Survival -- drug effects KW - Humans KW - Poly(ADP-ribose) Polymerases -- metabolism KW - Cell Survival -- physiology KW - Cell Line KW - Respiratory Mucosa -- metabolism KW - Respiratory Mucosa -- cytology KW - Oxidants -- pharmacology KW - DNA Damage KW - Apoptosis -- physiology KW - Hydrogen Peroxide -- pharmacology KW - Apoptosis -- drug effects KW - Adenosine Triphosphate -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72786740?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+lung+research&rft.atitle=Oxidant-induced+cell+death+in+respiratory+epithelial+cells+is+due+to+DNA+damage+and+loss+of+ATP.&rft.au=Nanavaty%2C+Uday+B%3BPawliczak%2C+Rafal%3BDoniger%2C+Jeremy%3BGladwin%2C+Mark+T%3BCowan%2C+Mark+J%3BLogun%2C+Carolea%3BShelhamer%2C+James+H&rft.aulast=Nanavaty&rft.aufirst=Uday&rft.date=2002-12-01&rft.volume=28&rft.issue=8&rft.spage=591&rft.isbn=&rft.btitle=&rft.title=Experimental+lung+research&rft.issn=01902148&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-09 N1 - Date created - 2002-12-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Disruption of neurogenesis by amyloid beta-peptide, and perturbed neural progenitor cell homeostasis, in models of Alzheimer's disease. AN - 72772825; 12472904 AB - Neurogenesis occurs in the adult mammalian brain and may play roles in learning and memory processes and recovery from injury, suggesting that abnormalities in neural progenitor cells (NPC) might contribute to the pathogenesis of disorders of learning and memory in humans. The objectives of this study were to determine whether NPC proliferation, survival and neuronal differentiation are impaired in a transgenic mouse model of Alzheimer's disease (AD), and to determine the effects of the pathogenic form of amyloid beta-peptide (Abeta) on the survival and neuronal differentiation of cultured NPC. The proliferation and survival of NPC in the dentate gyrus of the hippocampus was reduced in mice transgenic for a mutated form of amyloid precursor protein that causes early onset familial AD. Abeta impaired the proliferation and neuronal differentiation of cultured human and rodent NPC, and promoted apoptosis of neuron-restricted NPC by a mechanism involving dysregulation of cellular calcium homeostasis and the activation of calpains and caspases. Adverse effects of Abeta on NPC may contribute to the depletion of neurons and cognitive impairment in AD. JF - Journal of neurochemistry AU - Haughey, Norman J AU - Nath, Avi AU - Chan, Sic L AU - Borchard, A C AU - Rao, Mahendra S AU - Mattson, Mark P AD - Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, Baltimore, Maryland 21224, USA. Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 1509 EP - 1524 VL - 83 IS - 6 SN - 0022-3042, 0022-3042 KW - Amyloid beta-Peptides KW - 0 KW - Antigens, Differentiation KW - Peptide Fragments KW - amyloid beta-protein (1-42) KW - Calpain KW - EC 3.4.22.- KW - Caspases KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Peptide Fragments -- toxicity KW - Apoptosis KW - Humans KW - Antigens, Differentiation -- biosynthesis KW - Cell Division -- drug effects KW - Disease Models, Animal KW - Mice KW - Mice, Transgenic KW - Calpain -- metabolism KW - Caspases -- metabolism KW - Calcium -- metabolism KW - Cell Survival -- drug effects KW - Dentate Gyrus -- drug effects KW - Dentate Gyrus -- pathology KW - Cells, Cultured KW - Cell Differentiation -- drug effects KW - Mutation KW - Male KW - Stem Cells -- drug effects KW - Alzheimer Disease -- genetics KW - Neurons -- drug effects KW - Amyloid beta-Peptides -- toxicity KW - Stem Cells -- pathology KW - Homeostasis KW - Neurons -- pathology KW - Alzheimer Disease -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72772825?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Disruption+of+neurogenesis+by+amyloid+beta-peptide%2C+and+perturbed+neural+progenitor+cell+homeostasis%2C+in+models+of+Alzheimer%27s+disease.&rft.au=Haughey%2C+Norman+J%3BNath%2C+Avi%3BChan%2C+Sic+L%3BBorchard%2C+A+C%3BRao%2C+Mahendra+S%3BMattson%2C+Mark+P&rft.aulast=Haughey&rft.aufirst=Norman&rft.date=2002-12-01&rft.volume=83&rft.issue=6&rft.spage=1509&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 - 2003-01-16 N1 - Date created - 2002-12-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Introduction to the special issue on the impact of childhood psychopathology interventions on subsequent substance abuse: pieces of the puzzle. AN - 72768628; 12472297 AB - Studies of adolescents and adults have reported high levels of co-occurrence of substance abuse with other psychiatric disorders, suggesting influence between the conditions. The comorbidity seems complex and variable, indicating that there may be more than I type of association between the comorbid disorders. When occurring in childhood. some of the frequently comorbid psychopathologies typically precede later drug and alcohol abuse and may have implications for substance abuse prevention as early risk indicators and as targets for intervention. Research discussed in this article and in this special issue provides a foundation for investigating the question of whether effective treatment of childhood psychopathologies can prevent or at least mitigate substance abuse for some adolescents. Clinical, research, and policy implications are discussed. JF - Journal of consulting and clinical psychology AU - Glantz, Meyer D AD - Division of Epidemiology, Services, and Prevention Research, National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland 20892-9589, USA. mglantz@nida.gov Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 1203 EP - 1206 VL - 70 IS - 6 SN - 0022-006X, 0022-006X KW - Index Medicus KW - Humans KW - Adult KW - Outcome and Process Assessment (Health Care) KW - Child KW - Psychopathology KW - Adolescent KW - Comorbidity KW - Mental Disorders -- therapy KW - Child Behavior Disorders -- therapy KW - Child Behavior Disorders -- psychology KW - Mental Disorders -- psychology KW - Personality Development KW - Substance-Related Disorders -- psychology KW - Alcoholism -- psychology KW - Alcoholism -- prevention & control KW - Substance-Related Disorders -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72768628?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+consulting+and+clinical+psychology&rft.atitle=Introduction+to+the+special+issue+on+the+impact+of+childhood+psychopathology+interventions+on+subsequent+substance+abuse%3A+pieces+of+the+puzzle.&rft.au=Glantz%2C+Meyer+D&rft.aulast=Glantz&rft.aufirst=Meyer&rft.date=2002-12-01&rft.volume=70&rft.issue=6&rft.spage=1203&rft.isbn=&rft.btitle=&rft.title=Journal+of+consulting+and+clinical+psychology&rft.issn=0022006X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-10 N1 - Date created - 2002-12-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Suradista NSC 651016 inhibits the angiogenic activity of CXCL12-stromal cell-derived factor 1alpha. AN - 72760578; 12473612 AB - CXCL12 (stromal cell-derived factor 1alpha), a ligand for CXCR4, has been shown to induce endothelial cell chemotaxis and to stimulate angiogenesis, suggesting that it may be a significant target for antiangiogenic therapy. Here we have tested suradista NSC 651016, a compound known to inhibit CXCL12-induced monocyte chemotaxis, for its ability to inhibit CXCL12-induced angiogenic activity. NSC 651016 inhibited CXCL12-mediated endothelial cell chemotaxis in a dose-dependent manner. In addition, new vessel sprouting, by both rat and chick aorta in an angiogenesis model, was inhibited. Additionally, in vitro capillary-like structure formation induced by CXCL12 was inhibited by NSC 651016. Furthermore, NSC 651016 inhibited CXCL12-mediated angiogenesis in an in vivo s.c. assay. These data indicate that suradista NSC 651016 possesses in vitro and in vivo antiangiogenic activity and has the potential to interfere with neovacularization of tumors and their metastases. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Schneider, Gregory P AU - Salcedo, Rosalba AU - Dong, Hui Fang AU - Kleinman, Hynda K AU - Oppenheim, Joost J AU - Howard, O M Zack AD - Laboratory of Molecular Immunoregulation, Center for Cancer Research, Intramural Research Support Program, National Cancer Institute-Frederick, Frederick, Maryland 21702, USA. Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 3955 EP - 3960 VL - 8 IS - 12 SN - 1078-0432, 1078-0432 KW - CXCL12 protein, human KW - 0 KW - Chemokine CXCL12 KW - Chemokines, CXC KW - NSC 651016 KW - Naphthalenesulfonates KW - Index Medicus KW - Animals KW - Endothelium, Vascular -- metabolism KW - Humans KW - Cells, Cultured -- drug effects KW - Rats KW - Rats, Sprague-Dawley KW - Chickens KW - Endothelium, Vascular -- drug effects KW - In Vitro Techniques KW - Cell Movement -- drug effects KW - Monocytes -- drug effects KW - Chemotaxis -- drug effects KW - Chemokines, CXC -- antagonists & inhibitors KW - Stromal Cells -- drug effects KW - Naphthalenesulfonates -- pharmacology KW - Neovascularization, Pathologic -- chemically induced KW - Neovascularization, Pathologic -- prevention & control KW - Stromal Cells -- metabolism KW - Chemokines, CXC -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72760578?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Suradista+NSC+651016+inhibits+the+angiogenic+activity+of+CXCL12-stromal+cell-derived+factor+1alpha.&rft.au=Schneider%2C+Gregory+P%3BSalcedo%2C+Rosalba%3BDong%2C+Hui+Fang%3BKleinman%2C+Hynda+K%3BOppenheim%2C+Joost+J%3BHoward%2C+O+M+Zack&rft.aulast=Schneider&rft.aufirst=Gregory&rft.date=2002-12-01&rft.volume=8&rft.issue=12&rft.spage=3955&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 - 2003-01-21 N1 - Date created - 2002-12-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Difference between deoxyribose- and tetrahydrofuran-type abasic sites in the in vivo mutagenic responses in yeast. AN - 72758462; 12466536 AB - We have analyzed the mutagenic specificity of an abasic site in DNA using the yeast oligonucleotide transformation assay. Oligonucleotides containing an abasic site or its analog were introduced into B7528 or its derivatives, and nucleotide incorporation opposite abasic sites was analyzed. Cytosine was most frequently incorporated opposite a natural abasic site (O) ('C-rule'), followed by thymine. Deletion of REV1 decreased the transformation efficiency and the incorporation of cytosine nearly to a background level. In contrast, deletion of RAD30 did not affect them. We compared the mutagenic specificity with that of a tetrahydrofuran abasic site (F), an abasic analog used widely. Its mutation spectrum was clearly different from that of O. Adenine, not cytosine, was most favorably incorporated. However, deletion of REV1 decreased the transformation efficiency with F-containing oligonucleotide as in the case of O. These results suggest that the bypass mechanism of F is different from that of O, although the bypasses in both cases are dependent on REV1. We also found that the mutagenic specificity of F can be affected by not only the adjacent bases, but also a base located two positions away from F. JF - Nucleic acids research AU - Otsuka, Chie AU - Sanadai, Sachi AU - Hata, Yasuhiro AU - Okuto, Hisanori AU - Noskov, Vladimir N AU - Loakes, David AU - Negishi, Kazuo AD - Gene Research Center, Okayama University, Tsushima, Okayama 700-8530, Japan, National Cancer Institute, Bethesda, MD 20892, USA and. Medical Research Council, Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK. Y1 - 2002/12/01/ PY - 2002 DA - 2002 Dec 01 SP - 5129 EP - 5135 VL - 30 IS - 23 KW - Furans KW - 0 KW - Oligonucleotides KW - Uracil KW - 56HH86ZVCT KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Uracil -- chemistry KW - Oligonucleotides -- chemistry KW - Transformation, Genetic KW - Models, Genetic KW - Mutation KW - Oligonucleotides -- genetics KW - Saccharomyces cerevisiae -- genetics KW - Furans -- chemistry KW - DNA -- chemistry KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72758462?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Difference+between+deoxyribose-+and+tetrahydrofuran-type+abasic+sites+in+the+in+vivo+mutagenic+responses+in+yeast.&rft.au=Otsuka%2C+Chie%3BSanadai%2C+Sachi%3BHata%2C+Yasuhiro%3BOkuto%2C+Hisanori%3BNoskov%2C+Vladimir+N%3BLoakes%2C+David%3BNegishi%2C+Kazuo&rft.aulast=Otsuka&rft.aufirst=Chie&rft.date=2002-12-01&rft.volume=30&rft.issue=23&rft.spage=5129&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=1362-4962&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-12-23 N1 - Date created - 2002-12-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 2000 Mar 17;275(11):8233-9 [10713149] Cell. 1999 Aug 20;98(4):413-6 [10481906] Mol Microbiol. 2000 Aug;37(3):549-54 [10931348] Nucleic Acids Res. 2000 Nov 1;28(21):4138-46 [11058110] Nucleic Acids Res. 2001 Feb 15;29(4):928-35 [11160925] J Biol Chem. 2001 Mar 2;276(9):6861-6 [11106652] Genes Dev. 2001 Apr 15;15(8):945-54 [11316789] Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3764-9 [11891323] Mutat Res. 2002 May 22;502(1-2):53-60 [11996972] Biochemistry. 1982 Dec 21;21(26):6746-51 [6760893] Proc Natl Acad Sci U S A. 1983 Jan;80(2):487-91 [6300848] Biochemistry. 1983 Sep 13;22(19):4518-26 [6354260] Proc Natl Acad Sci U S A. 1984 Mar;81(5):1494-8 [6369329] Annu Rev Genet. 1986;20:201-30 [3545059] J Biol Chem. 1987 May 15;262(14):6864-70 [3571289] J Biol Chem. 1987 Jul 25;262(21):10171-9 [2440861] Genetics. 1987 Aug;116(4):541-5 [3305158] Proc Natl Acad Sci U S A. 1988 Jan;85(2):524-8 [2829192] Annu Rev Biochem. 1988;57:29-67 [3052275] J Biol Chem. 1989 Feb 15;264(5):2593-8 [2644266] Nucleic Acids Res. 1990 Apr 25;18(8):2153-7 [2186377] Proc Natl Acad Sci U S A. 1990 Jun;87(11):4193-7 [1693433] Biochem Biophys Res Commun. 1990 Dec 14;173(2):704-10 [2124487] Bioessays. 1991 Feb;13(2):79-84 [2029269] Mol Carcinog. 1992;6(1):32-42 [1503643] Nucleic Acids Res. 1992 Sep 11;20(17):4409-15 [1408742] J Mol Biol. 1992 Oct 20;227(4):981-4 [1433302] Yeast. 1992 Nov;8(11):935-48 [1336288] Nucleic Acids Res. 1994 May 25;22(10):1897-902 [8208616] Mutat Res. 1994 Jul 1;308(1):43-51 [7516485] J Mol Biol. 1994 Jul 29;240(5):416-20 [8046747] Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):8165-9 [7520176] Yeast. 1994 Dec;10(13):1793-808 [7747518] J Mol Biol. 1995 Aug 11;251(2):229-36 [7643399] Nature. 1996 Aug 22;382(6593):729-31 [8751446] J Biol Chem. 1997 May 23;272(21):13916-22 [9153253] Genes Dev. 1998 Oct 1;12(19):3137-43 [9765213] Yeast. 1999 Jul;15(10B):955-61 [10407275] Genes Dev. 2000 Jul 1;14(13):1589-94 [10887153] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification and functional characterization of new potentially defective alleles of human CYP2C19. AN - 72754040; 12464799 AB - CYP2C19 is a clinically important enzyme responsible for the metabolism of a number of therapeutic drugs, such as mephenytoin, omeprazole, diazepam, proguanil, propranolol and certain antidepressants. Genetic polymorphisms in this enzyme result in poor metabolizers of these drugs. There are racial differences in the incidence of the poor metabolizer trait, which represents 13-23% of Asians but only 3-5% of Caucasians. In this study, single nucleotide polymorphisms (SNPs) in CYP2C19 were identified by direct sequencing of genomic DNA from 92 individuals from three different racial groups of varied ethnic background, including Caucasians, Asians and blacks. Several new alleles were identified containing the coding changes Arg114 His (CYP2C19*9), Pro227 Leu (CYP2C19*10), Arg150 His (CYP2C19*11), stop491 Cys (CYP2C19*12), Arg410 Cys (CYP2C19*13), Leu17 Pro (CYP2C19*14) and Ile19 Leu (CYP2C19*15). When expressed in a bacterial cDNA expression system, CYP2C19*9 exhibited a modest decrease in the V(max) for 4'-hydroxylation of -mephenytoin, and no alteration in its affinity for reductase. CYP2C19*10 exhibited a dramatically higher K(m) and lower V(max) for mephenytoin. CYP2C19*12was unstable and expressed poorly in a bacterial cDNA expression system. Clinical studies will be required to confirm whether this allele is defective in vivo. CYP2C19*9, CYP2C19*10 and CYP2C19*12 all occurred in African-Americans, or individuals of African descent, and represent new potentially defective alleles of CYP2C19 which are predicted to alter risk of these populations to clinically important drugs. Copyright 2002 Lippincott Williams & Wilkins JF - Pharmacogenetics AU - Blaisdell, Joyce AU - Mohrenweiser, Harvey AU - Jackson, Jonathan AU - Ferguson, Stephen AU - Coulter, Sherry AU - Chanas, Brian AU - Xi, Tina AU - Ghanayem, Burhan AU - Goldstein, Joyce A AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 703 EP - 711 VL - 12 IS - 9 SN - 0960-314X, 0960-314X KW - DNA Primers KW - 0 KW - Recombinant Proteins KW - Mixed Function Oxygenases KW - EC 1.- KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - CYP2C19 protein, human KW - Cytochrome P-450 CYP2C19 KW - Mephenytoin KW - R420KW629U KW - Index Medicus KW - Gene Frequency KW - Humans KW - Recombinant Proteins -- genetics KW - Genotype KW - Mutagenesis, Site-Directed KW - Phenotype KW - Polymerase Chain Reaction KW - Recombinant Proteins -- isolation & purification KW - Tumor Cells, Cultured KW - Recombinant Proteins -- metabolism KW - Amino Acid Substitution KW - Mephenytoin -- metabolism KW - Aryl Hydrocarbon Hydroxylases -- metabolism KW - Alleles KW - Mixed Function Oxygenases -- metabolism KW - African Continental Ancestry Group -- genetics KW - Aryl Hydrocarbon Hydroxylases -- genetics KW - Polymorphism, Single Nucleotide -- genetics KW - European Continental Ancestry Group -- genetics KW - Ethnic Groups -- genetics KW - Mixed Function Oxygenases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72754040?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Identification+and+functional+characterization+of+new+potentially+defective+alleles+of+human+CYP2C19.&rft.au=Blaisdell%2C+Joyce%3BMohrenweiser%2C+Harvey%3BJackson%2C+Jonathan%3BFerguson%2C+Stephen%3BCoulter%2C+Sherry%3BChanas%2C+Brian%3BXi%2C+Tina%3BGhanayem%2C+Burhan%3BGoldstein%2C+Joyce+A&rft.aulast=Blaisdell&rft.aufirst=Joyce&rft.date=2002-12-01&rft.volume=12&rft.issue=9&rft.spage=703&rft.isbn=&rft.btitle=&rft.title=Pharmacogenetics&rft.issn=0960314X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-07 N1 - Date created - 2002-12-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hormone replacement therapy regimens and breast cancer risk(1). AN - 72751273; 12468157 AB - Hormone replacement therapy (HRT) has increased in the United States over the past 2 decades in response to reports of long-term health benefits. A relationship between HRT and breast cancer risk has been observed in a number of epidemiological studies. In 2002, the Women's Health Initiative Randomized Controlled Trial reported an association between continuous combined HRT and breast cancer risk. The objective of this study was to examine the association between breast cancer risk and HRT according to regimen and duration and recency of use.A multicenter, population-based, case-control study was conducted in five United States metropolitan areas from 1994 to 1998. Analyzed were data from 3823 postmenopausal white and black women (1870 cases and 1953 controls) aged 35-64 years. Odds ratios (ORs) were calculated as estimates of breast cancer risk using standard, unconditional, multivariable logistic regression analysis. Potential confounders were included in the final model if they altered ORs by 10% or more. Two-sided P values for trend were computed from the likelihood ratio statistic. Continuous combined HRT was associated with increased breast cancer risk among current users of 5 or more years (1.54; 95% confidence interval 1.10, 2.17). Additionally, a statistically significant trend indicating increasing breast cancer risk with longer duration of continuous combined HRT was observed among current users (P =.01). There were no positive associations between breast cancer risk and other HRT regimens. Our data suggest a positive association between continuous combined HRT and breast cancer risk among current, longer term users. Progestin administered in an uninterrupted regimen may be a contributing factor. Risk dissipates once use is discontinued. JF - Obstetrics and gynecology AU - Weiss, Linda K AU - Burkman, Ronald T AU - Cushing-Haugen, Kara L AU - Voigt, Lynda F AU - Simon, Michael S AU - Daling, Janet R AU - Norman, Sandra A AU - Bernstein, Leslie AU - Ursin, Giske AU - Marchbanks, Polly A AU - Strom, Brian L AU - Berlin, Jesse A AU - Weber, Anita L AU - Doody, David R AU - Wingo, Phyllis A AU - McDonald, Jill A AU - Malone, Kathleen E AU - Folger, Suzanne G AU - Spirtas, Robert AD - Population Studies and Prevention Program, Karmanos Cancer Institute at Wayne State University, Detroit, Michigan, USA. lw187q@nih.gov Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 1148 EP - 1158 VL - 100 IS - 6 SN - 0029-7844, 0029-7844 KW - Abridged Index Medicus KW - Index Medicus KW - Probability KW - Reference Values KW - Drug Administration Schedule KW - Odds Ratio KW - Age of Onset KW - Dose-Response Relationship, Drug KW - Humans KW - Prognosis KW - Age Distribution KW - Postmenopause KW - Logistic Models KW - Risk Factors KW - Adult KW - Cohort Studies KW - Case-Control Studies KW - Middle Aged KW - United States -- epidemiology KW - Time Factors KW - Female KW - Prevalence KW - Hormone Replacement Therapy -- adverse effects KW - Breast Neoplasms -- pathology KW - Breast Neoplasms -- etiology KW - Breast Neoplasms -- epidemiology KW - Hormone Replacement Therapy -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72751273?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Hormone+replacement+therapy+regimens+and+breast+cancer+risk%281%29.&rft.au=Weiss%2C+Linda+K%3BBurkman%2C+Ronald+T%3BCushing-Haugen%2C+Kara+L%3BVoigt%2C+Lynda+F%3BSimon%2C+Michael+S%3BDaling%2C+Janet+R%3BNorman%2C+Sandra+A%3BBernstein%2C+Leslie%3BUrsin%2C+Giske%3BMarchbanks%2C+Polly+A%3BStrom%2C+Brian+L%3BBerlin%2C+Jesse+A%3BWeber%2C+Anita+L%3BDoody%2C+David+R%3BWingo%2C+Phyllis+A%3BMcDonald%2C+Jill+A%3BMalone%2C+Kathleen+E%3BFolger%2C+Suzanne+G%3BSpirtas%2C+Robert&rft.aulast=Weiss&rft.aufirst=Linda&rft.date=2002-12-01&rft.volume=100&rft.issue=6&rft.spage=1148&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 - 2003-01-10 N1 - Date created - 2002-12-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunologic effects of dioxin: new results from Seveso and comparison with other studies. AN - 72729443; 12460794 AB - Animal studies indicate that the immune system is one of the most sensitive targets of the toxic effects of 2,3,7,8-tetrachloro-p-dibenzodioxin (TCDD). TCDD inhibits immunoglobulin secretion and decreases resistance to bacterial, viral, and parasitic infections in exposed animals. Nearly 20 years after the Seveso, Italy, accident, we measured immunoglobulin and complement plasma levels in a random sample of the population in the most highly exposed zones (n = 62) and in the surrounding noncontaminated area (n = 58). Plasma IgG levels decreased with increasing TCDD plasma concentration (r = -0.35, p = 0.0002). Median IgG concentration decreased from 1,526 mg/dL in the group with the lowest (< 3.5 ppt) TCDD levels to 1,163 mg/dL in the group with the highest (20.1-89.9 ppt) TCDD levels (p = 0.002). The association was significant (p = 0.0004) after adjusting for age, sex, smoking, and consumption of domestic livestock and poultry in multiple regression analysis and persisted after exclusion of subjects with inflammatory diseases and those using antibiotics or nonsteroidal anti-inflammatory drugs. IgM, IgA, C3, and C4 plasma concentrations did not exhibit any consistent association with TCDD levels. We performed a systematic review of all the articles published between 1966 and 2001 on human subjects exposed to TCDD reporting information on circulating levels of immunoglobulins and/or complement components. The literature indicates that the evidence for effects of TCDD on humoral immunity is sparse. Methodologic issues, results, and possible sources of variation between studies are discussed. The possible long-term immunologic effects of TCDD exhibited by the participants of the present study, coupled with the increased incidence of lymphatic tumors in the area of the accident, warrant further investigation. JF - Environmental health perspectives AU - Baccarelli, Andrea AU - Mocarelli, Paolo AU - Patterson, Donald G AU - Bonzini, Matteo AU - Pesatori, Angela C AU - Caporaso, Neil AU - Landi, Maria Teresa AD - Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 1169 EP - 1173 VL - 110 IS - 12 SN - 0091-6765, 0091-6765 KW - Carcinogens KW - 0 KW - Immunoglobulins KW - Polychlorinated Dibenzodioxins KW - Index Medicus KW - Humans KW - Aged KW - Child KW - Italy KW - Risk Assessment KW - Child, Preschool KW - Accidents KW - Public Health KW - Adult KW - Follow-Up Studies KW - Middle Aged KW - Female KW - Male KW - Immunoglobulins -- analysis KW - Polychlorinated Dibenzodioxins -- adverse effects KW - Environmental Exposure KW - Lymphoma -- chemically induced KW - Polychlorinated Dibenzodioxins -- immunology KW - Antibody Formation -- drug effects KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72729443?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Immunologic+effects+of+dioxin%3A+new+results+from+Seveso+and+comparison+with+other+studies.&rft.au=Baccarelli%2C+Andrea%3BMocarelli%2C+Paolo%3BPatterson%2C+Donald+G%3BBonzini%2C+Matteo%3BPesatori%2C+Angela+C%3BCaporaso%2C+Neil%3BLandi%2C+Maria+Teresa&rft.aulast=Baccarelli&rft.aufirst=Andrea&rft.date=2002-12-01&rft.volume=110&rft.issue=12&rft.spage=1169&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 - 2003-03-11 N1 - Date created - 2002-12-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Life Sci. 2000 Apr 21;66(22):2123-42 [10834297] Toxicol Lett. 1999 Sep 5;108(2-3):285-95 [10511273] Food Addit Contam. 2000 Apr;17(4):289-302 [10912243] J Pharmacol Exp Ther. 2000 Nov;295(2):705-16 [11046109] Toxicol Appl Pharmacol. 2001 Mar 15;171(3):157-64 [11243915] Chemosphere. 2001 May-Jun;43(4-7):1005-10 [11372817] Am J Epidemiol. 2001 Jun 1;153(11):1031-44 [11390319] Toxicology. 2002 Mar 5;172(1):49-58 [11844614] Ann Hematol. 2002 Feb;81(2):64-75 [11907785] Ann N Y Acad Sci. 1979 May 31;320:311-20 [287395] JAMA. 1986 Apr 18;255(15):2031-8 [3959286] Anal Chem. 1987 Aug 1;59(15):2000-5 [3631519] Br J Ind Med. 1988 Oct;45(10):701-4 [3264183] J Toxicol Environ Health. 1989;28(2):183-93 [2677396] Toxicology. 1991;69(3):219-55 [1949050] Occup Environ Med. 1994 Jul;51(7):479-86 [8044248] J Dermatol Sci. 1994 Oct;8(2):91-5 [7530995] Chemosphere. 1994 Nov-Dec;29(9-11):2423-37 [7850391] Cent Eur J Public Health. 1995 Aug;3(3):154-7 [8535375] Environ Health Perspect. 1995 Dec;103 Suppl 9:47-53 [8635439] Arch Toxicol Suppl. 1996;18:15-20 [8678791] Lancet. 1997 Jun 21;349(9068):1811 [9269218] Environ Health Perspect. 1998 Apr;106 Suppl 2:689-95 [9599718] Environ Health Perspect. 1998 May;106(5):273-7 [9520360] Occup Environ Med. 1998 Nov;55(11):742-9 [9924450] Am J Epidemiol. 1999 Jun 1;149(11):1038-46 [10355380] Occup Med (Lond). 1999 May;49(4):225-9 [10474913] Food Addit Contam. 2000 Apr;17(4):275-88 [10912242] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gamma-glutamyl transpeptidase and its role in melanogenesis: redox reactions and regulation of tyrosinase. AN - 72714903; 12453183 AB - Metabolism of glutathione by gamma-glutamyl transpeptidase (gamma-GT) at the level of cell membrane has been shown to generate hydrogen peroxide in many cell types including human melanomas. gamma-GT does not appear to be involved in cysteine uptake for pheomelanin production in melanoma cells and does not contribute significantly to the pheomelanin synthesized in B16 melanoma cells. We have therefore examined the possibility of gamma-GT mediated production of prooxidant reactions and its effect, if any, on pigmentation using B16 melanoma cells. Our results indicate that in B16 melanoma cells, gamma-GT activity leads to the production of hydrogen peroxide. We further show that the nuclear levels of the redox sensitive transcription factor NF-kappa B is regulated by H2O2 formed by the action of gamma-GT: stimulation and inhibition of gamma-GT affect the levels of NF-kappa B. Tumor necrosis factor alpha, a hypopigmenting cytokine, known to activate NF-kappa B also up-regulates the gamma-GT messenger RNA and activity. Stimulation of gamma-GT generated prooxidant reactions led to a decrease in tyrosinase activity. We therefore propose that prooxidant reactions mediated by gamma-GT in turn regulate the levels of tyrosinase in pigment cells. Our findings thus introduce a new aspect in the regulation of pigmentation and ascribe a novel role for gamma-GT in pigment cells. JF - Pigment cell research AU - Chaubal, Vaishali A AU - Nair, Sujit S AU - Ito, Shosuke AU - Wakamatsu, Kazumasa AU - Mojamdar, Manoj V AD - National Centre for Cell Science, NCCS Complex, Pune University Campus, Ganeshkhind, Pune, Maharashtra, India.chaubalv@mail.nih.gov Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 420 EP - 425 VL - 15 IS - 6 SN - 0893-5785, 0893-5785 KW - Antimetabolites KW - 0 KW - Antineoplastic Agents KW - Isoxazoles KW - NF-kappa B KW - Tumor Necrosis Factor-alpha KW - Hydrogen Peroxide KW - BBX060AN9V KW - Monophenol Monooxygenase KW - EC 1.14.18.1 KW - gamma-Glutamyltransferase KW - EC 2.3.2.2 KW - acivicin KW - O0X60K76I6 KW - Index Medicus KW - Oxidation-Reduction KW - Antimetabolites -- pharmacology KW - Animals KW - Oxidative Stress -- physiology KW - Tumor Cells, Cultured KW - Hydrogen Peroxide -- metabolism KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Oxidative Stress -- drug effects KW - Mice KW - Isoxazoles -- pharmacology KW - Antineoplastic Agents -- pharmacology KW - NF-kappa B -- metabolism KW - Monophenol Monooxygenase -- metabolism KW - gamma-Glutamyltransferase -- metabolism KW - Melanoma UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72714903?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pigment+cell+research&rft.atitle=Gamma-glutamyl+transpeptidase+and+its+role+in+melanogenesis%3A+redox+reactions+and+regulation+of+tyrosinase.&rft.au=Chaubal%2C+Vaishali+A%3BNair%2C+Sujit+S%3BIto%2C+Shosuke%3BWakamatsu%2C+Kazumasa%3BMojamdar%2C+Manoj+V&rft.aulast=Chaubal&rft.aufirst=Vaishali&rft.date=2002-12-01&rft.volume=15&rft.issue=6&rft.spage=420&rft.isbn=&rft.btitle=&rft.title=Pigment+cell+research&rft.issn=08935785&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-13 N1 - Date created - 2002-11-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic and genomic tools for Xenopus research: The NIH Xenopus initiative. AN - 72713766; 12454917 AB - The NIH Xenopus Initiative is establishing many of the genetic and genomic resources that have been recommended by the Xenopus research community. These resources include cDNA libraries, expressed sequence tags, full-length cDNA sequences, genomic libraries, pilot projects to mutagenize and phenotype X. tropicalis, and sequencing the X. tropicalis genome. This review describes the status of these projects and explains how to access their data and resources. Current information about these activities is available on the NIH Xenopus Web site (http://www.nih.gov/science/models/xenopus/). JF - Developmental dynamics : an official publication of the American Association of Anatomists AU - Klein, Steven L AU - Strausberg, Robert L AU - Wagner, Lukas AU - Pontius, Joan AU - Clifton, Sandra W AU - Richardson, Paul AD - Developmental Biology, Genetics and Teratology Branch, National Institute of Child Health and Human Development, Rockville, Maryland 20852, USA. kleins@exchange.nih.gov Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 384 EP - 391 VL - 225 IS - 4 SN - 1058-8388, 1058-8388 KW - DNA, Complementary KW - 0 KW - Index Medicus KW - United States KW - Phenotype KW - Software KW - Animals KW - Oligonucleotide Array Sequence Analysis KW - Databases as Topic KW - DNA, Complementary -- metabolism KW - National Institutes of Health (U.S.) KW - Mutation KW - Expressed Sequence Tags KW - Gene Library KW - Developmental Biology -- methods KW - Xenopus -- genetics KW - Xenopus -- embryology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72713766?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+dynamics+%3A+an+official+publication+of+the+American+Association+of+Anatomists&rft.atitle=Genetic+and+genomic+tools+for+Xenopus+research%3A+The+NIH+Xenopus+initiative.&rft.au=Klein%2C+Steven+L%3BStrausberg%2C+Robert+L%3BWagner%2C+Lukas%3BPontius%2C+Joan%3BClifton%2C+Sandra+W%3BRichardson%2C+Paul&rft.aulast=Klein&rft.aufirst=Steven&rft.date=2002-12-01&rft.volume=225&rft.issue=4&rft.spage=384&rft.isbn=&rft.btitle=&rft.title=Developmental+dynamics+%3A+an+official+publication+of+the+American+Association+of+Anatomists&rft.issn=10588388&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-30 N1 - Date created - 2002-11-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oxidative stress induces arachidonate release from human lung cells through the epithelial growth factor receptor pathway. AN - 72707803; 12444032 AB - Oxidative stress is thought to be a factor influencing many inflammatory responses, including arachidonic acid (AA) release. We have studied the effect of hydrogen peroxide on AA and prostaglandin E(2) release, cytosolic phospholipase (cPLA(2)) steady-state mRNA, cPLA(2) protein levels, cPLA(2) enzyme activity, and cPLA(2) phosphorylation in a human lung epithelial cell line: A549 cells. Hydrogen peroxide caused a dose-dependent increase of A23187-stimulated AA and prostaglandin E(2) release, with a maximum effect at 1 h. This effect is associated with a maximum specific cPLA(2) activity at 1 h, and with a significant increase in cPLA(2) Serine 505 phosphorylation. All these effects were abolished, in a dose-related manner, by the epithelial growth factor receptor kinase inhibitor, AG 1478. To further investigate the pathway leading to the increase cPLA(2) phosphorylation, we used cells transfected with a Ras dominant negative vector and mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK) and p38 kinase inhibitors. Cells transfected with the Ras dominant negative vector exhibited diminished hydrogen peroxide-induced AA release and cPLA(2) phosphorylation as compared with cells transfected with the Ras expression vector. Both MEK and p38 kinase inhibitors inhibited the hydrogen peroxide effect on AA release and specific cPLA(2) activity. Finally, cells stably transfected with an antisense cPLA(2) vector exhibited diminished A23187-stimulated AA release in response to hydrogen peroxide as compared with cells stably transfected with empty expression vector. Collectively, these data show that hydrogen peroxide increases cPLA(2) activity through its phosphorylation utilizing an epithelial growth factor/Ras/extracellular signal-regulated kinase and p38 pathway. JF - American journal of respiratory cell and molecular biology AU - Pawliczak, Rafal AU - Huang, Xiu-Li AU - Nanavaty, Uday B AU - Lawrence, Marion AU - Madara, Patricia AU - Shelhamer, James H AD - Critical Care Medicine Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 722 EP - 731 VL - 27 IS - 6 SN - 1044-1549, 1044-1549 KW - 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one KW - 0 KW - Antineoplastic Agents KW - Enzyme Inhibitors KW - Flavonoids KW - Imidazoles KW - Ionophores KW - Oxidants KW - Platelet Activating Factor KW - Pyridines KW - Quinazolines KW - RNA, Messenger KW - Tumor Necrosis Factor-alpha KW - Tyrphostins KW - tyrphostin AG 1478 KW - 170449-18-0 KW - Arachidonic Acid KW - 27YG812J1I KW - Tyrosine KW - 42HK56048U KW - Hydrogen Peroxide KW - BBX060AN9V KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Mitogen-Activated Protein Kinase 1 KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinase 3 KW - Mitogen-Activated Protein Kinases KW - p38 Mitogen-Activated Protein Kinases KW - MAP Kinase Kinase Kinase 1 KW - EC 2.7.11.25 KW - MAP3K1 protein, human KW - Phospholipases A KW - EC 3.1.1.32 KW - ras Proteins KW - EC 3.6.5.2 KW - SB 203580 KW - OU13V1EYWQ KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Imidazoles -- pharmacology KW - Protein-Serine-Threonine Kinases -- metabolism KW - Humans KW - Cytosol -- enzymology KW - Hydrogen Peroxide -- pharmacology KW - Protein-Serine-Threonine Kinases -- antagonists & inhibitors KW - Calcium -- metabolism KW - Ionophores -- pharmacology KW - Tyrosine -- metabolism KW - Flavonoids -- pharmacology KW - Tyrphostins -- pharmacology KW - Phospholipases A -- metabolism KW - ras Proteins -- genetics KW - Oxidants -- pharmacology KW - Mitogen-Activated Protein Kinases -- metabolism KW - Tumor Necrosis Factor-alpha -- pharmacology KW - RNA, Messenger -- analysis KW - Phosphorylation -- drug effects KW - Platelet Activating Factor -- pharmacology KW - Phospholipases A -- genetics KW - Cells, Cultured KW - Mitogen-Activated Protein Kinase 1 -- metabolism KW - Enzyme Inhibitors -- pharmacology KW - Mitogen-Activated Protein Kinases -- antagonists & inhibitors KW - ras Proteins -- metabolism KW - Antineoplastic Agents -- pharmacology KW - Pyridines -- pharmacology KW - Oxidative Stress -- physiology KW - Receptor, Epidermal Growth Factor -- metabolism KW - Lung -- cytology KW - Oxidative Stress -- drug effects KW - Lung -- metabolism KW - Arachidonic Acid -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72707803?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Oxidative+stress+induces+arachidonate+release+from+human+lung+cells+through+the+epithelial+growth+factor+receptor+pathway.&rft.au=Pawliczak%2C+Rafal%3BHuang%2C+Xiu-Li%3BNanavaty%2C+Uday+B%3BLawrence%2C+Marion%3BMadara%2C+Patricia%3BShelhamer%2C+James+H&rft.aulast=Pawliczak&rft.aufirst=Rafal&rft.date=2002-12-01&rft.volume=27&rft.issue=6&rft.spage=722&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 - 2003-01-08 N1 - Date created - 2002-11-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Overview of women's health. AN - 72699668; 12438885 JF - Clinical obstetrics and gynecology AU - Leppert, Phyllis C AD - Center for Population Research, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, 20892, USA. leppertp@mail.nih.gov Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 1073 EP - 1079 VL - 45 IS - 4 SN - 0009-9201, 0009-9201 KW - Index Medicus KW - Life Expectancy -- trends KW - Tobacco Use Disorder -- epidemiology KW - Humans KW - Mortality -- trends KW - Birth Rate -- trends KW - Health Policy KW - Social Conditions KW - Obesity -- epidemiology KW - United States -- epidemiology KW - Female KW - Prevalence KW - Women's Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72699668?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+obstetrics+and+gynecology&rft.atitle=Overview+of+women%27s+health.&rft.au=Leppert%2C+Phyllis+C&rft.aulast=Leppert&rft.aufirst=Phyllis&rft.date=2002-12-01&rft.volume=45&rft.issue=4&rft.spage=1073&rft.isbn=&rft.btitle=&rft.title=Clinical+obstetrics+and+gynecology&rft.issn=00099201&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-01-13 N1 - Date created - 2002-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hermansky-Pudlak syndrome type 1: gene organization, novel mutations, and clinical-molecular review of non-Puerto Rican cases. AN - 72695725; 12442288 AB - Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder causing oculocutaneous albinism and a platelet storage pool deficiency, reflecting defective biosynthesis and/or processing of melanosomes and platelet dense bodies. Four human genes (HPS1, ADTB3A, HPS3, HPS4) are associated with four subtypes of HPS. The most common is HPS-1. A 16-bp duplication in exon 15 of the HPS1 gene causes HPS-1 in 450 northwest Puerto Rican patients; 13 other HPS1 mutations have been reported in non-Puerto Rican patients. We screened 26 HPS patients, who lacked a molecular diagnosis, for HPS1 defects and identified six patients with six different HPS1 mutations. Four novel mutations were discovered, including the first HPS1 missense mutation, 922T>C, in exon 8. This mutation, along with 624delG in exon 6, preserve RNA transcription, while 561delC in exon 5 and [1581delA;1594C>A] in exon 14 produce no RNA on northern blot. One of six adult patients developed pulmonary fibrosis, and two patients ages 16 and 17 have granulomatous colitis. These complications are common among Puerto Rican HPS-1 patients but have not appeared in HPS-2 or HPS-3 patients. The diagnosis of HPS-1, available only on molecular grounds, has important prognostic and treatment implications. Copyright 2002 Wiley-Liss, Inc. JF - Human mutation AU - Hermos, Christina R AU - Huizing, Marjan AU - Kaiser-Kupfer, Muriel I AU - Gahl, William A AD - Heritable Disorders Branch, National Institute of Child Health and Human Development, NIH, Bethesda, Maryland 20892-1851, USA. Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 482 VL - 20 IS - 6 KW - HPS1 protein, human KW - 0 KW - Membrane Proteins KW - RNA KW - 63231-63-0 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Pedigree KW - Blotting, Northern KW - Humans KW - Child KW - Genes -- genetics KW - Frameshift Mutation KW - Infant KW - RNA -- metabolism KW - Adult KW - Molecular Sequence Data KW - Point Mutation KW - DNA -- chemistry KW - Adolescent KW - Male KW - Sequence Deletion KW - RNA -- genetics KW - Alternative Splicing -- genetics KW - DNA Mutational Analysis KW - Sequence Analysis, DNA KW - Child, Preschool KW - Base Sequence KW - DNA -- genetics KW - Mutation KW - Female KW - Mutagenesis, Insertional KW - Hermanski-Pudlak Syndrome -- genetics KW - Membrane Proteins -- genetics KW - Hermanski-Pudlak Syndrome -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72695725?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Hermansky-Pudlak+syndrome+type+1%3A+gene+organization%2C+novel+mutations%2C+and+clinical-molecular+review+of+non-Puerto+Rican+cases.&rft.au=Hermos%2C+Christina+R%3BHuizing%2C+Marjan%3BKaiser-Kupfer%2C+Muriel+I%3BGahl%2C+William+A&rft.aulast=Hermos&rft.aufirst=Christina&rft.date=2002-12-01&rft.volume=20&rft.issue=6&rft.spage=482&rft.isbn=&rft.btitle=&rft.title=Human+mutation&rft.issn=1098-1004&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-12-23 N1 - Date created - 2002-11-20 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 203300; OMIM; AF450133; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Similar regulation of cell surface human T-cell leukemia virus type 1 (HTLV-1) surface binding proteins in cells highly and poorly transduced by HTLV-1-pseudotyped virions. AN - 72695056; 12438598 AB - Little is known about the requirements for human T-cell leukemia virus type 1 (HTLV-1) entry, including the identity of the cellular receptor(s). Previous studies have shown that although the HTLV receptor(s) are widely expressed on cell lines of various cell types from different species, cell lines differ dramatically in their susceptibility to HTLV-Env-mediated fusion. Human cells (293, HeLa, and primary CD4(+) T cells) showed higher levels of binding at saturation than rodent (NIH 3T3 and NRK) cells to an HTLV-1 SU immunoadhesin. A direct comparison of the binding of the HTLV-1 surface glycoprotein (SU) immunoadhesin and transduction by HTLV-1 pseudotyped virus revealed parallels between the level of binding and the titer for various cell lines. When cells were treated with phorbol myristate acetate (PMA), which down-modulates a number of cell surface molecules, the level of SU binding was markedly reduced. However, PMA treatment only slightly reduced the titer of murine leukemia virus(HTLV-1) on both highly susceptible and poorly susceptible cells. Treatment of target cells with trypsin greatly reduced binding, indicating that the majority of HTLV SU binding is to proteins. Polycations, which enhance the infectivity of several other retroviruses, inhibited HTLV-1 Env-mediated binding and entry on both human and rodent cells. These results suggest that factors other than the number of primary binding receptors are responsible for the differences in the titers of HTLV-1 pseudotypes between highly susceptible cells and poorly susceptible cells. JF - Journal of virology AU - Jones, Kathryn S AU - Nath, Manisha AU - Petrow-Sadowski, Cari AU - Baines, Andrea C AU - Dambach, Megan AU - Huang, Ying AU - Ruscetti, Francis W AD - Basic Research Program, SAIC-Frederick, National Cancer Institute at Frederick, Frederick, MD 21702-1201, USA. Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 12723 EP - 12734 VL - 76 IS - 24 SN - 0022-538X, 0022-538X KW - Immunoglobulin G KW - 0 KW - Receptors, Virus KW - Viral Envelope Proteins KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - 3T3 Cells KW - HeLa Cells KW - Humans KW - Transduction, Genetic KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Mice KW - Immunoglobulin G -- metabolism KW - Human T-lymphotropic virus 1 -- physiology KW - Receptors, Virus -- physiology KW - Viral Envelope Proteins -- physiology KW - Virion -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72695056?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Similar+regulation+of+cell+surface+human+T-cell+leukemia+virus+type+1+%28HTLV-1%29+surface+binding+proteins+in+cells+highly+and+poorly+transduced+by+HTLV-1-pseudotyped+virions.&rft.au=Jones%2C+Kathryn+S%3BNath%2C+Manisha%3BPetrow-Sadowski%2C+Cari%3BBaines%2C+Andrea+C%3BDambach%2C+Megan%3BHuang%2C+Ying%3BRuscetti%2C+Francis+W&rft.aulast=Jones&rft.aufirst=Kathryn&rft.date=2002-12-01&rft.volume=76&rft.issue=24&rft.spage=12723&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 - 2002-12-19 N1 - Date created - 2002-11-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 2000 Oct;74(20):9797-801 [11000257] J Virol. 2000 Nov;74(21):10074-80 [11024136] Virology. 2000 Oct 25;276(2):229-37 [11040114] AIDS Res Hum Retroviruses. 2000 Nov 1;16(16):1731-6 [11080818] Appl Microbiol. 1971 Dec;22(6):1162-3 [4332936] Proc Natl Acad Sci U S A. 1980 Dec;77(12):7415-9 [6261256] Nature. 1981 Dec 24;294(5843):770-1 [6275274] Proc Natl Acad Sci U S A. 1982 Mar;79(6):2031-5 [6979048] Proc Natl Acad Sci U S A. 1982 Nov;79(22):6899-902 [6294664] Arch Virol. 1983;75(4):307-11 [6301409] Int J Cancer. 1983 Sep 15;32(3):321-8 [6604033] Science. 1983 Dec 9;222(4628):1125-7 [6316502] Cancer Lett. 1984 Jan;21(3):261-8 [6318970] Int J Cancer. 1985 Aug 15;36(2):191-8 [2991147] Nucleic Acids Res. 1995 Feb 25;23(4):628-33 [7899083] J Virol. 1995 Jun;69(6):3399-406 [7745686] Virology. 1995 Sep 10;212(1):196-203 [7676629] J Acquir Immune Defic Syndr Hum Retrovirol. 1996 May 1;12(1):1-5 [8624755] Virology. 1996 Apr 1;218(1):279-84 [8615036] J Virol. 1996 Oct;70(10):7322-6 [8794391] J Virol. 1996 Nov;70(11):7510-6 [8892869] Cell. 1996 Nov 29;87(5):845-55 [8945512] J Virol. 1997 Jan;71(1):259-66 [8985345] J Virol. 1997 Jan;71(1):601-7 [8985389] Virology. 1997 Mar 3;229(1):49-56 [9123877] J Virol. 1997 Aug;71(8):5828-40 [9223472] J Virol. 1997 Oct;71(10):7180-6 [9311790] Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11617-22 [9326659] J Virol. 1998 Nov;72(11):9101-8 [9765455] J Virol. 1998 Dec;72(12):9544-52 [9811687] J Virol. 1999 Feb;73(2):1205-12 [9882322] Lancet. 1985 Aug 24;2(8452):407-10 [2863442] Lancet. 1986 Jul 12;2(8498):104-5 [2873363] Blood. 1987 Nov;70(5):1303-11 [3499186] J Immunol. 1988 Feb 1;140(3):786-95 [3257504] Science. 1988 Dec 16;242(4885):1557-9 [3201246] Nature. 1989 Feb 9;337(6207):525-31 [2536900] J Virol. 1989 May;63(5):2374-8 [2784836] Nature. 1990 Apr 12;344(6267):667-70 [1970124] Virology. 1990 May;176(1):58-69 [1691887] J Virol. 1990 Nov;64(11):5682-7 [1976827] Virology. 1991 Jan;180(1):420-4 [1845835] J Virol. 1992 Jan;66(1):78-84 [1370096] J Virol. 1993 Jan;67(1):557-61 [8416382] Virology. 1993 May;194(1):1-9 [8480413] J Virol. 1993 Sep;67(9):5346-52 [8394452] Virology. 1993 Sep;196(1):25-33 [8356797] J Exp Med. 1993 Oct 1;178(4):1209-22 [8376930] Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8392-6 [7690960] J Virol. 1994 Feb;68(2):626-31 [8289366] J Virol. 1999 Jan;73(1):495-500 [9847355] Virology. 1999 Feb 15;254(2):235-44 [9986790] J Virol. 1999 Nov;73(11):9683-9 [10516085] AIDS Res Hum Retroviruses. 2001 Jan 20;17(2):125-35 [11177392] J Gen Virol. 2001 Apr;82(Pt 4):821-30 [11257187] Gene Ther. 2001 Apr;8(8):593-9 [11320405] J Virol. 2001 Jul;75(14):6375-83 [11413304] Am J Hematol. 2001 Jan;66(1):32-8 [11426489] J Virol. 2001 Aug;75(16):7351-61 [11462007] J Virol. 2001 Sep;75(17):8317-28 [11483777] Blood. 2001 Sep 15;98(6):1858-61 [11535522] Br Med Bull. 2001;58:43-59 [11714623] Virology. 1969 Jul;38(3):414-26 [4308055] J Cell Biol. 1997 Nov 3;139(3):651-64 [9348282] AIDS Res Hum Retroviruses. 1997 Nov 20;13(17):1517-23 [9390751] J Immunol. 1998 Feb 1;160(3):1522-31 [9570576] Protein Sci. 1998 Jul;7(7):1612-9 [9684894] J Virol. 1998 Sep;72(9):7609-14 [9696862] J Gen Virol. 1999 Dec;80 ( Pt 12):3049-64 [10567635] J Cell Sci. 2000 Jan;113 ( Pt 1):37-44 [10591623] Virology. 2000 Mar 1;268(1):41-8 [10683325] Hum Gene Ther. 2000 Mar 1;11(4):587-95 [10724037] J Virol. 2000 Jul;74(14):6614-21 [10864675] J Virol. 2000 Aug;74(15):7005-15 [10888639] Virology. 2000 Aug 1;273(2):364-73 [10915607] J Biol Chem. 2000 Aug 4;275(31):23417-20 [10851227] Microbiol Immunol. 2000;44(6):489-98 [10941932] J Virol. 2000 Oct;74(20):9540-5 [11000224] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prostaglandin A1 inhibits rotenone-induced apoptosis in SH-SY5Y cells. AN - 72694699; 12437580 AB - The degeneration of nigral dopamine neurons in Parkinson's disease (PD) reportedly involves a defect in brain mitochondrial complex I in association with the activation of nuclear factor-kappaB (NF-kappaB) and caspase-3. To elucidate molecular mechanisms possibly linking these events, as well as to evaluate the neuroprotective potential of the cyclopentenone prostaglandin A1 (PGA1), an inducer of heat shock proteins (HSPs), we exposed human dopaminergic SH-SY5Y cells to the complex I inhibitor rotenone. Dose-dependent apoptosis was preceded by the nuclear translocation of NF-kappaB and then the activation of caspase-3 over the ensuing 24 h. PGA1 increased the expression of HSP70 and HSP27 and protected against rotenone-induced apoptosis, without increasing necrotic death. PGA1 blocked the rotenone-induced nuclear translocation of NF-kappaB and attenuated, but did not abolish, the caspase-3 elevation. Unexpectedly, the caspase-3 inhibitor, Ac-DEVD.CHO (DEVD), at a concentration that completely prevented the caspase-3 elevation produced by rotenone, failed to protect against apoptosis. These results suggest that complex I deficiency in dopamine cells can induce apoptosis by a process involving early NF-kappaB nuclear translocation and caspase-3 activation. PGA1 appears to protect against rotenone-induced cell death by inducing HSPs and blocking nuclear translocation of NF-kappaB in a process that attenuates caspase-3 activation, but is not mediated by its inhibition. JF - Journal of neurochemistry AU - Wang, Xiaoxia AU - Qin, Zheng-Hong AU - Leng, Yan AU - Wang, Yumei AU - Jin, Xiannu AU - Chase, Thomas N AU - Bennett, M Catherine AD - National Institute of Neurological Disorders and Stroke, Experimental Therapeutics Branch, Bethesda, Maryland, USA. Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 1094 EP - 1102 VL - 83 IS - 5 SN - 0022-3042, 0022-3042 KW - Caspase Inhibitors KW - 0 KW - Enzyme Inhibitors KW - HSP27 Heat-Shock Proteins KW - HSP70 Heat-Shock Proteins KW - HSPB1 protein, human KW - Heat-Shock Proteins KW - NF-kappa B KW - Neoplasm Proteins KW - Neuroprotective Agents KW - Prostaglandins A KW - Uncoupling Agents KW - Rotenone KW - 03L9OT429T KW - CASP3 protein, human KW - EC 3.4.22.- KW - Caspase 3 KW - Caspases KW - prostaglandin A1 KW - VYR271N44P KW - Index Medicus KW - HSP70 Heat-Shock Proteins -- metabolism KW - Active Transport, Cell Nucleus -- drug effects KW - Dose-Response Relationship, Drug KW - Humans KW - Neuroblastoma -- metabolism KW - Caspases -- metabolism KW - Uncoupling Agents -- toxicity KW - Enzyme Inhibitors -- pharmacology KW - Neoplasm Proteins -- metabolism KW - Cell Line KW - NF-kappa B -- metabolism KW - Rotenone -- toxicity KW - Neurons -- metabolism KW - Prostaglandins A -- pharmacology KW - Neurons -- drug effects KW - Neurons -- cytology KW - Apoptosis -- drug effects KW - Neuroprotective Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72694699?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Prostaglandin+A1+inhibits+rotenone-induced+apoptosis+in+SH-SY5Y+cells.&rft.au=Wang%2C+Xiaoxia%3BQin%2C+Zheng-Hong%3BLeng%2C+Yan%3BWang%2C+Yumei%3BJin%2C+Xiannu%3BChase%2C+Thomas+N%3BBennett%2C+M+Catherine&rft.aulast=Wang&rft.aufirst=Xiaoxia&rft.date=2002-12-01&rft.volume=83&rft.issue=5&rft.spage=1094&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 - 2003-01-16 N1 - Date created - 2002-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Restraint of proinflammatory cytokine biosynthesis by mitogen-activated protein kinase phosphatase-1 in lipopolysaccharide-stimulated macrophages. AN - 72694187; 12444149 AB - Exposure of macrophages to LPS elicits the production of proinflammatory cytokines, such as TNF-alpha, through complex signaling mechanisms. Mitogen-activated protein (MAP) kinases play a critical role in this process. In the present study, we have addressed the role of MAP kinase phosphatase-1 (MKP-1) in regulating proinflammatory cytokine production using RAW264.7 macrophages. Analysis of MAP kinase activity revealed a transient activation of c-Jun N-terminal kinase (JNK) and p38 after LPS stimulation. Interestingly, MKP-1 was induced concurrently with the inactivation of JNK and p38, whereas blocking MKP-1 induction by triptolide prevented this inactivation. Ectopic expression of MKP-1 accelerated JNK and p38 inactivation and substantially inhibited the production of TNF-alpha and IL-6. Induction of MKP-1 by LPS was found to be extracellular signal-regulated kinase dependent and involved enhanced gene expression and increased protein stability. Finally, MKP-1 expression was also induced by glucocorticoids as well as cholera toxin B subunit, an agent capable of preventing autoimmune diseases in animal models. These findings highlight MKP-1 as a critical negative regulator of the macrophage inflammatory response, underscoring its premise as a potential target for developing novel anti-inflammatory drugs. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Chen, Peili AU - Li, Ji AU - Barnes, Janice AU - Kokkonen, Gertrude C AU - Lee, John C AU - Liu, Yusen AD - Stress Signaling Unit, Laboratory of Cellular and Molecular Biology, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 2002/12/01/ PY - 2002 DA - 2002 Dec 01 SP - 6408 EP - 6416 VL - 169 IS - 11 SN - 0022-1767, 0022-1767 KW - Cell Cycle Proteins KW - 0 KW - Cytokines KW - Diterpenes KW - Enzyme Inhibitors KW - Epoxy Compounds KW - Immediate-Early Proteins KW - Inflammation Mediators KW - Lipopolysaccharides KW - Phenanthrenes KW - RNA, Messenger KW - triptolide KW - 19ALD1S53J KW - Dexamethasone KW - 7S5I7G3JQL KW - Cholera Toxin KW - 9012-63-9 KW - JNK Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinases KW - p38 Mitogen-Activated Protein Kinases KW - Phosphoprotein Phosphatases KW - EC 3.1.3.16 KW - Protein Phosphatase 1 KW - Dual Specificity Phosphatase 1 KW - EC 3.1.3.48 KW - Dusp1 protein, mouse KW - Protein Tyrosine Phosphatases KW - Abridged Index Medicus KW - Index Medicus KW - Diterpenes -- pharmacology KW - Animals KW - Dexamethasone -- pharmacology KW - Cholera Toxin -- pharmacology KW - Gene Expression KW - Mice KW - RNA, Messenger -- genetics KW - RNA, Messenger -- metabolism KW - Enzyme Induction -- drug effects KW - Mitogen-Activated Protein Kinases -- antagonists & inhibitors KW - Lipopolysaccharides -- toxicity KW - Enzyme Inhibitors -- pharmacology KW - Enzyme Stability -- drug effects KW - Cell Line KW - Protein Tyrosine Phosphatases -- biosynthesis KW - Macrophages -- enzymology KW - Immediate-Early Proteins -- biosynthesis KW - Immediate-Early Proteins -- genetics KW - Macrophages -- immunology KW - Protein Tyrosine Phosphatases -- genetics KW - Cytokines -- biosynthesis KW - Macrophages -- drug effects KW - Inflammation Mediators -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72694187?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Restraint+of+proinflammatory+cytokine+biosynthesis+by+mitogen-activated+protein+kinase+phosphatase-1+in+lipopolysaccharide-stimulated+macrophages.&rft.au=Chen%2C+Peili%3BLi%2C+Ji%3BBarnes%2C+Janice%3BKokkonen%2C+Gertrude+C%3BLee%2C+John+C%3BLiu%2C+Yusen&rft.aulast=Chen&rft.aufirst=Peili&rft.date=2002-12-01&rft.volume=169&rft.issue=11&rft.spage=6408&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 - 2002-12-24 N1 - Date created - 2002-11-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Risk communication in the aftermath of the World Trade Center disaster. AN - 72694083; 12439880 JF - American journal of industrial medicine AU - Thurston, George D AU - Chen, Lung Chi AD - NYU-NIEHS Center of Excellence, Department of Environmental Medicine, NYU School of Medicine, Tuxedo, New York 10987, USA. thurston@env.med.nyu.edu Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 543 EP - 544 VL - 42 IS - 6 SN - 0271-3586, 0271-3586 KW - Air Pollutants KW - 0 KW - Dust KW - Carbon KW - 7440-44-0 KW - Index Medicus KW - Environmental Monitoring KW - New York City KW - Public Health KW - Dust -- analysis KW - Aircraft KW - Humans KW - Carbon -- adverse effects KW - Carbon -- analysis KW - Risk Assessment KW - Terrorism KW - Communication KW - Air Pollutants -- analysis KW - Air Pollutants -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72694083?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Risk+communication+in+the+aftermath+of+the+World+Trade+Center+disaster.&rft.au=Thurston%2C+George+D%3BChen%2C+Lung+Chi&rft.aulast=Thurston&rft.aufirst=George&rft.date=2002-12-01&rft.volume=42&rft.issue=6&rft.spage=543&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 - 2003-03-19 N1 - Date created - 2002-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A mouse is not a rat is not a human: species differences exist. AN - 72689118; 12441359 JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Cunningham, Michael L AD - National Toxicology Program and the National Center for Toxicogenomics, National Institute of Environmental Health Sciences, 111 Alexander Drive, Research Triangle Park, North Carolina 27709, USA. cunning1@niehs.nih.gov Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 157 EP - 158 VL - 70 IS - 2 SN - 1096-6080, 1096-6080 KW - Ethylene Glycols KW - 0 KW - n-butoxyethanol KW - I0P9XEZ9WV KW - Index Medicus KW - Rats KW - Animals KW - Genetic Predisposition to Disease -- genetics KW - Humans KW - Mice KW - Species Specificity KW - Ethylene Glycols -- toxicity KW - Liver -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72689118?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=A+mouse+is+not+a+rat+is+not+a+human%3A+species+differences+exist.&rft.au=Cunningham%2C+Michael+L&rft.aulast=Cunningham&rft.aufirst=Michael&rft.date=2002-12-01&rft.volume=70&rft.issue=2&rft.spage=157&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-06 N1 - Date created - 2002-11-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Toxicol Sci. 2002 Dec;70(2):252-60 [12441370] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Late health effects of childhood nasopharyngeal radium irradiation: nonmelanoma skin cancers, benign tumors, and hormonal disorders. AN - 72686456; 12438660 AB - Nasopharyngeal radium irradiation (NRI) was widely used from 1940 through 1970 to treat otitis serosa in children and barotrauma in airmen and submariners. We assessed whether NRI-exposed individuals were at higher risk for benign tumors, nonmelanoma skin cancer, thyroid disorders, and conditions related to regulatory control of anterior pituitary hormones, such as growth and reproductive characteristics. We conducted a retrospective cohort study in 3,440 NRI-exposed and 3,088 nonexposed subjects, who as children were treated at nine ear, nose and throat clinics in The Netherlands between 1945 and 1981. Based on information from original medical records, we traced vital status through follow-up at municipal population registries. Disease status (including medical confirmation) and indicators of pituitary gland radiation damage were assessed from a self-administered questionnaire in 1997. The average radiation doses were 11, 7, and 1.5 cGy for pituitary, parotid, and thyroid gland, respectively, and 3.2 cGy for the facial skin. Among exposed subjects, 23 benign head and neck tumors were observed, compared with 21 among nonexposed subjects. Elevated risk of basal cell carcinoma of the head and neck area was observed in exposed subjects (odds ratio = 2.6; 95% confidence interval: 1.0-6.7). Exposed and nonexposed groups did not differ substantially with regard to thyroid disorders, height, and reproductive characteristics, although exposed males more frequently reported a history of fertility problems compared with nonexposed males (odds ratio = 1.4; 95% confidence interval: 1.0-2.1). We found no evidence of highly elevated risk of benign head and neck tumors, nonmelanoma skin cancer, thyroid disorders, or indicators of pituitary radiation damage after childhood NRI in The Netherlands. JF - Pediatric research AU - Ronckers, Cécile M AU - Land, Charles E AU - Hayes, Richard B AU - Verduijn, Pieter G AU - Stovall, Marilyn AU - van Leeuwen, Flora E AD - Department of Ear, Nose and Throat Medicine, Reinaert Kliniek, Maastricht, The Netherlands. ronckerc@mail.nih.gov Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 850 EP - 858 VL - 52 IS - 6 SN - 0031-3998, 0031-3998 KW - Radium KW - W90AYD6R3Q KW - Index Medicus KW - Reproduction -- radiation effects KW - Carcinoma, Basal Cell -- etiology KW - Humans KW - Thyroid Diseases -- etiology KW - Retrospective Studies KW - Aged KW - Body Height -- radiation effects KW - Child KW - Pituitary Gland -- radiation effects KW - Child, Preschool KW - Infant KW - Head and Neck Neoplasms -- etiology KW - Risk Factors KW - Adult KW - Cohort Studies KW - Middle Aged KW - Netherlands KW - Adolescent KW - Male KW - Female KW - Radium -- administration & dosage KW - Endocrine System Diseases -- etiology KW - Radium -- adverse effects KW - Neoplasms, Radiation-Induced -- etiology KW - Skin Neoplasms -- etiology KW - Nasopharynx -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72686456?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Late+health+effects+of+childhood+nasopharyngeal+radium+irradiation%3A+nonmelanoma+skin+cancers%2C+benign+tumors%2C+and+hormonal+disorders.&rft.au=Ronckers%2C+C%C3%A9cile+M%3BLand%2C+Charles+E%3BHayes%2C+Richard+B%3BVerduijn%2C+Pieter+G%3BStovall%2C+Marilyn%3Bvan+Leeuwen%2C+Flora+E&rft.aulast=Ronckers&rft.aufirst=C%C3%A9cile&rft.date=2002-12-01&rft.volume=52&rft.issue=6&rft.spage=850&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 - 2003-06-09 N1 - Date created - 2002-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Microvessel density, mast cell density and thymidine phosphorylase expression in oral squamous carcinoma. AN - 72685647; 12429983 AB - To elucidate the role of angiogenesis in the carcinogenesis and progression of oral cancer, we investigated microvessel density (mVd), mast cell density (mCd) and thymidine phosphorylase (TP) expression in a series of 50 patients with T1-3 N0-1 M0 oral squamous carcinoma (OSC) and 21 patients with non-dysplastic oral leukoplakia (NDOLP). Paraffin-embedded pathological tissue was utilised for the immunohistochemical analysis of mVd and TP expression. Toluidine blue histochemical method was employed for mast cell identification. OSC and NDOLP were not significantly different with respect to mVd (mVd mean value +/- SD: 30+/-17 and 27+/-18, respectively) and mCd characteristics (mCd mean value +/- SD: 8+/-6 and 7+/-6 units, respectively). Conversely, tumour epithelia showed some degree of TP immunostaining in 100% of cases compared with 76% in NDOLP samples (p< or =0.001 by Fisher's test). A good correlation was found between mVd and mCd in both NDOLP (c.c. 0.632; p=0.002) and OSC (c.c. 0.496; p=0.000) tissue, whereas no association between TP expression and mVd or between mCd and TP status was evident. At a median follow-up of 18 months, patients with high mVd tumours showed a greater probability of survival than those with low mVd (75 and 40%, respectively; p=0.04 log-rank test). Our results suggest that the development of oral cancer epithelia is associated with a significant increase in TP expression. Conversely, the clinical outcome of OSC seems inversely related specifically to mVd. JF - International journal of oncology AU - Ranieri, Girolamo AU - Labriola, Angela AU - Achille, Gaetano AU - Florio, Gerolmina AU - Zito, Alfredo Francesco AU - Grammatica, Luciano AU - Paradiso, Angelo AD - Clinical and Experimental Oncology Laboratory, National Cancer Institute, I-70126 Bari, Italy. Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 1317 EP - 1323 VL - 21 IS - 6 SN - 1019-6439, 1019-6439 KW - Thymidine Phosphorylase KW - EC 2.4.2.4 KW - Index Medicus KW - Neoplasm Invasiveness KW - Cell Count KW - Humans KW - Middle Aged KW - Up-Regulation KW - Male KW - Immunoenzyme Techniques KW - Female KW - Carcinoma, Squamous Cell -- enzymology KW - Mouth Neoplasms -- blood supply KW - Mast Cells -- pathology KW - Carcinoma, Squamous Cell -- pathology KW - Carcinoma, Squamous Cell -- blood supply KW - Mouth Neoplasms -- enzymology KW - Neovascularization, Pathologic -- enzymology KW - Mouth Neoplasms -- pathology KW - Thymidine Phosphorylase -- metabolism KW - Neovascularization, Pathologic -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72685647?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+oncology&rft.atitle=Microvessel+density%2C+mast+cell+density+and+thymidine+phosphorylase+expression+in+oral+squamous+carcinoma.&rft.au=Ranieri%2C+Girolamo%3BLabriola%2C+Angela%3BAchille%2C+Gaetano%3BFlorio%2C+Gerolmina%3BZito%2C+Alfredo+Francesco%3BGrammatica%2C+Luciano%3BParadiso%2C+Angelo&rft.aulast=Ranieri&rft.aufirst=Girolamo&rft.date=2002-12-01&rft.volume=21&rft.issue=6&rft.spage=1317&rft.isbn=&rft.btitle=&rft.title=International+journal+of+oncology&rft.issn=10196439&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-14 N1 - Date created - 2002-11-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The DNA damaging agent etoposide activates a cell survival pathway involving alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors and mitogen-activated protein kinases in hippocampal neurons. AN - 72673984; 12424735 AB - Etoposide, an inhibitor of topoisomerase II that induces DNA damage and can trigger cell death, is used as a chemotherapeutic agent. Because chemotherapies can result in neurological complications and because DNA damage in neurons is implicated in the pathogenesis of several neurodegenerative disorders, we studied the effects of etoposide on cultured hippocampal neurons. We found that etoposide induces neuronal apoptosis and that, prior to the cell death commitment point, there is an increase in whole-cell alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)-induced current but no change in N-methyl-D-aspartate (NMDA)-induced current. Associated with the increase in AMPA-induced current was an increase in the amounts of AMPA receptor subunits GluR1 and GluR4, whereas levels of the NMDA receptor subunit NR1 were unaffected by etoposide. AMPA receptor activation can result in excitotoxic cell death but can also activate signaling pathways that promote synaptic plasticity and cell survival. We found that etoposide increases the activation of p42 and p44 mitogen-activated protein (MAP) kinases, and that activation of the MAP kinases by etoposide requires AMPA receptor activation. Pharmacological blockade of AMPA receptors and p42/p44 MAP kinases, but not of NMDA receptors, exacerbated etoposide-induced cell death. These findings suggest that, although etoposide is neurotoxic, it also activates a cell survival pathway involving AMPA receptor-mediated activation of p42/p44 MAP kinases. Agents that selectively inhibit the cell life or death pathways triggered by DNA damage may prove useful in the settings of cancer and neurodegenerative disorders, respectively. Published 2002 Wiley-Liss, Inc. JF - Journal of neuroscience research AU - Lu, Chengbiao AU - Fu, Weiming AU - Zhao, Daohong AU - Mattson, Mark P AD - Laboratory of Neurosciences, National Institute on Aging/NIH, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2002/12/01/ PY - 2002 DA - 2002 Dec 01 SP - 671 EP - 679 VL - 70 IS - 5 SN - 0360-4012, 0360-4012 KW - Nucleic Acid Synthesis Inhibitors KW - 0 KW - Receptors, AMPA KW - Etoposide KW - 6PLQ3CP4P3 KW - Mitogen-Activated Protein Kinase 1 KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinase 3 KW - Mitogen-Activated Protein Kinases KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Patch-Clamp Techniques KW - Cell Survival -- drug effects KW - Mitogen-Activated Protein Kinases -- metabolism KW - DNA Damage KW - Hippocampus -- cytology KW - Apoptosis -- drug effects KW - Membrane Potentials -- drug effects KW - Nucleic Acid Synthesis Inhibitors -- pharmacology KW - Etoposide -- pharmacology KW - Neurons -- drug effects KW - Mitogen-Activated Protein Kinase 1 -- metabolism KW - Neurons -- cytology KW - Neurons -- physiology KW - Receptors, AMPA -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72673984?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=The+DNA+damaging+agent+etoposide+activates+a+cell+survival+pathway+involving+alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate+receptors+and+mitogen-activated+protein+kinases+in+hippocampal+neurons.&rft.au=Lu%2C+Chengbiao%3BFu%2C+Weiming%3BZhao%2C+Daohong%3BMattson%2C+Mark+P&rft.aulast=Lu&rft.aufirst=Chengbiao&rft.date=2002-12-01&rft.volume=70&rft.issue=5&rft.spage=671&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 - 2003-01-23 N1 - Date created - 2002-11-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phosphorylation of Tyr342 in the linker region of Syk is critical for Fc epsilon RI signaling in mast cells. AN - 72643449; 12417718 AB - The linker region of Syk and ZAP70 tyrosine kinases plays an important role in regulating their function. There are three conserved tyrosines in this linker region; Tyr317 of Syk and its equivalent residue in ZAP70 were previously shown to negatively regulate the function of Syk and ZAP70. Here we studied the roles of the other two tyrosines, Tyr342 and Tyr346 of Syk, in Fc epsilon RI-mediated signaling. Antigen stimulation resulted in Tyr342 phosphorylation in mast cells. Syk with Y342F mutation failed to reconstitute Fc epsilon RI-initiated histamine release. In the Syk Y342F-expressing cells there was dramatically impaired receptor-induced phosphorylation of multiple signaling molecules, including LAT, SLP-76, phospholipase C-gamma2, but not Vav. Compared to wild-type Syk, Y342F Syk had decreased binding to phosphorylated immunoreceptor tyrosine-based activation motifs and reduced kinase activity. Surprisingly, mutation of Tyr346 had much less effect on Fc epsilon RI-dependent mast cell degranulation. An anti-Syk-phospho-346 tyrosine antibody indicated that antigen stimulation induced only a very minor increase in the phosphorylation of this tyrosine. Therefore, Tyr342, but not Tyr346, is critical for regulating Syk in mast cells and the function of these tyrosines in immune receptor signaling appears to be different from what has been previously reported for the equivalent residues of ZAP70. JF - Molecular and cellular biology AU - Zhang, Juan AU - Berenstein, Elsa AU - Siraganian, Reuben P AD - Receptors and Signal Transduction Section, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA. lzhang@didr.nidcr.nih.gov Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 8144 EP - 8154 VL - 22 IS - 23 SN - 0270-7306, 0270-7306 KW - Antibodies KW - 0 KW - Cell Cycle Proteins KW - Enzyme Precursors KW - Intracellular Signaling Peptides and Proteins KW - Ionophores KW - Isoenzymes KW - Peptides KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-vav KW - Receptors, IgE KW - VAV1 protein, human KW - Vav1 protein, rat KW - Immunoglobulin E KW - 37341-29-0 KW - Calcimycin KW - 37H9VM9WZL KW - Tyrosine KW - 42HK56048U KW - protein kinase D KW - EC 2.7.10.- KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - SYK protein, human KW - EC 2.7.10.2 KW - Syk Kinase KW - Syk protein, rat KW - Protein Kinase C KW - EC 2.7.11.13 KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Type C Phospholipases KW - EC 3.1.4.- KW - Phospholipase C gamma KW - EC 3.1.4.3 KW - rac1 GTP-Binding Protein KW - EC 3.6.5.2 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Cell Degranulation KW - Ionophores -- metabolism KW - Humans KW - Proto-Oncogene Proteins -- metabolism KW - Calcimycin -- metabolism KW - Isoenzymes -- metabolism KW - Type C Phospholipases -- metabolism KW - Immunoglobulin E -- metabolism KW - Calcium -- metabolism KW - Mutagenesis, Site-Directed KW - Rats KW - Phosphorylation KW - rac1 GTP-Binding Protein -- metabolism KW - Mitogen-Activated Protein Kinases -- metabolism KW - Peptides -- immunology KW - Peptides -- metabolism KW - Protein Binding KW - Protein Kinase C -- metabolism KW - Antibodies -- metabolism KW - Peptides -- genetics KW - Cell Line KW - Mast Cells -- immunology KW - Enzyme Precursors -- metabolism KW - Enzyme Precursors -- chemistry KW - Mast Cells -- enzymology KW - Protein-Tyrosine Kinases -- metabolism KW - Mast Cells -- cytology KW - Signal Transduction -- physiology KW - Enzyme Precursors -- immunology KW - Protein-Tyrosine Kinases -- immunology KW - Receptors, IgE -- metabolism KW - Protein-Tyrosine Kinases -- genetics KW - Receptors, IgE -- immunology KW - Mast Cells -- physiology KW - Tyrosine -- metabolism KW - Enzyme Precursors -- genetics KW - Protein-Tyrosine Kinases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72643449?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Phosphorylation+of+Tyr342+in+the+linker+region+of+Syk+is+critical+for+Fc+epsilon+RI+signaling+in+mast+cells.&rft.au=Zhang%2C+Juan%3BBerenstein%2C+Elsa%3BSiraganian%2C+Reuben+P&rft.aulast=Zhang&rft.aufirst=Juan&rft.date=2002-12-01&rft.volume=22&rft.issue=23&rft.spage=8144&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 - 2003-01-02 N1 - Date created - 2002-11-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Exp Med. 1995 Dec 1;182(6):1815-23 [7500027] J Biol Chem. 1994 Sep 2;269(35):22427-32 [8071371] Mol Cell Biol. 1996 Apr;16(4):1471-8 [8657120] J Biol Chem. 1996 Jun 28;271(26):15753-61 [8663155] J Biol Chem. 1994 Nov 25;269(47):29520-9 [7961936] Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11251-5 [7526394] Mol Cell Biol. 1995 Jan;15(1):272-81 [7528327] J Biol Chem. 1995 May 5;270(18):10498-502 [7537732] J Biol Chem. 1995 May 12;270(19):11590-4 [7538118] EMBO J. 1995 Jun 1;14(11):2499-508 [7781602] Semin Immunol. 1995 Feb;7(1):29-35 [7612892] J Biol Chem. 1995 Aug 11;270(32):18730-3 [7642520] Nature. 1995 Sep 7;377(6544):32-8 [7659156] J Biol Chem. 1999 Mar 5;274(10):6285-94 [10037717] EMBO J. 1999 Apr 1;18(7):1832-44 [10202147] J Biol Chem. 1999 May 14;274(20):14229-37 [10318843] J Clin Invest. 1999 Jun;103(12):1737-43 [10377180] J Immunol. 1999 Sep 1;163(5):2508-16 [10452987] J Biol Chem. 1999 Sep 10;274(37):26543-9 [10473617] J Exp Med. 1996 Jul 1;184(1):71-9 [8691151] Mol Cell Biol. 1996 Sep;16(9):5026-35 [8756661] J Biol Chem. 1996 Sep 13;271(37):22782-90 [8798454] J Biol Chem. 1996 Oct 11;271(41):25308-15 [8810294] EMBO J. 1996 Nov 15;15(22):6251-61 [8947048] Immunity. 1996 Dec;5(6):591-604 [8986718] J Biol Chem. 1997 Jan 10;272(2):1363-7 [8995445] Oncogene. 1996 Dec 19;13(12):2595-605 [9000133] J Immunol. 1997 Feb 15;158(4):1650-9 [9029101] Biochim Biophys Acta. 1997 Feb 4;1355(2):177-90 [9042338] Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1919-24 [9050880] J Exp Med. 1997 May 19;185(10):1877-82 [9151714] Eur J Biochem. 1997 Jun 1;246(2):447-51 [9208937] Mol Cell Biol. 1998 Mar;18(3):1388-99 [9488454] J Biol Chem. 1998 Apr 10;273(15):8867-74 [9535867] J Immunol. 1998 Jan 1;160(1):145-54 [9551966] EMBO J. 1998 May 1;17(9):2584-95 [9564041] J Biol Chem. 1998 Jun 19;273(25):15445-52 [9624129] J Mol Biol. 1998 Aug 21;281(3):523-37 [9698567] J Immunol. 1998 Oct 15;161(8):4366-74 [9780214] J Immunol. 1998 Nov 15;161(10):5276-83 [9820500] J Biol Chem. 1998 Nov 27;273(48):31932-8 [9822663] J Biol Chem. 1998 Dec 25;273(52):35273-81 [9857068] Mol Cell Biol. 1999 Jan;19(1):948-56 [9858619] J Immunol. 2000 Jan 1;164(1):338-44 [10605028] Immunity. 2000 May;12(5):525-35 [10843385] EMBO J. 2000 Jun 15;19(12):2935-45 [10856238] J Exp Med. 2000 Jun 19;191(12):2075-82 [10859332] Immunity. 2000 Jul;13(1):25-35 [10933392] J Biol Chem. 2000 Nov 10;275(45):35442-7 [10931839] Mol Cell Biol. 2001 Jun;21(11):3763-74 [11340169] J Exp Med. 2001 Aug 20;194(4):491-505 [11514605] J Exp Med. 2001 Aug 20;194(4):507-18 [11514606] J Immunol. 2002 May 1;168(9):4682-91 [11971018] Immunol Today. 1989 Nov;10(11):381-6 [2692594] Proc Natl Acad Sci U S A. 1990 Jul;87(14):5327-30 [1695377] Immunol Today. 1990 Dec;11(12):458-64 [2073318] Nature. 1992 Jan 2;355(6355):78-80 [1370575] Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9107-11 [1409610] Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9524-8 [1384056] Immunol Today. 1993 May;14(5):222-6 [8517921] J Biol Chem. 1993 Nov 5;268(31):23318-24 [7693687] J Exp Med. 1994 May 1;179(5):1725-9 [7513017] J Biol Chem. 1994 Jun 17;269(24):16902-8 [7515887] Mol Cell Biol. 1996 Apr;16(4):1305-15 [8657103] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential partitioning of maternal fatty acid and phospholipid in neonate mosquito larvae. AN - 72639073; 12409488 AB - In animals, lipids are a source of energy, cell membrane components, signaling pathway modulators and emulsifying agents. In egg-laying animals, maternal yolk lipids, imported into the egg before laying, are metabolized or distributed in the developing embryo to serve these functions. Studies with birds, reptiles and insects have described lipid metabolism in adults and in eggs, but no studies have addressed how lipids are distributed in developing organs in the embryo. Here we show that maternal fatty acid and phospholipids segregate differently in tissues of newly hatched mosquito larvae. In the mother, both lipids are colocalized in yolk granules of developing oocytes and distributed evenly. In neonate larvae, however, the maternal fatty acid is stored along the side of the body, especially at the base of the body hair, and in the thorax, where the muscles are located, probably to provide energy for the rapid movements needed to find food immediately after birth. Most maternal phospholipids, however, are concentrated in the motile intestinal gastric caeca, from which they are released into the gut lumen where they may act as emulsifiers, probably to facilitate assimilation of the food the neonate ingests. Similar phenomena were observed in both Anopheles gambiae and Aedes aegypti mosquitoes, suggesting that such differential segregation of lipids is common to both insects. This study may lead to improved delivery of larvicidal agents and to efficient killing of newly hatched mosquito larvae as a control strategy for mosquito-borne diseases. JF - The Journal of experimental biology AU - Atella, Georgia C AU - Shahabuddin, Mohammed AD - Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 3623 EP - 3630 VL - 205 SN - 0022-0949, 0022-0949 KW - Excipients KW - 0 KW - Fatty Acids KW - Insecticides KW - Phosphatidylcholines KW - Phosphatidylethanolamines KW - Phospholipids KW - Index Medicus KW - Animals KW - Oocytes -- metabolism KW - Phosphatidylcholines -- analysis KW - Intestines -- chemistry KW - Phosphatidylethanolamines -- analysis KW - Lipid Metabolism KW - Female KW - Anopheles -- growth & development KW - Anopheles -- embryology KW - Phospholipids -- analysis KW - Larva -- chemistry KW - Fatty Acids -- analysis KW - Aedes -- growth & development KW - Aedes -- embryology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72639073?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+biology&rft.atitle=Differential+partitioning+of+maternal+fatty+acid+and+phospholipid+in+neonate+mosquito+larvae.&rft.au=Atella%2C+Georgia+C%3BShahabuddin%2C+Mohammed&rft.aulast=Atella&rft.aufirst=Georgia&rft.date=2002-12-01&rft.volume=205&rft.issue=&rft.spage=3623&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+experimental+biology&rft.issn=00220949&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-06 N1 - Date created - 2002-10-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Endogenous cannabinoid, anandamide, acts as a noncompetitive inhibitor on 5-HT3 receptor-mediated responses in Xenopus oocytes. AN - 72127076; 12325042 AB - The cloned 5-HT3 receptor from NCB-20 neuroblastoma cells was expressed in Xenopus oocytes and the effect of the endogenous cannabinoid ligand, anandamide, was investigated on the function of this receptor. The oocytes expressing the cloned 5-HT3 receptors were voltage-clamped at -70 mV. Anandamide, at the concentration range of 0.1-100 microM, reversibly inhibited 1 microM 5-HT induced currents. The inhibition of 5-HT induced currents by anandamide was concentration-dependent with an EC50 of 3.7 microM and slope value of 0.94. This inhibitory effect was not dependent on the membrane potential and anandamide did not have an effect on the reversal potential of 5-HT-induced currents. In the presence of 10 microM anandamide, the maximum 5-HT-induced response was also inhibited and the respective EC50 values were 3.4 microM and 3.1 microM in the absence and presence of anandamide, indicating that anandamide acts as a noncompetitive antagonist on 5-HT3 receptors. CB1 receptor antagonist SR-141716A (1 microM) and pertussis toxin (5 microg/ml) did not cause a significant change on the inhibition of 5-HT responses by anandamide. The effect of anandamide was not changed by preincubating the oocytes with 0.2 mM 8-Br-cAMP, a membrane-permeable analog of cAMP, or Sp-cAMPS (0.1 mM), a membrane-permeable protein kinase A activator. These results suggest that the effect of anandamide is independent of the activation of cAMP pathway and not mediated by the activation of PTX sensitive G-proteins. In conclusion, we demonstrated that the endogenous cannabinoid anandamide inhibits the function of 5-HT3 receptors expressed in Xenopus oocytes in a cannabinoid-receptor independent and noncompetitive manner. JF - Synapse (New York, N.Y.) AU - Oz, Murat AU - Zhang, Li AU - Morales, Marisela AD - National Institute on Drug Abuse, Cellular Neurobiology Section, Baltimore, Maryland 21224, USA. moz@intra.nida.nih.gov Y1 - 2002/12/01/ PY - 2002 DA - 2002 Dec 01 SP - 150 EP - 156 VL - 46 IS - 3 SN - 0887-4476, 0887-4476 KW - Arachidonic Acids KW - 0 KW - Biguanides KW - Cannabinoids KW - Chelating Agents KW - Endocannabinoids KW - Enzyme Inhibitors KW - Indazoles KW - Piperidines KW - Polyunsaturated Alkamides KW - Pyrazoles KW - RNA, Complementary KW - Receptors, Serotonin, 5-HT3 KW - Serotonin 5-HT3 Receptor Antagonists KW - Serotonin Receptor Agonists KW - Thionucleotides KW - Tropanes KW - LY 278584 KW - 119193-37-2 KW - 8-Bromo Cyclic Adenosine Monophosphate KW - 23583-48-4 KW - adenosine-3',5'-cyclic phosphorothioate KW - 23645-17-2 KW - Serotonin KW - 333DO1RDJY KW - 1-(3-chlorophenyl)biguanide KW - 48144-44-1 KW - Egtazic Acid KW - 526U7A2651 KW - 2-methyl-5-HT KW - 78263-90-8 KW - Cyclic AMP KW - E0399OZS9N KW - Pertussis Toxin KW - EC 2.4.2.31 KW - 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid KW - K22DDW77C0 KW - rimonabant KW - RML78EN3XE KW - anandamide KW - UR5G69TJKH KW - Index Medicus KW - Serotonin Receptor Agonists -- pharmacology KW - Animals KW - Analysis of Variance KW - Drug Interactions KW - Cannabinoids -- metabolism KW - Dose-Response Relationship, Drug KW - Indazoles -- pharmacology KW - Pertussis Toxin -- pharmacology KW - Biguanides -- pharmacology KW - 8-Bromo Cyclic Adenosine Monophosphate -- pharmacology KW - Piperidines -- pharmacology KW - Xenopus laevis KW - Thionucleotides -- pharmacology KW - Pyrazoles -- pharmacology KW - Chelating Agents -- pharmacology KW - Tropanes -- pharmacology KW - Electrophysiology -- methods KW - RNA, Complementary -- biosynthesis KW - Enzyme Inhibitors -- pharmacology KW - Membrane Potentials -- drug effects KW - Female KW - Serotonin -- pharmacology KW - Egtazic Acid -- analogs & derivatives KW - Oocytes -- metabolism KW - Receptors, Serotonin, 5-HT3 -- metabolism KW - Cyclic AMP -- pharmacology KW - Oocytes -- drug effects KW - Cyclic AMP -- analogs & derivatives KW - Serotonin -- analogs & derivatives KW - Receptors, Serotonin, 5-HT3 -- genetics KW - Arachidonic Acids -- metabolism KW - Egtazic Acid -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72127076?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Endogenous+cannabinoid%2C+anandamide%2C+acts+as+a+noncompetitive+inhibitor+on+5-HT3+receptor-mediated+responses+in+Xenopus+oocytes.&rft.au=Oz%2C+Murat%3BZhang%2C+Li%3BMorales%2C+Marisela&rft.aulast=Oz&rft.aufirst=Murat&rft.date=2002-12-01&rft.volume=46&rft.issue=3&rft.spage=150&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 - 2004-06-21 N1 - Date created - 2002-09-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemical mixtures research: significance and future perspectives. AN - 21251360; 11704146 JF - Environmental Health Perspectives AU - Suk, William A AU - Olden, Kenneth AU - Yang, Raymond S H AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. Y1 - 2002/12// PY - 2002 DA - Dec 2002 SP - 891 EP - 892 PB - US Government Printing Office, Superintendent of Documents, P.O. Box 371954 Pittsburgh PA 15250-7954 USA VL - 110 IS - Suppl 6 SN - 0091-6765, 0091-6765 KW - Environment Abstracts KW - Chemistry KW - Environmental health KW - ENA 07:General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21251360?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aenvabstractsmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=Chemical+mixtures+research%3A+significance+and+future+perspectives.&rft.au=Suk%2C+William+A%3BOlden%2C+Kenneth%3BYang%2C+Raymond+S+H&rft.aulast=Suk&rft.aufirst=William&rft.date=2002-12-01&rft.volume=110&rft.issue=Suppl+6&rft.spage=891&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 - Chemistry; Environmental health ER - TY - JOUR T1 - H-ras oncogene mutations during development of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced rat mammary gland cancer AN - 19224552; 5806576 AB - Laser capture microdissection, polymerase chain reaction-restriction fragment length polymorphism analysis, and DNA sequencing was used to detect H-ras codon 12 and 13 mutations during the stages of mammary gland cancer development in rats exposed to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a carcinogen found in cooked meat. Ten oral doses of PhIP (75 mg/kg, p.o., once per day) were administered to adolescent female Sprague-Dawley rats and mammary glands examined histologically for intraductal proliferations (IDPs), carcinoma in situ and carcinomas 7-14 weeks later. Mammary gland epithelial cells from normal tissue and distinct lesions were collected from glass slides and analyzed for mutations. H-ras codon 12/13 mutations were detected in 73%, 75%, 100%, and 100% of normal mammary glands, IDPs, carcinoma in situ, and carcinoma, respectively, after PhIP treatment. The spectrum of activating mutations included G super(35) to A or C base substitution mutations in codon 12, and G super(37) to T or A base substitution mutations in codon 13. The spectrum of H-ras mutations was similar among normal mammary gland from PhIP treated rats, preneoplastic lesions, and carcinomas. Furthermore, the spectrum of mutations was consistent with the involvement of PhIP-guanine adduct formation. The results support the notion that mutations in H-ras codons 12 and 13 are largely PhIP-DNA adduct-induced and involved in the initiation and development of mammary gland cancer in rats exposed to PhIP. JF - Carcinogenesis AU - Yu, M AU - Snyderwine, E G AD - Chemical Carcinogenesis Section, Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA Y1 - 2002/12// PY - 2002 DA - Dec 2002 SP - 2123 EP - 2128 VL - 23 IS - 12 SN - 0143-3334, 0143-3334 KW - rats KW - H-ras gene KW - Toxicology Abstracts; Genetics Abstracts; Oncogenes & Growth Factors Abstracts KW - Epithelial cells KW - Amino acid substitution KW - Food KW - Carcinogens KW - 2-Amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - DNA sequencing KW - Mammary gland KW - Adducts KW - Adolescence KW - Polymorphism KW - Tumors KW - Cancer KW - Carcinoma KW - Meat KW - Lasers KW - Females KW - Mutation KW - Hras gene KW - X 24120:Food, additives & contaminants KW - B 26130:Ras and Ras related oncogenes (Rho/Rac/Ral) KW - G 07470:Cytogenetics & general UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19224552?accountid=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=H-ras+oncogene+mutations+during+development+of+2-amino-1-methyl-6-phenylimidazo%5B4%2C5-b%5Dpyridine+%28PhIP%29-induced+rat+mammary+gland+cancer&rft.au=Yu%2C+M%3BSnyderwine%2C+E+G&rft.aulast=Yu&rft.aufirst=M&rft.date=2002-12-01&rft.volume=23&rft.issue=12&rft.spage=2123&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 - Carcinogens; Food; Meat; 2-Amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; Mammary gland; Tumors; Cancer; Mutation; Carcinoma; DNA sequencing; Epithelial cells; Amino acid substitution; Lasers; Hras gene; Adolescence; Adducts; Polymorphism; Females ER - TY - JOUR T1 - Increased risk of early-stage breast cancer related to consumption of sweet foods among women less than age 45 in the United States AN - 18769452; 5645712 AB - To evaluate the associations of dietary macronutrients, food groups, and eating patterns with risk of breast cancer in a population-based case-control study. In this study among women 20-44 years of age, 568 cases with breast cancer and 1451 population-based controls were included. They completed a detailed in-person interview, a self-administered food-frequency questionnaire and were measured for anthropometric indices. Logistic regression was used to estimate odds ratios (OR) and their 95% confidence intervals (CI) of breast cancer, adjusted for age, study site, race, education, alcohol consumption, oral contraceptive usage, smoking status, and body mass index. There was no association between breast cancer risk and intake of calories, macronutrients, or types of fat. Risk of breast cancer was unrelated to intakes of a variety of food groups, including red meats, dairy, high-fat snacks and desserts, or foods high in animal fat. Increased risk was observed for high intake of a food group composed of sweet items, particularly sodas and desserts. Risk increased linearly with percent of calories from sweets and frequency of sweets intake. Consumption of sweets 9.8 or more times per week compared with <2.8 times per week was associated with an adjusted OR of 1.32 (95% CI = 1.0 1.8). This association did not appear to be due to the high-fat foods or carbonated beverages that comprised the food group. Compared with women reporting one or two meals and snacks per day, reduced risks were noted for women reporting six or more (OR = 0.69, 95% CI = 0.4-1.1). These data suggest a modest relationship between intakes of sweet items with risk of in-situ and localized breast cancer in young women. This relation is consistent with the hypothesized link of high insulin exposure and risk of breast cancer. There was some suggestion that women who ate many times during the day were at reduced risk of disease, which is also consistent with an insulin-related mechanism. JF - Cancer Causes & Control AU - Potischman, N AU - Coates, R J AU - Swanson, CA AU - Carroll, R J AU - Daling, J R AU - Brogan AU - Gammon, MD AU - Midthune, D AU - Curtin, J AU - Brinton, LA AD - Applied Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, 6130 Executive Blvd. MSC 7344, Bethesda, MD 20892-7344, USA, potischn@mail.nih.gov Y1 - 2002/12// PY - 2002 DA - Dec 2002 SP - 937 EP - 946 VL - 13 IS - 10 SN - 0957-5243, 0957-5243 KW - body mass KW - contraceptives KW - Health & Safety Science Abstracts KW - H 11000:Diseases/Injuries/Trauma UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18769452?accountid=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=Cancer+Causes+%26+Control&rft.atitle=Increased+risk+of+early-stage+breast+cancer+related+to+consumption+of+sweet+foods+among+women+less+than+age+45+in+the+United+States&rft.au=Potischman%2C+N%3BCoates%2C+R+J%3BSwanson%2C+CA%3BCarroll%2C+R+J%3BDaling%2C+J+R%3BBrogan%3BGammon%2C+MD%3BMidthune%2C+D%3BCurtin%2C+J%3BBrinton%2C+LA&rft.aulast=Potischman&rft.aufirst=N&rft.date=2002-12-01&rft.volume=13&rft.issue=10&rft.spage=937&rft.isbn=&rft.btitle=&rft.title=Cancer+Causes+%26+Control&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Dermal exposure assessment in occupational epidemiologic research AN - 18740854; 5616277 AB - Recognition of the importance of skin exposure in industrial settings has steadily increased over the last few decades. Unfortunately, the growing attention to dermal exposure in industrial hygiene has often not been reflected in the field of occupational epidemiology. An extensive literature survey was conducted to identify dermal exposure assessment methods that have been applied in epidemiologic studies. Subsequently, methodologies are postulated that could be applied to epidemiologic research. Attention is given to intensity, frequency, and duration of exposure, the exposed surface area, and personal, temporal and spatial variability in dermal exposure and uptake. It is anticipated that, in the near future, dermal exposure assessment in epidemiologic research will be based generally on expert judgment and to some degree on process-specific exposure models. Field studies collecting quantitative dermal exposure data and statistical modeling to identify exposure determinants will, however, be imperative if progress is to be made in the field of dermal exposure assessment for epidemiologic purposes. JF - Scandinavian Journal of Work, Environment & Health AU - Vermeulen, R AU - Stewart, P AU - Kromhout, H AD - Occupational Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, Rockville, MD 20892, USA, vermeulr@mail.nih.gov Y1 - 2002/12// PY - 2002 DA - Dec 2002 SP - 371 EP - 385 VL - 28 IS - 6 SN - 0355-3140, 0355-3140 KW - Health & Safety Science Abstracts KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18740854?accountid=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=Scandinavian+Journal+of+Work%2C+Environment+%26+Health&rft.atitle=Dermal+exposure+assessment+in+occupational+epidemiologic+research&rft.au=Vermeulen%2C+R%3BStewart%2C+P%3BKromhout%2C+H&rft.aulast=Vermeulen&rft.aufirst=R&rft.date=2002-12-01&rft.volume=28&rft.issue=6&rft.spage=371&rft.isbn=&rft.btitle=&rft.title=Scandinavian+Journal+of+Work%2C+Environment+%26+Health&rft.issn=03553140&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Protective Role of Kupffer Cells in Acetaminophen-Induced Hepatic Injury in Mice AN - 18716865; 5594940 AB - Hepatic injury induced by various toxic agents, including acetaminophen (APAP), has been attributed, in part, to the production of proinflammatory cytokines and other mediators by resident Kupffer cells within the liver. However, recent evidence from our laboratory has demonstrated that hepato-protective factors, such as interleukin (IL)-10 and cyclooxygenase-derived mediators, are also upregulated in response to hepatic damage to help protect against exacerbated injury, and Kupffer cells have been suggested to be a source of these modulatory factors. In other models, Kupffer cells also serve important regulatory functions in pathophysiological states of the liver. Therefore, we reevaluated the role of Kupffer cells in a murine model of APAP-induced liver injury using liposome-entrapped clodronate (liposome/clodronate) as an effective Kupffer cell-depleting agent. We show that in contrast to pretreatment of mice with a widely used macrophage inhibitor, gadolinium chloride, which did not deplete Kupffer cells but moderately protected against APAP-induced hepatotoxicity as reported previously, the intravenous injection of liposome/clodronate caused nearly complete elimination of Kupffer cells and significantly increased susceptibility to APAP-induced liver injury as compared with mice pretreated with empty liposomes. This increased susceptibility was apparently unrelated to the metabolism of APAP since liposome/clodronate pretreatment did not alter APAP-protein adduct levels. Instead, Kupffer cell depletion by liposome/clodronate led to significant decreases in the levels of hepatic mRNA expression of several hepato-regulatory cytokines and mediators, including IL-6, IL-10, IL-18 binding protein and complement 1q, suggesting that Kupffer cells are a significant source for production of these mediators in this model. Our findings indicate that, in addition to their protoxicant activities, Kupffer cells can also have an important protective function in the liver through the production of a variety of modulatory factors which may counteract inflammatory responses and/or stimulate liver regeneration. JF - Chemical Research in Toxicology AU - Ju, C AU - Reilly, T P AU - Bourdi, M AU - Radonovich, M F AU - Brady, J N AU - George, J W AU - Pohl, L R AD - Molecular and Cellular Toxicology Section, Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 1504 EP - 1513 PB - American Chemical Society, P.O. Box 182426 Columbus OH 43218-2426 USA, [mailto:service@acs.org] VL - 15 IS - 12 SN - 0893-228X, 0893-228X KW - mice KW - protection KW - Toxicology Abstracts KW - Kupffer cells KW - Liver KW - Analgesics KW - Acetaminophen KW - X 24112:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18716865?accountid=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=Protective+Role+of+Kupffer+Cells+in+Acetaminophen-Induced+Hepatic+Injury+in+Mice&rft.au=Ju%2C+C%3BReilly%2C+T+P%3BBourdi%2C+M%3BRadonovich%2C+M+F%3BBrady%2C+J+N%3BGeorge%2C+J+W%3BPohl%2C+L+R&rft.aulast=Ju&rft.aufirst=C&rft.date=2002-12-01&rft.volume=15&rft.issue=12&rft.spage=1504&rft.isbn=&rft.btitle=&rft.title=Chemical+Research+in+Toxicology&rft.issn=0893228X&rft_id=info:doi/10.1021%2Ftx0255976 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2016-05-27 N1 - SubjectsTermNotLitGenreText - Kupffer cells; Liver; Analgesics; Acetaminophen DO - http://dx.doi.org/10.1021/tx0255976 ER - TY - JOUR T1 - Site-Specific Mutagenesis in Escherichia coli by N super(2)-Deoxyguanosine Adducts Derived from the Highly Carcinogenic Fjord-Region Benzo[c]phenanthrene 3,4-Diol 1,2-Epoxides AN - 18713584; 5594953 AB - Although there have been numerous studies of site-specific mutagenesis by dGuo adducts of benzo[a]pyrene diol epoxides (B[a]P DEs), the present study represents the first example of site-specific mutagenesis by dGuo adducts of the highly carcinogenic benzo[c]phenanthrene 3,4-diol 1,2-epoxides (B[c]Ph DEs). The eight adducts that would result from cis- and trans-opening at C-1 of four optically active isomers of B[c]Ph DEs by the N super(2)-amino group of dGuo were incorporated into 5'-TTCGAATCCTTCCCCC (context III) and 5'-GGGGTTCCCGAGCGGC (context IV) at the underlined site. These modified oligonucleotides along with unmodified controls were ligated into single-stranded M13mp7L2, which were then used to transfect SOS-induced Escherichia coli. Upon replication of the lesions in each of the two sequence contexts, mutational analysis of the progeny was performed by differential hybridization. For the 16 adducts, the mutation frequencies varied over 2 orders of magnitude with a reasonably even distribution (0.4-1% for three adducts, 1-2% for six adducts, 3-7.4% for five adducts, and one adduct each at 11 and 39%). For all but this last adduct, the mutation frequency for a given B[c]Ph DE adduct was less than for its B[a]P analogue with the same stereochemistry in the same sequence. For the vectors containing adducts with S configuration at the site of attachment of the hydrocarbon to the dGuo base, the main base substitution was G arrow right T followed by G arrow right A. In contrast, for the vectors containing adducts with R configuration, the main base substitution was G arrow right A. The most notable observation in the present study is the low frequency of mutations induced by the B[c]Ph DE-dGuo adducts relative to their B[a]P counterparts. A possible structural basis for this difference is proposed. JF - Chemical Research in Toxicology AU - Ramos, LA AU - Ponten, I AU - Dipple, A AU - Kumar, S AU - Yagi, H AU - Sayer, J M AU - Kroth, H AU - Kalena, G AU - Jerina, D M AD - Laboratory of Comparative Carcinogenesis (Formerly Chemistry of Carcinogenesis Laboratory), National Cancer Institute-Frederick, Frederick, Maryland 21702, USA Y1 - 2002/12// PY - 2002 DA - December 2002 SP - 1619 EP - 1626 PB - American Chemical Society, P.O. Box 182426 Columbus OH 43218-2426 USA, [mailto:service@acs.org] VL - 15 IS - 12 SN - 0893-228X, 0893-228X KW - benzo(a)phenanthrene 3,4-diol-1,2-epoxides KW - Toxicology Abstracts KW - DNA adducts KW - Escherichia coli KW - Guanosine KW - Mutagenesis KW - X 24190:Polycyclic hydrocarbons UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18713584?accountid=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=Site-Specific+Mutagenesis+in+Escherichia+coli+by+N+super%282%29-Deoxyguanosine+Adducts+Derived+from+the+Highly+Carcinogenic+Fjord-Region+Benzo%5Bc%5Dphenanthrene+3%2C4-Diol+1%2C2-Epoxides&rft.au=Ramos%2C+LA%3BPonten%2C+I%3BDipple%2C+A%3BKumar%2C+S%3BYagi%2C+H%3BSayer%2C+J+M%3BKroth%2C+H%3BKalena%2C+G%3BJerina%2C+D+M&rft.aulast=Ramos&rft.aufirst=LA&rft.date=2002-12-01&rft.volume=15&rft.issue=12&rft.spage=1619&rft.isbn=&rft.btitle=&rft.title=Chemical+Research+in+Toxicology&rft.issn=0893228X&rft_id=info:doi/10.1021%2Ftx020073r LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2016-05-27 N1 - SubjectsTermNotLitGenreText - DNA adducts; Guanosine; Mutagenesis; Escherichia coli DO - http://dx.doi.org/10.1021/tx020073r ER - TY - JOUR T1 - Long-term abstinent alcoholics have a blunted blood glucose response to 2-deoxy-D-glucose AN - 18679618; 5575191 AB - Aims: In this study we explored the relationship between alcohol and carbohydrate consumption in long-term abstinent alcoholics. Methods: We employed an established laboratory paradigm which allowed us to stimulate and measure dietary intake. 2-Deoxy-D-glucose (2-DG) is a glucose analogue that causes an intracellular energy deprivation resulting in exaggerated food consumption and a compensatory metabolic response to raise blood glucose. Using a double-blind design, we gave an infusion of 25 mg/kg 2-DG or placebo to 20 long-term abstinent alcoholics and 19 healthy volunteers. Results: There were no baseline differences in any dietary, behavioural or biochemical variables. As expected, 2-DG increased caloric consumption and blood glucose levels in a time-dependent fashion. There were no differences in food consumption between the alcoholics and the healthy volunteers following the 2-DG stimulus. However, the alcoholic group had a significantly blunted response in blood glucose. Conclusions: The origin of this atypical blood glucose response may antedate the onset of alcoholism, or it may be secondary to alcohol-related damage that persists beyond 6 months. Previous accounts of increased sweet consumption in alcoholics were not substantiated, although they may be present in the peri-withdrawal period. JF - Alcohol and Alcoholism AU - Umhau, J C AU - Petrulis, S G AU - Diaz, R AU - Riggs, P A AU - Biddison, J R AU - George, D T AD - National Institute on Alcohol Abuse and Alcoholism, Laboratory of Clinical Studies, 10 Center Drive MSC-1610, Building 10, Room 6S-240, Bethesda, MD 20892-1610, USA Y1 - 2002/12// PY - 2002 DA - Dec 2002 SP - 586 EP - 590 VL - 37 IS - 6 SN - 0735-0414, 0735-0414 KW - 2-deoxy-D-glucose KW - abstinence KW - man KW - Toxicology Abstracts KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18679618?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcohol+and+Alcoholism&rft.atitle=Long-term+abstinent+alcoholics+have+a+blunted+blood+glucose+response+to+2-deoxy-D-glucose&rft.au=Umhau%2C+J+C%3BPetrulis%2C+S+G%3BDiaz%2C+R%3BRiggs%2C+P+A%3BBiddison%2C+J+R%3BGeorge%2C+D+T&rft.aulast=Umhau&rft.aufirst=J&rft.date=2002-12-01&rft.volume=37&rft.issue=6&rft.spage=586&rft.isbn=&rft.btitle=&rft.title=Alcohol+and+Alcoholism&rft.issn=07350414&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 Gln223Arg polymorphism of the leptin receptor in Pima Indians: influence on energy expenditure, physical activity and lipid metabolism AN - 18668481; 5560467 AB - Leptin regulates body weight by its receptor-mediated anorectic, thermogenic and antisteatotic effects. Recently, lower leptin binding to the soluble form of the leptin receptor (LEPR) was shown in carriers of the Arg223-encoding allele of the Gln223Arg polymorphism of the LEPR. To investigate whether this variant influences energy metabolism and adiposity in Pima Indians, we genotyped non-diabetic Pima Indians in whom we had measured body composition and 24 h energy expenditure (24 h EE), physical activity level (PAL) and 24 h respiratory quotient (24 h RQ) in a respiratory chamber (n = 268) and who had undergone percutaneous fat biopsies from the periumbilical region (n = 184). Genotype was not associated with percent body fat (P > 0.39), but was associated with 24 h EE, PAL and mean subcutaneous abdominal adipocyte size (SAAS all P < 0.05). Homozygotes for the Arg223-encoding allele had lower 24 h EE (P = 0.04) and PAL (P = 0.007), but larger SAAS (P = 0.01) than Gln homozygotes. These findings are consistent with a role of the Gln223Arg polymorphism in reducing peripheral and central leptin binding to the LEPR in humans. However, these effects do not seem to have a major impact on adiposity in this population. JF - International Journal of Obesity AU - Stefan, N AU - Vozarova, B AU - Del Parigi, A AU - Ossowski, V AU - Thompson, D B AU - Hanson, R L AU - Ravussin, E AU - Tataranni, P A AD - Clinical Diabetes and Nutrition Section, National Institutes of Health, 4212 N 16th Street, Rm 5-41, Phoenix, AZ 85016, USA, nstefan@mail.nih.gov Y1 - 2002/12// PY - 2002 DA - Dec 2002 SP - 1629 EP - 1632 VL - 26 IS - 12 SN - 0307-0565, 0307-0565 KW - Physical Education Index KW - PE 090:Sports Medicine & Exercise Sport Science UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18668481?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Obesity&rft.atitle=The+Gln223Arg+polymorphism+of+the+leptin+receptor+in+Pima+Indians%3A+influence+on+energy+expenditure%2C+physical+activity+and+lipid+metabolism&rft.au=Stefan%2C+N%3BVozarova%2C+B%3BDel+Parigi%2C+A%3BOssowski%2C+V%3BThompson%2C+D+B%3BHanson%2C+R+L%3BRavussin%2C+E%3BTataranni%2C+P+A&rft.aulast=Stefan&rft.aufirst=N&rft.date=2002-12-01&rft.volume=26&rft.issue=12&rft.spage=1629&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Obesity&rft.issn=03070565&rft_id=info:doi/10.1038%2Fsj.ijo.0802161 LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1038/sj.ijo.0802161 ER - TY - JOUR T1 - Dual-specific T cells combine proliferation and antitumor activity AN - 18668333; 5566509 AB - An effective immune response against cancer requires the activation and expansion of specific T cells. Tumor antigens, however, are generally poor immunogens. To achieve expansion of tumor-reactive T cells in vivo, we used a strategy of generating dual-specific T cells that could respond to a powerful immunogen while also possessing tumor reactivity. We generated dual-specific T cells by genetic modification of alloreactive T cells with a chimeric receptor recognizing folate-binding protein, an ovarian cancer-associated antigen. Mouse dual-specific T cells responded in vitro to both allogeneic antigen and tumor cells expressing folate-binding protein, and expanded in number in vivo in response to immunization with allogeneic cells. Most importantly, the combination of dual-specific T cells and immunization had an antitumor effect in vivo. We also generated human dual-specific T cells and characterized the dual-specific nature of individual clones. Assigning the tasks of expansion and tumor reactivity to different receptors within the same lymphocyte may help to overcome the problem of poor immunogenicity of tumor antigens. JF - Nature Biotechnology AU - Kershaw, M H AU - Westwood, JA AU - Hwu, P AD - Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA, Patrick_Hwu@nih.gov Y1 - 2002/12// PY - 2002 DA - Dec 2002 SP - 1221 EP - 1227 VL - 20 IS - 12 SN - 1087-0156, 1087-0156 KW - folate-binding protein KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - W3 33170:Cellular based KW - F 06756:Function KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18668333?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Biotechnology&rft.atitle=Dual-specific+T+cells+combine+proliferation+and+antitumor+activity&rft.au=Kershaw%2C+M+H%3BWestwood%2C+JA%3BHwu%2C+P&rft.aulast=Kershaw&rft.aufirst=M&rft.date=2002-12-01&rft.volume=20&rft.issue=12&rft.spage=1221&rft.isbn=&rft.btitle=&rft.title=Nature+Biotechnology&rft.issn=10870156&rft_id=info:doi/10.1038%2Fnbt756 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1038/nbt756 ER - TY - JOUR T1 - Genome-Wide Analysis of Synonymous Single Nucleotide Polymorphisms in Mycobacterium tuberculosis Complex Organisms: Resolution of Genetic Relationships Among Closely Related Microbial Strains AN - 18667390; 5557348 AB - Several human pathogens (e.g., Bacillus anthracis, Yersinia pestis, Bordetella pertussis, Plasmodium falciparum, and Mycobacterium tuberculosis) have very restricted unselected allelic variation in structural genes, which hinders study of the genetic relationships among strains and strain-trait correlations. To address this problem in a representative pathogen, 432 M. tuberculosis complex strains from global sources were genotyped on the basis of 230 synonymous (silent) single nucleotide polymorphisms (sSNPs) identified by comparison of four genome sequences. Eight major clusters of related genotypes were identified in M. tuberculosis sensu stricto, including a single cluster representing organisms responsible for several large outbreaks in the United States and Asia. All M. tuberculosis sensu stricto isolates of previously unknown phylogenetic position could be rapidly and unambiguously assigned to one of the eight major clusters, thus providing a facile strategy for identifying organisms that are clonally related by descent. Common clones of M. tuberculosis sensu stricto and M. bovis are distinct, deeply branching genotypic complexes whose extant members did not emerge directly from one another in the recent past. sSNP genotyping rapidly delineates relationships among closely related strains of pathogenic microbes and allows construction of genetic frameworks for examining the distribution of biomedically relevant traits such as virulence, transmissibility, and host range. JF - Genetics AU - Gutacker, M M AU - Smoot, J C AU - Migliaccio, CAL AU - Ricklefs, S M AU - Hua, S AU - Cousins, D V AU - Graviss, E A AU - Shashkina, E AU - Kreiswirth, B N AU - Musser, J M AD - Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 S. 4th St., Hamilton, MT 59840, jmusser@niaid.nih.gov Y1 - 2002/12// PY - 2002 DA - Dec 2002 SP - 1533 EP - 1543 VL - 162 IS - 4 SN - 0016-6731, 0016-6731 KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - G 07320:Bacterial genetics KW - J 02710:Identification, taxonomy and typing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18667390?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genetics&rft.atitle=Genome-Wide+Analysis+of+Synonymous+Single+Nucleotide+Polymorphisms+in+Mycobacterium+tuberculosis+Complex+Organisms%3A+Resolution+of+Genetic+Relationships+Among+Closely+Related+Microbial+Strains&rft.au=Gutacker%2C+M+M%3BSmoot%2C+J+C%3BMigliaccio%2C+CAL%3BRicklefs%2C+S+M%3BHua%2C+S%3BCousins%2C+D+V%3BGraviss%2C+E+A%3BShashkina%2C+E%3BKreiswirth%2C+B+N%3BMusser%2C+J+M&rft.aulast=Gutacker&rft.aufirst=M&rft.date=2002-12-01&rft.volume=162&rft.issue=4&rft.spage=1533&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Corresponding author: James M. Musser N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Lithium induces brain-derived neurotrophic factor and activates TrkB in rodent cortical neurons: An essential step for neuroprotection against glutamate excitotoxicity AN - 18643558; 5543037 AB - Mechanisms underlying the therapeutic effects of lithium for bipolar mood disorder remain poorly understood. Recent studies demonstrate that lithium has neuroprotective actions against a variety of insults in vitro and in vivo. This study was undertaken to investigate the role of the brain-derived neurotrophic factor (BDNF)/TrkB signaling pathway in mediating neuroprotection of lithium against glutamate excitotoxicity in cortical neurons. Pretreatment with either lithium or BDNF protected rat cerebral cortical neurons from glutamate excitotoxicity. The duration of treatment required to elicit maximal neuroprotection by BDNF (1 day) was much shorter than that by lithium (6 days). K252a, an inhibitor of Trk tyrosine kinases, and a BDNF neutralizing antibody suppressed the neuroprotective effect of lithium. Treatment of cortical neurons with lithium increased the cellular BDNF content in 3 days and the phosphorylation of TrkB at Tyr490 in 5 days, suggesting that long-term lithium administration enhances BDNF expression/secretion, leading to the activation of TrkB receptor. Lithium failed to protect against glutamate excitotoxicity in cortical neurons derived from homozygous and heterozygous BDNF knockout mice, although lithium fully protected cortical neurons prepared from wild type mice littermates. Taken together, these data suggest that the BDNF/TrkB pathway plays an essential role in mediating the neuroprotective effect of lithium. JF - Neuropharmacology AU - Hashimoto, R AU - Takei, N AU - Shimazu, K AU - Christ, L AU - Lu, B AU - Chuang, D-M AD - Molecular Neurobiology Section, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, 20892-1363, USA, chuang@helix.nih.gov Y1 - 2002/12// PY - 2002 DA - Dec 2002 SP - 1173 EP - 1179 VL - 43 IS - 7 SN - 0028-3908, 0028-3908 KW - rats KW - CSA Neurosciences Abstracts; Toxicology Abstracts KW - X 24117:Biochemistry KW - N3 11072:Neurotropic factors and their receptors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18643558?accountid=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=Neuropharmacology&rft.atitle=Lithium+induces+brain-derived+neurotrophic+factor+and+activates+TrkB+in+rodent+cortical+neurons%3A+An+essential+step+for+neuroprotection+against+glutamate+excitotoxicity&rft.au=Hashimoto%2C+R%3BTakei%2C+N%3BShimazu%2C+K%3BChrist%2C+L%3BLu%2C+B%3BChuang%2C+D-M&rft.aulast=Hashimoto&rft.aufirst=R&rft.date=2002-12-01&rft.volume=43&rft.issue=7&rft.spage=1173&rft.isbn=&rft.btitle=&rft.title=Neuropharmacology&rft.issn=00283908&rft_id=info:doi/10.1016%2FS0028-3908%2802%2900217-4 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0028-3908(02)00217-4 ER - TY - JOUR T1 - Assessing the consistency of a biomedical terminology through lexical knowledge AN - 18643386; 5547515 AB - Objective: We investigate the use of adjectival modification as a way of assessing the systematic use of linguistic phenomena to represent similar lexical or semantic features in the constituent terms of a vocabulary. Methods: Terms consisting of one or more adjectival modifiers followed by a head noun are selected from disease and procedure terms in SNOMED. Frequently co-occurring adjectival modifiers are systematically combined with the contexts (i.e. terms minus modifier) of each modifier. The existence of these combinations is checked in both SNOMED and the entire UMLS Metathesaurus; the term corresponding to the context alone is similarly checked. Relationships among terms sharing a context and between each of these terms and their context are studied. Results: Four pairs of modifiers were studied: (acute, chronic), (unilateral, bilateral), (primary, secondary), and (acquired, congenital). The numbers of contexts studied for each pair ranged from 73 to 974. The percentage of contexts associated with both modifiers ranged from 5 to 50% in SNOMED and from 10 to 60% in UMLS. The presence of the context term varied from 31 to 64% in SNOMED and from 43 to 79% in UMLS. Finally, 172 occurrences (9%) of synonymy between a modified term and the context term were found in SNOMED. One hundred and forty-five such occurrences (8%) were found in the entire Metathesaurus. JF - International Journal of Medical Informatics AU - Bodenreider, O AU - Burgun, A AU - Rindflesch, T C AD - US National Library of Medicine, 8600 Rockville Pike, MS 43, Bethesda, MD 20894, USA, olivier@nlm.nih.gov Y1 - 2002/12// PY - 2002 DA - Dec 2002 SP - 85 EP - 95 VL - 67 IS - 1-3 SN - 1386-5056, 1386-5056 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W4 140:Bioinformatics & Computers in Health & Medicine KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18643386?accountid=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+Medical+Informatics&rft.atitle=Assessing+the+consistency+of+a+biomedical+terminology+through+lexical+knowledge&rft.au=Bodenreider%2C+O%3BBurgun%2C+A%3BRindflesch%2C+T+C&rft.aulast=Bodenreider&rft.aufirst=O&rft.date=2002-12-01&rft.volume=67&rft.issue=1-3&rft.spage=85&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Medical+Informatics&rft.issn=13865056&rft_id=info:doi/10.1016%2FS1386-5056%2802%2900051-5 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S1386-5056(02)00051-5 ER - TY - JOUR T1 - Increased high-affinity nicotinic receptor-binding in rats exposed to lead during development AN - 18636814; 5546006 AB - Receptor autoradiography and membrane radioligand-binding assays were used to determine the expression of nicotinic cholinergic receptors in the brains of weanling rats exposed to low-levels of lead (Pb) during development. Nicotinic receptors were identified with the frog toxin epibatidine (EB) that binds with high affinity to a variety of receptors containing alpha and beta subunits. Rat pups were exposed to Pb from their mothers given 750-ppm Pb in the diet beginning on gestational day 0 through postnatal day (PN) 21. Blood Pb levels ranged from 36.5 to 46.5 mu g/dl in the PN21 pups, and this exposure did not alter their body weight when compared to control rats. Several brain regions identified by autoradiographic studies as having significant binding of EB were dissected from control and Pb-treated pups and used in saturation-binding experiments with membrane preparations to determine the affinity constant (Kd) and maximal-binding capacity (Bmax) of [ super(3)H]EB. Results indicate that the Bmax of [ super(3)H]EB was increased in several brain regions in Pb-treated rat pups, without a significant effect on Kd estimates. [ super(3)H]EB-binding to membranes from untreated rats was not affected by in vitro exposure to 20- mu M Pb, indicating that the effect of Pb on [ super(3)H]EB-binding in vivo was not likely due to direct influence of free Pb remaining in the tissue at the time of assay. The data therefore suggest that expression of nicotinic receptors that bind [ super(3)H]EB were increased by developmental exposure to Pb. Several possible mechanisms for these effects and the potential toxicological significance are discussed. JF - Neurotoxicology and Teratology AU - Jett, DA AU - Beckles, R A AU - Navoa, R V AU - McLemore, G L AD - Department of Environmental Health Science, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA, dj140o@nih.gov Y1 - 2002/12// PY - 2002 DA - Dec 2002 SP - 805 EP - 811 PB - Elsevier Science Inc. VL - 24 IS - 6 SN - 0892-0362, 0892-0362 KW - binding KW - development KW - rats KW - CSA Neurosciences Abstracts; Toxicology Abstracts KW - N3 11104:Mammals (except primates) KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18636814?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurotoxicology+and+Teratology&rft.atitle=Increased+high-affinity+nicotinic+receptor-binding+in+rats+exposed+to+lead+during+development&rft.au=Jett%2C+DA%3BBeckles%2C+R+A%3BNavoa%2C+R+V%3BMcLemore%2C+G+L&rft.aulast=Jett&rft.aufirst=DA&rft.date=2002-12-01&rft.volume=24&rft.issue=6&rft.spage=805&rft.isbn=&rft.btitle=&rft.title=Neurotoxicology+and+Teratology&rft.issn=08920362&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 - Impact of Physiologically Based Pharmacokinetic Modeling on Benchmark Dose Calculations for TCDD-Induced Biochemical Responses AN - 18633261; 5539624 AB - In risk assessment, noncancer risk is currently estimated using a no observed adverse effect level (NOAEL) from an experimental dose-response study, divided by uncertainty factors, to estimate a presumably safe level of human exposure. A benchmark dose approach, in which an effective dose (ED) resulting in a specified percentage increase over background for effects is estimated by empirical modeling, has been proposed as a replacement for the NOAEL methodology. The aim of this analysis is to compare methods for estimation of body burden resulting in a 1 or 10% maximum increase over background (BB sub(01) or BB sub(10)) for biochemical responses following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in female Sprague-Dawley rats. In one method, an ED resulting in a prespecified increase in response over background was estimated using average daily doses and an empirical Hill model. The ED was then converted to an equivalent body burden by a simple kinetic model assuming steady-state conditions, half-life of TCDD in the rat, and 100% absorption of TCDD. Alternatively, a mechanistic physiologically based pharmacokinetic (PBPK) model of TCDD in the rat was used to predict body burdens for administered doses. These PBPK-modeled body burdens were then used directly by the Hill model to calculate a BB sub(01) or BB sub(10). In general, the body burden values derived from EDs were within five-fold of BB sub(01) or BB sub(10) calculated from the PBPK model. BB sub(01) and BB sub(10) values from both methods were within two orders of magnitude of current human general population exposure to all dioxin-like compounds. [copy ] 2002 Elsevier Science (USA). JF - Regulatory Toxicology and Pharmacology AU - Kim, AH AU - Kohn, M C AU - Portier, C J AU - Walker, N J AD - Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709 Y1 - 2002/12// PY - 2002 DA - Dec 2002 SP - 287 EP - 296 PB - Academic Press VL - 36 IS - 3 SN - 0273-2300, 0273-2300 KW - biochemistry KW - rats KW - Toxicology Abstracts KW - X 24155:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18633261?accountid=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=Impact+of+Physiologically+Based+Pharmacokinetic+Modeling+on+Benchmark+Dose+Calculations+for+TCDD-Induced+Biochemical+Responses&rft.au=Kim%2C+AH%3BKohn%2C+M+C%3BPortier%2C+C+J%3BWalker%2C+N+J&rft.aulast=Kim&rft.aufirst=AH&rft.date=2002-12-01&rft.volume=36&rft.issue=3&rft.spage=287&rft.isbn=&rft.btitle=&rft.title=Regulatory+Toxicology+and+Pharmacology&rft.issn=02732300&rft_id=info:doi/10.1006%2Frtph.2002.1590 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1006/rtph.2002.1590 ER - TY - JOUR T1 - HapScope: a software system for automated and visual analysis of functionally annotated haplotypes AN - 18622076; 5533167 AB - We have developed a software analysis package, HapScope, which includes a comprehensive analysis pipeline and a sophisticated visualization tool for analyzing functionally annotated haplotypes. The HapScope analysis pipeline supports: (i) computational haplotype construction with an expectation-maximization or Bayesian statistical algorithm; (ii) SNP classification by protein coding change, homology to model organisms or putative regulatory regions; and (iii) minimum SNP subset selection by either a Brute Force Algorithm or a Greedy Partition Algorithm. The HapScope viewer displays genomic structure with haplotype information in an integrated environment, providing eight alternative views for assessing genetic and functional correlation. It has a user-friendly interface for: (i) haplotype block visualization; (ii) SNP subset selection; (iii) haplotype consolidation with subset SNP markers; (iv) incorporation of both experimentally determined haplotypes and computational results; and (v) data export for additional analysis. Comparison of haplotypes constructed by the statistical algorithms with those determined experimentally shows variation in haplotype prediction accuracies in genomic regions with different levels of nucleotide diversity. We have applied HapScope in analyzing haplotypes for candidate genes and genomic regions with extensive SNP and genotype data. We envision that the systematic approach of integrating functional genomic analysis with population haplotypes, supported by HapScope, will greatly facilitate current genetic disease research. JF - Nucleic Acids Research AU - Zhang, J AU - Rowe, W L AU - Struewing, J P AU - Buetow, KH AD - Laboratory of Population Genetics, National Cancer Institute/National Institutes of Health, 8424 Helgerman Court, Room 101, MSC 8302, Bethesda, MD 20892-8302, USA, jinghuiz@mail.nih.gov Y1 - 2002/12/01/ PY - 2002 DA - 2002 Dec 01 SP - 5213 EP - 5221 VL - 30 IS - 23 SN - 0305-1048, 0305-1048 KW - HapScope KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Genetics Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - N 14100:Reviews KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics KW - G 07300:Theoretical genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18622076?accountid=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=HapScope%3A+a+software+system+for+automated+and+visual+analysis+of+functionally+annotated+haplotypes&rft.au=Zhang%2C+J%3BRowe%2C+W+L%3BStruewing%2C+J+P%3BBuetow%2C+KH&rft.aulast=Zhang&rft.aufirst=J&rft.date=2002-12-01&rft.volume=30&rft.issue=23&rft.spage=5213&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Translesion replication of benzo[a]pyrene and benzo[c]phenanthrene diol epoxide adducts of deoxyadenosine and deoxyguanosine by human DNA polymerase AN - 18618914; 5533175 AB - Human DNA polymerase iota (pol iota ) is a Y-family polymerase whose cellular function is presently unknown. Here, we report on the ability of pol iota to bypass various stereoisomers of benzo[a]pyrene (BaP) diol epoxide (DE) and benzo[c]phenanthrene (BcPh) DE adducts at deoxyadenosine (dA) or deoxyguanosine (dG) bases in four different template sequence contexts in vitro. We find that the BaP DE dG adducts pose a strong block to pol iota ?-dependent replication and result in a high frequency of base misincorporations. In contrast, misincorporations opposite BaP DE and BcPh DE dA adducts generally occurred with a frequency ranging between 2 x 10 super(-3) and 6 x 10 super(-4). Although dTMP was inserted efficiently opposite all dA adducts, further extension was relatively poor, with one exception (a cis opened adduct derived from BcPh DE) where up to 58% extension past the lesion was observed. Interestingly, another human Y-family polymerase, pol iota , was able to extend dTMP inserted opposite a BaP DE dA adduct. We suggest that pol iota might therefore participate in the error-free bypass of DE-adducted dA in vivo by predominantly incorporating dTMP opposite the damaged base. In many cases, elongation would, however, require the participation of another polymerase more specialized in extension, such as pol iota . JF - Nucleic Acids Research AU - Frank, E G AU - Sayer, J M AU - Kroth, H AU - Ohashi, E AU - Ohmori, H AU - Jerina, D M AU - Woodgate, R AD - Section on DNA Replication, Repair, and Mutagenesis, Building 6, Room 1A13, National Institute of Child Health and Human Development, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892-2725 USA, woodgate@helix.nih.gov Y1 - 2002/12/01/ PY - 2002 DA - 2002 Dec 01 SP - 5284 EP - 5292 VL - 30 IS - 23 SN - 0305-1048, 0305-1048 KW - deoxyadenosine KW - deoxyguanosine KW - man KW - Biochemistry Abstracts 2: Nucleic Acids; Toxicology Abstracts 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/18618914?accountid=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=Nucleic+Acids+Research&rft.atitle=Translesion+replication+of+benzo%5Ba%5Dpyrene+and+benzo%5Bc%5Dphenanthrene+diol+epoxide+adducts+of+deoxyadenosine+and+deoxyguanosine+by+human+DNA+polymerase&rft.au=Frank%2C+E+G%3BSayer%2C+J+M%3BKroth%2C+H%3BOhashi%2C+E%3BOhmori%2C+H%3BJerina%2C+D+M%3BWoodgate%2C+R&rft.aulast=Frank&rft.aufirst=E&rft.date=2002-12-01&rft.volume=30&rft.issue=23&rft.spage=5284&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Mycobacterium avium Infection and Modulation of Human Macrophage Gene Expression AN - 18610463; 5490365 AB - Mycobacterium avium is a facultative intracellular pathogen cleared rapidly via intact host defense mechanisms. In the absence of adequate T cell function, as occurs in HIV-1-induced immunodeficiency, M. avium becomes an opportunistic infection with uncontrolled replication and reinfection of macrophage hosts. How M. avium infects, survives, and replicates in macrophages without signaling an effective microbicidal counterattack is unresolved. To address whether M. avium signals the expression of molecules, which influence mycobacterial survival or clearance, human monocyte-derived macrophage cultures were exposed to M. avium. Within minutes, M. avium, or its cell wall lipoarabinomannan, binds to the adherent macrophages and induces a spectrum of gene expression. In this innate response, the most abundant genes detected within 2 h by cDNA expression array involved proinflammatory chemokines, cytokines including TNF-[alpha] and IL-1, and adhesion molecules. Associated with this rapid initial up-regulation of recruitment and amplification molecules was enhanced expression of transcription factors and signaling molecules. By 24 h, this proinflammatory response subsided, and after 4 days, when some bacteria were being degraded, others escaped destruction to replicate within intracellular vacuoles. Under these conditions, inducible NO synthase was not up-regulated and increased transferrin receptors may facilitate iron-dependent mycobacterial growth. Sustained adhesion molecule and chemokine expression along with the formation of multinucleated giant cells appeared consistent with in vivo events. Thus, in the absence of T lymphocyte mediators, macrophages are insufficiently microbicidal and provide a nonhostile environment in which mycobacteria not only survive and replicate, but continue to promote recruitment of new macrophages to perpetuate the infection. JF - Journal of Immunology AU - Greenwell-Wild, T AU - Vazquez, N AU - Sim, D AU - Schito, M AU - Chatterjee, D AU - Orenstein, J M AU - Wahl, S M AD - Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research and Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD Y1 - 2002/12/01/ PY - 2002 DA - 2002 Dec 01 SP - 6286 EP - 6297 VL - 169 IS - 11 SN - 0022-1767, 0022-1767 KW - lipoarabinomannan KW - lipoarabinomannans KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - F 06801:Bacteria KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18610463?accountid=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=Mycobacterium+avium+Infection+and+Modulation+of+Human+Macrophage+Gene+Expression&rft.au=Greenwell-Wild%2C+T%3BVazquez%2C+N%3BSim%2C+D%3BSchito%2C+M%3BChatterjee%2C+D%3BOrenstein%2C+J+M%3BWahl%2C+S+M&rft.aulast=Greenwell-Wild&rft.aufirst=T&rft.date=2002-12-01&rft.volume=169&rft.issue=11&rft.spage=6286&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunology&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Marked Enhancement of the Antigen-Specific Immune Response by Combining Plasmid DNA-Based Immunization with a Schiff Base-Forming Drug AN - 18604683; 5490621 AB - Although plasmid DNA (pDNA)-based immunization has proven efficacy, the level of immune responses that is achieved by this route of vaccination is often lower than that induced by traditional vaccines, especially for primates and humans. We report here a simple and potent method to enhance pDNA-based vaccination by using two different plasmids encoding viral or bacterial antigens. This method is based on coadministration of low concentrations of a recently described immunopotentiating, Schiff base-forming drug called tucaresol which has led to significant augmentation of antigen-specific humoral and cellular immune responses. Our data suggest that enhancement of the immune response with tucaresol might provide a powerful tool for the further development of pDNA-based immunization for humans. JF - Infection and Immunity AU - Charo, J AU - Sundbaeck, M AU - Wasserman, K AU - Ciupitu, A T AU - Mirzai, B AU - Van der Zee, R AU - Kiessling, R AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Building 10, Room 2B42, 10 Center Dr., Bethesda, MD 20892, Jehad_Charo@nih.gov Y1 - 2002/12// PY - 2002 DA - Dec 2002 SP - 6652 EP - 6657 VL - 70 IS - 12 SN - 0019-9567, 0019-9567 KW - Primates KW - Schiff base KW - Schiff base-forming drugs KW - man KW - tucaresol KW - Biochemistry Abstracts 2: Nucleic Acids; Immunology Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology KW - F 06807:Active immunization KW - A 01116:Bacteria KW - N 14800:Immunological aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18604683?accountid=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=Infection+and+Immunity&rft.atitle=Marked+Enhancement+of+the+Antigen-Specific+Immune+Response+by+Combining+Plasmid+DNA-Based+Immunization+with+a+Schiff+Base-Forming+Drug&rft.au=Charo%2C+J%3BSundbaeck%2C+M%3BWasserman%2C+K%3BCiupitu%2C+A+T%3BMirzai%2C+B%3BVan+der+Zee%2C+R%3BKiessling%2C+R&rft.aulast=Charo&rft.aufirst=J&rft.date=2002-12-01&rft.volume=70&rft.issue=12&rft.spage=6652&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.70.12.6652-6657.2002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/IAI.70.12.6652-6657.2002 ER - TY - JOUR T1 - Transgenic Mice Expressing Human Interleukin-10 in the Antigen-Presenting Cell Compartment Show Increased Susceptibility to Infection with Mycobacterium avium Associated with Decreased Macrophage Effector Function and Apoptosis AN - 18537536; 5490585 AB - Interleukin-10 (IL-10) is thought to play an important role in the regulation of microbial immunity. While T-cell-derived IL-10 has been shown to suppress cell-mediated immunity, there has been debate as to whether antigen presenting cell (APC)-derived cytokine can perform the same function in vivo. To assess the influence of APC-produced IL-10 on host resistance to mycobacterial infection, transgenic mice expressing human IL-10 under the control of the major histocompatibility complex class II promoter (hu10Tg) were infected with Mycobacterium avium, and bacterial burdens and immune responses were compared with those observed in wild-type (wt) animals. Hu10Tg mice harbored substantially higher numbers of M. avium and succumbed 16 to 18 weeks postinfection. The granulomas in infected hu10Tg mice showed marked increases in both acid-fast bacilli and host macrophages. In addition, these animals displayed a dramatic increase in hepatic fibrosis. The increased susceptibility of the hu10Tg mice to M. avium infection is independent of T-cell-produced endogenous murine IL-10, since bacterial burdens in mice derived by crossing hu10Tg mice with murine IL-10-deficient mice were not significantly different from those in hu10Tg mice. Importantly, gamma interferon (IFN-[gamma]) responses were not decreased in the infected transgenic animals from those in wt animals, suggesting the normal development of Th1 effector cells. In contrast, mycobacterium-induced macrophage apoptosis as well as production of TNF, nitric oxide, and IL-12p40 were strongly inhibited in hu10Tg mice. Together, these data indicate that APC-derived IL-10 can exert a major inhibitory effect on control of mycobacterial infection by a mechanism involving the suppression of macrophage effector function and apoptosis. JF - Infection and Immunity AU - Feng, C G AU - Kullberg, M C AU - Jankovic, D AU - Cheever, A W AU - Caspar, P AU - Coffman, R L AU - Sher, A AD - Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 50 Room 6148, 50 South Dr., Bethesda, MD 20892-8003, cfeng@niaid.nih.gov Y1 - 2002/12// PY - 2002 DA - Dec 2002 SP - 6672 EP - 6679 VL - 70 IS - 12 SN - 0019-9567, 0019-9567 KW - mice KW - transgenic mice KW - Genetics Abstracts; Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - F 067735:Interleukins KW - F 06801:Bacteria KW - G 07397:Rodentia (mice) KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18537536?accountid=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=Transgenic+Mice+Expressing+Human+Interleukin-10+in+the+Antigen-Presenting+Cell+Compartment+Show+Increased+Susceptibility+to+Infection+with+Mycobacterium+avium+Associated+with+Decreased+Macrophage+Effector+Function+and+Apoptosis&rft.au=Feng%2C+C+G%3BKullberg%2C+M+C%3BJankovic%2C+D%3BCheever%2C+A+W%3BCaspar%2C+P%3BCoffman%2C+R+L%3BSher%2C+A&rft.aulast=Feng&rft.aufirst=C&rft.date=2002-12-01&rft.volume=70&rft.issue=12&rft.spage=6672&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.70.12.6672-6679.2002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/IAI.70.12.6672-6679.2002 ER - TY - JOUR T1 - Opsonophagocytosis-Inhibiting Mac Protein of Group A Streptococcus: Identification and Characteristics of Two Genetic Complexes AN - 18534968; 5490564 AB - Recently, it was reported that a streptococcal Mac protein (designated Mac sub(5005)) made by serotype M1 group A Streptococcus (GAS) is a homologue of human CD11b that inhibits opsonophagocytosis and killing of GAS by human polymorphonuclear leukocytes (PMNs) (B. Lei, F. R. DeLeo, N. P. Hoe, M. R. Graham, S. M. Mackie, R. L. Cole, M. Liu, H. R. Hill, D. E. Low, M. J. Federle, J. R. Scott, and J. M. Musser, Nat. Med. 7:1298-1305, 2001). To study mac variation and expression of the Mac protein, the gene in 67 GAS strains representing 36 distinct M protein serotypes was sequenced. Two distinct genetic complexes were identified, and they were designated complex I and complex II. Mac variants in each of the two complexes were closely related, but complex I and complex II variants differed on average at 50.66 plus or minus 5.8 amino acid residues, most of which were located in the middle one-third of the protein. Complex I Mac variants have greater homology with CD11b than complex II variants. GAS strains belonging to serotypes M1 and M3, the most abundant M protein serotypes responsible for human infections in many case series, have complex I Mac variants. The mac gene was cloned from representative strains assigned to complexes I and II, and the Mac proteins were purified to apparent homogeneity. Both Mac variants had immunoglobulin G (IgG)-endopeptidase activity. In contrast to Mac sub(5005) (complex I), Mac sub(8345) (complex II) underwent autooxidation of its cysteine residues, resulting in the loss of IgG-endopeptidase activity. A Mac sub(5005) Cys94Ala site-specific mutant protein was unable to cleave IgG but retained the ability to inhibit IgG-mediated phagocytosis by human PMNs. Thus, the IgG-endopeptidase activity was not essential for the key biological function of Mac sub(5005). Although Mac sub(5005) and Mac sub(8345) each have an Arg-Gly-Asp (RGD) motif, the proteins differed in their interactions with human integrins [alpha] sub(v) beta sub(3) and [alpha] sub(IIb) beta sub(3). Binding of Mac sub(5005) to integrins [alpha] sub(v) beta sub(3) and [alpha] sub(IIb) beta sub(3) was mediated primarily by the RGD motif in Mac sub(5005), whereas binding of Mac sub(8345) involved the RGD motif and a region in the middle one-third of the molecule whose sequence is different in Mac sub(8345) and Mac sub(5005). Taken together, the data add to the emerging theme in GAS pathogenesis that allelic variation in virulence genes contributes to fundamental differences in host-pathogen interactions among strains. JF - Infection and Immunity AU - Lei, B AU - DeLeo AU - Reid, S D AU - Voyich, J M AU - Magoun, L AU - Liu, M AU - Braughton, K R AU - Ricklefs, S AU - Hoe, N P AU - Cole, R L AU - Leong, J M AU - Musser, J M AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 S. 4th Street, Hamilton, MT 59840, jmusser@niaid.nih.gov Y1 - 2002/12// PY - 2002 DA - Dec 2002 SP - 6880 EP - 6890 VL - 70 IS - 12 SN - 0019-9567, 0019-9567 KW - Mac protein KW - cloning KW - integrins KW - mac gene KW - nucleotide sequence KW - streptococci KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18534968?accountid=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=Opsonophagocytosis-Inhibiting+Mac+Protein+of+Group+A+Streptococcus%3A+Identification+and+Characteristics+of+Two+Genetic+Complexes&rft.au=Lei%2C+B%3BDeLeo%3BReid%2C+S+D%3BVoyich%2C+J+M%3BMagoun%2C+L%3BLiu%2C+M%3BBraughton%2C+K+R%3BRicklefs%2C+S%3BHoe%2C+N+P%3BCole%2C+R+L%3BLeong%2C+J+M%3BMusser%2C+J+M&rft.aulast=Lei&rft.aufirst=B&rft.date=2002-12-01&rft.volume=70&rft.issue=12&rft.spage=6880&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.70.12.6880-6890.2002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/IAI.70.12.6880-6890.2002 ER - TY - JOUR T1 - Characterization of Two Novel Pyrogenic Toxin Superantigens Made by an Acute Rheumatic Fever Clone of Streptococcus pyogenes Associated with Multiple Disease Outbreaks AN - 18534446; 5490574 AB - The pathogenesis of acute rheumatic fever (ARF) is poorly understood. We identified two contiguous bacteriophage genes, designated speL and speM, encoding novel inferred superantigens in the genome sequence of an ARF strain of serotype M18 group A streptococcus (GAS). speL and speM were located at the same genomic site in 33 serotype M18 isolates, and no nucleotide sequence diversity was observed in the 33 strains analyzed. Furthermore, the genes were absent in 13 non-M18 strains tested. These data indicate a recent acquisition event by a distinct clone of serotype M18 GAS. speL and speM were transcribed in vitro and upregulated in the exponential phase of growth. Purified SpeL and SpeM were pyrogenic and mitogenic for rabbit splenocytes and human peripheral blood mononuclear cells in picogram amounts. SpeL preferentially expanded human T cells expressing T-cell receptors V beta 1, V beta 5.1, and V beta 23, and SpeM had specificity for V beta 1 and V beta 23 subsets, indicating that both proteins had superantigen activity. SpeL was lethal in two animal models of streptococcal toxic shock, and SpeM was lethal in one model. Serologic studies indicated that ARF patients were exposed to serotype M18 GAS, SpeL, and SpeM. The data demonstrate that SpeL and SpeM are pyrogenic toxin superantigens and suggest that they may participate in the host-pathogen interactions in some ARF patients. JF - Infection and Immunity AU - Smoot, L M AU - McCormick, J K AU - Smoot, J C AU - Hoe, N P AU - Strickland, I AU - Cole, R L AU - Barbian, K D AU - Earhart, CA AU - Ohlendorf, D H AU - Veasy, L G AU - Hill, H R AU - Leung, DYM AU - Schlievert, P M AU - Musser, J M AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th St., Hamilton, MT 59840, jmusser@niaid.nih.gov Y1 - 2002/12// PY - 2002 DA - Dec 2002 SP - 7095 EP - 7104 VL - 70 IS - 12 SN - 0019-9567, 0019-9567 KW - SpeL protein KW - SpeM protein KW - speL gene KW - speM gene KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - G 07320:Bacterial genetics KW - J 02823:In vitro and in vivo effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18534446?accountid=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=Characterization+of+Two+Novel+Pyrogenic+Toxin+Superantigens+Made+by+an+Acute+Rheumatic+Fever+Clone+of+Streptococcus+pyogenes+Associated+with+Multiple+Disease+Outbreaks&rft.au=Smoot%2C+L+M%3BMcCormick%2C+J+K%3BSmoot%2C+J+C%3BHoe%2C+N+P%3BStrickland%2C+I%3BCole%2C+R+L%3BBarbian%2C+K+D%3BEarhart%2C+CA%3BOhlendorf%2C+D+H%3BVeasy%2C+L+G%3BHill%2C+H+R%3BLeung%2C+DYM%3BSchlievert%2C+P+M%3BMusser%2C+J+M&rft.aulast=Smoot&rft.aufirst=L&rft.date=2002-12-01&rft.volume=70&rft.issue=12&rft.spage=7095&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.70.12.7095-7104.2002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/IAI.70.12.7095-7104.2002 ER - TY - JOUR T1 - Mitochondrial DNA repair and aging. AN - 72680342; 12427535 AB - The mitochondrial electron transport chain plays an important role in energy production in aerobic organisms and is also a significant source of reactive oxygen species that damage DNA, RNA and proteins in the cell. Oxidative damage to the mitochondrial DNA is implicated in various degenerative diseases, cancer and aging. The importance of mitochondrial ROS in age-related degenerative diseases is further strengthened by studies using animal models, Caenorhabditis elegans, Drosophila and yeast. Research in the last several years shows that mitochondrial DNA is more susceptible to various carcinogens and ROS when compared to nuclear DNA. DNA damage in mammalian mitochondria is repaired by base excision repair (BER). Studies have shown that mitochondria contain all the enzymes required for BER. Mitochondrial DNA damage, if not repaired, leads to disruption of electron transport chain and production of more ROS. This vicious cycle of ROS production and mtDNA damage ultimately leads to energy depletion in the cell and apoptosis. JF - Mutation research AU - Mandavilli, Bhaskar S AU - Santos, Janine H AU - Van Houten, Bennett AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, 111 Alexander Drive, P.O. Box 12233, Research Triangle Park, NC 27709, USA. Y1 - 2002/11/30/ PY - 2002 DA - 2002 Nov 30 SP - 127 EP - 151 VL - 509 IS - 1-2 SN - 0027-5107, 0027-5107 KW - DNA, Mitochondrial KW - 0 KW - Reactive Oxygen Species KW - Index Medicus KW - Models, Animal KW - Animals KW - Reactive Oxygen Species -- adverse effects KW - Electron Transport KW - Humans KW - Drosophila melanogaster KW - Caenorhabditis elegans KW - Mice KW - Mutation KW - Saccharomyces cerevisiae KW - DNA Repair KW - Aging -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72680342?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mitochondrial+DNA+repair+and+aging.&rft.au=Mandavilli%2C+Bhaskar+S%3BSantos%2C+Janine+H%3BVan+Houten%2C+Bennett&rft.aulast=Mandavilli&rft.aufirst=Bhaskar&rft.date=2002-11-30&rft.volume=509&rft.issue=1-2&rft.spage=127&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 - 2002-12-20 N1 - Date created - 2002-11-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA repair in neural cells: basic science and clinical implications. AN - 72676673; 12427533 AB - As one part of a distinguished scientific career, Dr. Bryn Bridges focused his attention on the issue of DNA damage and repair in stationary phase bacteria. His work in this area led to his interest in DNA repair and mutagenesis in another non-dividing cell population, the neurons in the mammalian nervous system. He has specifically taken an interest in the magnocellular neurons of the central nervous system, and the possibility that somatic mutations may be occurring in these neurons. As part of this special issue dedicated to Bryn Bridges upon his retirement, I will discuss the various DNA repair pathways known to be active in the nervous system. The importance of DNA repair to the nervous system is most graphically illustrated by the neurological abnormalities observed in patients with hereditary diseases associated with defects in DNA repair. I will consider the mechanisms underlying the neurological abnormalities observed in patients with four of these diseases: xeroderma pigmentosum (XP), Cockayne's syndrome (CS), ataxia telangectasia (AT) and AT-like disorder (ATLD). I will also propose a mechanism for one of the observations indicating that somatic mutation can occur in the magnocellular neurons of the aging rat brain. Finally, as a parallel to Bridges inquiry into how much DNA synthesis is going on in stationary phase bacteria, I will address the question of how much DNA synthesis in going on in neurons, and the implications of the answer to this question for recent studies of neurogenesis in adult mammals. JF - Mutation research AU - Brooks, P J AD - Section on Molecular Neurobiology, Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 12420 Parklawn Drive, MSC 8110, Bethesda, MD 20892-8110, USA. pjbrooks@mail.nih.gov Y1 - 2002/11/30/ PY - 2002 DA - 2002 Nov 30 SP - 93 EP - 108 VL - 509 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Index Medicus KW - Brain -- abnormalities KW - Ataxia Telangiectasia -- genetics KW - Heredodegenerative Disorders, Nervous System -- etiology KW - Brain -- cytology KW - Humans KW - Cockayne Syndrome -- genetics KW - Xeroderma Pigmentosum -- genetics KW - Mutation KW - Aging -- genetics KW - DNA Repair KW - Neurons -- physiology KW - Nervous System Malformations -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72676673?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=DNA+repair+in+neural+cells%3A+basic+science+and+clinical+implications.&rft.au=Brooks%2C+P+J&rft.aulast=Brooks&rft.aufirst=P&rft.date=2002-11-30&rft.volume=509&rft.issue=1-2&rft.spage=93&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 - 2002-12-20 N1 - Date created - 2002-11-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Mutat Res. 2003 Apr 9;525(1-2):133 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of Origin and Optimization of Expansion and Transduction of Circulating Peripheral Blood Endothelial Progenitor Cells in the Rhesus Macaque Model AN - 18663590; 5561737 AB - Adult marrow-derived cells have been shown to contribute to various nonhematologic tissues and, conversely, primitive cells isolated from nonhematopoietic tissues have been shown to reconstitute hematopoiesis. Circulating endothelial progenitor cells (EPCs) have been reported to be at least partially donor derived after allogeneic bone marrow transplantation, and shown to contribute to neovascularization in murine ischemia models. However, it is unknown whether these EPCs are actually clonally derived from the same population of stem and progenitor cells that reconstitute hematopoiesis, or from another cell population found in the marrow or mobilized blood that is transferred during transplantation. To approach this question, we characterized circulating EPCs and also endothelial cells from large vessels harvested at autopsy from rhesus macaques previously transplanted with retrovirally transduced autologous CD34-enriched peripheral blood stem cells (PBSCs). Endothelial cells were grown in culture for 21-28 days and were characterized as CD31 super(+)CD14 super(-) via flow cytometry, as acLDL super(+)UEA-1 super(+) via immunohistochemistry, and as Flk-1 super(+) by reverse transcriptase-polymerase chain reaction (RT-PCR). Animals had stable vector marking in hematopoietic lineages of 2-15%. Neither cultured circulating EPCs collected in steady state (n = 3), nor endothelial cells grown from large vessels (n = 2), had detectable retroviral marking. EPCs were CD34 super(+) and could be mobilized into the circulation with granulocyte colony-stimulating factor. Under ex vivo culture conditions, in which CD34 super(+) cells were optimized to transduce hematopoietic progenitor and stem cells, there was a marked depletion of EPCs. Transduction of EPCs was much more efficient under conditions supporting endothelial cell growth. Further elucidation of the origin and in vivo behavior of EPCs may be possible, using optimized transduction conditions and a vascular injury model. JF - Human Gene Therapy AU - Hu, J AU - Takatoku, M AU - Sellers, SE AU - Agricola, BA AU - Metzger, ME AU - Donahue, R E AU - Dunbar, CE AD - Building 10, Room 7C103, Hematology Branch, NHLBI, NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA, dunbarc@nhlbi.nih.gov Y1 - 2002/11/30/ PY - 2002 DA - 2002 Nov 30 SP - 2041 EP - 2050 VL - 13 IS - 17 SN - 1043-0342, 1043-0342 KW - CD31 antigen KW - Rhesus monkey KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W 30965:Miscellaneous, Reviews KW - W4 120:Genetic Engineering in Medicine KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18663590?accountid=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=Analysis+of+Origin+and+Optimization+of+Expansion+and+Transduction+of+Circulating+Peripheral+Blood+Endothelial+Progenitor+Cells+in+the+Rhesus+Macaque+Model&rft.au=Hu%2C+J%3BTakatoku%2C+M%3BSellers%2C+SE%3BAgricola%2C+BA%3BMetzger%2C+ME%3BDonahue%2C+R+E%3BDunbar%2C+CE&rft.aulast=Hu&rft.aufirst=J&rft.date=2002-11-30&rft.volume=13&rft.issue=17&rft.spage=2041&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Distinct molecular basis for differential sensitivity of the serotonin type 3A receptor to ethanol in the absence and presence of agonist. AN - 72726245; 12368287 AB - Ethanol can potentiate serotonin type 3 (5-HT(3)) receptor-mediated responses in various neurons and in cells expressing 5-HT(3A) receptors. However, the molecular basis for alcohol modulation of 5-HT(3) receptor function has not been determined. Here we report that point mutations of the arginine at amino acid 222 in the N-terminal domain of the 5-HT(3A) receptor can alter the EC(50) value of the 5-HT concentration-response curve. Some point mutations at amino acid 222 resulted in spontaneous opening of the 5-HT(3A) receptor channel and an inward current activated by ethanol in the absence of agonist. Among these mutant receptors, the amplitude of the current activated by ethanol in the absence of agonist was correlated with the amplitude of the current resulting from spontaneous channel openings, suggesting that the sensitivity of the receptor to ethanol in the absence of agonist is, at least in part, dependent on the preexisting conformational equilibrium of the receptor protein. On the other hand, point mutations that conferred greater sensitivity to ethanol potentiation of agonist-activated responses were less sensitive or insensitive to ethanol in the absence of agonist. For these receptors, the magnitude of the potentiation of agonist-activated responses by ethanol was inversely correlated with the EC(50) values of the 5-HT concentration-response curves, suggesting that these mutations may modulate ethanol sensitivity of the receptor by altering the EC(50) value of the receptor. Thus, distinct molecular processes may determine the sensitivity of 5-HT(3A) receptors to ethanol in the absence and presence of agonist. JF - The Journal of biological chemistry AU - Zhang, Li AU - Hosoi, Masako AU - Fukuzawa, Misa AU - Sun, Hui AU - Rawlings, Robert R AU - Weight, Forrest F AD - Laboratory of Molecular and Cellular Neurobiology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892-8115, USA. lzhang@niaaa.nih.gov Y1 - 2002/11/29/ PY - 2002 DA - 2002 Nov 29 SP - 46256 EP - 46264 VL - 277 IS - 48 SN - 0021-9258, 0021-9258 KW - Ligands KW - 0 KW - Receptors, Serotonin KW - Receptors, Serotonin, 5-HT3 KW - Serotonin Receptor Agonists KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Humans KW - Mice KW - Amino Acid Sequence KW - Ion Channel Gating -- drug effects KW - Serotonin Receptor Agonists -- pharmacology KW - Receptors, Serotonin -- drug effects KW - Ethanol -- pharmacology KW - Receptors, Serotonin -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72726245?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Distinct+molecular+basis+for+differential+sensitivity+of+the+serotonin+type+3A+receptor+to+ethanol+in+the+absence+and+presence+of+agonist.&rft.au=Zhang%2C+Li%3BHosoi%2C+Masako%3BFukuzawa%2C+Misa%3BSun%2C+Hui%3BRawlings%2C+Robert+R%3BWeight%2C+Forrest+F&rft.aulast=Zhang&rft.aufirst=Li&rft.date=2002-11-29&rft.volume=277&rft.issue=48&rft.spage=46256&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 - 2003-01-08 N1 - Date created - 2002-11-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of acidic residues in the extracellular loops of the seven-transmembrane domain of the human Ca2+ receptor critical for response to Ca2+ and a positive allosteric modulator. AN - 72718649; 12297503 AB - We investigated the role of the eight acidic residues in the extracellular loops (exo-loops) of the seven-transmembrane domain of the human Ca(2+) receptor (hCaR) in receptor activation by Ca(2+) and in response to a positive allosteric modulator, NPS R-568. Both in the context of the full-length receptor and of a truncated receptor lacking the extracellular domain (Rho-C-hCaR), we mutated each acidic residue to alanine, singly and in combination, and tested the effect on expression of the receptor, on activation by Ca(2+), and on NPS R-568 augmentation of sensitivity to Ca(2+). Of the eight acidic residues, mutation of any of three in exo-loop 2, Asp(758), Glu(759), and Glu(767), increased the sensitivity of both the full-length hCaR and of Rho-C-hCaR to activation by Ca(2+). Mutation of all five acidic residues in exo-loop 2, whether in the full-length receptor or in Rho-C-hCaR, impaired cell surface expression of the mutant receptor and thereby largely abolished response to Ca(2+). Mutation of Glu(837) in exo-loop 3 to alanine did not alter Ca(2+) sensitivity of the full-length receptor, but in both the latter context and in Rho-C-hCaR, alanine substitution of Glu(837) drastically reduced sensitivity to NPS R-568. Our data point to a key role of three specific acidic residues in exo-loop 2 in hCaR activation and to Glu(837) at the junction between exo-loop 3 and transmembrane helix seven in response to NPS R-568. We speculate on the basis of these results that the three acidic residues we identified in exo-loop 2 help maintain an inactive conformation of the seven-transmembrane domain of the hCaR. JF - The Journal of biological chemistry AU - Hu, Jianxin AU - Reyes-Cruz, Guadalupe AU - Chen, Wangzhong AU - Jacobson, Kenneth A AU - Spiegel, Allen M AD - Molecular Pathophysiology Section, NIDCD, and the Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. jianxinh@ intra.niddk.nih.gov Y1 - 2002/11/29/ PY - 2002 DA - 2002 Nov 29 SP - 46622 EP - 46631 VL - 277 IS - 48 SN - 0021-9258, 0021-9258 KW - Calcium-Binding Proteins KW - 0 KW - Alanine KW - OF5P57N2ZX KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Blotting, Western KW - Alanine -- metabolism KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Allosteric Regulation KW - Immunohistochemistry KW - Cell Line KW - Calcium -- metabolism KW - Calcium-Binding Proteins -- genetics KW - Calcium-Binding Proteins -- metabolism KW - Calcium-Binding Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72718649?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+acidic+residues+in+the+extracellular+loops+of+the+seven-transmembrane+domain+of+the+human+Ca2%2B+receptor+critical+for+response+to+Ca2%2B+and+a+positive+allosteric+modulator.&rft.au=Hu%2C+Jianxin%3BReyes-Cruz%2C+Guadalupe%3BChen%2C+Wangzhong%3BJacobson%2C+Kenneth+A%3BSpiegel%2C+Allen+M&rft.aulast=Hu&rft.aufirst=Jianxin&rft.date=2002-11-29&rft.volume=277&rft.issue=48&rft.spage=46622&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 - 2003-01-08 N1 - Date created - 2002-11-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 2000 May 26;275(21):16382-9 [10747888] Mol Pharmacol. 1999 Aug;56(2):448-54 [10419566] Endocrinology. 2000 Nov;141(11):4156-63 [11089548] Physiol Rev. 2001 Jan;81(1):239-297 [11152759] Cell Biochem Biophys. 2000;33(1):63-95 [11322513] Mol Pharmacol. 2001 Nov;60(5):963-71 [11641424] Proc Natl Acad Sci U S A. 2001 Nov 6;98(23):13402-7 [11606768] Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14643-8 [11724957] J Clin Endocrinol Metab. 2002 Mar;87(3):1309-18 [11889203] J Biol Chem. 2002 May 24;277(21):18908-13 [11880385] Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9231-6 [12093923] J Bone Miner Res. 2002 Aug;17(8):1461-9 [12162500] Gen Comp Endocrinol. 2002 Jun 15;127(2):117-27 [12383439] Nature. 1993 Dec 9;366(6455):575-80 [8255296] J Biol Chem. 1996 Mar 15;271(11):5972-5 [8626377] J Biol Chem. 1996 Aug 9;271(32):19537-45 [8702647] Am J Physiol. 1997 Sep;273(3 Pt 2):R1008-16 [9321880] J Biol Chem. 1997 Dec 12;272(50):31355-61 [9395465] Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):4040-5 [9520489] Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5178-81 [9560249] J Clin Endocrinol Metab. 1998 Jul;83(7):2497-502 [9661634] J Biol Chem. 1998 Dec 18;273(51):34558-67 [9852126] Cell. 1998 Dec 23;95(7):917-26 [9875846] Mol Pharmacol. 1999 Mar;55(3):453-61 [10051528] Mol Pharmacol. 1999 Apr;55(4):642-8 [10101021] EMBO J. 1999 Apr 1;18(7):1723-9 [10202136] FEBS Lett. 1999 Apr 1;448(1):180-4 [10217436] J Biol Chem. 1999 Jun 25;274(26):18382-6 [10373443] Nature. 2000 Oct 26;407(6807):971-7 [11069170] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Crystal Structure of the Heterodimeric Complex of the Adaptor, ClpS, with the N-domain of the Van de super(+) Chaperone, ClpA AN - 18610404; 5511301 AB - Substrate selectivity and proteolytic activity for the E. coli ATP-dependent protease, ClpAP, is modulated by an adaptor protein, ClpS. ClpS binds to ClpA, the regulatory component of the ClpAP complex. We report the crystal structure of ClpS in complex with the isolated N-terminal domain of ClpA in two different crystal forms at 2.3- and 3.3-Aa resolution. The ClpS structure forms an [alpha]/[beta]-sandwich and is topologically analogous to the C-terminal domain of the ribosomal protein L7/L12. ClpS contacts two surfaces on the N-terminal domain in both crystal forms; the more extensive interface was shown to be favored in solution by protease protection experiments. The N-terminal 20 residues of ClpS are not visible in the crystal structures; the removal of the first 17 residues produces ClpS[Delta]N, which binds to the ClpA N-domain but no longer inhibits ClpA activity. A zinc binding site involving two His and one Glu residue was identified crystallographically in the N-terminal domain of ClpA. In a model of ClpS bound to hexameric ClpA, ClpS is oriented with its N terminus directed toward the distal surface of ClpA, suggesting that the N-terminal region of ClpS may affect productive substrate interactions at the apical surface or substrate entry into the ClpA translocation channel. JF - Journal of Biological Chemistry AU - Guo, F AU - Esser, L AU - Singh, S K AU - Maurizi, M R AU - Di, Xi AD - Laboratory of Cell Biology, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland, dixia@helix.nih.gov. Y1 - 2002/11/29/ PY - 2002 DA - 2002 Nov 29 SP - 46753 EP - 46762 VL - 277 IS - 48 SN - 0021-9258, 0021-9258 KW - ClpA protein KW - ClpAP protein KW - ClpS protein KW - Microbiology Abstracts B: Bacteriology KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18610404?accountid=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=Crystal+Structure+of+the+Heterodimeric+Complex+of+the+Adaptor%2C+ClpS%2C+with+the+N-domain+of+the+Van+de+super%28%2B%29+Chaperone%2C+ClpA&rft.au=Guo%2C+F%3BEsser%2C+L%3BSingh%2C+S+K%3BMaurizi%2C+M+R%3BDi%2C+Xi&rft.aulast=Guo&rft.aufirst=F&rft.date=2002-11-29&rft.volume=277&rft.issue=48&rft.spage=46753&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 - Crystal Structure of ClpA, an Hsp100 Chaperone and Regulator of ClpAP Protease AN - 18608306; 5511300 AB - Escherichia coli ClpA, an Hsp100/Clp chaperone and an integral component of the ATP-dependent ClpAP protease, participates in regulatory protein degradation and the dissolution and degradation of protein aggregates. The crystal structure of the ClpA subunit reveals an N-terminal domain with pseudo-twofold symmetry and two Van de super(+) modules (D1 and D2) each consisting of a large and a small sub-domain with ADP bound in the sub-domain junction. The N-terminal domain interacts with the D1 domain in a manner similar to adaptor-binding domains of other AAA super(+) proteins. D1 and D2 are connected head-to-tail consistent with a cooperative and vectorial translocation of protein substrates. In a planar hexamer model of ClpA, built by assembling ClpA D1 and D2 into homohexameric rings of known structures of AAA super(+) modules, the differences in D1-D1 and D2-D2 interfaces correlate with their respective contributions to hexamer stability and ATPase activity. JF - Journal of Biological Chemistry AU - Guo, F AU - Maurizi, M R AU - Esser, L AU - Di, Xi AD - Laboratory of Cell Biology, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland, dixia@helix.hih.gov. Y1 - 2002/11/29/ PY - 2002 DA - 2002 Nov 29 SP - 46743 EP - 46752 VL - 277 IS - 48 SN - 0021-9258, 0021-9258 KW - ClpA protein KW - ClpAP protein KW - Microbiology Abstracts B: Bacteriology KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18608306?accountid=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=Crystal+Structure+of+ClpA%2C+an+Hsp100+Chaperone+and+Regulator+of+ClpAP+Protease&rft.au=Guo%2C+F%3BMaurizi%2C+M+R%3BEsser%2C+L%3BDi%2C+Xi&rft.aulast=Guo&rft.aufirst=F&rft.date=2002-11-29&rft.volume=277&rft.issue=48&rft.spage=46743&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 - Importance of the conserved Walker B glutamate residues, 556 and 1201, for the completion of the catalytic cycle of ATP hydrolysis by human P-glycoprotein (ABCB1). AN - 72685969; 12437356 AB - The human MDR1 (ABCB1) gene product, P-glycoprotein (Pgp), functions as an ATP-dependent efflux pump for a variety of chemotherapeutic drugs. In this study, we assessed the role of conserved glutamate residues in the Walker B domain of the two ATP sites (E556 and E1201, respectively) during the catalytic cycle of human Pgp. The mutant Pgps (E556Q, E556A, E1201Q, E1201A, E556/1201Q, and E556/1201A) were characterized using a vaccinia virus based expression system. Although steady-state ATP hydrolysis and drug transport activities were abrogated in both E556Q and E1201Q mutant Pgps, [alpha-(32)P]-8-azidoADP was trapped in the presence of vanadate (Vi), and the release of trapped [alpha-(32)P]-8-azidoADP occurred to a similar extent as in wild-type Pgp. This indicates that these mutations do not affect either the first hydrolysis event or the ADP release step. Similar results were also obtained when Glu residues were replaced with Ala (E556A and E1201A). Following the first hydrolysis event and release of [alpha-(32)P]-8-azidoADP, both E556Q and E1201Q mutant Pgps failed to undergo another cycle of Vi-induced [alpha-(32)P]-8-azidoADP trapping. Interestingly, the double mutants E556/1201Q and E556/1201A trapped [alpha-(32)P]-8-azidoADP even in the absence of Vi, and the occluded nucleotide was not released after incubation at 37 degrees C for an extended period. In addition, the properties of transition state conformation of the double mutants generated in the absence of Vi were found to be similar to that of the wild-type protein trapped in the presence of Vi (Pgp x [alpha-(32)P]-8-azidoADP xVi). Thus, in contrast to the single mutants, the double mutants appear to be defective in the ADP release step. In aggregate, these data suggest that E556 and E1201 residues in the Walker B domains may not be critical as catalytic carboxylates for the cleavage of the bond between the gamma-P and the beta-P of ATP during hydrolysis but are essential for the second ATP hydrolysis step and completion of the catalytic cycle. JF - Biochemistry AU - Sauna, Zuben E AU - Müller, Marianna AU - Peng, Xiang-Hong AU - Ambudkar, Suresh V AD - Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4254, USA. Y1 - 2002/11/26/ PY - 2002 DA - 2002 Nov 26 SP - 13989 EP - 14000 VL - 41 IS - 47 SN - 0006-2960, 0006-2960 KW - DNA Primers KW - 0 KW - P-Glycoprotein KW - Recombinant Proteins KW - Glutamic Acid KW - 3KX376GY7L KW - Vanadates KW - 3WHH0066W5 KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Index Medicus KW - Vanadates -- pharmacology KW - Humans KW - Amino Acid Sequence KW - Hydrolysis KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Conserved Sequence KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Recombinant Proteins -- chemistry KW - Amino Acid Substitution KW - Catalysis KW - P-Glycoprotein -- metabolism KW - Adenosine Triphosphate -- metabolism KW - P-Glycoprotein -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72685969?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Importance+of+the+conserved+Walker+B+glutamate+residues%2C+556+and+1201%2C+for+the+completion+of+the+catalytic+cycle+of+ATP+hydrolysis+by+human+P-glycoprotein+%28ABCB1%29.&rft.au=Sauna%2C+Zuben+E%3BM%C3%BCller%2C+Marianna%3BPeng%2C+Xiang-Hong%3BAmbudkar%2C+Suresh+V&rft.aulast=Sauna&rft.aufirst=Zuben&rft.date=2002-11-26&rft.volume=41&rft.issue=47&rft.spage=13989&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-01-09 N1 - Date created - 2002-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Micronucleus induction in mice exposed to diazoaminobenzene or its metabolites, benzene and aniline: implications for diazoaminobenzene carcinogenicity AN - 18616023; 5514798 AB - Diazoaminobenzene (DAAB), a manufacturing intermediate metabolized primarily to the known carcinogens benzene and aniline, has been identified as an impurity in a number of dyes and coloring agents that are components of cosmetics, food products, and pharmaceuticals. Several structural analogs of DAAB are carcinogenic as well. DAAB was selected for metabolism and toxicity studies by the National Toxicology Program (NTP) based on the potential for human exposure, positive Salmonella data, and lack of adequate toxicological data. In the toxicology studies in mice, DAAB exhibited properties similar to benzene and aniline. Because both these metabolites induce micronuclei (MN) in rodent bone marrow erythrocytes, DAAB was tested for induction of micronuclei in male B6C3F1 mice. DAAB was administered twice by corn oil gavage at 24h intervals, at doses of 25, 50, and 100mg/kg per day. In addition, comparative micronucleus tests were conducted with benzene, aniline, and a mixture of benzene plus aniline; doses were based on the respective molar equivalents of each metabolite to DAAB. It was hypothesized that any observed increase in micronuclei seen in DAAB-treated mice would be due primarily to the effects of the benzene metabolite, as benzene is a more potent inducer of chromosomal damage than aniline. Results of this study showed that DAAB and benzene were effective inducers of micronuclei, with stronger responses noted for DAAB at higher doses. Positive results were also obtained with the mixture of benzene and aniline, although the magnitude of the response was lower than for DAAB. Aniline gave a weak positive response at doses exceeding its molar equivalent to 100mg/kg DAAB. Overall, the data indicated that DAAB is a potent inducer of micronuclei in mice, and its activity appears to be closely related to the activity of benzene, one of its primary metabolites. The results are consistent with a prediction of carcinogenicity for DAAB. JF - Mutation Research-Genetic Toxicology and Environmental Mutagenesis AU - Ress, N B AU - Witt, K L AU - Xu, J AU - Haseman, J K AU - Bucher, J R AD - National Institute of Environmental Health Sciences, 79 Alexander Drive, Mail Drop EC-34, Research Triangle Park, Triangle Park, NC 27709, USA, bucher@niehs.nih.gov Y1 - 2002/11/26/ PY - 2002 DA - 2002 Nov 26 SP - 201 EP - 208 PB - Elsevier Science VL - 521 IS - 1-2 SN - 1383-5718, 1383-5718 KW - diazoaminobenzene KW - mice KW - Toxicology Abstracts KW - X 24155:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18616023?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+Research-Genetic+Toxicology+and+Environmental+Mutagenesis&rft.atitle=Micronucleus+induction+in+mice+exposed+to+diazoaminobenzene+or+its+metabolites%2C+benzene+and+aniline%3A+implications+for+diazoaminobenzene+carcinogenicity&rft.au=Ress%2C+N+B%3BWitt%2C+K+L%3BXu%2C+J%3BHaseman%2C+J+K%3BBucher%2C+J+R&rft.aulast=Ress&rft.aufirst=N&rft.date=2002-11-26&rft.volume=521&rft.issue=1-2&rft.spage=201&rft.isbn=&rft.btitle=&rft.title=Mutation+Research-Genetic+Toxicology+and+Environmental+Mutagenesis&rft.issn=13835718&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - A genomic-scale view of the cAMP response element-enhancer decoy: A tumor target-based genetic tool AN - 18609482; 5516217 AB - Enhancer DNA decoy oligodeoxynucleotides (ODNs) inhibit transcription by competing for transcription factors. A decoy ODN composed of the cAMP response element (CRE) inhibits CRE-directed gene transcription and tumor growth without affecting normal cell growth. Here, we use DNA microarrays to analyze the global effects of the CRE-decoy ODN in cancer cell lines and in tumors grown in nude mice. The CRE-decoy up-regulates the AP-2[beta] transcription factor gene in tumors but not in the livers of host animals. The up-regulated expression of AP-2[beta] is clustered with the up-regulation of other genes involved in development and cell differentiation. Concomitantly, another cluster of genes involved in cell proliferation and transformation is down-regulated. The observed alterations indicate that CRE-directed transcription favors tumor growth. The CRE-decoy ODN, therefore, may serve as a target-based genetic tool to treat cancer and other diseases in which CRE-directed transcription is abnormally used. JF - Proceedings of the National Academy of Sciences, USA AU - Cho, Y S AU - Kim, M AU - Cheadle, C AU - Neary, C AU - Park, Y G AU - Becker, K G AU - Cho-Chung, Y S AD - Cellular Biochemistry Section, Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, chochung@helix.nih.gov Y1 - 2002/11/26/ PY - 2002 DA - 2002 Nov 26 SP - 15626 EP - 15631 VL - 99 IS - 24 SN - 0027-8424, 0027-8424 KW - AP-2 beta protein KW - DNA microarrays KW - double prime AP-2 beta protein KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - W3 33056:Animal models of human disease KW - N 14250:Biological properties KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18609482?accountid=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=A+genomic-scale+view+of+the+cAMP+response+element-enhancer+decoy%3A+A+tumor+target-based+genetic+tool&rft.au=Cho%2C+Y+S%3BKim%2C+M%3BCheadle%2C+C%3BNeary%2C+C%3BPark%2C+Y+G%3BBecker%2C+K+G%3BCho-Chung%2C+Y+S&rft.aulast=Cho&rft.aufirst=Y&rft.date=2002-11-26&rft.volume=99&rft.issue=24&rft.spage=15626&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.242617799 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1073/pnas.242617799 ER - TY - JOUR T1 - Measurement of resiniferatoxin in cerebrospinal fluid by high-performance liquid chromatography. AN - 72632400; 12401376 AB - A sensitive and simple high-performance liquid chromatographic (HPLC) assay was developed for the quantification of resiniferatoxin (RTX) in canine cerebrospinal fluid (CSF). A reversed-phase C(18) column and acetonitrile in 0.02 M NaH(2)PO(4) as mobile phase provided satisfactory resolution for RTX analysis. Direct HPLC analysis of the CSF samples without sample extraction or preparation improves the accuracy and detection limits of this assay. This assay was applied to measure CSF RTX content to test this method for research and clinical applications related to studies examining its analgesia effects. Copyright 2002 Elsevier Science B.V. JF - Journal of chromatography. B, Analytical technologies in the biomedical and life sciences AU - Mannes, Andrew J AU - Cimino Brown, Dorothy AU - Perkowski, Sandra Z AU - Keller, Jason AU - Caudle, Robert M AU - Iadarola, Michael J AU - Meng, Qing C AD - PPCS/DASS/NIDCR/NIH, National Institutes of Health, Building 10, Room 1N117, Rockville Pike, Bethesda, MD 20892, USA. amannes@maail.nih.gov Y1 - 2002/11/25/ PY - 2002 DA - 2002 Nov 25 SP - 475 EP - 479 VL - 780 IS - 2 SN - 1570-0232, 1570-0232 KW - Diterpenes KW - 0 KW - Neurotoxins KW - resiniferatoxin KW - A5O6P1UL4I KW - Index Medicus KW - Animals KW - Reproducibility of Results KW - Reference Standards KW - Dogs KW - Diterpenes -- cerebrospinal fluid KW - Neurotoxins -- cerebrospinal fluid KW - Chromatography, High Pressure Liquid -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72632400?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+chromatography.+B%2C+Analytical+technologies+in+the+biomedical+and+life+sciences&rft.atitle=Measurement+of+resiniferatoxin+in+cerebrospinal+fluid+by+high-performance+liquid+chromatography.&rft.au=Mannes%2C+Andrew+J%3BCimino+Brown%2C+Dorothy%3BPerkowski%2C+Sandra+Z%3BKeller%2C+Jason%3BCaudle%2C+Robert+M%3BIadarola%2C+Michael+J%3BMeng%2C+Qing+C&rft.aulast=Mannes&rft.aufirst=Andrew&rft.date=2002-11-25&rft.volume=780&rft.issue=2&rft.spage=475&rft.isbn=&rft.btitle=&rft.title=Journal+of+chromatography.+B%2C+Analytical+technologies+in+the+biomedical+and+life+sciences&rft.issn=15700232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-01 N1 - Date created - 2002-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - U.S. Public Health Service Task Force recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV-1 transmission in the United States. AN - 72776826; 12489844 AB - These recommendations update the February 4,2002, guidelines developed by the Public Health Service for the use of zidovudine (ZDV) to reduce the risk for perinatal human immunodeficiency virus type 1 (HIV-1) transmission. This report provides healthcare providers with information for discussion with HIV-1-infected pregnant women to enable such women to make an informed decision regarding the use of antiretroviral drugs during pregnancy and use of elective cesarean delivery to reduce perinatal HIV-1 transmission. Various circumstances that commonly occur in clinical practice are presented, and the factors influencing treatment considerations are highlighted in this report. The Perinatal HIV Guidelines Working Group recognizes that strategies to prevent perinatal transmission and concepts related to management of HIV disease in pregnant women are rapidly evolving and will continually review new data and provide regular updates to the guidelines. The most recent information is available from the HIV/AIDS Treatment Information Service (available at http.//www.hivatis.org). In February 1994, the results of Pediatric AIDS Clinical Trials Group (PACTG) Protocol 076 documented that ZDV chemoprophylaxis could reduce perinatal HIV-1 transmission by nearly 70%. Epidemiologic data have since confirmed the efficacy of ZDV for reduction of perinatal transmission and have extended this efficacy to children of women with advanced disease, low CD4+ T-lymphocyte counts, and prior ZDV therapy. Additionally, substantial advances have been made in the understanding of the pathogenesis of HIV-1 infection and in the treatment and monitoring of persons with HIV-1 disease. These advances have resulted in changes in standard antiretroviral therapy for HIV-1-infected adults. More aggressive combination drug regimens that maximally suppress viral replication are now recommended. Although considerations associated with pregnancy may affect decisions regarding timing and choice of therapy pregnancy is not a reason to defer standard therapy. Use of antiretroviral drugs in pregnancy requires unique considerations, including the possible need to alter dosage as a result of physiologic changes associated with pregnancy the potential for adverse short- or long-term effects on the fetus and newborn, and the effectiveness of the drugs in reducing the risk for perinatal transmission. Data to address many of these considerations are not yet available. Therefore, offering antiretroviral therapy to HIV-1-infected women during pregnancy, whether primarily for HIV-1 infection, for reduction of perinatal transmission, or for both purposes, should be accompanied by a discussion of the known and unknown short- and long-term benefits and risks of such therapy to infected women and their infants. Standard antiretroviral therapy should be discussed with and offered to HIV-1-infected pregnant women. Additionally, to prevent perinatal transmission, ZDV chemoprophylaxis should be incorporated into the antiretroviral regimen. JF - MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports AU - Mofenson, Lynne M AU - Centers for Disease Control and Prevention, U.S. Public Health Service Task Force AD - Center for Research for Mothers and Children, National Institute of Child Health and Human Development, National Institutes of Health, USA. ; Centers for Disease Control and Prevention, U.S. Public Health Service Task Force Y1 - 2002/11/22/ PY - 2002 DA - 2002 Nov 22 SP - 1 EP - 38; quiz CE1-4 VL - 51 SN - 1057-5987, 1057-5987 KW - Anti-HIV Agents KW - 0 KW - DNA, Mitochondrial KW - HIV Protease Inhibitors KW - Index Medicus KW - United States KW - Delivery, Obstetric KW - Labor, Obstetric KW - Humans KW - Clinical Trials as Topic KW - Infant, Newborn KW - HIV Protease Inhibitors -- therapeutic use KW - HIV-1 KW - Pregnancy KW - Viral Load KW - Registries KW - DNA, Mitochondrial -- drug effects KW - Preconception Care KW - Antiretroviral Therapy, Highly Active -- standards KW - Drug Resistance, Viral KW - Hyperglycemia KW - HIV Protease Inhibitors -- adverse effects KW - Female KW - Pregnancy Outcome KW - Infectious Disease Transmission, Vertical -- prevention & control KW - Anti-HIV Agents -- therapeutic use KW - HIV Infections -- transmission KW - HIV Infections -- drug therapy KW - Pregnancy Complications, Infectious -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72776826?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=MMWR.+Recommendations+and+reports+%3A+Morbidity+and+mortality+weekly+report.+Recommendations+and+reports&rft.atitle=U.S.+Public+Health+Service+Task+Force+recommendations+for+use+of+antiretroviral+drugs+in+pregnant+HIV-1-infected+women+for+maternal+health+and+interventions+to+reduce+perinatal+HIV-1+transmission+in+the+United+States.&rft.au=Mofenson%2C+Lynne+M%3BCenters+for+Disease+Control+and+Prevention%2C+U.S.+Public+Health+Service+Task+Force&rft.aulast=Mofenson&rft.aufirst=Lynne&rft.date=2002-11-22&rft.volume=51&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=MMWR.+Recommendations+and+reports+%3A+Morbidity+and+mortality+weekly+report.+Recommendations+and+reports&rft.issn=10575987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-12-31 N1 - Date created - 2002-12-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - E.coli cell-cycle regulation by bacteriophage lambda. AN - 72700299; 12441108 AB - We re-examined the old but surprising claim of Kourilsky and Knapp that transient expression of genes located downstream of the p(L) promoter of bacteriophage lambda can induce cell-cycle synchrony in a population of Escherichia coli cells. Although we were unable to reproduce a lasting synchrony, a cessation of division, followed by one or two fairly synchronous cell divisions was observed. This line up of the cell cycle was found to be due to two genetically separable events: a temporary block of cell division and, at the same time, a block to the initiation of new rounds of DNA replication. These blocks then release after about one mass doubling so that chromosome replication and cell division occur during a short time interval in all the cells in the population. The cell division block is a result of the transient expression of the lambda kil gene. The block to initiation of DNA replication requires a region that we term bin (blocks initiation) immediately upstream of the xis gene. The region consists of ea22 and ea8.5 and two small open reading frames (ORFs) that flank them. Deletion-substitution mutagenesis suggests that all four ORFs may be required for the initiation block. The ability of the phage to modify two aspects of the host cell cycle presumably reflects a stratagem that provides the phage with an advantage for lysogeny or lytic growth. JF - Journal of molecular biology AU - Sergueev, Kirill AU - Court, Donald AU - Reaves, Lucretia AU - Austin, Stuart AD - Gene Regulation and Chromosome Biology Laboratory, National Cancer Institute, NCI-FCRDC, PO Box B, Building 539, Frederick, MD 21702-1201, USA. Y1 - 2002/11/22/ PY - 2002 DA - 2002 Nov 22 SP - 297 EP - 307 VL - 324 IS - 2 SN - 0022-2836, 0022-2836 KW - Bacterial Proteins KW - 0 KW - Codon, Initiator KW - DNA Primers KW - DNA-Binding Proteins KW - Escherichia coli Proteins KW - Repressor Proteins KW - Viral Proteins KW - Viral Regulatory and Accessory Proteins KW - gam protein, Coliphage KW - kil protein, E coli KW - phage repressor proteins KW - Index Medicus KW - Bacterial Proteins -- genetics KW - Codon, Initiator -- genetics KW - Open Reading Frames KW - Gene Expression KW - Gene Deletion KW - Lysogeny KW - F Factor KW - Replication Origin KW - Recombination, Genetic KW - Chromosomes, Bacterial KW - Point Mutation KW - DNA Replication KW - Cell Division KW - DNA Primers -- chemistry KW - Escherichia coli -- cytology KW - Cell Cycle -- physiology KW - Bacteriophage lambda -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72700299?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=E.coli+cell-cycle+regulation+by+bacteriophage+lambda.&rft.au=Sergueev%2C+Kirill%3BCourt%2C+Donald%3BReaves%2C+Lucretia%3BAustin%2C+Stuart&rft.aulast=Sergueev&rft.aufirst=Kirill&rft.date=2002-11-22&rft.volume=324&rft.issue=2&rft.spage=297&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 - 2002-12-23 N1 - Date created - 2002-11-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interaction of the DnaK and DnaJ chaperone system with a native substrate, P1 RepA. AN - 72688778; 12237299 AB - DnaK, the Hsp70 chaperone of Escherichia coli interacts with protein substrates in an ATP-dependent manner, in conjunction with DnaJ and GrpE co-chaperones, to carry out protein folding, protein remodeling, and assembly and disassembly of multisubunit protein complexes. To understand how DnaJ targets specific proteins for recognition by the DnaK chaperone system, we investigated the interaction of DnaJ and DnaK with a known natural substrate, bacteriophage P1 RepA protein. By characterizing RepA deletion derivatives, we found that DnaJ interacts with a region of RepA located between amino acids 180 and 200 of the 286-amino acid protein. A peptide corresponding to amino acids 180-195 inhibited the interaction of RepA and DnaJ. Two site-directed RepA mutants with alanine substitutions in this region were about 4-fold less efficiently activated for oriP1 DNA binding by DnaJ and DnaK than wild type RepA. We also identified by deletion analysis a site in RepA, in the region of amino acids 35-49, which interacts with DnaK. An alanine substitution mutant in amino acids 36-39 was constructed and found defective in activation by DnaJ and DnaK. Taken together the results suggest that DnaJ and DnaK interact with separate sites on RepA. JF - The Journal of biological chemistry AU - Kim, Soon-Young AU - Sharma, Suveena AU - Hoskins, Joel R AU - Wickner, Sue AD - Laboratory of Molecular Biology, NCI, National Institutes of Health, Bethesda, Maryland 20892-4264, USA. Y1 - 2002/11/22/ PY - 2002 DA - 2002 Nov 22 SP - 44778 EP - 44783 VL - 277 IS - 47 SN - 0021-9258, 0021-9258 KW - DNA-Binding Proteins KW - 0 KW - DnaJ protein, E coli KW - Escherichia coli Proteins KW - HSP40 Heat-Shock Proteins KW - HSP70 Heat-Shock Proteins KW - Heat-Shock Proteins KW - Molecular Chaperones KW - Peptides KW - Proteins KW - Trans-Activators KW - replication initiator protein KW - DNA KW - 9007-49-2 KW - dnaK protein, E coli KW - EC 3.6.1.- KW - DNA Helicases KW - EC 3.6.4.- KW - Alanine KW - OF5P57N2ZX KW - Index Medicus KW - DNA -- metabolism KW - Peptides -- metabolism KW - Amino Acid Sequence KW - Protein Binding KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Alanine -- metabolism KW - Replication Origin KW - DNA Replication -- physiology KW - Molecular Sequence Data KW - Peptides -- genetics KW - DNA-Binding Proteins -- metabolism KW - Heat-Shock Proteins -- metabolism KW - HSP70 Heat-Shock Proteins -- metabolism KW - Escherichia coli Proteins -- metabolism KW - Molecular Chaperones -- metabolism KW - Proteins -- metabolism KW - Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72688778?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Interaction+of+the+DnaK+and+DnaJ+chaperone+system+with+a+native+substrate%2C+P1+RepA.&rft.au=Kim%2C+Soon-Young%3BSharma%2C+Suveena%3BHoskins%2C+Joel+R%3BWickner%2C+Sue&rft.aulast=Kim&rft.aufirst=Soon-Young&rft.date=2002-11-22&rft.volume=277&rft.issue=47&rft.spage=44778&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 - 2003-01-07 N1 - Date created - 2002-11-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CPAPER T1 - Technical issues requiring resolution for power reactors to use the entombment decommissioning option AN - 39592760; 3716488 AU - Genoa, PH Y1 - 2002/11/21/ PY - 2002 DA - 2002 Nov 21 KW - CPI, Conference Papers Index KW - U 4300:Environmental Science UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39592760?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Technical+issues+requiring+resolution+for+power+reactors+to+use+the+entombment+decommissioning+option&rft.au=Genoa%2C+PH&rft.aulast=Genoa&rft.aufirst=PH&rft.date=2002-11-21&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Nuclear Society, Inc., 555 N. Kensington Ave., La Grange Park, IL 60525, USA; phone: 708-352-6611; fax: 708-352-0499; URL: www.ans.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Role of cytokines and chemokines in neurological disease induced by polytropic retrovirus infection in mice AN - 39577000; 3712460 AU - Peterson, KE Y1 - 2002/11/21/ PY - 2002 DA - 2002 Nov 21 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39577000?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Role+of+cytokines+and+chemokines+in+neurological+disease+induced+by+polytropic+retrovirus+infection+in+mice&rft.au=Peterson%2C+KE&rft.aulast=Peterson&rft.aufirst=KE&rft.date=2002-11-21&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Neuroscience 2002, c/o AKM Congress Service GmbH, Rheinterrasse Dusseldorf, Joseph-Beuys-Ufer 33, 40479 Dusseldorf, Germany; phone: 49 (0) 211-49 77 712; fax: 49 (0) 211-49 77 743. Poster Paper No. P128 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Matrix metalloproteinase-1 activates a G protein-coupled receptor AN - 39576961; 3712447 AU - Haughey, N Y1 - 2002/11/21/ PY - 2002 DA - 2002 Nov 21 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39576961?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Matrix+metalloproteinase-1+activates+a+G+protein-coupled+receptor&rft.au=Haughey%2C+N&rft.aulast=Haughey&rft.aufirst=N&rft.date=2002-11-21&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Neuroscience 2002, c/o AKM Congress Service GmbH, Rheinterrasse Dusseldorf, Joseph-Beuys-Ufer 33, 40479 Dusseldorf, Germany; phone: 49 (0) 211-49 77 712; fax: 49 (0) 211-49 77 743. Poster Paper No. P115 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Cytokine and chemokine gene expression profile in HTLV-I Tax transfected astrocytes AN - 39573463; 3712494 AU - Tomaru, U Y1 - 2002/11/21/ PY - 2002 DA - 2002 Nov 21 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39573463?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Cytokine+and+chemokine+gene+expression+profile+in+HTLV-I+Tax+transfected+astrocytes&rft.au=Tomaru%2C+U&rft.aulast=Tomaru&rft.aufirst=U&rft.date=2002-11-21&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Neuroscience 2002, c/o AKM Congress Service GmbH, Rheinterrasse Dusseldorf, Joseph-Beuys-Ufer 33, 40479 Dusseldorf, Germany; phone: 49 (0) 211-49 77 712; fax: 49 (0) 211-49 77 743. Poster Paper No. P161 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Detection of human herpesvirus 6 (HHV-6) in human central nervous system tissue AN - 39527534; 3712580 AU - Donati, D Y1 - 2002/11/21/ PY - 2002 DA - 2002 Nov 21 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39527534?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Detection+of+human+herpesvirus+6+%28HHV-6%29+in+human+central+nervous+system+tissue&rft.au=Donati%2C+D&rft.aulast=Donati&rft.aufirst=D&rft.date=2002-11-21&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Neuroscience 2002, c/o AKM Congress Service GmbH, Rheinterrasse Dusseldorf, Joseph-Beuys-Ufer 33, 40479 Dusseldorf, Germany; phone: 49 (0) 211-49 77 712; fax: 49 (0) 211-49 77 743. Poster Paper No. P248 N1 - Last updated - 2010-05-03 ER - TY - JOUR T1 - Potential use of imatinib in Ewing's Sarcoma: evidence for in vitro and in vivo activity. AN - 72701999; 12441322 AB - Ewing's sarcoma cells express c-kit, a receptor tyrosine kinase, and its ligand, stem cell factor (SCF), creating a potential autocrine loop that may promote tumor survival. We thus examined whether the specific tyrosine kinase inhibitor imatinib mesylate (hereafter imatinib; formerly STI571) could inhibit the proliferation of Ewing's sarcoma cells in vitro and in vivo. The effect of imatinib on c-kit expression and phosphorylation in Ewing's sarcoma cells was examined by immunoblotting. The effect of imatinib on cell growth and apoptosis was examined with an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay and with a morphologic test and Annexin V staining, respectively. The effect of imatinib oral therapy (every 12 hours for 5-7 days) on primary tumor growth was assessed in Ewing's sarcoma xenografts in SCID/bg mice (5 or 10 mice per group). All Ewing's sarcoma cell lines tested were sensitive to imatinib-mediated apoptosis with a concentration inhibiting growth by 50% (IC50) of 10-12 micro M. Imatinib inhibited SCF-mediated c-kit phosphorylation (IC50 = 0.1-0.5 microM). In the xenograft model, imatinib treatment resulted in the regression or control of primary Ewing's sarcomas. After 6 days of treatment, the mean lower extremity volume including xenograft tumor was 3744 mm3 (95% confidence interval [CI] = 3050 to 4437 mm3), 1442 mm3 (95% CI = 931 to 1758 mm3), and 346 mm3 (95% CI = 131 to 622 mm3) in mice treated with carrier alone or with imatinib at 50 mg/kg or at 100 mg/kg, respectively. Imatinib interferes with growth of all Ewing's sarcoma cell lines tested in vitro and in vivo. Targeted inhibition of tyrosine kinase-dependent autocrine loops, therefore, may be a viable therapeutic strategy for Ewing's sarcoma. JF - Journal of the National Cancer Institute AU - Merchant, Melinda S AU - Woo, Chan-Wook AU - Mackall, Crystal L AU - Thiele, Carol J AD - Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. merchanm@mail.nih.gov Y1 - 2002/11/20/ PY - 2002 DA - 2002 Nov 20 SP - 1673 EP - 1679 VL - 94 IS - 22 SN - 0027-8874, 0027-8874 KW - Antineoplastic Agents KW - 0 KW - Benzamides KW - Enzyme Inhibitors KW - Piperazines KW - Pyrimidines KW - Stem Cell Factor KW - Imatinib Mesylate KW - 8A1O1M485B KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Proto-Oncogene Proteins c-kit KW - Index Medicus KW - Animals KW - Immunoblotting KW - Humans KW - Disease Models, Animal KW - Precipitin Tests KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Phosphorylation -- drug effects KW - Tumor Cells, Cultured KW - Apoptosis -- drug effects KW - Transplantation, Heterologous KW - Inhibitory Concentration 50 KW - Time Factors KW - Stem Cell Factor -- metabolism KW - Bone Neoplasms -- immunology KW - Proto-Oncogene Proteins c-kit -- drug effects KW - Bone Neoplasms -- metabolism KW - Sarcoma, Ewing -- metabolism KW - Pyrimidines -- pharmacology KW - Piperazines -- pharmacology KW - Sarcoma, Ewing -- drug therapy KW - Bone Neoplasms -- enzymology KW - Protein-Tyrosine Kinases -- antagonists & inhibitors KW - Proto-Oncogene Proteins c-kit -- metabolism KW - Sarcoma, Ewing -- immunology KW - Bone Neoplasms -- drug therapy KW - Enzyme Inhibitors -- pharmacology KW - Sarcoma, Ewing -- enzymology KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72701999?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Potential+use+of+imatinib+in+Ewing%27s+Sarcoma%3A+evidence+for+in+vitro+and+in+vivo+activity.&rft.au=Merchant%2C+Melinda+S%3BWoo%2C+Chan-Wook%3BMackall%2C+Crystal+L%3BThiele%2C+Carol+J&rft.aulast=Merchant&rft.aufirst=Melinda&rft.date=2002-11-20&rft.volume=94&rft.issue=22&rft.spage=1673&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 - 2002-12-11 N1 - Date created - 2002-11-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Natl Cancer Inst. 2002 Nov 20;94(22):1660-1 [12441314] J Natl Cancer Inst. 2003 Jul 16;95(14):1087-8; author reply 1088-9 [12865456] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Arsenic-Related Chromosomal Alterations in Bladder Cancer AN - 18628129; 5532763 AB - Background: Previous studies have demonstrated that ingestion of arsenic in drinking water is a strong risk factor for several forms of cancer, including bladder cancer. It is not known whether arsenic-related cancers are genetically similar to cancers in unexposed individuals or what mechanisms of carcinogenesis may underlie their formation. This study was designed to compare chromosomal alterations in bladder cancers of arsenic-exposed individuals to provide insight into the mechanism of how arsenic may induce or promote cancer. Methods: A case-case study was conducted in Argentina and Chile examining chromosomal alterations in bladder tumor DNA in 123 patients who had been exposed to arsenic in their drinking water. Patients were placed into one of four arsenic exposure categories according to their average 5-year peak arsenic exposure. Patients were also classified as ever smokers or never smokers. Conclusions: Bladder tumors in patients with higher levels of arsenic exposure showed higher levels of chromosomal instability. Most of the chromosomal alterations associated with arsenic exposure were also associated with tumor stage and grade, raising the possibility that bladder tumors from arsenic-exposed patients may behave more aggressively than tumors from unexposed patients. JF - Journal of the National Cancer Institute AU - Moore, LE AU - Smith, AH AU - Eng, C AU - Kalman, D AU - DeVries, S AU - Bhargava, V AU - Chew, K AU - Moore, D II AU - Ferreccio, C AU - Rey, O A AU - Waldman, F M AD - Occupational Epidemiology Branch, NCI, 6120 Executive Blvd., EPS 8118, MSC 7240, Bethesda, MD 20892-7240, USA, moorele@mail.nih.gov Y1 - 2002/11/20/ PY - 2002 DA - 2002 Nov 20 SP - 1688 EP - 1696 VL - 94 IS - 22 SN - 0027-8874, 0027-8874 KW - urinary bladder KW - Risk Abstracts; Health & Safety Science Abstracts; Pollution Abstracts KW - H 11000:Diseases/Injuries/Trauma KW - R2 23060:Medical and environmental health KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18628129?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Arsenic-Related+Chromosomal+Alterations+in+Bladder+Cancer&rft.au=Moore%2C+LE%3BSmith%2C+AH%3BEng%2C+C%3BKalman%2C+D%3BDeVries%2C+S%3BBhargava%2C+V%3BChew%2C+K%3BMoore%2C+D+II%3BFerreccio%2C+C%3BRey%2C+O+A%3BWaldman%2C+F+M&rft.aulast=Moore&rft.aufirst=LE&rft.date=2002-11-20&rft.volume=94&rft.issue=22&rft.spage=1688&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - CPAPER T1 - Analysis of the ADAR2 RNA-editing reaction using substrate analogues modified at the atomic level AN - 39617458; 3703563 AU - Easterwood, L M AU - Veliz, E A AU - Yi-Brunozzi, H AU - Beal, P A Y1 - 2002/11/19/ PY - 2002 DA - 2002 Nov 19 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39617458?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Analysis+of+the+ADAR2+RNA-editing+reaction+using+substrate+analogues+modified+at+the+atomic+level&rft.au=Easterwood%2C+L+M%3BVeliz%2C+E+A%3BYi-Brunozzi%2C+H%3BBeal%2C+P+A&rft.aulast=Easterwood&rft.aufirst=L&rft.date=2002-11-19&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: RNA 2002, 800 Langdon Street, Madison, WI 53706, USA; phone: 608-265-6534; email: rna2002@union.wisc.edu; URL: www.union.wisc.edu/conferenceservices/rna/ N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Unphosphorylated-Ser366 La antigen accumulates in nucleoli and is not associated with nascent RNA polymerase III transcripts AN - 39590804; 3703657 AU - Intine, R AU - Dundr, M AU - Sakulich, A AU - Misteli, T AU - Maraia, R Y1 - 2002/11/19/ PY - 2002 DA - 2002 Nov 19 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39590804?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Unphosphorylated-Ser366+La+antigen+accumulates+in+nucleoli+and+is+not+associated+with+nascent+RNA+polymerase+III+transcripts&rft.au=Intine%2C+R%3BDundr%2C+M%3BSakulich%2C+A%3BMisteli%2C+T%3BMaraia%2C+R&rft.aulast=Intine&rft.aufirst=R&rft.date=2002-11-19&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: RNA 2002, 800 Langdon Street, Madison, WI 53706, USA; phone: 608-265-6534; email: rna2002@union.wisc.edu; URL: www.union.wisc.edu/conferenceservices/rna/ N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Suppression of mRNA nonsense mediated decay in Smith-Lemli-Opitz syndrome AN - 39590496; 3703527 AU - Correa-Cerro, L S AU - Krakowiak, P A AU - Wassif, CA AU - Porter, F D Y1 - 2002/11/19/ PY - 2002 DA - 2002 Nov 19 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39590496?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Suppression+of+mRNA+nonsense+mediated+decay+in+Smith-Lemli-Opitz+syndrome&rft.au=Correa-Cerro%2C+L+S%3BKrakowiak%2C+P+A%3BWassif%2C+CA%3BPorter%2C+F+D&rft.aulast=Correa-Cerro&rft.aufirst=L&rft.date=2002-11-19&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: RNA 2002, 800 Langdon Street, Madison, WI 53706, USA; phone: 608-265-6534; email: rna2002@union.wisc.edu; URL: www.union.wisc.edu/conferenceservices/rna/ N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Pre-clinical and clinical safety (critical review) AN - 39588261; 3707091 AU - Black, R Y1 - 2002/11/19/ PY - 2002 DA - 2002 Nov 19 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39588261?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Pre-clinical+and+clinical+safety+%28critical+review%29&rft.au=Black%2C+R&rft.aulast=Black&rft.aufirst=R&rft.date=2002-11-19&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Microbicides 2002, Nationalestraat 155, B-2000 Antwerp, Belgium; phone: 32 3 247 65 39; fax: 32 3 247 65 32; email: yjacob@itg.be; URL: www.itg.be/micro2002/index.html N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Dynamic conformational model for the role of ITS2 in pre-rRNA processing in yeast AN - 39573268; 3703528 AU - Cote, CA AU - Greer, CL AU - Peculis, BA Y1 - 2002/11/19/ PY - 2002 DA - 2002 Nov 19 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39573268?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Dynamic+conformational+model+for+the+role+of+ITS2+in+pre-rRNA+processing+in+yeast&rft.au=Cote%2C+CA%3BGreer%2C+CL%3BPeculis%2C+BA&rft.aulast=Cote&rft.aufirst=CA&rft.date=2002-11-19&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: RNA 2002, 800 Langdon Street, Madison, WI 53706, USA; phone: 608-265-6534; email: rna2002@union.wisc.edu; URL: www.union.wisc.edu/conferenceservices/rna/ N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Co-receptor use ex vivo AN - 39572472; 3707116 AU - Margolis, L Y1 - 2002/11/19/ PY - 2002 DA - 2002 Nov 19 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39572472?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Co-receptor+use+ex+vivo&rft.au=Margolis%2C+L&rft.aulast=Margolis&rft.aufirst=L&rft.date=2002-11-19&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Microbicides 2002, Nationalestraat 155, B-2000 Antwerp, Belgium; phone: 32 3 247 65 39; fax: 32 3 247 65 32; email: yjacob@itg.be; URL: www.itg.be/micro2002/index.html N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Novel HIV-1 neutralizing protein based on sequential receptor interactions: Potential use as a topical microbicide against sexual transmission AN - 39557149; 3707115 AU - Berger, E Y1 - 2002/11/19/ PY - 2002 DA - 2002 Nov 19 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39557149?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Novel+HIV-1+neutralizing+protein+based+on+sequential+receptor+interactions%3A+Potential+use+as+a+topical+microbicide+against+sexual+transmission&rft.au=Berger%2C+E&rft.aulast=Berger&rft.aufirst=E&rft.date=2002-11-19&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Microbicides 2002, Nationalestraat 155, B-2000 Antwerp, Belgium; phone: 32 3 247 65 39; fax: 32 3 247 65 32; email: yjacob@itg.be; URL: www.itg.be/micro2002/index.html N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Xenopus LSm proteins bind U8 snoRNA via an internal evolutionarily conserved octamer sequence AN - 39542866; 3704040 AU - Peculis, BA AU - Tomasevic, N AU - Robbins, K Y1 - 2002/11/19/ PY - 2002 DA - 2002 Nov 19 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39542866?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Xenopus+LSm+proteins+bind+U8+snoRNA+via+an+internal+evolutionarily+conserved+octamer+sequence&rft.au=Peculis%2C+BA%3BTomasevic%2C+N%3BRobbins%2C+K&rft.aulast=Peculis&rft.aufirst=BA&rft.date=2002-11-19&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: RNA 2002, 800 Langdon Street, Madison, WI 53706, USA; phone: 608-265-6534; email: rna2002@union.wisc.edu; URL: www.union.wisc.edu/conferenceservices/rna/ N1 - Last updated - 2010-05-03 ER - TY - JOUR T1 - Enhanced locomotor, reinforcing, and neurochemical effects of cocaine in serotonin 5-hydroxytryptamine 2C receptor mutant mice. AN - 72686446; 12427861 AB - Brain serotonin [5-hydroxytryptamine (5-HT)] systems substantially influence the effects of cocaine; however, the contributions of individual 5-HT receptor subtypes to the regulation of cocaine responses are unclear. A line of mutant mice devoid of 5-HT2C receptors was used to examine the contribution of this receptor subtype to the serotonergic modulation of cocaine responses. Mutants display enhanced exploration of a novel environment and increased sensitivity to the locomotor stimulant effects of cocaine. In an operant intravenous self-administration model under a progressive ratio schedule of reinforcement, mutants display elevated levels of lever pressing for cocaine injections, indicating that the drug is more reinforcing in these mice. Moreover, mutants exhibit enhanced cocaine-induced elevations of dopamine (DA) levels in the nucleus accumbens, a brain region implicated in the stimulant and rewarding properties of cocaine. In contrast, phenotypic differences in dorsal striatal DA levels were not produced by cocaine treatment. These findings strongly implicate 5-HT2C receptors in the serotonergic suppression of DA-mediated behavioral responses to cocaine and as a potential therapeutic target for cocaine abuse. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Rocha, Beatriz A AU - Goulding, Evan H AU - O'Dell, Laura E AU - Mead, Andy N AU - Coufal, Nicole G AU - Parsons, Loren H AU - Tecott, Laurence H AD - National Institute on Drug Abuse/Intramural Research Program, Baltimore, Maryland 21224, USA. Y1 - 2002/11/15/ PY - 2002 DA - 2002 Nov 15 SP - 10039 EP - 10045 VL - 22 IS - 22 KW - Receptor, Serotonin, 5-HT2C KW - 0 KW - Receptors, Serotonin KW - Cocaine KW - I5Y540LHVR KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Conditioning, Operant -- drug effects KW - Animals KW - Drug Resistance -- genetics KW - Nucleus Accumbens -- drug effects KW - Brain Chemistry -- drug effects KW - Corpus Striatum -- metabolism KW - Disease Models, Animal KW - Dopamine -- metabolism KW - Mice KW - Microdialysis KW - Behavior, Animal -- drug effects KW - Mice, Mutant Strains KW - Self Administration KW - Exploratory Behavior -- drug effects KW - Mice, Inbred C57BL KW - Nucleus Accumbens -- metabolism KW - Corpus Striatum -- drug effects KW - Dopamine -- analysis KW - Male KW - Cocaine-Related Disorders -- genetics KW - Receptors, Serotonin -- deficiency KW - Reinforcement (Psychology) KW - Motor Activity -- drug effects KW - Cocaine -- pharmacology KW - Receptors, Serotonin -- genetics KW - Cocaine-Related Disorders -- metabolism KW - Cocaine -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72686446?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Enhanced+locomotor%2C+reinforcing%2C+and+neurochemical+effects+of+cocaine+in+serotonin+5-hydroxytryptamine+2C+receptor+mutant+mice.&rft.au=Rocha%2C+Beatriz+A%3BGoulding%2C+Evan+H%3BO%27Dell%2C+Laura+E%3BMead%2C+Andy+N%3BCoufal%2C+Nicole+G%3BParsons%2C+Loren+H%3BTecott%2C+Laurence+H&rft.aulast=Rocha&rft.aufirst=Beatriz&rft.date=2002-11-15&rft.volume=22&rft.issue=22&rft.spage=10039&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=1529-2401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-18 N1 - Date created - 2002-11-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Correlation between electron-donating ability of a series of 3-nitroflavones and their efficacy to inhibit the onset and progression of aberrant crypt foci in the rat colon. AN - 72681268; 12438244 AB - A series of five 3-nitroflavones were tested for their ability to inhibit the formation of colon aberrant crypt foci (ACF) induced by a s.c. injection of azoxymethane (C2H6N2O) in rats. Our aim was to relate the electron-donating effects of the 3-nitroflavones as characterized by their Hammett substitution constants with their efficacy in inhibiting ACF. In a first assay (initiation, protocol A) the 3-nitroflavone as well as the 4'-substituted nitro-, methoxy-, fluoro-, and hydroxy-3-nitroflavones were continuously present in the diet. In a second assay (postinitiation, protocol B) they were given for a period of 4 weeks after the last azoxymethane injection. The different substituents of the 3-nitroflavones at the 4'-position spanned a spectrum of Hammett constants (sigma(p+)), going from +0.79 for the electron-withdrawing group, NO2, to -0.92 for the electron-donating group, OH. For both protocols the percentages of inhibition plotted versus the Hammett substitution constants showed a linear correlation, the most efficacious ACF inhibition being produced by the molecules with the most electron-donating substituents. Moreover, the nitroflavones were not only chemoprotective during initiation of the ACF, but also therapeutic in the postinitiation progression assay. The above correlations may be of predictive value in the search for new chemoprotective agents. The overall molecular mechanism of the inhibition of ACF by the 3-nitroflavones under study appears to involve redox reactions. JF - Cancer research AU - Steele, Vernon E AU - Boone, Charles W AU - Dauzonne, Daniel AU - Rao, Chinthalapally V AU - Bensasson, René V AD - Division of Cancer Prevention, National Cancer Institute, NIH, Bethesda, Maryland 20892-7322, USA. vs1y@nih.gov Y1 - 2002/11/15/ PY - 2002 DA - 2002 Nov 15 SP - 6506 EP - 6509 VL - 62 IS - 22 SN - 0008-5472, 0008-5472 KW - Anticarcinogenic Agents KW - 0 KW - Carcinogens KW - Flavonoids KW - Nitro Compounds KW - Reducing Agents KW - Azoxymethane KW - MO0N1J0SEN KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Structure-Activity Relationship KW - Nitro Compounds -- chemistry KW - Flavonoids -- chemistry KW - Precancerous Conditions -- chemically induced KW - Precancerous Conditions -- prevention & control KW - Anticarcinogenic Agents -- pharmacology KW - Anticarcinogenic Agents -- chemistry KW - Reducing Agents -- chemistry KW - Flavonoids -- pharmacology KW - Reducing Agents -- pharmacology KW - Nitro Compounds -- pharmacology KW - Colonic Neoplasms -- prevention & control KW - Colonic Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72681268?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Correlation+between+electron-donating+ability+of+a+series+of+3-nitroflavones+and+their+efficacy+to+inhibit+the+onset+and+progression+of+aberrant+crypt+foci+in+the+rat+colon.&rft.au=Steele%2C+Vernon+E%3BBoone%2C+Charles+W%3BDauzonne%2C+Daniel%3BRao%2C+Chinthalapally+V%3BBensasson%2C+Ren%C3%A9+V&rft.aulast=Steele&rft.aufirst=Vernon&rft.date=2002-11-15&rft.volume=62&rft.issue=22&rft.spage=6506&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 - 2002-12-17 N1 - Date created - 2002-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Multiple HLA class II-restricted melanocyte differentiation antigens are recognized by tumor-infiltrating lymphocytes from a patient with melanoma. AN - 72665686; 12421991 AB - Dramatic clinical responses were observed in patient 888 following the adoptive transfer of autologous tumor-infiltrating lymphocytes (TIL). Previously, extensive analysis of the specificity of class I-restricted T cells from patient 888 TIL has revealed that these T cells recognize a mutated, as well as several nonmutated tumor Ags. Additional studies that were conducted on TIL from patient 888 indicated that they contained CD4-positive T cells that recognized the autologous tumor that had been induced to express HLA class II molecules. Tumor-reactive CD4-positive T cell clones were isolated from TIL and tested for their ability to react with Ags that are recognized by HLA class I-restricted, melanoma-reactive T cells. Using this approach, T cell clones were identified that recognized an epitope expressed in both the tyrosinase-related protein 1 and tyrosinase-related protein 2 Ags in the context of the HLA-DRbeta1*1502 class II gene product. Additional clones were found to recognize an epitope of gp100 in the context of the same HLA-DR restriction element. These observations provide an impetus to develop strategies directed toward generating HLA class II-restricted tumor-reactive T cells. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Robbins, Paul F AU - El-Gamil, Mona AU - Li, Yong F AU - Zeng, Gang AU - Dudley, Mark AU - Rosenberg, Steven A AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Building 10, Room 2B42, Bethesda, MD 20892-7502, USA. Y1 - 2002/11/15/ PY - 2002 DA - 2002 Nov 15 SP - 6036 EP - 6047 VL - 169 IS - 10 SN - 0022-1767, 0022-1767 KW - Antigens, Differentiation KW - 0 KW - Antigens, Neoplasm KW - Epitopes, T-Lymphocyte KW - HLA Antigens KW - HLA-DR Antigens KW - HLA-DRB1 Chains KW - HLA-DRB5 Chains KW - Histocompatibility Antigens Class II KW - Isoantigens KW - Membrane Glycoproteins KW - Neoplasm Proteins KW - PMEL protein, human KW - Proteins KW - gp100 Melanoma Antigen KW - Oxidoreductases KW - EC 1.- KW - TYRP1 protein, human KW - EC 1.14.18.- KW - tyrosinase-related protein-1 KW - Abridged Index Medicus KW - Index Medicus KW - Clone Cells KW - Animals KW - COS Cells KW - Humans KW - HLA-DR Antigens -- genetics KW - CD4-Positive T-Lymphocytes -- immunology KW - HLA-DR Antigens -- metabolism KW - Epitopes, T-Lymphocyte -- immunology KW - Alleles KW - Tumor Cells, Cultured KW - Molecular Sequence Data KW - Isoantigens -- immunology KW - Isoantigens -- metabolism KW - Neoplasm Proteins -- metabolism KW - Neoplasm Proteins -- immunology KW - Amino Acid Sequence KW - Proteins -- metabolism KW - Proteins -- immunology KW - Epitopes, T-Lymphocyte -- metabolism KW - HLA-DR Antigens -- immunology KW - CD4-Positive T-Lymphocytes -- metabolism KW - Lymphocyte Activation -- immunology KW - Cytotoxicity Tests, Immunologic KW - Membrane Glycoproteins -- immunology KW - Membrane Glycoproteins -- metabolism KW - Lymphocytes, Tumor-Infiltrating -- immunology KW - Antigens, Differentiation -- metabolism KW - Melanocytes -- metabolism KW - Antigens, Differentiation -- immunology KW - Histocompatibility Antigens Class II -- immunology KW - Melanoma -- immunology KW - Melanoma -- metabolism KW - Lymphocytes, Tumor-Infiltrating -- metabolism KW - HLA Antigens -- metabolism KW - Histocompatibility Antigens Class II -- metabolism KW - HLA Antigens -- immunology KW - Antigens, Neoplasm -- metabolism KW - Melanocytes -- immunology KW - Antigens, Neoplasm -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72665686?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Multiple+HLA+class+II-restricted+melanocyte+differentiation+antigens+are+recognized+by+tumor-infiltrating+lymphocytes+from+a+patient+with+melanoma.&rft.au=Robbins%2C+Paul+F%3BEl-Gamil%2C+Mona%3BLi%2C+Yong+F%3BZeng%2C+Gang%3BDudley%2C+Mark%3BRosenberg%2C+Steven+A&rft.aulast=Robbins&rft.aufirst=Paul&rft.date=2002-11-15&rft.volume=169&rft.issue=10&rft.spage=6036&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 - 2003-01-14 N1 - Date created - 2002-11-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: N Engl J Med. 1995 Oct 19;333(16):1038-44 [7675046] J Immunol. 1996 Apr 1;156(7):2495-502 [8786310] J Exp Med. 1996 Mar 1;183(3):1185-92 [8642260] J Exp Med. 1996 May 1;183(5):1965-71 [8642306] J Immunol. 1996 Mar 15;156(6):2205-13 [8690910] J Virol. 1996 Aug;70(8):5701-5 [8764092] J Immunother Emphasis Tumor Immunol. 1996 Sep;19(5):357-63 [8941875] J Immunol. 1999 Dec 1;163(11):5820-6 [10570265] J Immunol. 1997 Jul 1;159(1):303-8 [9200467] J Invest Dermatol. 1997 Dec;109(6):788-95 [9406822] J Exp Med. 1998 Jul 20;188(2):277-86 [9670040] Cancer Immunol Immunother. 1998 Sep;47(1):32-8 [9755876] J Immunol. 1999 Jan 15;162(2):989-94 [9916724] J Exp Med. 1999 Mar 1;189(5):757-66 [10049939] Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2982-7 [10077623] J Biol Chem. 1999 Apr 30;274(18):12780-9 [10212263] J Exp Med. 1999 May 17;189(10):1659-68 [10330445] Science. 1999 May 21;284(5418):1351-4 [10334988] Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14809-14 [8962137] Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):400-5 [10618430] J Exp Med. 2000 Feb 21;191(4):625-30 [10684854] J Immunother. 2000 Jan;23(1):17-27 [10687134] J Immunol. 2000 Apr 1;164(7):3535-42 [10725708] J Immunol. 2000 Jul 15;165(2):1153-9 [10878395] Surgery. 2000 Aug;128(2):273-80 [10923004] Cancer Res. 2000 Sep 1;60(17):4855-63 [10987298] Cancer Res. 2000 Sep 1;60(17):4946-52 [10987311] Cancer Immunol Immunother. 2001 Mar;50(1):3-15 [11315507] Virology. 2001 Aug 15;287(1):79-88 [11504544] Cell Immunol. 2001 Jun 15;210(2):96-105 [11520076] J Immunol. 2001 Oct 15;167(8):4758-64 [11591807] Cancer Res. 2001 Oct 15;61(20):7577-84 [11606397] Br J Cancer. 2001 Nov 30;85(11):1738-45 [11742496] J Exp Med. 1984 Jul 1;160(1):255-69 [6204001] J Exp Med. 1991 Oct 1;174(4):809-13 [1833502] Cancer Res. 1994 Jun 15;54(12):3124-6 [8205528] J Clin Oncol. 1994 Jul;12(7):1475-83 [8021739] J Immunol. 1995 Jan 15;154(2):772-9 [7814883] J Exp Med. 1995 Feb 1;181(2):765-7 [7836928] J Immunol. 1995 Apr 15;154(8):3961-8 [7706734] J Immunol. 1995 Jun 1;154(11):5944-50 [7751637] J Interferon Cytokine Res. 1995 Aug;15(8):739-46 [8528947] J Exp Med. 1995 Nov 1;182(5):1609-14 [7595233] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Postoperative adjuvant chemoradiation in completely resected locally advanced gastric cancer. AN - 72663065; 12419433 AB - The 5-year survival of patients with completely resected node-positive gastric cancer ranges from 15% to 25%. We explored the feasibility of a chemoradiation regime consisting of concomitant hyperfractionated radiotherapy and 5-fluorouracil protracted venous infusion (5-FU PVI). Forty patients received a total or partial gastrectomy operation and D2 nodal resection for Stage III gastric cancer; they were then irradiated by linac with 6-15-MV photons. The target included the gastric bed, the anastomosis, stumps, and regional nodes. A total dose of 55 Gy was given in 50 fractions using 1.1 Gy b.i.d. All patients received a concomitant 200 mg/m2/day 5-FU PVI. Patients were examined during the follow-up period as programmed. Toxicity was recorded according to RTOG criteria. After a median follow-up of 75.6 months (range: 22-136 months), 24 (60%) patients had died, and 16 (40%) were alive and free of disease. The 5-year actuarial incidence of relapse was 39%, 22%, and 2% for distant metastases, out-field peritoneal seeding, and in-field local regional recurrences, respectively. The 5-year actuarial cause-specific survival was 43%. Three patients survived more than 11 years. Acute > or = Grade 3 toxicity consisted of hematologic (22.5%) and gastrointestinal toxicity (nausea and vomiting 22.5%, diarrhea 2.8%, and abdominal pain 2.6%). No late toxicity was observed. This regime of concomitant 5-FU PVI and hyperfractionated radiotherapy was well tolerated and resulted in successful locoregional control and satisfactory survival. JF - International journal of radiation oncology, biology, physics AU - Arcangeli, Giorgio AU - Saracino, Biancamaria AU - Arcangeli, Giancarlo AU - Angelini, Francesco AU - Marchetti, Paolo AU - Tirindelli Danesi, Donatella AD - Division of Radiation Oncology, Regina Elena National Cancer Institute, Via E. Chianesi 53, 00144 Rome, Italy. arcangeli@ifo.it Y1 - 2002/11/15/ PY - 2002 DA - 2002 Nov 15 SP - 1069 EP - 1075 VL - 54 IS - 4 SN - 0360-3016, 0360-3016 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Survival Rate KW - Combined Modality Therapy KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Neoplasm Recurrence, Local KW - Gastrectomy KW - Lymph Node Excision KW - Male KW - Female KW - Radiotherapy -- adverse effects KW - Antineoplastic Agents -- adverse effects KW - Stomach Neoplasms -- mortality KW - Stomach Neoplasms -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72663065?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Postoperative+adjuvant+chemoradiation+in+completely+resected+locally+advanced+gastric+cancer.&rft.au=Arcangeli%2C+Giorgio%3BSaracino%2C+Biancamaria%3BArcangeli%2C+Giancarlo%3BAngelini%2C+Francesco%3BMarchetti%2C+Paolo%3BTirindelli+Danesi%2C+Donatella&rft.aulast=Arcangeli&rft.aufirst=Giorgio&rft.date=2002-11-15&rft.volume=54&rft.issue=4&rft.spage=1069&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 - 2002-12-10 N1 - Date created - 2002-11-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recommendations for prevention of and therapy for exposure to B virus (cercopithecine herpesvirus 1). AN - 72645293; 12410479 AB - B virus (Cercopithecine herpesvirus 1) is a zoonotic agent that can cause fatal encephalomyelitis in humans. The virus naturally infects macaque monkeys, resulting in disease that is similar to herpes simplex virus infection in humans. Although B virus infection generally is asymptomatic or mild in macaques, it can be fatal in humans. Previously reported cases of B virus disease in humans usually have been attributed to animal bites, scratches, or percutaneous inoculation with infected materials; however, the first fatal case of B virus infection due to mucosal splash exposure was reported in 1998. This case prompted the Centers for Disease Control and Prevention (Atlanta, Georgia) to convene a working group in 1999 to reconsider the prior recommendations for prevention and treatment of B virus exposure. The present report updates previous recommendations for the prevention, evaluation, and treatment of B virus infection in humans and considers the role of newer antiviral agents in postexposure prophylaxis. JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America AU - Cohen, Jeffrey I AU - Davenport, David S AU - Stewart, John A AU - Deitchman, Scott AU - Hilliard, Julia K AU - Chapman, Louisa E AU - B Virus Working Group AD - Medical Virology Section, Laboratory of Clinical Investigation, National Institutes of Health, Bethesda, Maryland 20892, USA. jcohen@niaid.nih.gov ; B Virus Working Group Y1 - 2002/11/15/ PY - 2002 DA - 2002 Nov 15 SP - 1191 EP - 1203 VL - 35 IS - 10 KW - Antiviral Agents KW - 0 KW - Valine KW - HG18B9YRS7 KW - valacyclovir KW - MZ1IW7Q79D KW - Acyclovir KW - X4HES1O11F KW - Index Medicus KW - Animals KW - Primates -- virology KW - Humans KW - Follow-Up Studies KW - Chemoprevention -- standards KW - Drug Therapy -- standards KW - Herpesviridae Infections -- transmission KW - Antiviral Agents -- therapeutic use KW - Herpesvirus 1, Cercopithecine -- immunology KW - Acyclovir -- therapeutic use KW - Valine -- adverse effects KW - Acyclovir -- adverse effects KW - Encephalomyelitis -- drug therapy KW - Herpesviridae Infections -- prevention & control KW - Herpesviridae Infections -- physiopathology KW - Health Planning Guidelines KW - Valine -- analogs & derivatives KW - Herpesviridae Infections -- drug therapy KW - Valine -- therapeutic use KW - Antiviral Agents -- adverse effects KW - Encephalomyelitis -- etiology KW - Herpesvirus 1, Cercopithecine -- drug effects KW - Acyclovir -- analogs & derivatives KW - Encephalomyelitis -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72645293?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.atitle=Recommendations+for+prevention+of+and+therapy+for+exposure+to+B+virus+%28cercopithecine+herpesvirus+1%29.&rft.au=Cohen%2C+Jeffrey+I%3BDavenport%2C+David+S%3BStewart%2C+John+A%3BDeitchman%2C+Scott%3BHilliard%2C+Julia+K%3BChapman%2C+Louisa+E%3BB+Virus+Working+Group&rft.aulast=Cohen&rft.aufirst=Jeffrey&rft.date=2002-11-15&rft.volume=35&rft.issue=10&rft.spage=1191&rft.isbn=&rft.btitle=&rft.title=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.issn=1537-6591&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-18 N1 - Date created - 2002-10-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Homologues of Human Macrophage Migration Inhibitory Factor from a Parasitic Nematode. GENE CLONING, PROTEIN ACTIVITY, AND CRYSTAL STRUCTURE AN - 19932995; 5489007 AB - Cytokines are the molecular messengers of the vertebrate immune system, coordinating the local and systemic immune responses to infective organisms. We report here functional and structural data on cytokine-like proteins from a eukaryotic pathogen. Two homologues of the human cytokine macrophage migration inhibitory factor (MIF) have been isolated from the parasitic nematode Brugia malayi. Both molecules (Bm-MIF-1 and Bm-MIF-2) show parallel functions to human MIF. They are chemotactic for human monocytes and activate them to produce IL-8, TNF-[alpha], and endogenous MIF. The human and nematode MIF homologues share a tautomerase enzyme activity, which is in each case abolished by the mutation of the N-terminal proline residue. The crystal structure of Bm-MIF-2 at 1.8-Aa resolution has been determined, revealing a trimeric assembly with an inner pore created by [beta]-stranded sheets from each subunit. Both biological activity and crystal structure reveal remarkable conservation between a human cytokine and its parasite counterpart despite the considerable phylogenetic divide among these organisms. The strength of the similarity implies that MIF-mediated pathways play an important role in nematode immune evasion strategies. JF - Journal of Biological Chemistry AU - Zang, X AU - Taylor, P AU - Wang, J M AU - Meyer, D J AU - Scott, AL AU - Walkinshaw, MD AU - Maizels, R M AD - Institute of Cell, Animal & Population Biology, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom, Institute of Cell and Molecular Biology, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom, Laboratory of Molecular Immunoregulation, NCI, National Institutes of Health, Frederick Cancer Research and Development Center, Bethesda, Maryland 21702-1201, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom, and Department of Molecular Microbiology and Immunology, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland, xxzang@uclink4.berkeley.edu. Y1 - 2002/11/15/ PY - 2002 DA - 2002 Nov 15 SP - 44261 EP - 44267 VL - 277 IS - 46 SN - 0021-9258, 0021-9258 KW - Genetics Abstracts; Biotechnology and Bioengineering Abstracts; Immunology Abstracts KW - Phylogeny KW - Parasites KW - Proline KW - Data processing KW - Macrophage migration inhibitory factor KW - Immune system KW - Enzymes KW - Pathogens KW - Interleukin 8 KW - Pores KW - Brugia malayi KW - Structure-function relationships KW - Crystal structure KW - Cytokines KW - Conservation KW - Monocytes KW - Immune response KW - Mutation KW - Nematoda KW - W 30925:Genetic Engineering KW - F 06910:Microorganisms & Parasites KW - G 07700:Molecular Genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19932995?accountid=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=Homologues+of+Human+Macrophage+Migration+Inhibitory+Factor+from+a+Parasitic+Nematode.+GENE+CLONING%2C+PROTEIN+ACTIVITY%2C+AND+CRYSTAL+STRUCTURE&rft.au=Zang%2C+X%3BTaylor%2C+P%3BWang%2C+J+M%3BMeyer%2C+D+J%3BScott%2C+AL%3BWalkinshaw%2C+MD%3BMaizels%2C+R+M&rft.aulast=Zang&rft.aufirst=X&rft.date=2002-11-15&rft.volume=277&rft.issue=46&rft.spage=44261&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 - 2008-08-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Phylogeny; Parasites; Proline; Data processing; Macrophage migration inhibitory factor; Immune system; Enzymes; Pathogens; Interleukin 8; Pores; Structure-function relationships; Crystal structure; Conservation; Cytokines; Immune response; Monocytes; Mutation; Brugia malayi; Nematoda ER - TY - JOUR T1 - Nicotinic receptors mediate increased GABA release in brain through a tetrodotoxin-insensitive mechanism during prolonged exposure to nicotine AN - 18634847; 5545448 AB - The effects of nicotine on the spontaneous release of GABA from nerve terminals in the chick lateral spiriform nucleus were examined using whole cell patch-clamp recording in brain slices. Exposure to 1 mu M nicotine produced an early immediate increase in the frequency of spontaneous postsynaptic GABAergic currents. This effect was blocked in the presence of 0.5 mu M tetrodotoxin. However, a prolonged application of 0.1-1 mu M nicotine (>3 min) caused a tetrodotoxin-insensitive increase in the frequency of spontaneous GABAergic currents. This late tetrodotoxin-insensitive effect was blocked by the nicotinic antagonists dihydro- beta -erythroidine (30 mu M) and mecamylamine (10 mu M), but not by methyllycaconitine (50-100 nM), indicating that activation of high affinity nicotine receptors was mainly responsible for this effect. This enhancement was inhibited by the high threshold Ca super(2+) channel blocker Cd super(2+) (100 mu M), but not by dantrolene or ryanodine. The tetrodotoxin-insensitive enhancement of the frequency of GABA currents by nicotine was reduced by inhibition of cAMP-dependent protein kinase with HA1004 (30 mu M), but not by inhibition of protein kinase C with staurosporine (1 mu M), and was facilitated by forskolin (10 mu M) or bromo-cAMP (50 mu M). The results indicate that nicotine-enhanced GABA release can operate through both tetrodotoxin-sensitive and -insensitive mechanisms in a single brain region and that a second messenger cascade may be involved in the tetrodotoxin-insensitive enhancement by nicotine. JF - Neuroscience AU - Zhu, P J AU - Chiappinelli, V A AD - Laboratory of Molecular and Cellular Neurobiology, NIAAA/NIH, 12420 Parklawn Drive, Park Building/Room 118, Rockville, MD 20852, USA, pzhu@mail.nih.gov Y1 - 2002/11/15/ PY - 2002 DA - 2002 Nov 15 SP - 137 EP - 144 VL - 115 IS - 1 SN - 0306-4522, 0306-4522 KW - chickens KW - dihydro- beta -erythroidine KW - in vitro KW - Toxicology Abstracts KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18634847?accountid=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=Neuroscience&rft.atitle=Nicotinic+receptors+mediate+increased+GABA+release+in+brain+through+a+tetrodotoxin-insensitive+mechanism+during+prolonged+exposure+to+nicotine&rft.au=Zhu%2C+P+J%3BChiappinelli%2C+V+A&rft.aulast=Zhu&rft.aufirst=P&rft.date=2002-11-15&rft.volume=115&rft.issue=1&rft.spage=137&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&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 - Rescue of neurodegeneration in Niemann-Pick C mice by a prion-promoter-driven Npc1 cDNA transgene AN - 18624656; 5534934 AB - Niemann-Pick disease type C (NPC) is a neurodegenerative disorder with major visceral complications, including liver disease that can be fatal before onset of neurodegeneration. We have sought to determine the extent to which visceral disease contributes to neurodegeneration by making transgenic mice in which the wild-type NPC1 protein is expressed primarily in the CNS using the prion promoter. When the transgene was introduced into the npc1 super(-/-) animals neurodegeneration was prevented, a 'normal' lifespan occurred and the sterility of npc1 super(-/-) mice was corrected. The rescue did not provide complete neurological correction in the CNS as GM2 and GM3 gangliosides were observed to accumulate in some neurons and glia of transgenic animals. Two of three transgenic lines demonstrated some low-level ectopic expression resulting in correction of visceral phenotypes in liver and spleen. Interestingly, the third transgenic line continued to have moderate histocytosis in liver and spleen, yet had no detectable neurodegeneration. Thus, it is primarily the lack of NPC1 in the CNS and not the secondary effects of the visceral involvement that causes the neurological decline in NPC disease. In addition, the expression levels of NPC1 found in the CNS of transgenic animals were much greater than in normal littermates, demonstrating that overexpression of NPC1 is not harmful and allowing possibilities for genetic therapy interventions that utilize overexpression. JF - Human Molecular Genetics AU - Loftus, S K AU - Erickson, R P AU - Walkley, SU AU - Bryant, MA AU - Incao, A AU - Heidenreich, R A AU - Pavan, W J AD - National Institutes of Health, National Human Genome Research Institute, Genetic Disease Research Branch, 49 Convent Dr., Building 49, Room 4A67, Bethesda, MD 20892, USA, bpavan@nhgri.nih.gov Y1 - 2002/11/15/ PY - 2002 DA - 2002 Nov 15 SP - 3107 EP - 3114 VL - 11 IS - 24 SN - 0964-6906, 0964-6906 KW - Npc1 protein KW - Biotechnology and Bioengineering Abstracts; CSA Neurosciences Abstracts; Bioengineering Abstracts KW - N3 11054:Mammals (except primates) KW - W 30965:Miscellaneous, Reviews KW - W4 120:Genetic Engineering in Medicine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18624656?accountid=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+Molecular+Genetics&rft.atitle=Rescue+of+neurodegeneration+in+Niemann-Pick+C+mice+by+a+prion-promoter-driven+Npc1+cDNA+transgene&rft.au=Loftus%2C+S+K%3BErickson%2C+R+P%3BWalkley%2C+SU%3BBryant%2C+MA%3BIncao%2C+A%3BHeidenreich%2C+R+A%3BPavan%2C+W+J&rft.aulast=Loftus&rft.aufirst=S&rft.date=2002-11-15&rft.volume=11&rft.issue=24&rft.spage=3107&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Nickel(II)-Induced Apoptosis in Murine T Cell Hybridoma Cells Is Associated with Increased Fas Ligand Expression AN - 18624257; 5539415 AB - Nickel(II) exposure has multiple effects on the immune system, including thymic involution, decreased T cell number in the spleen, and decreased natural killer cell activity. Using a murine T cell hybridoma cell line (KMls 8.3.5.1) to model nickel-induced cell death in immune cells, we found that nickel(II) acetate treatment rapidly induced apoptosis in these cells, as signified by membrane blebbing, chromatin condensation, increased annexin V staining, and an increased proportion of cells with hypodiploid DNA. Preceding these morphological changes, nickel(II) treatment increased expression of Fas ligand (FasL) mRNA and protein levels and also increased caspase-3-like protease activity. Coincubation with caspase inhibitors markedly inhibited nickel(II)-induced apoptosis, with Z-IETD-FMK, an inhibitor of caspase-8 and granzyme B, nearly as effective as less selective caspase inhibitors. Agents that generate reactive oxygen species (ROS) cause apoptosis in a variety of cells by inducing expression of FasL. Given that nickel(II) can directly generate ROS, exposure to nickel(II) may lead to apoptosis through a similar mechanism. [copy ] 2002 Elsevier Science (USA). JF - Toxicology and Applied Pharmacology AU - Kim, K AU - Lee, S AU - Seo, Y AU - Perkins, S N AU - Kasprzak, K S AD - Office of Preventive Oncology, Laboratory of Biosystems and Cancer, Division of Cancer Prevention, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, 20892, perkinss@mail.ncifcrf.gov Y1 - 2002/11/15/ PY - 2002 DA - 2002 Nov 15 SP - 41 EP - 47 PB - Academic Press VL - 185 IS - 1 SN - 0041-008X, 0041-008X KW - FasL protein KW - KMls 8.3.5.1 KW - mice KW - Toxicology Abstracts KW - X 24155:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18624257?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+Applied+Pharmacology&rft.atitle=Nickel%28II%29-Induced+Apoptosis+in+Murine+T+Cell+Hybridoma+Cells+Is+Associated+with+Increased+Fas+Ligand+Expression&rft.au=Kim%2C+K%3BLee%2C+S%3BSeo%2C+Y%3BPerkins%2C+S+N%3BKasprzak%2C+K+S&rft.aulast=Kim&rft.aufirst=K&rft.date=2002-11-15&rft.volume=185&rft.issue=1&rft.spage=41&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+Applied+Pharmacology&rft.issn=0041008X&rft_id=info:doi/10.1006%2Ftaap.2002.9513 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1006/taap.2002.9513 ER - TY - JOUR T1 - Analysis of the Molecular Mechanisms of Human Estrogen Receptors [alpha] and [beta] Reveals Differential Specificity in Target Promoter Regulation by Xenoestrogens AN - 18507621; 5488987 AB - Most of the currently available information on the transcriptional activities of endocrine-disrupting chemicals (xenoestrogens) through estrogen receptors [alpha] (ER[alpha]) and [beta] (ER[beta]) has been derived from transactivation studies on synthetic estrogen-responsive reporters. Thus, the ability of the xenoestrogen-liganded ERs to regulate endogenous estrogen-responsive gene expression has not been well characterized. Here, we have evaluated the activities of xenoestrogens through ER[alpha] and ER[beta] on the vitellogenin A2 estrogen-response element (ERE) and the human pS2, lactoferrin, and complement 3 physiological target gene promoters. Using mammalian cell transient transfection assays, we found that the activities of xenoestrogens were mediated in a promoter-specific manner. For example, when bound to all ligands examined, ER[alpha] displayed high levels of transcription on the vitellogenin ERE and the lactoferrin promoter, but substantially lower activity on the complement 3 and pS2 promoters. However, one of the most important observations was that there were significant differences in the relative transcriptional activities of xenoestrogen-bound ER[alpha] and ER[beta] on different promoters, suggesting that ER[alpha] and ER[beta] make unique contributions to xenoestrogen action in target cells. When probing the molecular mechanism of the promoter-specific activities observed, we found that the transcriptional activity of the ERs correlated with the ability of each receptor to assume an active conformation on specific promoters. Taken together, the results indicate that the transcriptional activities of xenoestrogens are mediated in a promoter-specific manner and that estrogen-responsive promoters communicate differently with ER[alpha] and ER[beta] by influencing their structures in a distinct manner that leads to diversity in their transcriptional responses. JF - Journal of Biological Chemistry AU - Hall, J M AU - Korach, K S AD - Receptor Biology Section, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina Y1 - 2002/11/15/ PY - 2002 DA - 2002 Nov 15 SP - 44455 EP - 44461 VL - 277 IS - 46 SN - 0021-9258, 0021-9258 KW - man KW - specificity KW - Toxicology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - X 24240:Miscellaneous KW - N 14930:Transcription factors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18507621?accountid=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=Analysis+of+the+Molecular+Mechanisms+of+Human+Estrogen+Receptors+%5Balpha%5D+and+%5Bbeta%5D+Reveals+Differential+Specificity+in+Target+Promoter+Regulation+by+Xenoestrogens&rft.au=Hall%2C+J+M%3BKorach%2C+K+S&rft.aulast=Hall&rft.aufirst=J&rft.date=2002-11-15&rft.volume=277&rft.issue=46&rft.spage=44455&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 - Differential protection by nitroxides and hydroxylamines to radiation-induced and metal ion-catalyzed oxidative damage. AN - 72632824; 12399020 AB - Modulation of radiation- and metal ion-catalyzed oxidative-induced damage using plasmid DNA, genomic DNA, and cell survival, by three nitroxides and their corresponding hydroxylamines, were examined. The antioxidant property of each compound was independently determined by reacting supercoiled DNA with copper II/1,10-phenanthroline complex fueled by the products of hypoxanthine/xanthine oxidase (HX/XO) and noting the protective effect as assessed by agarose gel electrophoresis. The nitroxides and their corresponding hydroxylamines protected approximately to the same degree (33-47% relaxed form) when compared to 76.7% relaxed form in the absence of protectors. Likewise, protection by both the nitroxide and corresponding hydroxylamine were observed for Chinese hamster V79 cells exposed to hydrogen peroxide. In contrast, when plasmid DNA damage was induced by ionizing radiation (100 Gy), only nitroxides (10 mM) provide protection (32.4-38.5% relaxed form) when compared to radiation alone or in the presence of hydroxylamines (10 mM) (79.8% relaxed form). Nitroxide protection was concentration dependent. Radiation cell survival studies and DNA double-strand break (DBS) assessment (pulse field electrophoresis) showed that only the nitroxide protected or prevented damage, respectively. Collectively, the results show that nitroxides and hydroxylamines protect equally against the damage mediated by oxidants generated by the metal ion-catalyzed Haber-Weiss reaction, but only nitroxides protect against radiation damage, suggesting that nitroxides may more readily react with intermediate radical species produced by radiation than hydroxylamines. JF - Biochimica et biophysica acta AU - Xavier, Sandhya AU - Yamada, Ken-ichi AU - Samuni, Ayelet M AU - Samuni, Amram AU - DeGraff, William AU - Krishna, Murali C AU - Mitchell, James B AD - Radiation Biology Branch, National Cancer Institute, Bldg. 10, Room B3/B69, 9000 Rockville Pike, Bethesda, MD 20892-1002, USA. Y1 - 2002/11/14/ PY - 2002 DA - 2002 Nov 14 SP - 109 EP - 120 VL - 1573 IS - 2 SN - 0006-3002, 0006-3002 KW - Antioxidants KW - 0 KW - Cyclic N-Oxides KW - Hydroxylamines KW - Nitrogen Oxides KW - Phenanthrolines KW - Radiation-Protective Agents KW - Spin Labels KW - tempamine KW - 14691-88-4 KW - Triacetoneamine-N-Oxyl KW - 2896-70-0 KW - Copper KW - 789U1901C5 KW - DNA KW - 9007-49-2 KW - Hydrogen Peroxide KW - BBX060AN9V KW - nitroxyl KW - GFQ4MMS07W KW - tempol KW - U78ZX2F65X KW - 1,10-phenanthroline KW - W4X6ZO7939 KW - Index Medicus KW - Animals KW - Electrophoresis -- methods KW - Dose-Response Relationship, Drug KW - DNA -- analysis KW - Dose-Response Relationship, Radiation KW - Plasmids KW - Cell Survival KW - DNA -- drug effects KW - Oxidation-Reduction KW - Cyclic N-Oxides -- pharmacology KW - Triacetoneamine-N-Oxyl -- pharmacology KW - DNA -- radiation effects KW - Cell Line KW - Antioxidants -- pharmacology KW - Nitrogen Oxides -- pharmacology KW - DNA Damage KW - Radiation-Protective Agents -- pharmacology KW - Hydroxylamines -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72632824?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Differential+protection+by+nitroxides+and+hydroxylamines+to+radiation-induced+and+metal+ion-catalyzed+oxidative+damage.&rft.au=Xavier%2C+Sandhya%3BYamada%2C+Ken-ichi%3BSamuni%2C+Ayelet+M%3BSamuni%2C+Amram%3BDeGraff%2C+William%3BKrishna%2C+Murali+C%3BMitchell%2C+James+B&rft.aulast=Xavier&rft.aufirst=Sandhya&rft.date=2002-11-14&rft.volume=1573&rft.issue=2&rft.spage=109&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 - 2003-02-25 N1 - Date created - 2002-10-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Growth hormone and sex steroid administration in healthy aged women and men: a randomized controlled trial. AN - 72674671; 12425705 AB - Hormone administration to elderly individuals can increase lean body mass (LBM) and decrease fat, but interactive effects of growth hormone (GH) and sex steroids and their influence on strength and endurance are unknown. To evaluate the effects of recombinant human GH and/or sex steroids on body composition, strength, endurance, and adverse outcomes in aged persons. A 26-week randomized, double-blind, placebo-controlled parallel-group trial in healthy, ambulatory, community-dwelling US women (n = 57) and men (n = 74) aged 65 to 88 years recruited between June 1992 and July 1998. Participants were randomized to receive GH (starting dose, 30 micro g/kg, reduced to 20 micro g/kg, subcutaneously 3 times/wk) + sex steroids (women: transdermal estradiol, 100 micro g/d, plus oral medroxyprogesterone acetate, 10 mg/d, during the last 10 days of each 28-day cycle [HRT]; men: testosterone enanthate, biweekly intramuscular injections of 100 mg) (n = 35); GH + placebo sex steroid (n = 30); sex steroid + placebo GH (n = 35); or placebo GH + placebo sex steroid (n = 31) in a 2 x 2 factorial design. Lean body mass, fat mass, muscle strength, maximum oxygen uptake (VO(2)max) during treadmill test, and adverse effects. In women, LBM increased by 0.4 kg with placebo, 1.2 kg with HRT (P =.09), 1.0 kg with GH (P =.001), and 2.1 kg with GH + HRT (P<.001). Fat mass decreased significantly in the GH and GH + HRT groups. In men, LBM increased by 0.1 kg with placebo, 1.4 kg with testosterone (P =.06), 3.1 kg with GH (P<.001), and 4.3 kg with GH + testosterone (P<.001). Fat mass decreased significantly with GH and GH + testosterone. Women's strength decreased in the placebo group and increased nonsignificantly with HRT (P =.09), GH (P =.29), and GH + HRT (P =.14). Men's strength also did not increase significantly except for a marginally significant increase of 13.5 kg with GH + testosterone (P =.05). Women's VO(2)max declined by 0.4 mL/min/kg in the placebo and HRT groups but increased with GH (P =.07) and GH + HRT (P =.06). Men's VO(2)max declined by 1.2 mL/min/kg with placebo and by 0.4 mL/min/kg with testosterone (P =.49) but increased with GH (P =.11) and with GH + testosterone (P<.001). Changes in strength (r = 0.355; P<.001) and in VO(2)max (r = 0.320; P =.002) were directly related to changes in LBM. Edema was significantly more common in women taking GH (39% vs 0%) and GH + HRT (38% vs 0%). Carpal tunnel symptoms were more common in men taking GH + testosterone (32% vs 0%) and arthralgias were more common in men taking GH (41% vs 0%). Diabetes or glucose intolerance occurred in 18 GH-treated men vs 7 not receiving GH (P =.006). In this study, GH with or without sex steroids in healthy, aged women and men increased LBM and decreased fat mass. Sex steroid + GH increased muscle strength marginally and VO( 2)max in men, but women had no significant change in strength or cardiovascular endurance. Because adverse effects were frequent (importantly, diabetes and glucose intolerance), GH interventions in the elderly should be confined to controlled studies. JF - JAMA AU - Blackman, Marc R AU - Sorkin, John D AU - Münzer, Thomas AU - Bellantoni, Michele F AU - Busby-Whitehead, Jan AU - Stevens, Thomas E AU - Jayme, Jocelyn AU - O'Connor, Kieran G AU - Christmas, Colleen AU - Tobin, Jordan D AU - Stewart, Kerry J AU - Cottrell, Ernest AU - St Clair, Carol AU - Pabst, Katharine M AU - Harman, S Mitchell AD - Division of Endocrinology and Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. blackmam@mail.nih.gov Y1 - 2002/11/13/ PY - 2002 DA - 2002 Nov 13 SP - 2282 EP - 2292 VL - 288 IS - 18 SN - 0098-7484, 0098-7484 KW - Blood Glucose KW - 0 KW - Steroids KW - Human Growth Hormone KW - 12629-01-5 KW - Testosterone KW - 3XMK78S47O KW - Estradiol KW - 4TI98Z838E KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - testosterone enanthate KW - 7Z6522T8N9 KW - Medroxyprogesterone Acetate KW - C2QI4IOI2G KW - Abridged Index Medicus KW - Index Medicus KW - Oxygen Consumption -- drug effects KW - Double-Blind Method KW - Blood Glucose -- drug effects KW - Humans KW - Estradiol -- pharmacology KW - Diabetes Mellitus KW - Aged KW - Insulin-Like Growth Factor I -- metabolism KW - Medroxyprogesterone Acetate -- blood KW - Muscle, Skeletal -- drug effects KW - Estradiol -- blood KW - Aged, 80 and over KW - Hematocrit KW - Medroxyprogesterone Acetate -- pharmacology KW - Female KW - Male KW - Testosterone -- analogs & derivatives KW - Testosterone -- pharmacology KW - Hormone Replacement Therapy -- adverse effects KW - Steroids -- blood KW - Testosterone -- blood KW - Steroids -- pharmacology KW - Body Composition -- drug effects KW - Physical Endurance -- drug effects KW - Human Growth Hormone -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72674671?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Growth+hormone+and+sex+steroid+administration+in+healthy+aged+women+and+men%3A+a+randomized+controlled+trial.&rft.au=Blackman%2C+Marc+R%3BSorkin%2C+John+D%3BM%C3%BCnzer%2C+Thomas%3BBellantoni%2C+Michele+F%3BBusby-Whitehead%2C+Jan%3BStevens%2C+Thomas+E%3BJayme%2C+Jocelyn%3BO%27Connor%2C+Kieran+G%3BChristmas%2C+Colleen%3BTobin%2C+Jordan+D%3BStewart%2C+Kerry+J%3BCottrell%2C+Ernest%3BSt+Clair%2C+Carol%3BPabst%2C+Katharine+M%3BHarman%2C+S+Mitchell&rft.aulast=Blackman&rft.aufirst=Marc&rft.date=2002-11-13&rft.volume=288&rft.issue=18&rft.spage=2282&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-26 N1 - Date created - 2002-11-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: JAMA. 2003 Jul 23;290(4):462 [12876087] JAMA. 2003 Jul 23;290(4):462 [12876088] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemosensors for the Marine Toxin Saxitoxin AN - 19235593; 5813469 AB - Eleven anthracylmethyl crown ethers have been synthesized and evaluated as fluorescence sensors for the marine toxin saxitoxin. Fluorescence enhancement data are consistent with a 1:1 binding complex for all crowns. The binding constants are in the range of 10 super(4) M super(-1) in ammonium phosphate buffer (pH 7.1) in 80% ethanol solvent. Selectivity for sensing saxitoxin versus several organic analytes has been demonstrated for the first time. Possible modes of binding are presented, and relevance to saxitoxin monitoring programs are discussed. JF - Journal of the American Chemical Society AU - Gawley, R E AU - Pinet, S AU - Cardona, C M AU - Datta, P K AU - Ren, T AU - Guida, W C AU - Nydick, J AU - Leblanc, R M AD - Department of Chemistry, and NIEHS Marine and Freshwater Biomedical Sciences Center, University of Miami, P.O. Box 249118, Coral Gables, FL 33124-0431, USA Y1 - 2002/11/13/ PY - 2002 DA - 2002 Nov 13 SP - 13448 EP - 13453 VL - 124 IS - 45 SN - 0002-7863, 0002-7863 KW - anthracylmethyl crown ethers KW - Chemosensors KW - Saxitoxin KW - Toxicology Abstracts KW - Synthesis KW - Binding KW - Toxins KW - Paralytic shellfish poisoning KW - Ethanol KW - X 24171:Microbial KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19235593?accountid=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+the+American+Chemical+Society&rft.atitle=Chemosensors+for+the+Marine+Toxin+Saxitoxin&rft.au=Gawley%2C+R+E%3BPinet%2C+S%3BCardona%2C+C+M%3BDatta%2C+P+K%3BRen%2C+T%3BGuida%2C+W+C%3BNydick%2C+J%3BLeblanc%2C+R+M&rft.aulast=Gawley&rft.aufirst=R&rft.date=2002-11-13&rft.volume=124&rft.issue=45&rft.spage=13448&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Chemical+Society&rft.issn=00027863&rft_id=info:doi/10.1021%2Fja027507p LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Paralytic shellfish poisoning; Toxins; Synthesis; Binding; Ethanol DO - http://dx.doi.org/10.1021/ja027507p ER - TY - JOUR T1 - Mutations in Mcoln3 associated with deafness and pigmentation defects in varitint-waddler (Va) mice. AN - 72680503; 12403827 AB - Deafness in spontaneously occurring mouse mutants is often associated with defects in cochlea sensory hair cells, opening an avenue to systematically identify genes critical for hair cell structure and function. The classical semidominant mouse mutant varitint-waddler (Va) exhibits early-onset hearing loss, vestibular defects, pigmentation abnormalities, and perinatal lethality. A second allele, Va(J), which arose in a cross segregating for Va, shows a less severe phenotype. By using a positional cloning strategy, we identify two additional members of the mucolipin gene family (Mcoln2 and Mcoln3) in the 350-kb Va(J) minimal interval and provide evidence for Mcoln3 as the gene mutated in varitint-waddler. Mcoln3 encodes a putative six-transmembrane-domain protein with sequence and motif similarities to the family of nonselective transient-receptor-potential (TRP) ion channels. In the Va allele an Ala419Pro substitution occurs in the fifth transmembrane domain of Mcoln3, and in Va(J), a second sequence alteration (Ile362Thr) occurring in cis partially rescues the Va allele. Mcoln3 localizes to cytoplasmic compartments of hair cells and plasma membrane of stereocilia. Hair cell defects are apparent by embryonic day 17.5, assigning Mcoln3 an essential role during early hair cell maturation. Our data suggest that Mcoln3 is involved in ion homeostasis and acts cell-autonomously. Hence, we identify a molecular link between hair cell physiology and melanocyte function. Last, MCOLN2 and MCOLN3 are candidate genes for hereditary and/or sporadic forms of neurosensory disorders in humans. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Di Palma, Federica AU - Belyantseva, Inna A AU - Kim, Hung J AU - Vogt, Thomas F AU - Kachar, Bechara AU - Noben-Trauth, Konrad AD - Section on Neurogenetics, Laboratory of Molecular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 5 Research Court, Rockville, MD 20850, USA. Y1 - 2002/11/12/ PY - 2002 DA - 2002 Nov 12 SP - 14994 EP - 14999 VL - 99 IS - 23 SN - 0027-8424, 0027-8424 KW - DNA Primers KW - 0 KW - Mcoln3 protein, mouse KW - Membrane Proteins KW - Proteins KW - TRPM Cation Channels KW - Transient Receptor Potential Channels KW - Index Medicus KW - Animals KW - Disease Models, Animal KW - Amino Acid Sequence KW - Chromosomes, Artificial, Bacterial KW - Mice KW - Binding Sites KW - Mice, Inbred Strains KW - Mice, Mutant Strains KW - Base Sequence KW - Sequence Alignment KW - Hair Cells, Auditory -- abnormalities KW - Molecular Sequence Data KW - Mice, Inbred C57BL KW - Mice, Inbred C3H KW - Crosses, Genetic KW - Cochlea -- abnormalities KW - Sequence Homology, Amino Acid KW - Gene Library KW - Pigmentation Disorders -- genetics KW - Deafness -- genetics KW - Membrane Proteins -- genetics KW - Proteins -- genetics KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72680503?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutations+in+Mcoln3+associated+with+deafness+and+pigmentation+defects+in+varitint-waddler+%28Va%29+mice.&rft.au=Di+Palma%2C+Federica%3BBelyantseva%2C+Inna+A%3BKim%2C+Hung+J%3BVogt%2C+Thomas+F%3BKachar%2C+Bechara%3BNoben-Trauth%2C+Konrad&rft.aulast=Di+Palma&rft.aufirst=Federica&rft.date=2002-11-12&rft.volume=99&rft.issue=23&rft.spage=14994&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 - 2003-01-15 N1 - Date created - 2002-11-13 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AY083532; GENBANK; AY083531; AY083533; AC068974; AC079941 N1 - SuppNotes - Cited By: Nat Genet. 2000 Jan;24(1):23-5 [10615122] Cell. 1988 Oct 7;55(1):185-92 [2458842] Science. 2000 Mar 24;287(5461):2229-34 [10744543] Neuron. 2000 Apr;26(1):35-43 [10798390] Annu Rev Neurosci. 2000;23:89-125 [10845060] Cell. 1990 Oct 5;63(1):225-33 [1698557] Nature. 1990 Oct 18;347(6294):667-9 [1699134] Cell. 1993 Jul 30;74(2):395-404 [8343963] Pigment Cell Res. 1994 Feb;7(1):17-32 [7521050] Mech Dev. 1995 Apr;50(2-3):139-50 [7619726] Cell. 1996 May 31;85(5):661-71 [8646775] Hear Res. 1997 May;107(1-2):102-12 [9165351] J Inherit Metab Dis. 1997 Sep;20(5):625-32 [9323557] J Neurosci. 1997 Nov 1;17(21):8259-69 [9334401] Hear Res. 1998 Sep;123(1-2):125-36 [9745961] Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):7933-8 [10859366] Nat Genet. 2000 Sep;26(1):118-23 [10973263] Nat Cell Biol. 2000 Oct;2(10):695-702 [11025659] Hum Mol Genet. 2000 Oct 12;9(17):2471-8 [11030752] Am J Hum Genet. 2000 Nov;67(5):1110-20 [11013137] Cell. 2000 Oct 27;103(3):525-35 [11081638] J Neurosci. 2000 Dec 15;20(24):RC116 [11125015] Nature. 2000 Dec 21-28;408(6815):990-4 [11140688] Nat Genet. 2001 Feb;27(2):143-9 [11175778] Proc Natl Acad Sci U S A. 2001 Jan 30;98(3):1182-7 [11252306] Gene. 2001 Apr 18;267(2):243-53 [11313151] Nat Genet. 2001 May;28(1):64-8 [11326278] Nat Rev Neurosci. 2001 Jun;2(6):387-96 [11389472] Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10238-43 [11504925] Sci STKE. 2001 Jul 10;2001(90):re1 [11752662] Nat Cell Biol. 2002 Mar;4(3):191-7 [11854751] Cell. 2002 Mar 8;108(5):705-15 [11893340] Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4355-60 [11904372] Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4471-6 [11917121] Nat Cell Biol. 2002 Apr;4(4):271-8 [11887186] J Assoc Res Otolaryngol. 2003 Mar;4(1):83-90 [12209292] J Hered. 1972 May-Jun;63(3):135-40 [4557539] J Hered. 1984 May-Jun;75(3):233-4 [6203959] Nature. 1988 Sep 1;335(6185):88-9 [2457811] Comment In: Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14613-5 [12417743] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Repair of topoisomerase I covalent complexes in the absence of the tyrosyl-DNA phosphodiesterase Tdp1. AN - 72668333; 12397185 AB - Accidental or drug-induced interruption of the breakage and reunion cycle of eukaryotic topoisomerase I (Top1) yields complexes in which the active site tyrosine of the enzyme is covalently linked to the 3' end of broken DNA. The enzyme tyrosyl-DNA phosphodiesterase (Tdp1) hydrolyzes this protein-DNA link and thus functions in the repair of covalent complexes, but genetic studies in yeast show that alternative pathways of repair exist. Here, we have evaluated candidate genes for enzymes that might act in parallel to Tdp1 so as to generate free ends of DNA. Despite finding that the yeast Apn1 protein has a Tdp1-like biochemical activity, genetic inactivation of all known yeast apurinic endonucleases does not increase the sensitivity of a tdp1 mutant to direct induction of Top1 damage. In contrast, assays of growth in the presence of the Top1 poison camptothecin (CPT) indicate that the structure-specific nucleases dependent on RAD1 and MUS81 can contribute independently of TDP1 to repair, presumably by cutting off a segment of DNA along with the topoisomerase. However, cells in which all three enzymes are genetically inactivated are not as sensitive to the lethal effects of CPT as are cells defective in double-strand break repair. We show that the MRE11 gene is even more critical than the RAD52 gene for double-strand break repair of CPT lesions, and comparison of an mre11 mutant with a tdp1 rad1 mus81 triple mutant demonstrates that other enzymes complementary to Tdp1 remain to be discovered. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Liu, Chunyan AU - Pouliot, Jeffrey J AU - Nash, Howard A AD - Laboratory of Molecular Biology, National Institute of Mental Health, Bethesda, MD 20892-4034, USA. Y1 - 2002/11/12/ PY - 2002 DA - 2002 Nov 12 SP - 14970 EP - 14975 VL - 99 IS - 23 SN - 0027-8424, 0027-8424 KW - Phosphoric Diester Hydrolases KW - EC 3.1.4.- KW - tyrosyl-DNA phosphodiesterase KW - Carbon-Oxygen Lyases KW - EC 4.2.- KW - DNA-(Apurinic or Apyrimidinic Site) Lyase KW - EC 4.2.99.18 KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Saccharomyces cerevisiae -- genetics KW - Carbon-Oxygen Lyases -- metabolism KW - Camptothecin -- pharmacology KW - Models, Genetic KW - Kinetics KW - Saccharomyces cerevisiae -- enzymology KW - Time Factors KW - Saccharomyces cerevisiae -- drug effects KW - Carbon-Oxygen Lyases -- genetics KW - Phosphoric Diester Hydrolases -- genetics KW - DNA Repair -- genetics KW - Phosphoric Diester Hydrolases -- metabolism KW - DNA Topoisomerases, Type I -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72668333?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Repair+of+topoisomerase+I+covalent+complexes+in+the+absence+of+the+tyrosyl-DNA+phosphodiesterase+Tdp1.&rft.au=Liu%2C+Chunyan%3BPouliot%2C+Jeffrey+J%3BNash%2C+Howard+A&rft.aulast=Liu&rft.aufirst=Chunyan&rft.date=2002-11-12&rft.volume=99&rft.issue=23&rft.spage=14970&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 - 2003-01-15 N1 - Date created - 2002-11-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cancer Res. 2000 Jan 15;60(2):328-33 [10667584] Science. 1999 Oct 15;286(5439):552-5 [10521354] Mutagenesis. 2000 Jul;15(4):367-74 [10887218] Mutat Res. 2000 Jun 30;451(1-2):39-51 [10915864] Methods Mol Biol. 2001;95:303-13 [11089242] J Biol Chem. 2000 Dec 1;275(48):37347-56 [10980204] Mol Cell Biol. 2001 Mar;21(5):1656-61 [11238902] Annu Rev Pharmacol Toxicol. 2001;41:53-77 [11264450] Genetics. 2001 May;158(1):109-22 [11333222] Genes Cells. 2001 Aug;6(8):677-87 [11532027] J Biol Chem. 2001 Sep 21;276(38):35458-64 [11454871] Mol Cell Biol. 2001 Nov;21(21):7191-8 [11585902] Genes Dev. 2001 Oct 15;15(20):2730-40 [11641278] Cell. 2001 Nov 30;107(5):551-4 [11733053] Clin Cancer Res. 2002 Mar;8(3):641-61 [11895891] Nat Rev Mol Cell Biol. 2002 May;3(5):317-27 [11988766] J Biol Chem. 2002 Jul 26;277(30):27162-8 [12023295] Nat Genet. 2002 Oct;32(2):267-72 [12244316] Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13669-74 [12368472] Mutat Res. 1974 Aug;26(4):257-64 [4605044] Proc Natl Acad Sci U S A. 1985 Jul;82(13):4374-8 [2989818] Genetics. 1986 Jul;113(3):531-50 [3015717] Proc Natl Acad Sci U S A. 1988 Oct;85(20):7501-5 [2845409] Proc Natl Acad Sci U S A. 1990 Jun;87(11):4193-7 [1693433] Methods Enzymol. 1991;194:3-21 [2005794] Mol Cell Biol. 1991 Sep;11(9):4537-44 [1715020] EMBO J. 1993 Mar;12(3):869-77 [8458343] Annu Rev Biochem. 1994;63:915-48 [7979257] Bioessays. 1995 Aug;17(8):713-9 [7661852] J Biol Chem. 1996 Aug 23;271(34):20551-8 [8702799] Annu Rev Biochem. 1996;65:635-92 [8811192] Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11534-9 [8876170] Adv Pharmacol. 1994;29B:201-26 [8996609] J Biol Chem. 1997 May 9;272(19):12801-8 [9139740] Genetics. 1997 Jul;146(3):781-95 [9215887] Genetics. 1997 Jul;146(3):797-816 [9215888] J Biol Chem. 1997 Oct 17;272(42):26441-7 [9334220] Yeast. 1998 Jan 30;14(2):115-32 [9483801] Genes Dev. 1998 Oct 1;12(19):3137-43 [9765213] Cell. 1998 Nov 25;95(5):705-16 [9845372] Chem Res Toxicol. 1998 Dec;11(12):1580-5 [9860504] Mol Cell Biol. 1999 Jan;19(1):556-66 [9858579] Mol Cell Biol. 1999 Mar;19(3):1800-9 [10022867] Microbiol Mol Biol Rev. 1999 Jun;63(2):349-404 [10357855] Curr Opin Genet Dev. 2000 Feb;10(1):17-25 [10679395] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reactivity of atropaldehyde, a felbamate metabolite in human liver tissue in vitro. AN - 72635376; 12399159 AB - Antiepileptic therapy with a broad spectrum drug felbamate (FBM) has been limited due to reports of hepatotoxicity and aplastic anemia associated with its use. It was proposed that a bioactivation of FBM leading to formation of alpha,beta-unsaturated aldehyde, atropaldehyde (ATPAL) could be responsible for toxicities associated with the parent drug. Other members of this class of compounds, acrolein and 4-hydroxynonenal (HNE), are known for their reactivity and toxicity. It has been proposed that the bioactivation of FBM to ATPAL proceeds though a more stable cyclized product, 4-hydroxy-5-phenyltetrahydro-1,3-oxazin-2-one (CCMF) whose formation has been shown recently. Aldehyde dehydrogenase (ALDH) and glutathione transferase (GST) are detoxifying enzymes and targets for reactive aldehydes. This study examined effects of ATPAL and its precursor, CCMF on ALDH, GST and cell viability in liver, the target tissue for its metabolism and toxicity. A known toxin, HNE, which is also a substrate for ALDH and GST, was used for comparison. Interspecies difference in metabolism of FBM is well documented, therefore, human tissue was deemed most relevant and used for these studies. ATPAL inhibited ALDH and GST activities and led to a loss of hepatocyte viability. Several fold greater concentrations of CCMF were necessary to demonstrate a similar degree of ALDH inhibition or cytotoxicity as observed with ATPAL. This is consistent with CCMF requiring prior conversion to the more proximate toxin, ATPAL. GSH was shown to protect against ALDH inhibition by ATPAL. In this context, ALDH and GST are detoxifying pathways and their inhibition would lead to an accumulation of reactive species from FBM metabolism and/or metabolism of other endogenous or exogenous compounds and predisposing to or causing toxicity. Therefore, mechanisms of reactive aldehydes toxicity could include direct interaction with critical cellular macromolecules or indirect interference with cellular detoxification mechanisms. JF - Chemico-biological interactions AU - Kapetanovic, Izet M AU - Torchin, Cynthia D AU - Strong, John M AU - Yonekawa, Wayne D AU - Lu, Chuang AU - Li, Albert P AU - Dieckhaus, Christine M AU - Santos, Webster L AU - Macdonald, Timothy L AU - Sofia, R Duane AU - Kupferberg, Harvey J AD - Laboratory of Clinical Pharmacology, CDER, US FDA, MOD-1, Laurel, MD 20708, USA. kapetani@mail.nih.gov Y1 - 2002/11/10/ PY - 2002 DA - 2002 Nov 10 SP - 119 EP - 134 VL - 142 IS - 1-2 SN - 0009-2797, 0009-2797 KW - Aldehydes KW - 0 KW - Anticonvulsants KW - Enzyme Inhibitors KW - Phenylcarbamates KW - Propylene Glycols KW - tert-4-hydroxy-2-nonenal KW - Aldehyde Dehydrogenase KW - EC 1.2.1.3 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - felbamate KW - X72RBB02N8 KW - Index Medicus KW - Aldehydes -- toxicity KW - Glutathione Transferase -- antagonists & inhibitors KW - Humans KW - Microsomes, Liver -- metabolism KW - Glutathione Transferase -- metabolism KW - Aldehydes -- pharmacology KW - Microsomes, Liver -- enzymology KW - Aldehydes -- metabolism KW - Microsomes, Liver -- drug effects KW - Enzyme Inhibitors -- pharmacology KW - Aldehyde Dehydrogenase -- antagonists & inhibitors KW - Aldehyde Dehydrogenase -- metabolism KW - Liver -- enzymology KW - Liver -- drug effects KW - Propylene Glycols -- toxicity KW - Propylene Glycols -- metabolism KW - Anticonvulsants -- toxicity KW - Anticonvulsants -- metabolism KW - Liver -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72635376?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Reactivity+of+atropaldehyde%2C+a+felbamate+metabolite+in+human+liver+tissue+in+vitro.&rft.au=Kapetanovic%2C+Izet+M%3BTorchin%2C+Cynthia+D%3BStrong%2C+John+M%3BYonekawa%2C+Wayne+D%3BLu%2C+Chuang%3BLi%2C+Albert+P%3BDieckhaus%2C+Christine+M%3BSantos%2C+Webster+L%3BMacdonald%2C+Timothy+L%3BSofia%2C+R+Duane%3BKupferberg%2C+Harvey+J&rft.aulast=Kapetanovic&rft.aufirst=Izet&rft.date=2002-11-10&rft.volume=142&rft.issue=1-2&rft.spage=119&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 - 2002-12-19 N1 - Date created - 2002-10-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Trigger Factor Retards Protein Export in Escherichia coli AN - 18503390; 5474861 AB - Trigger factor (TF) is a ribosome-associated protein that interacts with a wide variety of nascent polypeptides in Escherichia coli. Previous studies have indicated that TF cooperates with DnaK to facilitate protein folding, but the basis of this cooperation is unclear. In this study we monitored protein export in E. coli that lack or overproduce TF to obtain further insights into its function. Whereas inactivation of genes encoding most molecular chaperones (including dnaK) impairs protein export, inactivation of the TF gene accelerated protein export and suppressed the need for targeting factors to maintain the translocation competence of presecretory proteins. Furthermore, overproduction of TF (but not DnaK) markedly retarded protein export. Manipulation of TF levels produced similar effects on the export of a cytosolic enzyme fused to a signal peptide. The data strongly suggest that TF has a unique ability to sequester nascent polypeptides for a relatively prolonged period. Based on our results, we propose that TF and DnaK promote protein folding by distinct (but complementary) mechanisms. JF - Journal of Biological Chemistry AU - Lee, H C AU - Bernstein, H D AD - Genetics and Biochemistry Branch, NIDDK, National Institutes of Health, Bethesda, Maryland, harris_bernstein@nih.gov. Y1 - 2002/11/08/ PY - 2002 DA - 2002 Nov 08 SP - 43527 EP - 43535 VL - 277 IS - 45 SN - 0021-9258, 0021-9258 KW - DnaK protein KW - trigger factor KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - N 14400:General KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18503390?accountid=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=Trigger+Factor+Retards+Protein+Export+in+Escherichia+coli&rft.au=Lee%2C+H+C%3BBernstein%2C+H+D&rft.aulast=Lee&rft.aufirst=H&rft.date=2002-11-08&rft.volume=277&rft.issue=45&rft.spage=43527&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 - Novel p53 inactivators with neuroprotective action: syntheses and pharmacological evaluation of 2-imino-2,3,4,5,6,7-hexahydrobenzothiazole and 2-imino-2,3,4,5,6,7-hexahydrobenzoxazole derivatives. AN - 72645148; 12408720 AB - Tumor suppressor protein, p53, is an intracellular protein that is critical within the biochemical cascade that leads to cell death via apoptosis. Recent studies identified the tetrahydrobenzothiazole analogue, pifithrin-alpha (2), as a p53 inhibitor that was effective in protecting neuronal cells against a variety of lethal insults and reducing the side effects of anticancer drugs. As up-regulation of p53 has been described as a common feature of several neurodegenerative disorders, including Alzheimer's disease, 2 and novel analogues (3-16) were synthesized to (i) assess the value of tetrahydrobenzothiazole analogues as neuroprotective agents and (ii) define the structural requirements for p53 inactivation. Not only did 2 exhibit neuroprotective activity in both tissue culture and in vivo stroke models but also compounds 6, 7, 10, 13, 15, and 16 proved to be highly potent in protecting PC12 cells and compounds 3, 4, and 6 were highly potent in protecting primary hippocampal cells against death induced by the DNA-damaging agent, camptothecin. JF - Journal of medicinal chemistry AU - Zhu, Xiaoxiang AU - Yu, Qian-Sheng AU - Cutler, Roy G AU - Culmsee, Carsten W AU - Holloway, Harold W AU - Lahiri, Debomoy K AU - Mattson, Mark P AU - Greig, Nigel H AD - Laboratory of Neurosciences, Gerontology Research Center, National Institute on Aging, Intramural Research Program, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, Maryland 21224, USA. Y1 - 2002/11/07/ PY - 2002 DA - 2002 Nov 07 SP - 5090 EP - 5097 VL - 45 IS - 23 SN - 0022-2623, 0022-2623 KW - Benzoxazoles KW - 0 KW - Imines KW - Neuroprotective Agents KW - Thiazoles KW - Transcription Factors KW - Tumor Suppressor Protein p53 KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Animals KW - Imines -- pharmacology KW - Ischemic Attack, Transient -- drug therapy KW - Structure-Activity Relationship KW - Hippocampus -- drug effects KW - Rats KW - Ischemic Attack, Transient -- prevention & control KW - Rats, Sprague-Dawley KW - Culture Techniques KW - Imines -- chemistry KW - Apoptosis -- drug effects KW - Camptothecin -- toxicity KW - Hippocampus -- cytology KW - Imines -- chemical synthesis KW - PC12 Cells KW - Thiazoles -- pharmacology KW - Benzoxazoles -- pharmacology KW - Thiazoles -- chemistry KW - Thiazoles -- chemical synthesis KW - Neuroprotective Agents -- chemistry KW - Tumor Suppressor Protein p53 -- antagonists & inhibitors KW - Transcription Factors -- antagonists & inhibitors KW - Benzoxazoles -- chemistry KW - Neuroprotective Agents -- chemical synthesis KW - Benzoxazoles -- chemical synthesis KW - Neuroprotective Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72645148?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Novel+p53+inactivators+with+neuroprotective+action%3A+syntheses+and+pharmacological+evaluation+of+2-imino-2%2C3%2C4%2C5%2C6%2C7-hexahydrobenzothiazole+and+2-imino-2%2C3%2C4%2C5%2C6%2C7-hexahydrobenzoxazole+derivatives.&rft.au=Zhu%2C+Xiaoxiang%3BYu%2C+Qian-Sheng%3BCutler%2C+Roy+G%3BCulmsee%2C+Carsten+W%3BHolloway%2C+Harold+W%3BLahiri%2C+Debomoy+K%3BMattson%2C+Mark+P%3BGreig%2C+Nigel+H&rft.aulast=Zhu&rft.aufirst=Xiaoxiang&rft.date=2002-11-07&rft.volume=45&rft.issue=23&rft.spage=5090&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 - 2002-12-09 N1 - Date created - 2002-10-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genomic BLAST: custom-defined virtual databases for complete and unfinished genomes AN - 18551877; 5514541 AB - BLAST (Basic Local Alignment Search Tool) searches against DNA and protein sequence databases have become an indispensable tool for biomedical research. The proliferation of the genome sequencing projects is steadily increasing the fraction of genome-derived sequences in the public databases and their importance as a public resource. We report here the availability of Genomic BLAST, a novel graphical tool for simplifying BLAST searches against complete and unfinished genome sequences. This tool allows the user to compare the query sequence against a virtual database of DNA and/or protein sequences from a selected group of organisms with finished or unfinished genomes. The organisms for such a database can be selected using either a graphic taxonomy-based tree or an alphabetical list of organism-specific sequences. The first option is designed to help explore the evolutionary relationships among organisms within a certain taxonomy group when performing BLAST searches. The use of an alphabetical list allows the user to perform a more elaborate set of selections, assembling any given number of organism-specific databases from unfinished or complete genomes. This tool, available at the NCBI web site JF - FEMS Microbiology Letters AU - Cummings, L AU - Riley, L AU - Black, L AU - Souvorov, A AU - Resenchuk, S AU - Dondoshansky, I AU - Tatusova, T AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA, tatiana@ncbi.nlm.nih.gov Y1 - 2002/11/05/ PY - 2002 DA - 2002 Nov 05 SP - 133 EP - 138 PB - Federation of European Microbiological Societies VL - 216 IS - 2 SN - 0378-1097, 0378-1097 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Microbiology Abstracts B: Bacteriology KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18551877?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FEMS+Microbiology+Letters&rft.atitle=Genomic+BLAST%3A+custom-defined+virtual+databases+for+complete+and+unfinished+genomes&rft.au=Cummings%2C+L%3BRiley%2C+L%3BBlack%2C+L%3BSouvorov%2C+A%3BResenchuk%2C+S%3BDondoshansky%2C+I%3BTatusova%2C+T&rft.aulast=Cummings&rft.aufirst=L&rft.date=2002-11-05&rft.volume=216&rft.issue=2&rft.spage=133&rft.isbn=&rft.btitle=&rft.title=FEMS+Microbiology+Letters&rft.issn=03781097&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Functional crosstalk between hOgg1 and the helicase domain of Cockayne syndrome group B protein. AN - 72824837; 12531019 AB - We have previously reported that the Cockayne syndrome group B gene product (CSB) contributes to base excision repair (BER) of 8-hydroxyguanine (8-OH-Gua) and the importance of motifs V and VI of the putative helicase domains of CSB in BER of 8-OH-Gua. To further elucidate the function of CSB in BER, we investigated its role in the pathway involving human 8-OH-Gua glycosylase/apurinic lyase (hOgg1). Depletion of CSB protein with anti-CSB antibody reduced the 8-OH-Gua incision rate of wild type cell extracts but not of CSB null and motif VI mutant cell extracts, suggesting a direct contribution of CSB to the catalytic process of 8-OH-Gua incision and the importance of its motif VI in this pathway. Introduction of recombinant purified CSB partially complemented the depletion of CSB as shown by the recovery of the incision activity. This complementation could not fully recover the deficiency of the incision activity in WCE from CS-B null and mutant cell lines, suggesting that some additional factor(s) are necessary for the full activity. Electrophoretic mobility shift assays (EMSAs) showed a defect in binding of CSB null and motif VI mutant cell extracts to 8-OH-Gua-containing oligonucleotides. We detected less hOgg1 transcript and protein in the cell extracts from CS-B null and mutant cells, suggesting hOgg1 may be the missing component. Pull-down of hOgg1 by histidine-tagged CSB and co-localization of those two proteins after gamma-radiation indicated their co-existence in vivo, particularly under cellular stress. However, we did not detect any functional and physical interaction between purified CSB and hOgg1 by incision, gel shift and yeast two-hybrid assays, suggesting that even though hOgg1 and CSB might be in a common protein complex, they may not interact directly. We conclude that CSB functions in the catalysis of 8-OH-Gua BER and in the maintenance of efficient hOgg1 expression, and that motif VI of the putative helicase domain of CSB is crucial in these functions. JF - DNA repair AU - Tuo, Jingsheng AU - Chen, Catheryne AU - Zeng, Xianmin AU - Christiansen, Mette AU - Bohr, Vilhelm A AD - Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 2002/11/03/ PY - 2002 DA - 2002 Nov 03 SP - 913 EP - 927 VL - 1 IS - 11 SN - 1568-7864, 1568-7864 KW - Cell Extracts KW - 0 KW - DNA Primers KW - Recombinant Proteins KW - 8-hydroxyguanine KW - 5614-64-2 KW - Guanine KW - 5Z93L87A1R KW - DNA KW - 9007-49-2 KW - N-Glycosyl Hydrolases KW - EC 3.2.2.- KW - DNA-Formamidopyrimidine Glycosylase KW - EC 3.2.2.23 KW - DNA Helicases KW - EC 3.6.4.- KW - ERCC6 protein, human KW - EC 3.6.4.12 KW - DNA Repair Enzymes KW - EC 6.5.1.- KW - Index Medicus KW - Humans KW - Two-Hybrid System Techniques KW - Electrophoretic Mobility Shift Assay KW - Saccharomyces cerevisiae KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Blotting, Western KW - Amino Acid Motifs KW - Transfection KW - Recombinant Proteins -- metabolism KW - Cells, Cultured KW - Cockayne Syndrome -- genetics KW - Mutation -- genetics KW - Cell Line, Transformed KW - Fluorescent Antibody Technique KW - DNA Primers -- chemistry KW - DNA Repair KW - DNA Helicases -- physiology KW - DNA -- genetics KW - Promoter Regions, Genetic -- genetics KW - Guanine -- analogs & derivatives KW - Guanine -- metabolism KW - N-Glycosyl Hydrolases -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72824837?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+repair&rft.atitle=Functional+crosstalk+between+hOgg1+and+the+helicase+domain+of+Cockayne+syndrome+group+B+protein.&rft.au=Tuo%2C+Jingsheng%3BChen%2C+Catheryne%3BZeng%2C+Xianmin%3BChristiansen%2C+Mette%3BBohr%2C+Vilhelm+A&rft.aulast=Tuo&rft.aufirst=Jingsheng&rft.date=2002-11-03&rft.volume=1&rft.issue=11&rft.spage=913&rft.isbn=&rft.btitle=&rft.title=DNA+repair&rft.issn=15687864&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-03 N1 - Date created - 2003-01-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A single 8,5'-cyclo-2'-deoxyadenosine lesion in a TATA box prevents binding of the TATA binding protein and strongly reduces transcription in vivo. AN - 72823961; 12531024 AB - 8,5'-Cyclo-2'-deoxypurine (cPu) lesions result from the action of the hydroxyl radical on DNA. These lesions represent a unique class of oxidative DNA lesions in that they are repaired by the nucleotide excision repair (NER) pathway but not by base excision repair (BER) or direct repair. Previous work has shown that cyclopurines can block mammalian DNA and RNA polymerases. Thus, these lesions are of interest because of their potential role in the neurodegeneration as well as internal cancers observed in patients with xeroderma pigmentosum (XP) who lack the capacity to carry out NER. In the present work, we found that the S-isomer of 8,5'-cyclo-2'-deoxyadenosine (cA) can prevent binding of the TATA binding protein (TBP) to the TATA box from the CMV promoter. To assess the functional importance of this effect in living cells, we transfected constructs containing a single cA in the CMV TATA box into XP cells to determine the effect of the lesion on gene expression in vivo. Using this approach, we found that the lesion reduced gene expression by approximately 75%. This effect was comparable to the effect of an inactivating mutation of the TATA box in the same promoter. These findings identify an additional biological effect of cyclopurine lesions in mammalian cells, which is the ability to interfere with transcription by preventing transcription factor binding to cognate recognition sequences. In addition, the approach we used in this study represents a novel method for assessing the effects of DNA lesions in non-transcribed sequences on gene expression in living cells. JF - DNA repair AU - Marietta, Cheryl AU - Gulam, Huzaefah AU - Brooks, P J AD - Section on Molecular Neurobiology, Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD 20892-8110, USA. Y1 - 2002/11/03/ PY - 2002 DA - 2002 Nov 03 SP - 967 EP - 975 VL - 1 IS - 11 SN - 1568-7864, 1568-7864 KW - DNA Primers KW - 0 KW - Deoxyadenosines KW - TATA-Box Binding Protein KW - 8,5'-cyclo-2'-deoxyadenosine KW - 117182-88-4 KW - Luciferases KW - EC 1.13.12.- KW - Index Medicus KW - Transcription, Genetic -- drug effects KW - Humans KW - Electrophoretic Mobility Shift Assay KW - Luciferases -- metabolism KW - Plasmids KW - DNA Damage -- drug effects KW - Mutagenesis, Site-Directed KW - Transfection KW - Cells, Cultured KW - Oxidative Stress KW - Cytomegalovirus -- genetics KW - Mutation -- genetics KW - Promoter Regions, Genetic -- genetics KW - TATA Box -- genetics KW - Deoxyadenosines -- pharmacology KW - Xeroderma Pigmentosum -- genetics KW - TATA-Box Binding Protein -- metabolism KW - Xeroderma Pigmentosum -- metabolism KW - Gene Expression Regulation -- drug effects KW - DNA Repair -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72823961?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+repair&rft.atitle=A+single+8%2C5%27-cyclo-2%27-deoxyadenosine+lesion+in+a+TATA+box+prevents+binding+of+the+TATA+binding+protein+and+strongly+reduces+transcription+in+vivo.&rft.au=Marietta%2C+Cheryl%3BGulam%2C+Huzaefah%3BBrooks%2C+P+J&rft.aulast=Marietta&rft.aufirst=Cheryl&rft.date=2002-11-03&rft.volume=1&rft.issue=11&rft.spage=967&rft.isbn=&rft.btitle=&rft.title=DNA+repair&rft.issn=15687864&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-03 N1 - Date created - 2003-01-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hepatocellular carcinoma: systemic treatments. AN - 85359789; pmid-12394214 AB - Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, with increasing incidence in Western countries. Many pharmacologic treatments have been tested against HCC; most of them belong to three categories: chemotherapy, hormone therapy, and immunotherapy. Neither single agent nor combination chemotherapy have demonstrated a clear reproducible advantage in terms of overall survival; therefore, systemic or intraarterial chemotherapy should not be considered as standard strategies for patients with HCC. Tamoxifen and antiandrogen therapy were not effective in prolonging survival when tested in randomized, controlled trials. Promising results have been obtained with octreotide in a small randomized trial, but confirmation studies are needed. Although adoptive immunotherapy was effective in the adjuvant setting, interferon should be further investigated in this setting or investigated as a preventive strategy in cirrhotic patients. On the contrary, interferon does not seem to have a role in advanced disease, where it is tolerated poorly. In the future, innovative and promising therapeutic strategies will be tested in HCC, including new biologic target-based drugs, cyclooxygenase inhibitors, and gene therapy. JF - Journal of clinical gastroenterology AU - Di Maio, Massimo AU - De Maio, Ermelinda AU - Perrone, Francesco AU - Pignata, Sandro AU - Daniele, Bruno AD - Medical Oncology, National Cancer Institute, Naples, Italy. bdaniele@sirio-oncology.it Y1 - 2002/11// PY - 2002 DA - Nov 2002 SP - S109 EP - S114 VL - 35 IS - 5 Suppl 2 SN - 0192-0790, 0192-0790 KW - Index Medicus KW - National Library of Medicine KW - *Antineoplastic Combined Chemotherapy Protocols: therapeutic use KW - Antiviral Agents: therapeutic use KW - *Carcinoma, Hepatocellular: therapy KW - Doxorubicin: administration & dosage KW - Gene Therapy KW - Genes, p53 KW - Humans KW - Immunotherapy, Adoptive KW - Interferon-alpha: therapeutic use KW - *Liver Neoplasms: therapy KW - Octreotide: administration & dosage KW - Polyethylene Glycols: therapeutic use KW - Recombinant Proteins KW - Treatment Outcome UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85359789?accountid=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=Hepatocellular+carcinoma%3A+systemic+treatments.&rft.au=Di+Maio%2C+Massimo%3BDe+Maio%2C+Ermelinda%3BPerrone%2C+Francesco%3BPignata%2C+Sandro%3BDaniele%2C+Bruno&rft.aulast=Di+Maio&rft.aufirst=Massimo&rft.date=2002-11-01&rft.volume=35&rft.issue=5+Suppl+2&rft.spage=S109&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+gastroenterology&rft.issn=01920790&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Mutation of a transcription factor, TFCP2L3, causes progressive autosomal dominant hearing loss, DFNA28. AN - 85283528; pmid-12393799 AB - We ascertained a large American family with an autosomal dominant form of progressive non-syndromic sensorineural hearing loss. After excluding linkage to known deafness loci, we performed a genome-wide scan and found linkage to marker GAAT1A4 on chromosome 8q22 (LOD=5.12 at theta=0), and this locus was designated DFNA28. Sequencing of six candidate genes in the 1.4 cM linked region identified a frameshift mutation (1609-1610insC) resulting in a premature translation stop codon in exon 14 of the gene TFCP2L3 (transcription factor cellular promoter 2-like 3). TFCP2L3 is a member of a family of transcription factor genes whose archetype is TFCP2, a mammalian homolog of the Drosophila gene grainyhead. Northern blot analyses and in situ hybridization studies show that mouse Tfcp2l3 is expressed in many epithelial tissues, including cells lining the cochlear duct, at embryonic day 18.5 and postnatal day 5. JF - Human Molecular Genetics AU - Peters, Linda M AU - Anderson, David W AU - Griffith, Andrew James AU - Grundfast, Kenneth M AU - San Agustin Theresa B AU - Madeo, Anne C AU - Friedman, Thomas B AU - Morell, Robert J AD - Section on Human Genetics, Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USA.; National Institute on Deafness and Other Communication Disorders PY - 2002 SP - 2877 EP - 2885 VL - 11 IS - 23 SN - 0964-6906, 0964-6906 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85283528?accountid=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=Mutation+of+a+transcription+factor%2C+TFCP2L3%2C+causes+progressive+autosomal+dominant+hearing+loss%2C+DFNA28.&rft.au=Peters%2C+Linda+M%3BAnderson%2C+David+W%3BGriffith%2C+Andrew+James%3BGrundfast%2C+Kenneth+M%3BSan+Agustin+Theresa+B%3BMadeo%2C+Anne+C%3BFriedman%2C+Thomas+B%3BMorell%2C+Robert+J&rft.aulast=Peters&rft.aufirst=Linda&rft.date=2002-11-01&rft.volume=11&rft.issue=23&rft.spage=2877&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 - Fibroblast growth factor signaling regulates pillar cell development in the organ of corti. AN - 85272161; pmid-12417662 AB - One of the most striking aspects of the cellular pattern within the sensory epithelium of the mammalian cochlea is the presence of two rows of pillar cells in the region between the single row of inner hair cells and the first row of outer hair cells. The factors that regulate pillar cell development have not been determined; however, previous results suggested a key role for fibroblast growth factor receptor 3 (FGFR3). To examine the specific effects of FGFR3 on pillar cell development, we inhibited receptor activation in embryonic cochlear explant cultures. Results indicated that differentiation of pillar cells is dependent on continuous activation of FGFR3. Moreover, transient inhibition of FGFR3 did not inhibit the pillar cell fate permanently, because reactivation of FGFR3 resulted in the resumption of pillar cell differentiation. The effects of increased FGFR3 activation were determined by exposing cochlear explants to FGF2, a strong ligand for several FGF receptors. Treatment with FGF2 led to a significant increase in the number of pillar cells and to a small increase in the number of inner hair cells. These effects were not dependent on cellular proliferation, suggesting that additional pillar cells and inner hair cells were a result of increased recruitment into the prosensory domain. These results indicate that FGF signaling plays a critical role in the commitment and differentiation of pillar cells. Moreover, the position of the pillar cells appears to be determined by the activation of FGFR3 in a subset of the progenitor cells that initially express this receptor. JF - The Journal of Neuroscience AU - Mueller, Kristen L AU - Jacques, Bonnie E AU - Kelley, Matthew W AD - Section on Developmental Neuroscience, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, Maryland 20850, USA.; Department of Cell Biology, School of Medicine, Georgetown University Medical Center, Georgetown University PY - 2002 SP - 9368 EP - 9377 VL - 22 IS - 21 SN - 0270-6474, 0270-6474 KW - Animals KW - Mice, Inbred ICR KW - Support, U.S. Gov't, P.H.S. KW - Cell Count KW - Dose-Response Relationship, Drug KW - Morphogenesis KW - Cell Differentiation KW - Mice KW - Pyrroles KW - Organ of Corti KW - Receptors, Fibroblast Growth Factor KW - Fibroblast Growth Factor 2 KW - Cells, Cultured KW - Hair Cells, Inner KW - Support, Non-U.S. Gov't KW - Stem Cells KW - Receptors, Nerve Growth Factor KW - Fibroblast Growth Factors KW - Signal Transduction KW - Cell Division UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85272161?accountid=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=Fibroblast+growth+factor+signaling+regulates+pillar+cell+development+in+the+organ+of+corti.&rft.au=Mueller%2C+Kristen+L%3BJacques%2C+Bonnie+E%3BKelley%2C+Matthew+W&rft.aulast=Mueller&rft.aufirst=Kristen&rft.date=2002-11-01&rft.volume=22&rft.issue=21&rft.spage=9368&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 - [Risk factors of malignant skin melanoma in Italian population: review of results of a case-control study]. TT - Fattori di rischio per melanoma cutaneo maligno in una popolazione italiana: sintesi dei risultati di uno studio caso-controllo. AN - 72862135; 12619494 AB - Cutaneous melanoma incidence rates are rapidly increasing worldwide, including in the Mediterranean countries. Sunlight exposure has been associated with melanoma, but the mechanisms of UV radiation-induced carcinogenesis is still largely unknown. In mammalian cells, UV radiation induces DNA damage that can be repaired mostly by the nucleotide excision repair system. We summarize here the results of a case-control study conducted at the Bufalini Hospital in Cesena, Italy to assess host and environmental risk factors for melanoma. We recruited 183 incident cutaneous melanoma cases and 179 controls selected predominantly among partners or close friends of the cases. Presence of dysplasticlatypical nevi (OR: 4.2; 95% CI: 2.4-7.4), low propensity to tan (OR: 2.4; 95% CI 1.1-5.0), light skin (OR: 4.1; 95% CI: 1.4-12.1), and light eye color (OR: 2.4; 95% CI: 1.1-5.2) were the strongest risk factors for melanoma in this population. A chart identifying melanoma risk associated with multiple combinations of these factors is presented. We used the host-cell reactivation assay on subjects' lymphocytes to measure individual DNA repair capacity (DRC) after UV-induced DNA damage. Subjects with low tanning ability and low DRC had a higher melanoma risk (OR: 8.6; 95% CI: 2.7-27.5) than those with higher tanning ability and high DRC. Subjects with dysplastic nevi and low DRC had a higher risk (OR: 6.7; 95% CI: 2.4-18.6) than those lacking dysplastic nevi and with high DRC. These results may help identify high-risk subjects in the Mediterranean populations who would the benefit from preventive measures. JF - Epidemiologia e prevenzione AU - Baccarelli, Andrea AU - Landi, Maria Teresa AD - Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute/NIH 6120 Executive Blvd., EPS 7110, Bethesda, MD 20892-7236, USA. baccarea@mail.nih.gov PY - 2002 SP - 293 EP - 299 VL - 26 IS - 6 SN - 1120-9763, 1120-9763 KW - Index Medicus KW - DNA Damage KW - Risk Factors KW - Humans KW - Ultraviolet Rays -- adverse effects KW - Case-Control Studies KW - Middle Aged KW - Italy -- epidemiology KW - Male KW - Female KW - Skin Neoplasms -- epidemiology KW - Melanoma -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72862135?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epidemiologia+e+prevenzione&rft.atitle=%5BRisk+factors+of+malignant+skin+melanoma+in+Italian+population%3A+review+of+results+of+a+case-control+study%5D.&rft.au=Baccarelli%2C+Andrea%3BLandi%2C+Maria+Teresa&rft.aulast=Baccarelli&rft.aufirst=Andrea&rft.date=2002-11-01&rft.volume=26&rft.issue=6&rft.spage=293&rft.isbn=&rft.btitle=&rft.title=Epidemiologia+e+prevenzione&rft.issn=11209763&rft_id=info:doi/ LA - Italian DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-15 N1 - Date created - 2003-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neoadjuvant chemotherapy for intermediate/high-grade soft tissue sarcomas: five-year results with epirubicin and ifosfamide. AN - 72837392; 12552955 AB - Neoadjuvant chemotherapy for intermediate/high-grade soft tissue sarcomas (STS) may provide some advantages for facilitating the surgical resection of the tumor and for disease control. However its role as induction therapy before surgery should still be proved. Twenty-one patients with intermediate/high-grade STS and tumor size > or = 5 cm were consecutively treated from 1997 to 2001 with neoadjuvant chemotherapy based on epirubicin 60 mg/m2/day on days 1 and 2 and ifosfamide 1.8 gr/m2/day on days 1 through 5 every three weeks. Evaluation of objective tumor response and toxicity were carried out according to WHO criteria. Nine partial responses were documented; stable disease in 11 patients, progressive disease in one patient. Apart from nine cases of grade 4 neutropenia, the treatment was generally well-tolerated. Twelve patients underwent conservative and limb salvage surgery. This therapeutic approach seems to be effective in facilitating surgery. Neutropenia was the most significant toxicity but it was preventable or medically treatable with G-CSF support. JF - Anticancer research AU - Ottaiano, A AU - De Chiara, A AU - Fazioli, F AU - De Rosa, V AU - Ravo, V AU - Boccia, V AU - Botti, G AU - Petrillo, A AU - Fiore, F AU - Mori, S AU - Mozzillo, N AU - Iaffaioli, V R AU - Apice, G AD - Department of Medical Oncology B, Division of Medical Oncology B, National Cancer Institute, G. Pascale, Via M. Semmola, 80131, Naples, Italy. ale.otto@libero.it PY - 2002 SP - 3555 EP - 3559 VL - 22 IS - 6B SN - 0250-7005, 0250-7005 KW - Epirubicin KW - 3Z8479ZZ5X KW - Ifosfamide KW - UM20QQM95Y KW - Index Medicus KW - Disease-Free Survival KW - Humans KW - Neoadjuvant Therapy KW - Adult KW - Aged KW - Middle Aged KW - Follow-Up Studies KW - Epirubicin -- administration & dosage KW - Male KW - Female KW - Ifosfamide -- administration & dosage KW - Soft Tissue Neoplasms -- pathology KW - Soft Tissue Neoplasms -- drug therapy KW - Sarcoma -- surgery KW - Sarcoma -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Soft Tissue Neoplasms -- surgery KW - Sarcoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72837392?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anticancer+research&rft.atitle=Neoadjuvant+chemotherapy+for+intermediate%2Fhigh-grade+soft+tissue+sarcomas%3A+five-year+results+with+epirubicin+and+ifosfamide.&rft.au=Ottaiano%2C+A%3BDe+Chiara%2C+A%3BFazioli%2C+F%3BDe+Rosa%2C+V%3BRavo%2C+V%3BBoccia%2C+V%3BBotti%2C+G%3BPetrillo%2C+A%3BFiore%2C+F%3BMori%2C+S%3BMozzillo%2C+N%3BIaffaioli%2C+V+R%3BApice%2C+G&rft.aulast=Ottaiano&rft.aufirst=A&rft.date=2002-11-01&rft.volume=22&rft.issue=6B&rft.spage=3555&rft.isbn=&rft.btitle=&rft.title=Anticancer+research&rft.issn=02507005&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-24 N1 - Date created - 2003-01-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nicotine delivery from smoking bidis and an additive-free cigarette. AN - 72815518; 12521408 AB - The present study was conducted to determine whether smoking bidis, an additive-free cigarette, and conventional cigarettes caused similar biochemical, physiological and subjective effects. This was an open-label, within-subject design. In each session, subjects (n = 10) smoked a single cigarette: an unfiltered Natural American Spirit, an unfiltered Irie bidi, an unfiltered Sher bidi, or one of the participant's own brand. The presentation of the cigarettes was randomized. Before and up to 1 h after smoking, biochemical markers [plasma nicotine levels and exhaled carbon monoxide (CO)] and physiological effects of nicotine (heart rate and blood pressure) were measured. After smoking, subjects completed two standardized tests of cigarette liking and cigarette sensations. American Spirit (32.1 ng/ml) and Irie bidi (26.0 ng/ml) cigarettes increased plasma nicotine more than the participant's own brand (18.5 ng/ml). Subjects smoked longer and took more puffs to consume the American Spirit (452.8 s, 14 puffs) and Sher bidi (354.4 s, 14 puffs) than the participant's own brand (297.4 s, 10 puffs). In spite of differences in nicotine delivery, participants rated all cigarettes as similar in nicotine content. Overall, the results indicate that bidis and the additive-free cigarette delivered nicotine, CO and (presumably) other toxic components of tobacco smoke in equal or greater amounts than conventional cigarettes. These results do not support an emerging belief that bidi cigarettes are safer than conventional brands. JF - Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco AU - Malson, Jennifer L AU - Lee, Eun M AU - Moolchan, Eric T AU - Pickworth, Wallace B AD - Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA. Y1 - 2002/11// PY - 2002 DA - November 2002 SP - 485 EP - 490 VL - 4 IS - 4 SN - 1462-2203, 1462-2203 KW - Carbon Dioxide KW - 142M471B3J KW - Nicotine KW - 6M3C89ZY6R KW - Index Medicus KW - Tobacco -- chemistry KW - Humans KW - Adult KW - Surveys and Questionnaires KW - Carbon Dioxide -- metabolism KW - Male KW - Female KW - Smoking KW - Plants, Toxic -- chemistry KW - Nicotine -- analysis KW - Nicotine -- administration & dosage KW - Nicotine -- blood KW - Personal Satisfaction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72815518?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nicotine+%26+tobacco+research+%3A+official+journal+of+the+Society+for+Research+on+Nicotine+and+Tobacco&rft.atitle=Nicotine+delivery+from+smoking+bidis+and+an+additive-free+cigarette.&rft.au=Malson%2C+Jennifer+L%3BLee%2C+Eun+M%3BMoolchan%2C+Eric+T%3BPickworth%2C+Wallace+B&rft.aulast=Malson&rft.aufirst=Jennifer&rft.date=2002-11-01&rft.volume=4&rft.issue=4&rft.spage=485&rft.isbn=&rft.btitle=&rft.title=Nicotine+%26+tobacco+research+%3A+official+journal+of+the+Society+for+Research+on+Nicotine+and+Tobacco&rft.issn=14622203&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-22 N1 - Date created - 2003-01-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Diet and kidney diseases in rats. AN - 72802959; 12512864 AB - Diet-associated kidney diseases of rats includes nephropathy in both sexes and nephrocalcinosis in females. High protein content of diets appears to be the major cause for severe nephropathy and changing the source of protein to one such as soy protein, restricting caloric intake, or modifying the diet to decrease protein consumption could decrease the severity of nephropathy. The NTP-2000 diet with lower protein content than most diets decreases the severity of nephropathy and increases the survival of Fischer 344 rats without substantial changes in growth patterns and body weights. Nephrocalcinosis, characterized by mineralization of renal tubules at the corticomedullary junction, has been reported in young and adult female rats of most strains and stocks suggesting a major contribution of female sex hormones to the development of this lesion. Calcium (Ca), phosphorous (P), magnesium (Mg), and chloride (Cl) imbalances, especially a Ca:P ratio of less than 1.0 in diet, are considered to be associated with this lesion. Most commercial diets commonly used for toxicology studies have a Ca:P molar ratio of less than 1.0. Increasing the Ca:P molar ratio to more than 1.0 and closer to 1.3 in the AIN-93 purified diet and NTP-2000 nonpurified diet prevents the development of this lesion. Genetics will predispose rats to some diseases and environmental factors will influence the severity of these diseases. Diet is one of the most important environmental factors. Diets balanced for nutrients without excesses could markedly improve the health of rats used in chronic studies leading to substantial increases in survival and thereby accomplish the objective of chronic toxicity and carcinogenicity studies. JF - Toxicologic pathology AU - Rao, Ghanta N AD - National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Rao@niehs.nih.gov PY - 2002 SP - 651 EP - 656 VL - 30 IS - 6 SN - 0192-6233, 0192-6233 KW - Proteins KW - 0 KW - Phosphorus KW - 27YLU75U4W KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Drinking KW - Animals KW - Kidney -- pathology KW - Sex Characteristics KW - Calcium -- analysis KW - Food, Formulated KW - Nephrocalcinosis -- veterinary KW - Rats KW - Diet, Protein-Restricted KW - Nephrocalcinosis -- pathology KW - Rats, Inbred F344 KW - Nephrocalcinosis -- etiology KW - Proteins -- analysis KW - Female KW - Male KW - Phosphorus -- analysis KW - Kidney Diseases -- pathology KW - Kidney Diseases -- etiology KW - Diet KW - Rodent Diseases -- etiology KW - Rodent Diseases -- pathology KW - Kidney Diseases -- veterinary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72802959?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Diet+and+kidney+diseases+in+rats.&rft.au=Rao%2C+Ghanta+N&rft.aulast=Rao&rft.aufirst=Ghanta&rft.date=2002-11-01&rft.volume=30&rft.issue=6&rft.spage=651&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 - 2003-06-03 N1 - Date created - 2003-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effect of chronic progressive nephropathy on the incidence of renal tubule cell neoplasms in control male F344 rats. AN - 72802298; 12512869 AB - Chronic progressive nephropathy (CPN) is the most frequently diagnosed lesion in the rat kidney. It has many components including degeneration and regeneration of renal tubule (RT) epithelium, glomerular lesions and interstitial inflammation and fibrosis. The incidence and severity of CPN is strain, age, and sex dependent and may be altered by a number of factors including exposure to xenobiotics. In National Toxicology Program (NTP) 2-year bioassays, xenobiotic-associated increased severity (exacerbation) of CPN often occurs in association with a marginal increased incidence of renal tubule cell neoplasms (RTCN). The relationship between CPN and RTCN development has not been definitively determined. The present study evaluated the association between severity of CPN and the occurrence of RTCN in control male F344 rats. A slight but statistically significant increase in CPN severity was present in those animals with RTCN compared to aged-matched controls without RTCN. Although these data suggest there is a positive correlation between CPN and RTCN, cause and effect were not determined. This marginal association suggests that the number of RTCNs that may develop secondary to chemically exacerbated nephropathy would be few. JF - Toxicologic pathology AU - Seely, John C AU - Haseman, Joseph K AU - Nyska, Abraham AU - Wolf, Douglas C AU - Everitt, Jeffrey I AU - Hailey, James R AD - Experimental Pathology Laboratories, Inc, Research Triangle Park, North Carolina 27709, USA. seely1@niehs.nih.gov PY - 2002 SP - 681 EP - 686 VL - 30 IS - 6 SN - 0192-6233, 0192-6233 KW - Index Medicus KW - United States KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Microtomy -- methods KW - Epithelial Cells -- pathology KW - National Institutes of Health (U.S.) KW - Retrospective Studies KW - Disease Progression KW - Male KW - Kidney Neoplasms -- pathology KW - Kidney Failure, Chronic -- pathology KW - Kidney Tubules -- pathology KW - Carcinoma -- etiology KW - Carcinoma -- pathology KW - Adenoma -- etiology KW - Kidney Neoplasms -- etiology KW - Adenoma -- pathology KW - Kidney Failure, Chronic -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72802298?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=The+effect+of+chronic+progressive+nephropathy+on+the+incidence+of+renal+tubule+cell+neoplasms+in+control+male+F344+rats.&rft.au=Seely%2C+John+C%3BHaseman%2C+Joseph+K%3BNyska%2C+Abraham%3BWolf%2C+Douglas+C%3BEveritt%2C+Jeffrey+I%3BHailey%2C+James+R&rft.aulast=Seely&rft.aufirst=John&rft.date=2002-11-01&rft.volume=30&rft.issue=6&rft.spage=681&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 - 2003-06-03 N1 - Date created - 2003-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mice with a mutation in the thyroid hormone receptor beta gene spontaneously develop thyroid carcinoma: a mouse model of thyroid carcinogenesis. AN - 72789805; 12490073 AB - The molecular genetic basis of thyroid carcinogenesis is not well understood. Most of the existing models of thyroid cancer only rarely show metastases, and this has limited progress in the understanding of the molecular events in thyroid cancer invasion and metastasis. We have recently generated a mutant mouse by introducing a dominant negative mutant thyroid hormone nuclear receptor gene, TRbetaPV, into the TRbeta gene locus. In this TRbetaPV mouse, the regulation of the thyroid-pituitary axis is disrupted, leading to a mouse with high levels of circulating thyroid-stimulating hormone and extensive hyperplasia of follicular epithelium within the thyroid. As TRbeta(PV/PV) mice, but not TRbeta(PV/+) mice, aged, metastatic thyroid carcinoma developed. Histologic evaluation of thyroids of 5-14-month-old mice showed capsular invasion (91%), vascular invasion (74%), anaplasia (35%), and metastasis to the lung and heart (30%). Previous models of thyroid cancer have focused on genes that control initial carcinogenesis, but this model provides an unusual opportunity to study the alterations in gene regulation that occur with clinically relevant changes during progression and metastasis in a predictable fashion. JF - Thyroid : official journal of the American Thyroid Association AU - Suzuki, Hideyo AU - Willingham, Mark C AU - Cheng, Sheue-Yann AD - Gene Regulation Section, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892-4264, USA. Y1 - 2002/11// PY - 2002 DA - November 2002 SP - 963 EP - 969 VL - 12 IS - 11 SN - 1050-7256, 1050-7256 KW - Receptors, Thyroid Hormone KW - 0 KW - Thyroid Hormone Receptors beta KW - Index Medicus KW - Animals KW - Hyperplasia KW - Disease Progression KW - Anaplasia KW - Mice KW - Mice, Mutant Strains KW - Thyroid Neoplasms -- genetics KW - Receptors, Thyroid Hormone -- genetics KW - Disease Models, Animal KW - Thyroid Neoplasms -- pathology KW - Carcinoma, Papillary, Follicular -- secondary KW - Carcinoma, Papillary, Follicular -- mortality KW - Thyroid Neoplasms -- mortality KW - Carcinoma, Papillary, Follicular -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72789805?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Thyroid+%3A+official+journal+of+the+American+Thyroid+Association&rft.atitle=Mice+with+a+mutation+in+the+thyroid+hormone+receptor+beta+gene+spontaneously+develop+thyroid+carcinoma%3A+a+mouse+model+of+thyroid+carcinogenesis.&rft.au=Suzuki%2C+Hideyo%3BWillingham%2C+Mark+C%3BCheng%2C+Sheue-Yann&rft.aulast=Suzuki&rft.aufirst=Hideyo&rft.date=2002-11-01&rft.volume=12&rft.issue=11&rft.spage=963&rft.isbn=&rft.btitle=&rft.title=Thyroid+%3A+official+journal+of+the+American+Thyroid+Association&rft.issn=10507256&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-22 N1 - Date created - 2002-12-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Geranylgeranyl pyrophosphate counteracts the cataractogenic effect of lovastatin on cultured rat lenses. AN - 72727380; 12457872 AB - Statins are commonly prescribed cholesterol-lowering agents which inhibit the rate-limiting enzyme of the cholesterol biosynthetic pathway. In addition to inhibiting cholesterol synthesis, statins also inhibit the synthesis of other sterol and non-sterol compounds produced by the pathway including the isoprenoids, farnesyl (FP) and geranylgeranyl pyrophosphate (GGP). Certain proteins, most notably small GTP-binding proteins of the Ras superfamily, must be post-translationally modified by addition of a farnesyl or geranylgeranyl moiety in order to be properly targeted to membranes and to be active. Statins have been shown to affect cellular processes such as proliferation, signaling and apoptosis and it is likely that these effects are due, at least in part, to decreased isoprenoid synthesis. Certain statins have been shown to produce cataracts in experimental animals. We have previously demonstrated that lenses exposed to lovastatin during organ culture may develop cataracts as well, and we proposed that this resulted from decreased prenylation of small GTP-binding proteins. To test our hypothesis, rat lenses were exposed to lovastatin in organ culture with concomitant supplementation of the medium with GGP and/or FP. The results clearly demonstrated that GGP strongly inhibited lovastatin-induced lens opacification in this system while FP had little effect. GGP also markedly reduced the histological changes and the increased epithelial cell apoptosis induced in the cultured lenses by lovastatin. The data indicate that inhibition of protein prenylation, perhaps of Rho GTPases, is an important factor in the lovastatin-induced cataract in vitro. JF - Experimental eye research AU - Cheng, Qiufang AU - Gerald Robison, W AU - Samuel Zigler, J AD - Laboratory of Mechanisms of Ocular Diseases, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2002/11// PY - 2002 DA - November 2002 SP - 603 EP - 609 VL - 75 IS - 5 SN - 0014-4835, 0014-4835 KW - Anticholesteremic Agents KW - 0 KW - Polyisoprenyl Phosphates KW - Sesquiterpenes KW - geranylgeranyl pyrophosphate KW - 6699-20-3 KW - farnesyl pyrophosphate KW - 79W6B01D07 KW - Lovastatin KW - 9LHU78OQFD KW - Index Medicus KW - Rats KW - In Situ Nick-End Labeling KW - Animals KW - Cells, Cultured KW - Apoptosis -- drug effects KW - Epithelium -- pathology KW - Epithelium -- drug effects KW - Protein Prenylation KW - Lens Capsule, Crystalline -- pathology KW - Cataract -- pathology KW - Polyisoprenyl Phosphates -- pharmacology KW - Cataract -- prevention & control KW - Cataract -- chemically induced KW - Lovastatin -- toxicity KW - Lens Capsule, Crystalline -- drug effects KW - Anticholesteremic Agents -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72727380?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+eye+research&rft.atitle=Geranylgeranyl+pyrophosphate+counteracts+the+cataractogenic+effect+of+lovastatin+on+cultured+rat+lenses.&rft.au=Cheng%2C+Qiufang%3BGerald+Robison%2C+W%3BSamuel+Zigler%2C+J&rft.aulast=Cheng&rft.aufirst=Qiufang&rft.date=2002-11-01&rft.volume=75&rft.issue=5&rft.spage=603&rft.isbn=&rft.btitle=&rft.title=Experimental+eye+research&rft.issn=00144835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-12-13 N1 - Date created - 2002-11-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Focus on lymphomas. AN - 72726173; 12450791 JF - Cancer cell AU - Staudt, Louis M AU - Wilson, Wyndham H AD - Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. lstaudt@mail.nih.gov Y1 - 2002/11// PY - 2002 DA - November 2002 SP - 363 EP - 366 VL - 2 IS - 5 SN - 1535-6108, 1535-6108 KW - Anti-Bacterial Agents KW - 0 KW - Antibodies, Monoclonal KW - Antibodies, Monoclonal, Humanized KW - Antibodies, Monoclonal, Murine-Derived KW - Antibodies, Neoplasm KW - Antineoplastic Agents KW - Interleukin-2 KW - Vaccines KW - alemtuzumab KW - 3A189DH42V KW - Rituximab KW - 4F4X42SYQ6 KW - Vincristine KW - 5J49Q6B70F KW - Etoposide KW - 6PLQ3CP4P3 KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Prednisone KW - VB0R961HZT KW - Index Medicus KW - Anti-Bacterial Agents -- therapeutic use KW - Prednisone -- therapeutic use KW - Humans KW - Etoposide -- therapeutic use KW - Antibodies, Neoplasm -- therapeutic use KW - Gene Expression KW - Survival KW - Vaccines -- therapeutic use KW - Antibodies, Monoclonal -- therapeutic use KW - Cyclophosphamide -- therapeutic use KW - Vincristine -- therapeutic use KW - Risk Factors KW - Interleukin-2 -- therapeutic use KW - Chromosome Aberrations KW - Doxorubicin -- therapeutic use KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Lymphoma -- therapy KW - Lymphoma -- diagnosis KW - Lymphoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72726173?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cell&rft.atitle=Focus+on+lymphomas.&rft.au=Staudt%2C+Louis+M%3BWilson%2C+Wyndham+H&rft.aulast=Staudt&rft.aufirst=Louis&rft.date=2002-11-01&rft.volume=2&rft.issue=5&rft.spage=363&rft.isbn=&rft.btitle=&rft.title=Cancer+cell&rft.issn=15356108&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-03 N1 - Date created - 2002-11-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The roles of REV3 and RAD57 in double-strand-break-repair-induced mutagenesis of Saccharomyces cerevisiae. AN - 72717488; 12454056 AB - The DNA synthesis associated with recombinational repair of chromosomal double-strand breaks (DSBs) has a lower fidelity than normal replicative DNA synthesis. Here, we use an inverted-repeat substrate to monitor the fidelity of repair of a site-specific DSB. DSB induction made by the HO endonuclease stimulates recombination >5000-fold and is associated with a >1000-fold increase in mutagenesis of an adjacent gene. We demonstrate that most break-repair-induced mutations (BRIMs) are point mutations and have a higher proportion of frameshifts than do spontaneous mutations of the same substrate. Although the REV3 translesion DNA polymerase is not required for recombination, it introduces approximately 75% of the BRIMs and approximately 90% of the base substitution mutations. Recombinational repair of the DSB is strongly dependent upon genes of the RAD52 epistasis group; however, the residual recombinants present in rad57 mutants are associated with a 5- to 20-fold increase in BRIMs. The spectrum of mutations in rad57 mutants is similar to that seen in the wild-type strain and is similarly affected by REV3. We also find that REV3 is required for the repair of MMS-induced lesions when recombinational repair is compromised. Our data suggest that Rad55p/Rad57p help limit the generation of substrates that require pol zeta during recombination. JF - Genetics AU - Rattray, Alison J AU - Shafer, Brenda K AU - McGill, Carolyn B AU - Strathern, Jeffrey N AD - Gene Regulation and Chromosome Biology Laboratory, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA. Y1 - 2002/11// PY - 2002 DA - November 2002 SP - 1063 EP - 1077 VL - 162 IS - 3 SN - 0016-6731, 0016-6731 KW - DNA-Binding Proteins KW - 0 KW - Fungal Proteins KW - RAD52 protein, S cerevisiae KW - Rad52 DNA Repair and Recombination Protein KW - Saccharomyces cerevisiae Proteins KW - RAD51 protein, S cerevisiae KW - EC 2.7.7.- KW - Rad51 Recombinase KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - REV3 protein, S cerevisiae KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - RAD57 protein, S cerevisiae KW - DNA Repair Enzymes KW - EC 6.5.1.- KW - Index Medicus KW - DNA Repair -- physiology KW - Blotting, Southern KW - Point Mutation KW - DNA-Binding Proteins -- physiology KW - Saccharomyces cerevisiae Proteins -- physiology KW - Saccharomyces cerevisiae -- genetics KW - Fungal Proteins -- physiology KW - DNA-Directed DNA Polymerase -- physiology KW - Mutation -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72717488?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+roles+of+REV3+and+RAD57+in+double-strand-break-repair-induced+mutagenesis+of+Saccharomyces+cerevisiae.&rft.au=Rattray%2C+Alison+J%3BShafer%2C+Brenda+K%3BMcGill%2C+Carolyn+B%3BStrathern%2C+Jeffrey+N&rft.aulast=Rattray&rft.aufirst=Alison&rft.date=2002-11-01&rft.volume=162&rft.issue=3&rft.spage=1063&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-10 N1 - Date created - 2002-11-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5089-94 [10220423] Genetics. 1995 Jun;140(2):443-56 [7498727] J Biol Chem. 2000 May 26;275(21):15895-904 [10748203] Mutat Res. 2000 Jun 30;451(1-2):277-93 [10915878] Nature. 2000 Aug 31;406(6799):1015-9 [10984059] Nature. 2000 Nov 9;408(6809):216-21 [11089977] Mol Cell Biol. 2000 Dec;20(24):9162-72 [11094068] Immunity. 2000 Nov;13(5):589-97 [11114372] Philos Trans R Soc Lond B Biol Sci. 2001 Jan 29;356(1405):41-6 [11205328] Mol Cell. 2000 Dec;6(6):1491-9 [11163221] Curr Opin Immunol. 2001 Apr;13(2):208-18 [11228415] Mol Cell Biol. 2001 Mar;21(6):2048-56 [11238940] Genetics. 2001 May;158(1):109-22 [11333222] Genetics. 2001 May;158(1):177-86 [11333228] Genetics. 2001 May;158(1):369-78 [11333245] Immunity. 2001 May;14(5):643-53 [11371365] Science. 1996 Jun 14;272(5268):1646-9 [8658138] Genetics. 1996 Mar;142(3):693-704 [8849880] Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10729-34 [8855248] Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13919-24 [8943036] Cell. 1997 Jan 24;88(2):253-63 [9008166] Genes Dev. 1997 May 1;11(9):1111-21 [9159392] EMBO J. 1997 Jun 2;16(11):3303-11 [9214645] Genetics. 1997 Nov;147(3):1017-24 [9383049] Nature. 1998 Jan 22;391(6665):401-4 [9450758] Nature. 1998 Jan 22;391(6665):404-7 [9450759] Nature. 1998 Jan 22;391(6665):407-10 [9450760] Genetics. 1998 Apr;148(4):1491-505 [9560369] Genetics. 1998 Apr;148(4):1525-33 [9560371] Immunity. 1998 Dec;9(6):859-69 [9881976] Mol Cell Biol. 1999 Apr;19(4):2929-35 [10082560] Microbiol Mol Biol Rev. 1999 Jun;63(2):349-404 [10357855] Genetics. 2001 Jun;158(2):597-611 [11404325] Mutat Res. 2001 Aug 9;486(3):167-84 [11459630] J Bacteriol. 1971 May;106(2):543-50 [4929867] J Bacteriol. 1983 Jan;153(1):163-8 [6336730] Methods Enzymol. 1983;101:202-11 [6310324] Methods Enzymol. 1983;101:228-45 [6310326] Cancer Invest. 1984;2(3):223-31 [6733565] Cell. 1983 May;33(1):25-35 [6380756] Gene. 1987;57(2-3):267-72 [3319781] Genetics. 1989 May;122(1):19-27 [2659436] Genetics. 1989 Jul;122(3):535-42 [2668115] J Bacteriol. 1989 Oct;171(10):5659-67 [2676986] Cell. 1992 May 1;69(3):457-70 [1581961] Mol Cell Biol. 1992 Jul;12(7):3224-34 [1620127] Curr Genet. 1993 May-Jun;23(5-6):430-4 [8319299] Gene. 1994 May 3;142(1):103-6 [8181742] Nature. 1995 Jan 5;373(6509):84-6 [7800045] Genetics. 1995 Jan;139(1):45-56 [7705645] Science. 1995 Jun 16;268(5217):1616-9 [7777859] Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):6925-9 [7624345] Mol Cell Biol. 1995 Sep;15(9):4843-50 [7651402] Genetics. 1995 Jul;140(3):965-72 [7672595] Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12017-20 [8618835] Genetics. 2000 Apr;154(4):1427-37 [10747042] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enzymatic cytosine deamination: friend and foe. AN - 72715569; 12453402 JF - Molecular cell AU - Kunkel, Thomas A AU - Diaz, Marilyn AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 2002/11// PY - 2002 DA - November 2002 SP - 962 EP - 963 VL - 10 IS - 5 SN - 1097-2765, 1097-2765 KW - Cytosine KW - 8J337D1HZY KW - DNA KW - 9007-49-2 KW - AICDA (activation-induced cytidine deaminase) KW - EC 3.5.4.- KW - APOBEC-1 Deaminase KW - EC 3.5.4.36 KW - Apobec1 protein, mouse KW - Cytidine Deaminase KW - EC 3.5.4.5 KW - Index Medicus KW - Animals KW - Escherichia coli -- metabolism KW - DNA Repair KW - DNA -- metabolism KW - Base Pair Mismatch KW - Mice KW - Mutation KW - Mutagenesis KW - Cytidine Deaminase -- physiology KW - Cytosine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72715569?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cell&rft.atitle=Enzymatic+cytosine+deamination%3A+friend+and+foe.&rft.au=Kunkel%2C+Thomas+A%3BDiaz%2C+Marilyn&rft.aulast=Kunkel&rft.aufirst=Thomas&rft.date=2002-11-01&rft.volume=10&rft.issue=5&rft.spage=962&rft.isbn=&rft.btitle=&rft.title=Molecular+cell&rft.issn=10972765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-01-09 N1 - Date created - 2002-11-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lowering of pI by acylation improves the renal uptake of 99mTc-labeled anti-Tac dsFv: effect of different acylating reagents. AN - 72714647; 12453588 AB - Anti-Tac disulfide-stabilized variable region fragment (dsFv) was labeled with 99mTc by a preformed chelate approach using 99mTc-MAG3-trifluorophenyl (TFP) ester. Simultaneously it was acylated with TFP-lactate or succinic anhydride to decrease the isoelectric point of dsFv (pI 10). Acylation of dsFv (0.04 mM) with the lactate at a 73 times molar excess reduced the pI to 5.0-6.7, whereas acylation with succinic anhydride at a 30 times molar excess reduced the pI to 4.9-8.7. Comparative biodistribution studies performed in mice (n = 5) showed the reduced renal accumulation of the 99mTc proportional to the pI reduction. The effect of the pI on the reduced renal uptake was especially pronounced at 15 min postinjection. The reduced renal uptake was also reflected in the reduced whole-body retention, indicating that lowering the pI inhibited the tubular reabsorption of the labeled dsFv. JF - Nuclear medicine and biology AU - Kim, Insook AU - Kobayashi, Hisataka AU - Yoo, Tae M AU - Kim, Meyong-kon AU - Le, Nhat AU - Han, Eui-sik AU - Wang, Q C AU - Pastan, Ira AU - Carrasquillo, Jorge A AU - Paik, Chang H AD - Department of Nuclear Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892-1180, USA. Y1 - 2002/11// PY - 2002 DA - November 2002 SP - 795 EP - 801 VL - 29 IS - 8 SN - 0969-8051, 0969-8051 KW - Ampholyte Mixtures KW - 0 KW - Antibodies, Monoclonal KW - Lactates KW - Organotechnetium Compounds KW - Radiopharmaceuticals KW - Succinates KW - technetium-99m-MAG3-dsFV KW - Index Medicus KW - Sensitivity and Specificity KW - Radiopharmaceuticals -- pharmacokinetics KW - Animals KW - Succinates -- pharmacokinetics KW - Reproducibility of Results KW - Body Burden KW - Isoelectric Point KW - Lactates -- chemistry KW - Radiopharmaceuticals -- chemistry KW - Mice KW - Mice, Nude KW - Organ Specificity KW - Tissue Distribution KW - Acylation KW - Radionuclide Imaging KW - Lactates -- pharmacokinetics KW - Whole-Body Counting KW - Succinates -- chemistry KW - Female KW - Kidney -- diagnostic imaging KW - Ampholyte Mixtures -- chemistry KW - Kidney -- metabolism KW - Antibodies, Monoclonal -- pharmacokinetics KW - Isotope Labeling -- methods KW - Ampholyte Mixtures -- pharmacokinetics KW - Organotechnetium Compounds -- pharmacokinetics KW - Organotechnetium Compounds -- chemistry KW - Antibodies, Monoclonal -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72714647?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nuclear+medicine+and+biology&rft.atitle=Lowering+of+pI+by+acylation+improves+the+renal+uptake+of+99mTc-labeled+anti-Tac+dsFv%3A+effect+of+different+acylating+reagents.&rft.au=Kim%2C+Insook%3BKobayashi%2C+Hisataka%3BYoo%2C+Tae+M%3BKim%2C+Meyong-kon%3BLe%2C+Nhat%3BHan%2C+Eui-sik%3BWang%2C+Q+C%3BPastan%2C+Ira%3BCarrasquillo%2C+Jorge+A%3BPaik%2C+Chang+H&rft.aulast=Kim&rft.aufirst=Insook&rft.date=2002-11-01&rft.volume=29&rft.issue=8&rft.spage=795&rft.isbn=&rft.btitle=&rft.title=Nuclear+medicine+and+biology&rft.issn=09698051&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-02 N1 - Date created - 2002-11-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Opposing roles of STAT1 and STAT3 in T cell-mediated hepatitis: regulation by SOCS. AN - 72696159; 12438448 AB - T cell-mediated fulminant hepatitis is a life-threatening event for which the underlying mechanism is not fully understood. Injection of concanavalin A (Con A) into mice recapitulates the histological and pathological sequelae of T cell-mediated hepatitis. In this model, both signal transducer and activator of transcription factor 1 (STAT1) and STAT3 are activated in the liver. Disruption of the STAT1 gene by way of genetic knockout attenuates liver injury, suppresses CD4(+) and NK T cell activation, and downregulates expression of proapoptotic interferon regulatory factor-1 protein and suppressor of cytokine signaling-1 (SOCS1), but enhances STAT3 activation and STAT3-controlled antiapoptotic signals. Studies from IFN-gamma-deficient mice indicate that IFN-gamma not only is the major cytokine responsible for STAT1 activation but also partially accounts for STAT3 activation. Moreover, downregulation of STAT3 activation in IL-6-deficient mice is associated with decreased STAT3-controlled antiapoptotic signals and expression of SOCS3, but upregulation of STAT1 activation and STAT1-induced proapoptotic signals and exacerbation of liver injury. Taken together, these findings suggest that STAT1 plays a harmful role in Con A-mediated hepatitis by activation of CD4(+) and NK T cells and directly inducing hepatocyte death, whereas STAT3 protects against liver injury by suppression of IFN-gamma signaling and induction of antiapoptotic protein Bcl-X(L). STAT1 and STAT3 in hepatocytes also negatively regulate one another through the induction of SOCS. JF - The Journal of clinical investigation AU - Hong, Feng AU - Jaruga, Barbara AU - Kim, Won Ho AU - Radaeva, Svetlana AU - El-Assal, Osama N AU - Tian, Zhigang AU - Nguyen, Van-Anh AU - Gao, Bin AD - Section on Liver Biology, Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/11// PY - 2002 DA - November 2002 SP - 1503 EP - 1513 VL - 110 IS - 10 SN - 0021-9738, 0021-9738 KW - Carrier Proteins KW - 0 KW - DNA-Binding Proteins KW - Interleukin-6 KW - Intracellular Signaling Peptides and Proteins KW - Proteins KW - RNA, Messenger KW - Repressor Proteins KW - SOCS1 protein, human KW - SOCS3 protein, human KW - STAT1 Transcription Factor KW - STAT1 protein, human KW - STAT3 Transcription Factor KW - STAT3 protein, human KW - Socs1 protein, mouse KW - Socs3 protein, mouse KW - Stat1 protein, mouse KW - Stat3 protein, mouse KW - Suppressor of Cytokine Signaling 1 Protein KW - Suppressor of Cytokine Signaling 3 Protein KW - Suppressor of Cytokine Signaling Proteins KW - Trans-Activators KW - Transcription Factors KW - Concanavalin A KW - 11028-71-0 KW - Interferon-gamma KW - 82115-62-6 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Interferon-gamma -- genetics KW - Carrier Proteins -- metabolism KW - Concanavalin A -- toxicity KW - Carrier Proteins -- genetics KW - Humans KW - Interleukin-6 -- deficiency KW - Mice KW - RNA, Messenger -- genetics KW - Mice, Inbred BALB C KW - Models, Biological KW - Mice, Knockout KW - RNA, Messenger -- metabolism KW - Interferon-gamma -- deficiency KW - Interleukin-6 -- genetics KW - Mice, Inbred C57BL KW - Signal Transduction KW - Male KW - Trans-Activators -- metabolism KW - Trans-Activators -- deficiency KW - Hepatitis, Autoimmune -- metabolism KW - DNA-Binding Proteins -- genetics KW - Hepatitis, Autoimmune -- immunology KW - Proteins -- genetics KW - Proteins -- metabolism KW - DNA-Binding Proteins -- deficiency KW - Trans-Activators -- genetics KW - Hepatitis, Autoimmune -- pathology KW - T-Lymphocytes -- immunology KW - DNA-Binding Proteins -- metabolism KW - Hepatitis, Autoimmune -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72696159?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Opposing+roles+of+STAT1+and+STAT3+in+T+cell-mediated+hepatitis%3A+regulation+by+SOCS.&rft.au=Hong%2C+Feng%3BJaruga%2C+Barbara%3BKim%2C+Won+Ho%3BRadaeva%2C+Svetlana%3BEl-Assal%2C+Osama+N%3BTian%2C+Zhigang%3BNguyen%2C+Van-Anh%3BGao%2C+Bin&rft.aulast=Hong&rft.aufirst=Feng&rft.date=2002-11-01&rft.volume=110&rft.issue=10&rft.spage=1503&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 - 2003-01-31 N1 - Date created - 2002-11-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Hepatology. 1999 Nov;30(5):1241-51 [10534346] EMBO J. 1999 Jan 15;18(2):375-85 [9889194] Exp Cell Res. 1999 Nov 25;253(1):7-14 [10579906] Curr Top Microbiol Immunol. 2000;242:299-325 [10592666] Hepatology. 2000 Jan;31(1):149-59 [10613740] J Exp Med. 2000 Jan 3;191(1):105-14 [10620609] Gastroenterology. 2000 Feb;118(2):404-21 [10648469] J Biol Chem. 2000 Mar 3;275(9):6462-8 [10692450] Proc Natl Acad Sci U S A. 2000 May 9;97(10):5498-503 [10792025] J Tongji Med Univ. 1998;18(4):247-9 [10806857] J Immunol. 2000 Jun 1;164(11):5833-43 [10820262] Immunity. 2000 Sep;13(3):287-90 [11021526] Dig Liver Dis. 2000 Jun-Jul;32(5):440-6 [11030191] Curr Opin Oncol. 2000 Nov;12(6):543-9 [11085453] Clin Immunol. 2000 Dec;97(3):221-33 [11112361] Hepatology. 2001 Jan;33(1):267-76 [11124845] Cold Spring Harb Symp Quant Biol. 1999;64:397-404 [11232314] Gastroenterology. 2001 May;120(6):1485-501 [11313320] J Immunol. 2001 May 15;166(10):5889-97 [11342603] Int J Hematol. 2001 Apr;73(3):271-7 [11345192] Immunity. 2001 May;14(5):535-45 [11371356] J Clin Invest. 2001 May;107(10):1285-92 [11375418] J Biol Chem. 2001 Jul 13;276(28):26605-13 [11349125] J Allergy Clin Immunol. 1993 Dec;92(6):902-8 [8258624] Immunol Today. 1994 Feb;15(2):74-80 [7512342] J Exp Med. 1994 May 1;179(5):1529-37 [8163936] Science. 1994 Jun 3;264(5164):1415-21 [8197455] Hepatology. 1995 Jan;21(1):113-9 [7806143] J Pediatr Gastroenterol Nutr. 1995 Jan;20(1):23-7 [7884614] Cell. 1996 Feb 9;84(3):331-4 [8608586] Cell. 1996 Feb 9;84(3):431-42 [8608597] EMBO J. 1999 Apr 15;18(8):2127-36 [10205167] Biochem Biophys Res Commun. 1999 Apr 21;257(3):672-7 [10208842] Semin Liver Dis. 1999;19(2):157-69 [10422198] Semin Liver Dis. 1999;19(2):205-19 [10422201] Am J Physiol. 1999 Sep;277(3 Pt 1):G702-8 [10484397] Cell. 1999 Sep 3;98(5):597-608 [10490099] J Immunol. 2001 Jan 15;166(2):1300-7 [11145713] J Gastroenterol. 2001 Aug;36(8):544-51 [11519833] Hepatology. 2002 Jan;35(1):7-13 [11786954] Hepatology. 2002 Jan;35(1):190-8 [11786976] Oncogene. 2002 Jan 3;21(1):32-43 [11791174] Gastroenterology. 2002 Apr;122(4):1020-34 [11910354] J Clin Invest. 1992 Jul;90(1):196-203 [1634608] Gastroenterology. 1993 Jul;105(1):254-66 [8514042] Cell. 1996 Feb 9;84(3):443-50 [8608598] Hepatology. 1996 Jun;23(6):1608-15 [8675184] Gastroenterology. 1996 Aug;111(2):462-71 [8690213] J Immunol. 1996 Aug 15;157(4):1415-21 [8759721] Hepatology. 1996 Oct;24(4):759-65 [8855173] Science. 1996 Nov 22;274(5291):1379-83 [8910279] Hepatology. 1996 Dec;24(6):1416-21 [8938173] J Clin Invest. 1997 Apr 1;99(7):1472-7 [9119989] J Biol Chem. 1997 May 16;272(20):13432-6 [9148968] Nature. 1997 Jun 26;387(6636):917-21 [9202125] J Immunol. 1997 Aug 1;159(3):1418-28 [9233639] J Immunol. 1998 Apr 15;160(8):4082-9 [9558119] Eur J Immunol. 1998 Dec;28(12):4105-13 [9862346] Trends Biochem Sci. 1999 Oct;24(10):394-8 [10500304] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oxazolone colitis, a Th2 colitis model resembling ulcerative colitis, is mediated by IL-13-producing NK-T cells. AN - 72694877; 12433369 AB - Oxazolone colitis (OC) is an experimental colitis that has a histologic resemblance to human ulcerative colitis. Here we show that IL-13 production is a significant pathologic factor in OC since its neutralization by IL-13Ralpha2-Fc administration prevents colitis. We further show that OC is mediated by NK-T cells since it can be induced neither in mice depleted of NK-T cells nor in mice that cannot present antigen to NK-T cells and mice lacking an NK-T cell-associated TCR. Finally, we show that NK-T cells are the source of the IL-13, since they produce IL-13 upon stimulation by alpha-galactosylceramide, an NK-T cell-specific antigen. These data thus describe a cellular mechanism underlying an experimental colitis that may explain the pathogenesis of ulcerative colitis. JF - Immunity AU - Heller, Frank AU - Fuss, Ivan J AU - Nieuwenhuis, Edward E AU - Blumberg, Richard S AU - Strober, Warren AD - Mucosal Immunity Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2002/11// PY - 2002 DA - November 2002 SP - 629 EP - 638 VL - 17 IS - 5 SN - 1074-7613, 1074-7613 KW - Adjuvants, Immunologic KW - 0 KW - Interleukin-13 KW - Oxazolone KW - 15646-46-5 KW - Index Medicus KW - Animals KW - Humans KW - Mice, Inbred C57BL KW - Disease Models, Animal KW - Mice KW - Male KW - Interleukin-13 -- immunology KW - Interleukin-13 -- biosynthesis KW - Colitis -- immunology KW - Colitis, Ulcerative -- etiology KW - Colitis -- chemically induced KW - Th2 Cells -- immunology KW - Killer Cells, Natural -- immunology KW - Colitis, Ulcerative -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72694877?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Immunity&rft.atitle=Oxazolone+colitis%2C+a+Th2+colitis+model+resembling+ulcerative+colitis%2C+is+mediated+by+IL-13-producing+NK-T+cells.&rft.au=Heller%2C+Frank%3BFuss%2C+Ivan+J%3BNieuwenhuis%2C+Edward+E%3BBlumberg%2C+Richard+S%3BStrober%2C+Warren&rft.aulast=Heller&rft.aufirst=Frank&rft.date=2002-11-01&rft.volume=17&rft.issue=5&rft.spage=629&rft.isbn=&rft.btitle=&rft.title=Immunity&rft.issn=10747613&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-12-13 N1 - Date created - 2002-11-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differences in base excision repair capacity may modulate the effect of dietary antioxidant intake on prostate cancer risk: an example of polymorphisms in the XRCC1 gene. AN - 72687636; 12433703 AB - We propose a hypothesis that differences in base excision repair capacity modulate the effect of dietary antioxidant intake on prostate cancer risk. As a preliminary test of this hypothesis, we conducted a pilot case-control study to evaluate prostate cancer risk in men with polymorphisms in the XRCC1 gene, a key player in base excision repair, across different strata of antioxidant intake. Seventy-seven prostate cancer patients and 183 community controls, for whom we have detailed dietary information, were frequency matched on age and race. We found a somewhat lower prostate cancer risk for men with one or two copies of the variant alleles at the XRCC1 codons 194 and 399 than for those who were homozygous for the common allele [codon 194: odds ratio (OR) = 0.8; 95% confidence interval (CI), 0.4-1.8 and codon 399: OR = 0.8; 95% CI, 0.5-1.3]. The variant at codon 280 was associated with a slightly increased prostate cancer risk (OR = 1.5; 95% CI, 0.7-3.6). Only the codon 399 polymorphism occurred frequently enough to investigate its joint effect with antioxidant intake. Prostate cancer risk was highest among men who were homozygous for the common allele at codon 399 and had low dietary intake of vitamin E (OR = 2.4; 95% CI, 1.0-5.6) or lycopene (OR = 2.0; 95% CI, 0.8-4.9), whereas low intake of these antioxidants in men without this genotype hardly increased prostate cancer risk. The polymorphism did not modulate risk associated with low intake of vitamin C, A, or beta-carotene. The data give some support for our hypothesis but should be regarded as preliminary, because it is limited by small sample size. We discuss what kind of data and what kind of studies are needed for future evaluation of this hypothesis. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - van Gils, Carla H AU - Bostick, Roberd M AU - Stern, Mariana C AU - Taylor, Jack A AD - Molecular and Genetic Epidemiology Section, Laboratory of Molecular Carcinogenesis. National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709, USA. Y1 - 2002/11// PY - 2002 DA - November 2002 SP - 1279 EP - 1284 VL - 11 IS - 11 SN - 1055-9965, 1055-9965 KW - Antioxidants KW - 0 KW - Codon KW - DNA-Binding Proteins KW - X-ray repair cross complementing protein 1 KW - beta Carotene KW - 01YAE03M7J KW - Vitamin E KW - 1406-18-4 KW - Carotenoids KW - 36-88-4 KW - Ascorbic Acid KW - PQ6CK8PD0R KW - lycopene KW - SB0N2N0WV6 KW - Index Medicus KW - Polymorphism, Genetic -- drug effects KW - Ascorbic Acid -- therapeutic use KW - Codon -- genetics KW - Neoplasm Staging KW - Humans KW - DNA-Binding Proteins -- genetics KW - Vitamin E -- therapeutic use KW - Aged KW - Pilot Projects KW - Genotype KW - Codon -- drug effects KW - Gene Frequency -- drug effects KW - Carotenoids -- therapeutic use KW - beta Carotene -- therapeutic use KW - Risk Factors KW - Treatment Outcome KW - Case-Control Studies KW - DNA-Binding Proteins -- drug effects KW - Middle Aged KW - Follow-Up Studies KW - Gene Frequency -- genetics KW - Male KW - Eating -- physiology KW - DNA Repair -- physiology KW - Prostatic Neoplasms -- epidemiology KW - Antioxidants -- therapeutic use KW - Prostatic Neoplasms -- physiopathology KW - Prostatic Neoplasms -- diet therapy KW - DNA Repair -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72687636?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Differences+in+base+excision+repair+capacity+may+modulate+the+effect+of+dietary+antioxidant+intake+on+prostate+cancer+risk%3A+an+example+of+polymorphisms+in+the+XRCC1+gene.&rft.au=van+Gils%2C+Carla+H%3BBostick%2C+Roberd+M%3BStern%2C+Mariana+C%3BTaylor%2C+Jack+A&rft.aulast=van+Gils&rft.aufirst=Carla&rft.date=2002-11-01&rft.volume=11&rft.issue=11&rft.spage=1279&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 - 2003-03-07 N1 - Date created - 2002-11-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effects of gender and gonadal steroids on the neuroendocrine and temperature response to m-chlorophenylpiperazine in leuprolide-induced hypogonadism in women and men. AN - 72682164; 12431854 AB - Studies of the effects of gender and gonadal steroids on serotonergic activity in humans are few in number and often contradictory. We examined the neuroendocrine and core temperature response to a serotonergic stimulus, m-chlorophenylpiperazine (m-CPP) (0.08 mg/kg body weight, IV), in asymptomatic female and male volunteers during induced hypogonadism (leuprolide acetate) and hormone replacement (estradiol (E2) or progesterone (P4) in women; testosterone (T) in men). Compared with the hypogonadal state, basal prolactin (PRL) secretion was significantly higher during both P4 and E2 replacement (p <.05) in women and during T replacement in men (p <.05). m-CPP stimulated PRL secretion was significantly greater only during P4 (p <.05) but not E2 (women) or T (men) replacement, compared with hypogonadism. Basal but not stimulated plasma growth hormone (GH) levels were significantly higher during P4 in women and T in men (p <.05), and no significant differences in basal or m-CPP stimulated plasma levels of ACTH or cortisol were observed. Finally, basal core temperatures were significantly higher during P4 replacement compared with either E2 replacement or the hypogonadal condition (p <.01) in women, with no differences observed in men. Comparisons of measures by gender (and matched for baseline plasma T levels) revealed that during the hypogonadal state m-CPP-stimulated GH secretion was significantly greater (p <.01) and m-CPP-stimulated ACTH (p <.05) and cortisol (p <.01) significantly less in women compared with men. Although our data are limited to those components of the central serotonergic system influenced by m-CPP administration, our findings suggest the following: the regulatory effects of gonadal steroids on serotonergic function are modest in humans during leuprolide-induced hypogonadism; menstrual cycle phase effects of serotonergic agents on PRL secretion may reflect both the effects of P4 and E2; the effects of P4 in humans may occur without E2 priming of the progesterone receptor; and gender differences in GH secretion occur independent of the presence of gonadal steroids. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Schmidt, Peter J AU - Raju, Jamuna AU - Danaceau, Merry AU - Murphy, Dennis L AU - Berlin, Robin E AD - Behavioral Endocrinology Branch, National Institute of Mental Health, Bethesda, MD 20892-1276, USA. Peter.Schmidt@NIH.GOV Y1 - 2002/11// PY - 2002 DA - November 2002 SP - 800 EP - 812 VL - 27 IS - 5 SN - 0893-133X, 0893-133X KW - Gonadal Steroid Hormones KW - 0 KW - Piperazines KW - Progesterone KW - 4G7DS2Q64Y KW - Estradiol KW - 4TI98Z838E KW - Leuprolide KW - EFY6W0M8TG KW - 1-(3-chlorophenyl)piperazine KW - REY0CNO998 KW - Index Medicus KW - Hypothalamo-Hypophyseal System -- drug effects KW - Analysis of Variance KW - Area Under Curve KW - Double-Blind Method KW - Progesterone -- pharmacology KW - Humans KW - Estradiol -- pharmacology KW - Hypothalamo-Hypophyseal System -- metabolism KW - Adult KW - Pituitary-Adrenal System -- metabolism KW - Pituitary-Adrenal System -- drug effects KW - Female KW - Male KW - Leuprolide -- adverse effects KW - Body Temperature -- drug effects KW - Sex Characteristics KW - Body Temperature -- physiology KW - Piperazines -- pharmacology KW - Gonadal Steroid Hormones -- blood KW - Hypogonadism -- chemically induced KW - Hypogonadism -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72682164?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.atitle=The+effects+of+gender+and+gonadal+steroids+on+the+neuroendocrine+and+temperature+response+to+m-chlorophenylpiperazine+in+leuprolide-induced+hypogonadism+in+women+and+men.&rft.au=Schmidt%2C+Peter+J%3BRaju%2C+Jamuna%3BDanaceau%2C+Merry%3BMurphy%2C+Dennis+L%3BBerlin%2C+Robin+E&rft.aulast=Schmidt&rft.aufirst=Peter&rft.date=2002-11-01&rft.volume=27&rft.issue=5&rft.spage=800&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 - 2002-12-26 N1 - Date created - 2002-11-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human articular chondrocytes immortalized by HPV-16 E6 and E7 genes: Maintenance of differentiated phenotype under defined culture conditions. AN - 72681506; 12435333 AB - To establish an immortalized normal human articular chondrocyte line which could be useful for a better understanding of cell molecular mechanisms relevant for the development of new therapeutic approaches in rheumatic diseases. Chondrocytes from human adult articular healthy cartilage were transfected in primary culture with a plasmid containing two human papilloma virus type 16 (HPV-16) early function genes: E6 and E7, using the highly efficient cationic liposome-mediated (lipofection) procedure. The transfection was verified by reverse transcriptase-polymerase chain reaction analysis of E7 mRNA and by immunofluorence localization of the E7 protein in the cell cytoplasm. The established chondrocyte cell line was examined in monolayer and in two culture conditions that were described to re-induce differentiated characteristics: culturing in a serum-free defined medium supplemented with an insulin-containing serum substitute and seeding on a hyaluronan-based non-woven structured biomaterial. The expression of markers characteristic of cartilage was shown in the mRNA by reverse transcriptase-polymerase chain reaction. Immunohistological staining and Western blotting analysis were performed to evaluate type II collagen synthesis. Proteoglycans deposition was detected by Alcian Blue staining. A Field Emission In Lens Scanning Microscopy was used to look at the morphology of the immortalized cells at very high magnification. Normal human articular chondrocytes were efficiently transfected leading to the establishment of an immortalized cell line as confirmed by HPV-16 E7 mRNA and protein detection. These cells were able to re-express type II collagen both at mRNA and protein levels under the two defined cultured conditions we used, still maintaining type I collagen expression. Collagen IX mRNA was present only in early primary culture while collagen type X and aggrecan transcripts were always detected. Alcian Blue staining showed a proteoglycan-rich matrix production. The ultrastructural analysis of the immortalized cells revealed that their morphology strictly resembled that of normal chondrocytes. The cell line that we obtained may be a useful tool for increasing our knowledge of the genetic and biochemical events involved in the processes of cartilage growth and differentiation. Moreover, it appears to be a suitable model for pharmacological and toxicological studies related to rheumatic diseases relevant to humans. JF - Osteoarthritis and cartilage AU - Grigolo, B AU - Roseti, L AU - Neri, S AU - Gobbi, P AU - Jensen, P AU - Major, E O AU - Facchini, A AD - Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA. Y1 - 2002/11// PY - 2002 DA - November 2002 SP - 879 EP - 889 VL - 10 IS - 11 SN - 1063-4584, 1063-4584 KW - Oncogene Proteins, Viral KW - 0 KW - RNA, Messenger KW - RNA, Viral KW - Index Medicus KW - Phenotype KW - Blotting, Western KW - Transfection KW - Humans KW - RNA, Messenger -- analysis KW - Gene Expression KW - Papillomaviridae -- genetics KW - Middle Aged KW - Reverse Transcriptase Polymerase Chain Reaction KW - Fluorescent Antibody Technique KW - Male KW - RNA, Viral -- analysis KW - Microscopy, Electron, Scanning KW - Cell Line -- pathology KW - Oncogene Proteins, Viral -- genetics KW - Chondrocytes -- pathology KW - Cartilage, Articular -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72681506?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Osteoarthritis+and+cartilage&rft.atitle=Human+articular+chondrocytes+immortalized+by+HPV-16+E6+and+E7+genes%3A+Maintenance+of+differentiated+phenotype+under+defined+culture+conditions.&rft.au=Grigolo%2C+B%3BRoseti%2C+L%3BNeri%2C+S%3BGobbi%2C+P%3BJensen%2C+P%3BMajor%2C+E+O%3BFacchini%2C+A&rft.aulast=Grigolo&rft.aufirst=B&rft.date=2002-11-01&rft.volume=10&rft.issue=11&rft.spage=879&rft.isbn=&rft.btitle=&rft.title=Osteoarthritis+and+cartilage&rft.issn=10634584&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-01-23 N1 - Date created - 2002-11-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antitumor activity of UCN-01 in carcinomas of the head and neck is associated with altered expression of cyclin D3 and p27(KIP1). AN - 72674666; 12429646 AB - Altered and deregulated cyclin-dependent kinase (cdk) activity is now believed to play a major role in the pathogenesis of head and neck squamous cell carcinomas (HNSCC), thus providing a suitable cellular target for therapeutic intervention. UCN-01 (7-hydroxy-staurosporine), a known protein kinase C and cdk modulator, demonstrates antiproliferative and antitumor properties in many experimental tumor models and may represent a potential candidate to test in HNSCC. In this study, UCN-01 displayed potent antiproliferative properties (IC50 of approximately 17-80 nM) in HNSCC cells. Cell cycle analysis revealed that UCN-01 treatment of HNSCC cells for 24 h leads to a G1 block with a concomitant loss of cells in S and G2-M and the emerging sub-G1 cell population, confirmed to be apoptotic by terminal deoxynucleotidyl transferase-mediated nick end labeling analysis. Additional in vitro studies demonstrated a G1 arrest that was preceded by depletion in cyclin D3, elevation of p21(WAF1) and p27(KIP1) leading to a loss in activity of G1 cdks (cdk2, cdk4), and reduction in pRb phosphorylation. Antitumor properties of UCN-01 were also assessed in vivo by treating HN12 xenografts (7.5 mg/kg/i.p./daily) with UCN-01 for 5 consecutive days. Total sustained abolition of tumor growth (P < 0.00001) was obtained with only one cycle of UCN-01 treatment. Terminal deoxynucleotidyl transferase-mediated nick end labeling staining of xenograft samples revealed a higher incidence of apoptosis in treated tissues when compared with control. Additional tissue analysis demonstrated that elevated p27(KIP1) with minimal increase in p21(WAF1) and reduced cyclin D3 levels were readily detected in those animals treated with UCN-01, similar to those observed in HNSCC cells. Thus, UCN-01 exhibits both in vitro and in vivo antitumor properties in HNSCC models, and these effects are associated with a decrease in cyclin D3 and an increase in p27(KIP1) protein levels, thus providing appropriate surrogate markers to follow treatment efficacy in vivo and, therefore, a suitable drug candidate for treating HNSCC patients. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Patel, Vyomesh AU - Lahusen, Tyler AU - Leethanakul, Chidchanok AU - Igishi, Tadashi AU - Kremer, Marcus AU - Quintanilla-Martinez, Leticia AU - Ensley, John F AU - Sausville, Edward A AU - Gutkind, J Silvio AU - Senderowicz, Adrian M AD - Oral & Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/11// PY - 2002 DA - November 2002 SP - 3549 EP - 3560 VL - 8 IS - 11 SN - 1078-0432, 1078-0432 KW - Alkaloids KW - 0 KW - Antineoplastic Agents KW - CCND3 protein, human KW - CDKN1A protein, human KW - Ccnd3 protein, mouse KW - Cdkn1a protein, mouse KW - Cdkn1b protein, mouse KW - Cell Cycle Proteins KW - Cyclin D3 KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - Proto-Oncogene Proteins KW - Tumor Suppressor Proteins KW - Cyclin-Dependent Kinase Inhibitor p27 KW - 147604-94-2 KW - 7-hydroxystaurosporine KW - 7BU5H4V94A KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - CDC2-CDC28 Kinases KW - EC 2.7.11.22 KW - CDK2 protein, human KW - CDK4 protein, human KW - Cdk2 protein, mouse KW - Cdk4 protein, mouse KW - Cyclin-Dependent Kinase 2 KW - Cyclin-Dependent Kinase 4 KW - Cyclin-Dependent Kinases KW - Staurosporine KW - H88EPA0A3N KW - Index Medicus KW - Animals KW - Apoptosis KW - Protein-Serine-Threonine Kinases -- metabolism KW - Humans KW - Mice, Nude KW - Tumor Cells, Cultured KW - Flow Cytometry KW - G1 Phase KW - Inhibitory Concentration 50 KW - Time Factors KW - Cell Cycle KW - Cyclin-Dependent Kinases -- metabolism KW - 3T3 Cells KW - Dose-Response Relationship, Drug KW - Prognosis KW - S Phase KW - Mice KW - Staurosporine -- analogs & derivatives KW - Neoplasm Transplantation KW - In Situ Nick-End Labeling KW - Kinetics KW - Immunohistochemistry KW - Tumor Suppressor Proteins -- biosynthesis KW - Cyclins -- biosynthesis KW - Cell Cycle Proteins -- biosynthesis KW - Cyclins -- metabolism KW - Alkaloids -- pharmacology KW - Head and Neck Neoplasms -- drug therapy KW - Carcinoma, Squamous Cell -- drug therapy KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72674666?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Antitumor+activity+of+UCN-01+in+carcinomas+of+the+head+and+neck+is+associated+with+altered+expression+of+cyclin+D3+and+p27%28KIP1%29.&rft.au=Patel%2C+Vyomesh%3BLahusen%2C+Tyler%3BLeethanakul%2C+Chidchanok%3BIgishi%2C+Tadashi%3BKremer%2C+Marcus%3BQuintanilla-Martinez%2C+Leticia%3BEnsley%2C+John+F%3BSausville%2C+Edward+A%3BGutkind%2C+J+Silvio%3BSenderowicz%2C+Adrian+M&rft.aulast=Patel&rft.aufirst=Vyomesh&rft.date=2002-11-01&rft.volume=8&rft.issue=11&rft.spage=3549&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 - 2003-06-16 N1 - Date created - 2002-11-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Angiotensin AT(1)-receptors depolarize neonatal spinal motoneurons and other ventral horn neurons via two different conductances. AN - 72667691; 12424318 AB - Angiotensin receptors are highly expressed in neonatal spinal cord. To identify their influence on neuronal excitability, we used patch-clamp recordings in spinal cord slices to assess responses of neonatal rat (5-12 days) ventral horn neurons to bath-applied angiotensin II (ANG II; 1 microM). In 14/34 identified motoneurons tested under current clamp, ANG II induced a slowly rising and prolonged membrane depolarization, blockable with Losartan (n = 5) and (Sar(1), Val(5), Ala(8))-ANG II (Saralasin, n = 4) but not PD123319 (1 microM each; n = 4). Under voltage clamp (V(H) -65 mV), 7/22 motoneurons displayed an ANG-II-induced tetrodotoxin-resistant inward current (-128 +/- 31 pA) with a similar time course, an associated reduction in membrane conductance and net current reversal at -98.8 +/- 3.9 mV. Losartan-sensitive ANG II responses were also evoked in 27/78 tested ventral horn "interneurons." By contrast with motoneurons, their ANG-II-induced inward current was smaller (-39.9 +/- 5.2 pA) and analysis of their I-V plots revealed three patterns. In eight cells, membrane conductance decreased with net inward current reversing at -103.8 +/- 4.1 mV. In seven cells, membrane conductance increased with net current reversing at -37.9 +/- 3.6 mV. In 12 cells, I-V lines remained parallel with no reversal within the current range tested. Intracellular dialysis with GTP-gamma-S significantly prolonged the ANG II effect in seven responsive interneurons and GDP-beta-S significantly reduced the ANG II response in four other cells. Peak inward currents were significantly reduced in all 13 responding neurons recorded in slices incubated in pertussis toxin (5 microgram/ml) for 12-18 h or in 12 neurons perfused with N-ethylmaleimide. Of 29 interneurons sensitive to pertussis toxin or N-ethylmaleimide treatment, 9 cells displayed a decrease in membrane conductance that reversed at -101.3 +/- 3.8 mV. In eight cells, membrane conductance increased and reversed at -38.7 +/- 3.4 mV. In 12 cells, the I-V lines remained parallel with no reversal within the current range tested, suggesting that both conductances are modulated by pertussis toxin-sensitive G proteins. These observations reveal a direct, G-protein-mediated depolarizing action of ANG II on neonatal rat ventral horn neurons. They also imply involvement of two distinct conductances that are differentially distributed among different cell types. JF - Journal of neurophysiology AU - Oz, Murat AU - Renaud, Leo P AD - National Institute on Drug Abuse, Intramural Research Program, Baltimore, Maryland 21224, USA. moz@intra.nida.nih.gov Y1 - 2002/11// PY - 2002 DA - November 2002 SP - 2857 EP - 2863 VL - 88 IS - 5 SN - 0022-3077, 0022-3077 KW - Anesthetics, Local KW - 0 KW - Angiotensin Receptor Antagonists KW - Ion Channels KW - Receptor, Angiotensin, Type 1 KW - Receptors, Angiotensin KW - Guanosine 5'-O-(3-Thiotriphosphate) KW - 37589-80-3 KW - Tetrodotoxin KW - 4368-28-9 KW - Pertussis Toxin KW - EC 2.4.2.31 KW - Ethylmaleimide KW - O3C74ACM9V KW - Index Medicus KW - Animals KW - Anesthetics, Local -- pharmacology KW - Membrane Potentials -- physiology KW - Pertussis Toxin -- pharmacology KW - Electrophysiology KW - Ion Channels -- physiology KW - Guanosine 5'-O-(3-Thiotriphosphate) -- pharmacology KW - Rats KW - Rats, Sprague-Dawley KW - Patch-Clamp Techniques KW - Excitatory Postsynaptic Potentials -- drug effects KW - Interneurons -- physiology KW - Tetrodotoxin -- pharmacology KW - Ethylmaleimide -- pharmacology KW - Excitatory Postsynaptic Potentials -- physiology KW - Female KW - Male KW - Neural Conduction -- physiology KW - Motor Neurons -- physiology KW - Receptors, Angiotensin -- agonists KW - Receptors, Angiotensin -- physiology KW - Anterior Horn Cells -- physiology KW - Spinal Cord -- physiology KW - Animals, Newborn -- physiology KW - Spinal Cord -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72667691?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurophysiology&rft.atitle=Angiotensin+AT%281%29-receptors+depolarize+neonatal+spinal+motoneurons+and+other+ventral+horn+neurons+via+two+different+conductances.&rft.au=Oz%2C+Murat%3BRenaud%2C+Leo+P&rft.aulast=Oz&rft.aufirst=Murat&rft.date=2002-11-01&rft.volume=88&rft.issue=5&rft.spage=2857&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurophysiology&rft.issn=00223077&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-01-14 N1 - Date created - 2002-11-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Microglia enhance beta-amyloid peptide-induced toxicity in cortical and mesencephalic neurons by producing reactive oxygen species. AN - 72665051; 12421370 AB - The purpose of this study was to assess and compare the toxicity of beta-amyloid (Abeta) on primary cortical and mesencephalic neurons cultured with and without microglia in order to determine the mechanism underlying microglia-mediated Abeta-induced neurotoxicity. Incubation of cortical or mesencephalic neuron-enriched and mixed neuron-glia cultures with Abeta(1-42) over the concentration range 0.1-6.0 microm caused concentration-dependent neurotoxicity. High concentrations of Abeta (6.0 microm for cortex and 1.5-2.0 microm for mesencephalon) directly injured neurons in neuron-enriched cultures. In contrast, lower concentrations of Abeta (1.0-3.0 microm for cortex and 0.25-1.0 microm for mesencephalon) caused significant neurotoxicity in mixed neuron-glia cultures, but not in neuron- enriched cultures. Several lines of evidence indicated that microglia mediated the potentiated neurotoxicity of Abeta, including the observations that low concentrations of Abeta activated microglia morphologically in neuron-glia cultures and that addition of microglia to cortical neuron-glia cultures enhanced Abeta-induced neurotoxicity. To search for the mechanism underlying the microglia-mediated effects, several proinflammatory factors were examined in neuron-glia cultures. Low doses of Abeta significantly increased the production of superoxide anions, but not of tumor necrosis factor-alpha, interleukin-1beta or nitric oxide. Catalase and superoxide dismutase significantly protected neurons from Abeta toxicity in the presence of microglia. Inhibition of NADPH oxidase activity by diphenyleneiodonium also prevented Abeta-induced neurotoxicity in neuron-glia mixed cultures. The role of NADPH oxidase-generated superoxide in mediating Abeta-induced neurotoxicity was further substantiated by a study which showed that Abeta caused less of a decrease in dopamine uptake in mesencephalic neuron-glia cultures from NADPH oxidase-deficient mutant mice than in that from wild-type controls. This study demonstrates that one of the mechanisms by which microglia can enhance the neurotoxicity of Abeta is via the production of reactive oxygen species. JF - Journal of neurochemistry AU - Qin, Liya AU - Liu, Yuxin AU - Cooper, Cynthia AU - Liu, Bin AU - Wilson, Belinda AU - Hong, Jau-Shyong AD - Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. qin1@niehs.nih.gov Y1 - 2002/11// PY - 2002 DA - November 2002 SP - 973 EP - 983 VL - 83 IS - 4 SN - 0022-3042, 0022-3042 KW - Amyloid beta-Peptides KW - 0 KW - Enzyme Inhibitors KW - Interleukin-1 KW - Neuroprotective Agents KW - Reactive Oxygen Species KW - Tumor Necrosis Factor-alpha KW - Superoxides KW - 11062-77-4 KW - Nitric Oxide KW - 31C4KY9ESH KW - Catalase KW - EC 1.11.1.6 KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - NADPH Oxidase KW - EC 1.6.3.1 KW - Index Medicus KW - NADPH Oxidase -- metabolism KW - Animals KW - Coculture Techniques KW - Superoxides -- analysis KW - NADPH Oxidase -- antagonists & inhibitors KW - Mice KW - Interleukin-1 -- analysis KW - Catalase -- pharmacology KW - Neuroprotective Agents -- pharmacology KW - Rats KW - Nitric Oxide -- analysis KW - Superoxides -- metabolism KW - Rats, Inbred F344 KW - Superoxide Dismutase -- pharmacology KW - Cells, Cultured KW - Tumor Necrosis Factor-alpha -- analysis KW - Mice, Inbred C57BL KW - Enzyme Inhibitors -- pharmacology KW - Reactive Oxygen Species -- metabolism KW - Cerebral Cortex -- cytology KW - Neurons -- drug effects KW - Amyloid beta-Peptides -- toxicity KW - Neurons -- cytology KW - Microglia -- cytology KW - Mesencephalon -- cytology KW - Microglia -- drug effects KW - Microglia -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72665051?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Microglia+enhance+beta-amyloid+peptide-induced+toxicity+in+cortical+and+mesencephalic+neurons+by+producing+reactive+oxygen+species.&rft.au=Qin%2C+Liya%3BLiu%2C+Yuxin%3BCooper%2C+Cynthia%3BLiu%2C+Bin%3BWilson%2C+Belinda%3BHong%2C+Jau-Shyong&rft.aulast=Qin&rft.aufirst=Liya&rft.date=2002-11-01&rft.volume=83&rft.issue=4&rft.spage=973&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 - 2002-12-24 N1 - Date created - 2002-11-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human melanomas of fibroblast and epithelial morphology differ widely in their ability to synthesize retinyl esters. AN - 72660898; 12419830 AB - Reduced retinyl ester synthesis has been associated with several forms of cancer; we therefore proposed studying melanoma development from the perspective of this biochemical pathway. Cultures of human melanoma cells with fibroblastoid morphology showed negligible retinyl ester synthesis; in sharp contrast, those with epithelioid morphology were capable of retinol esterification. Further, isolated proliferating epidermal melanocytes (HFSC/2) esterified retinol, whereas proliferating normal skin fibroblasts (F:CCD-1121.Sk) did not. A primary site cutaneous melanoma and its metastatic match (both of epithelioid morphology) were capable of retinol esterification, while a matched fibroblastoid tumor pair did not synthesize retinyl esters; nevertheless, LRAT (lecithin:retinol acyltransferase) protein was found in microsomal fractions from all four tumors. A mutation screen in the LRAT coding region and adjacent intronic sequences revealed several novel mutations in these melanomas as well as in HFSC/2 and F:CCD-1121.Sk cells: a single nucleotide polymorphism in exon 1(37A-->G), a silent mutation in exon 2a (188 A-->G/186 G-->A), and an insertion in the 5'UTR (9-10insC). CRBP-1 basal expression was present in the HFSC/2, and in both sets of matched tumor pairs; however, steady-state levels in the fibroblastoid melanoma pair were one-third that found in the epithelioid matched tumor pair. Co-culture of human primary site epithelioid melanoma with proliferating normal human skin fibroblasts abrogated retinol esterification within 96 h and increased the expression of the active form of TGFbeta-1 by 2.4-fold. A concomitant 3.2-fold downregulation of CRBP-1 expression took place. This is the first study to (1) demonstrate an association between retinyl ester synthesis and cutaneous melanoma morphological phenotypes; (2) suggest the existence of a soluble, diffusible inhibitor of the retinol esterification pathway; (3) report the ability of the isolated, proliferating human epidermal melanocyte to esterify retinol; and (4) provide evidence of DNA variants in the coding region of LRAT. JF - Carcinogenesis AU - Simmons, Denise Perry AU - Andreola, Fausto AU - De Luca, Luigi M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892-4255, USA. Y1 - 2002/11// PY - 2002 DA - November 2002 SP - 1821 EP - 1830 VL - 23 IS - 11 SN - 0143-3334, 0143-3334 KW - Biological Factors KW - 0 KW - Esters KW - Neoplasm Proteins KW - RBP1 protein, human KW - Retinol-Binding Proteins KW - Retinol-Binding Proteins, Cellular KW - TGFB1 protein, human KW - Transforming Growth Factor beta KW - Transforming Growth Factor beta1 KW - Vitamin A KW - 11103-57-4 KW - Acyltransferases KW - EC 2.3.- KW - lecithin-retinol acyltransferase KW - EC 2.3.1.- KW - Index Medicus KW - Polymorphism, Single Nucleotide KW - Tumor Cells, Cultured -- metabolism KW - DNA Mutational Analysis KW - Humans KW - Biological Factors -- metabolism KW - Microsomes -- enzymology KW - Fibroblasts -- metabolism KW - Esters -- metabolism KW - Epithelial Cells -- metabolism KW - Gene Expression Regulation, Neoplastic KW - Retinol-Binding Proteins -- biosynthesis KW - Transforming Growth Factor beta -- physiology KW - Genes KW - Retinol-Binding Proteins -- genetics KW - Esterification KW - Cells, Cultured KW - Neoplasm Metastasis KW - Introns KW - Diffusion KW - Mutagenesis, Insertional KW - Neoplastic Stem Cells -- pathology KW - Skin Neoplasms -- pathology KW - Vitamin A -- metabolism KW - Melanoma -- metabolism KW - Skin Neoplasms -- metabolism KW - Neoplastic Stem Cells -- metabolism KW - Skin Neoplasms -- genetics KW - Melanoma -- pathology KW - Acyltransferases -- genetics KW - Melanoma -- genetics KW - Neoplasm Proteins -- genetics KW - Acyltransferases -- metabolism KW - Neoplasm Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72660898?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Human+melanomas+of+fibroblast+and+epithelial+morphology+differ+widely+in+their+ability+to+synthesize+retinyl+esters.&rft.au=Simmons%2C+Denise+Perry%3BAndreola%2C+Fausto%3BDe+Luca%2C+Luigi+M&rft.aulast=Simmons&rft.aufirst=Denise&rft.date=2002-11-01&rft.volume=23&rft.issue=11&rft.spage=1821&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-12-20 N1 - Date created - 2002-11-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutations in tetranucleotide repeats following DNA damage depend on repeat sequence and carcinogenic agent. AN - 72654231; 12414628 AB - Sporadic microsatellite mutations are frequently observed in lung, bladder, and head and neck tumors with intact DNA mismatch repair. AAAG tetranucleotide repeats appear to be especially prone to the accumulation of these mutations. We hypothesized that occurrences of microsatellite mutations in these cancers may be linked to DNA damage caused by exposure to carcinogens in tobacco smoke. To test this hypothesis, we developed a model system based on reactivation of green fluorescent protein (GFP) in which a plasmid vector carries a microsatellite repeat that places the GFP sequence out of frame for protein translation. In this reporter system, DNA slippage mutations can restore the GFP reading frame and become detectable by flow cytometry as GFP-positive cells. Pools of stably transfected RKO cells were treated at four dose levels each of gamma-irradiation, benzo(a)pyrene diol epoxide, N-methyl-N-nitro-N-nitrosoguanidine (MNNG), t-butyl hydrogen peroxide, and UV irradiation and assayed for GFP-positive cells 48 h later. We studied the microsatellite repeats AAAG, ATAG, CAGT, and CA, as well as a control sequence lacking any repetitive elements. A log-linear regression approach was used to discriminate between the effects of repeat unit and dose for each agent. A statistically significant increase in GFP-positive cells was found with increasing dose with all agents, although repeat unit-specific response patterns were only observed with MNNG, t-butyl hydrogen peroxide, and UV irradiation. With MNNG, significant differences in response were observed between dinucleotide and tetranucleotide repeat units. The effects of UV irradiation were consistent with the predicted number of pyrimidine dimers/repeat unit, with higher GFP activation in repeats that had large numbers of adjacent pyrimidines. We found no evidence to indicate that the AAAG repeat responded to any of the DNA-damaging agents with higher levels of GFP activation than other repeat units. These results provide evidence that DNA damage can induce slippage mutations and increase mutation rates in repeated sequences and that there are sequence-specific responses to different types of DNA damage. Our results are compatible with the hypothesis that sporadic microsatellite mutations in human cancer may reflect DNA damage caused by carcinogen exposure. JF - Cancer research AU - Slebos, Robbert J C AU - Oh, Daniel S AU - Umbach, David M AU - Taylor, Jack A AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709, USA. slebos@niehs.nih.gov Y1 - 2002/11/01/ PY - 2002 DA - 2002 Nov 01 SP - 6052 EP - 6060 VL - 62 IS - 21 SN - 0008-5472, 0008-5472 KW - Carcinogens KW - 0 KW - Luminescent Proteins KW - Mutagens KW - Methylnitronitrosoguanidine KW - 12H3O2UGSF KW - Green Fluorescent Proteins KW - 147336-22-9 KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide KW - 55097-80-8 KW - tert-Butylhydroperoxide KW - 955VYL842B KW - Index Medicus KW - Ultraviolet Rays KW - Microsatellite Repeats -- genetics KW - Methylnitronitrosoguanidine -- toxicity KW - Luminescent Proteins -- analysis KW - Humans KW - Mutagens -- toxicity KW - Colorectal Neoplasms -- genetics KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- toxicity KW - Tumor Cells, Cultured KW - Microsatellite Repeats -- drug effects KW - Transfection KW - Flow Cytometry KW - tert-Butylhydroperoxide -- toxicity KW - Luminescent Proteins -- biosynthesis KW - Luminescent Proteins -- genetics KW - Carcinogens -- toxicity KW - DNA Damage -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72654231?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+tetranucleotide+repeats+following+DNA+damage+depend+on+repeat+sequence+and+carcinogenic+agent.&rft.au=Slebos%2C+Robbert+J+C%3BOh%2C+Daniel+S%3BUmbach%2C+David+M%3BTaylor%2C+Jack+A&rft.aulast=Slebos&rft.aufirst=Robbert+J&rft.date=2002-11-01&rft.volume=62&rft.issue=21&rft.spage=6052&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 - 2002-12-10 N1 - Date created - 2002-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dopamine D3 receptor antagonism inhibits cocaine-seeking and cocaine-enhanced brain reward in rats. AN - 72651743; 12417684 AB - dopamine D3 receptor is preferentially localized to the mesocorticolimbic dopaminergic system and has been hypothesized to play a role in cocaine addiction. To study the involvement of the D3 receptor in brain mechanisms and behaviors commonly assumed to be involved in the addicting properties of cocaine, the potent and selective D3 receptor antagonist trans-N-[4-[2-(6-cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl] cyclohexyl]-4-quinolininecarboxamide (SB-277011-A) was administered to laboratory rats, and the following measures were assessed: (1) cocaine-enhanced electrical brain-stimulation reward, (2) cocaine-induced conditioned place preference, and (3) cocaine-triggered reinstatement of cocaine seeking behavior. Systemic injections of SB-277011-A were found to (1) block enhancement of electrical brain stimulation reward by cocaine, (2) dose-dependently attenuate cocaine-induced conditioned place preference, and (3) dose-dependently attenuate cocaine-triggered reinstatement of cocaine seeking behavior. Thus, D3 receptor blockade attenuates both the rewarding effects of cocaine and cocaine-induced drug-seeking behavior. These data suggest an important role for D3 receptors in mediating the addictive properties of cocaine and suggest that blockade of dopamine D3 receptors may constitute a new and useful target for prospective pharmacotherapies for cocaine addiction. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Vorel, Stanislav R AU - Ashby, Charles R AU - Paul, Mousumi AU - Liu, Xinhe AU - Hayes, Robert AU - Hagan, Jim J AU - Middlemiss, Derek N AU - Stemp, Geoffrey AU - Gardner, Eliot L AD - Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA. Y1 - 2002/11/01/ PY - 2002 DA - 2002 Nov 01 SP - 9595 EP - 9603 VL - 22 IS - 21 KW - Dopamine Antagonists KW - 0 KW - Dopamine D2 Receptor Antagonists KW - Drd3 protein, rat KW - Nitriles KW - Quinolines KW - Receptors, Dopamine D2 KW - Receptors, Dopamine D3 KW - SB 277011 KW - Tetrahydroisoquinolines KW - Cocaine KW - I5Y540LHVR KW - Haloperidol KW - J6292F8L3D KW - Index Medicus KW - Haloperidol -- adverse effects KW - Conditioning, Operant -- drug effects KW - Animals KW - Catalepsy -- chemically induced KW - Rats, Long-Evans KW - Electrodes, Implanted KW - Quinolines -- adverse effects KW - Electric Stimulation KW - Rats KW - Behavior, Animal -- drug effects KW - Spatial Behavior -- drug effects KW - Male KW - Haloperidol -- therapeutic use KW - Dose-Response Relationship, Drug KW - Quinolines -- therapeutic use KW - Reinforcement (Psychology) KW - Nitriles -- therapeutic use KW - Cocaine -- administration & dosage KW - Receptors, Dopamine D2 -- metabolism KW - Catalepsy -- physiopathology KW - Rats, Sprague-Dawley KW - Self Administration KW - Nitriles -- adverse effects KW - Secondary Prevention KW - Brain -- physiopathology KW - Reward KW - Dopamine Antagonists -- therapeutic use KW - Brain -- drug effects KW - Cocaine-Related Disorders -- drug therapy KW - Cocaine-Related Disorders -- physiopathology KW - Dopamine Antagonists -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72651743?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Dopamine+D3+receptor+antagonism+inhibits+cocaine-seeking+and+cocaine-enhanced+brain+reward+in+rats.&rft.au=Vorel%2C+Stanislav+R%3BAshby%2C+Charles+R%3BPaul%2C+Mousumi%3BLiu%2C+Xinhe%3BHayes%2C+Robert%3BHagan%2C+Jim+J%3BMiddlemiss%2C+Derek+N%3BStemp%2C+Geoffrey%3BGardner%2C+Eliot+L&rft.aulast=Vorel&rft.aufirst=Stanislav&rft.date=2002-11-01&rft.volume=22&rft.issue=21&rft.spage=9595&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=1529-2401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-25 N1 - Date created - 2002-11-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The flexible loop of human FEN1 endonuclease is required for flap cleavage during DNA replication and repair. AN - 72650743; 12411510 AB - The conserved, structure-specific flap endonuclease FEN1 cleaves 5' DNA flaps that arise during replication or repair. To address in vivo mechanisms of flap cleavage, we developed a screen for human FEN1 mutants that are toxic when expressed in yeast. Two targets were revealed: the flexible loop domain and the catalytic site. Toxic mutants caused G(2) arrest and cell death and were unable to repair methyl methanesulfonate lesions. All the mutant proteins retained flap binding. Unlike the catalytic site mutants, which lacked cleavage of any 5' flaps, the loop mutants exhibited partial ability to cut 5' flaps when an adjacent single nucleotide 3' flap was present. We suggest that the flexible loop is important for efficient cleavage through positioning the 5' flap and the catalytic site. JF - The EMBO journal AU - Storici, Francesca AU - Henneke, Ghislaine AU - Ferrari, Elena AU - Gordenin, Dmitry A AU - Hübscher, Ulrich AU - Resnick, Michael A AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 2002/11/01/ PY - 2002 DA - 2002 Nov 01 SP - 5930 EP - 5942 VL - 21 IS - 21 SN - 0261-4189, 0261-4189 KW - DNA KW - 9007-49-2 KW - Endodeoxyribonucleases KW - EC 3.1.- KW - Exodeoxyribonucleases KW - Flap Endonucleases KW - FEN1 protein, human KW - EC 3.1.11.- KW - Exodeoxyribonuclease V KW - EC 3.1.11.5 KW - Index Medicus KW - Base Sequence KW - Models, Molecular KW - Humans KW - Catalytic Domain KW - Mutation KW - Hydrolysis KW - DNA Repair -- physiology KW - Endodeoxyribonucleases -- chemistry KW - Exodeoxyribonucleases -- physiology KW - DNA Replication -- physiology KW - Endodeoxyribonucleases -- genetics KW - Endodeoxyribonucleases -- metabolism KW - Exodeoxyribonucleases -- genetics KW - Exodeoxyribonucleases -- metabolism KW - Endodeoxyribonucleases -- physiology KW - Exodeoxyribonucleases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72650743?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+flexible+loop+of+human+FEN1+endonuclease+is+required+for+flap+cleavage+during+DNA+replication+and+repair.&rft.au=Storici%2C+Francesca%3BHenneke%2C+Ghislaine%3BFerrari%2C+Elena%3BGordenin%2C+Dmitry+A%3BH%C3%BCbscher%2C+Ulrich%3BResnick%2C+Michael+A&rft.aulast=Storici&rft.aufirst=Francesca&rft.date=2002-11-01&rft.volume=21&rft.issue=21&rft.spage=5930&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 - 2002-12-10 N1 - Date created - 2002-11-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nat Biotechnol. 2001 Aug;19(8):773-6 [11479573] Mol Cell Biol. 2001 Aug;21(15):4889-99 [11438646] J Biol Chem. 2002 Jan 4;277(1):746-54 [11687589] J Biol Chem. 2002 Apr 26;277(17):14379-89 [11825897] Anal Biochem. 1976 May 7;72:248-54 [942051] Science. 1988 Jul 15;241(4863):317-22 [3291120] Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5613-7 [8516308] Nature. 1994 Jan 13;367(6459):138-46 [8114910] J Biol Chem. 1995 Mar 3;270(9):4503-8 [7876218] J Biol Chem. 1995 Sep 22;270(38):22109-12 [7673186] J Biol Chem. 1995 Dec 22;270(51):30377-83 [8530463] J Biol Chem. 1996 Apr 19;271(16):9173-6 [8621570] Nature. 1996 Jul 4;382(6586):90-3 [8657312] Cell. 1997 Jan 24;88(2):253-63 [9008166] Bioessays. 1997 Mar;19(3):233-40 [9080773] J Biol Chem. 1997 Feb 21;272(8):4647-50 [9081985] EMBO J. 1997 Jun 2;16(11):3341-8 [9214649] Nucleic Acids Res. 1997 Aug 15;25(16):3332-8 [9241249] Hum Mol Genet. 1998 Jan;7(1):69-74 [9384605] EMBO J. 1998 Apr 15;17(8):2412-25 [9545252] Trends Biochem Sci. 1998 May;23(5):171-3 [9612080] Nat Struct Biol. 1998 Aug;5(8):707-13 [9699635] J Biol Chem. 1998 Oct 16;273(42):27154-61 [9765234] J Biol Chem. 1998 Dec 4;273(49):33064-72 [9830061] J Biol Chem. 1998 Dec 18;273(51):34222-9 [9852084] J Biol Chem. 1999 Jul 23;274(30):21387-94 [10409700] Mol Cell Biol. 1999 Aug;19(8):5373-82 [10409728] Mol Cell Biol. 1999 Aug;19(8):5675-84 [10409756] Nat Genet. 1999 Sep;23(1):81-5 [10471504] Biochemistry. 1999 Oct 5;38(40):13347-54 [10529210] Hum Mol Genet. 1999 Nov;8(12):2263-73 [10545607] J Biol Chem. 2000 Apr 7;275(14):10498-505 [10744741] J Biol Chem. 2000 Jun 2;275(22):16420-7 [10748145] Mutat Res. 2000 Jun 30;451(1-2):1-11 [10915861] Mol Cell Biol. 2000 Oct;20(20):7490-504 [11003646] Biochemistry. 2001 Mar 13;40(10):3208-14 [11258937] Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14298-303 [11724925] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Minimizing radiation-induced skin injury in interventional radiology procedures. AN - 72649380; 12409563 AB - Skin injury is a deterministic effect of radiation. Once a threshold dose has been exceeded, the severity of the radiation effect at any point on the skin increases with increasing dose. Peak skin dose is defined as the highest dose delivered to any portion of the patient's skin. Reducing peak skin dose can reduce the likelihood and type of skin injury. Unfortunately, peak skin dose is difficult to measure in real time, and most currently available fluoroscopic systems do not provide the operator with sufficient information to minimize skin dose. Measures that reduce total radiation dose will reduce peak skin dose, as well as dose to the operator and assistants. These measures include minimizing fluoroscopy time, the number of images obtained, and dose by controlling technical factors. Specific techniques-dose spreading and collimation-reduce both peak skin dose and the size of skin area subjected to peak skin dose. For optimum effect, real-time knowledge of skin-dose distribution is invaluable. A trained operator using well-maintained state-of-the art equipment can minimize peak skin dose in all fluoroscopically guided procedures. JF - Radiology AU - Miller, Donald L AU - Balter, Stephen AU - Noonan, Patrick T AU - Georgia, Jeffrey D AD - Department of Radiology, National Naval Medical Center, 8901 Wisconsin Ave, Bethesda, MD 20889-5600, USA. dm72v@nih.gov Y1 - 2002/11// PY - 2002 DA - November 2002 SP - 329 EP - 336 VL - 225 IS - 2 SN - 0033-8419, 0033-8419 KW - Abridged Index Medicus KW - Index Medicus KW - Skin -- radiation effects KW - Risk Factors KW - Humans KW - Dose-Response Relationship, Radiation KW - Radiodermatitis -- etiology KW - Time and Motion Studies KW - Radiology, Interventional KW - Radiodermatitis -- prevention & control KW - Radiometry -- methods KW - Fluoroscopy -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72649380?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Radiology&rft.atitle=Minimizing+radiation-induced+skin+injury+in+interventional+radiology+procedures.&rft.au=Miller%2C+Donald+L%3BBalter%2C+Stephen%3BNoonan%2C+Patrick+T%3BGeorgia%2C+Jeffrey+D&rft.aulast=Miller&rft.aufirst=Donald&rft.date=2002-11-01&rft.volume=225&rft.issue=2&rft.spage=329&rft.isbn=&rft.btitle=&rft.title=Radiology&rft.issn=00338419&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-19 N1 - Date created - 2002-10-31 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Radiology. 2002 Nov;225(2):327-8 [12409562] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - PML-dependent apoptosis after DNA damage is regulated by the checkpoint kinase hCds1/Chk2. AN - 72647948; 12402044 AB - The promyelocytic leukaemia (PML) gene is translocated in most acute promyelocytic leukaemias and encodes a tumour suppressor protein. PML is involved in multiple apoptotic pathways and is thought to be pivotal in gamma irradiation-induced apoptosis. The DNA damage checkpoint kinase hCds1/Chk2 is necessary for p53-dependent apoptosis after gamma irradiation. In addition, gamma irradiation-induced apoptosis also occurs through p53-independent mechanisms, although the molecular mechanism remains largely unknown. Here, we report that hCds1/Chk2 mediates gamma irradiation-induced apoptosis in a p53-independent manner through an ataxia telangiectasia-mutated (ATM)-hCds1/Chk2-PML pathway. Our results provide the first evidence of a functional relationship between PML and a checkpoint kinase in gamma irradiation-induced apoptosis. JF - Nature cell biology AU - Yang, Shutong AU - Kuo, Christin AU - Bisi, John E AU - Kim, Myung K AD - Laboratory of Biochemical Genetics, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2002/11// PY - 2002 DA - November 2002 SP - 865 EP - 870 VL - 4 IS - 11 SN - 1465-7392, 1465-7392 KW - Cell Cycle Proteins KW - 0 KW - DNA-Binding Proteins KW - Neoplasm Proteins KW - Nuclear Proteins KW - Promyelocytic Leukemia Protein KW - Recombinant Fusion Proteins KW - Transcription Factors KW - Tumor Suppressor Protein p53 KW - Tumor Suppressor Proteins KW - PML protein, human KW - 143220-95-5 KW - Serine KW - 452VLY9402 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Checkpoint Kinase 2 KW - EC 2.7.1.11 KW - ATM protein, human KW - EC 2.7.11.1 KW - Ataxia Telangiectasia Mutated Proteins KW - CHEK2 protein, human KW - Protein-Serine-Threonine Kinases KW - Index Medicus KW - Microscopy, Confocal KW - Electroporation KW - DNA Damage KW - Cell Nucleus -- metabolism KW - Humans KW - Recombinant Fusion Proteins -- metabolism KW - Phosphorylation KW - Time Factors KW - Plasmids -- metabolism KW - Gamma Rays KW - HeLa Cells KW - Glutathione Transferase -- metabolism KW - Dose-Response Relationship, Radiation KW - Precipitin Tests KW - Tumor Suppressor Protein p53 -- metabolism KW - Serine -- chemistry KW - Adenoviridae -- genetics KW - Transfection KW - U937 Cells KW - Protein Transport KW - Transcription Factors -- physiology KW - Protein-Serine-Threonine Kinases -- metabolism KW - Apoptosis KW - Neoplasm Proteins -- physiology KW - Transcription Factors -- metabolism KW - Neoplasm Proteins -- metabolism KW - Protein-Serine-Threonine Kinases -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72647948?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cell+biology&rft.atitle=PML-dependent+apoptosis+after+DNA+damage+is+regulated+by+the+checkpoint+kinase+hCds1%2FChk2.&rft.au=Yang%2C+Shutong%3BKuo%2C+Christin%3BBisi%2C+John+E%3BKim%2C+Myung+K&rft.aulast=Yang&rft.aufirst=Shutong&rft.date=2002-11-01&rft.volume=4&rft.issue=11&rft.spage=865&rft.isbn=&rft.btitle=&rft.title=Nature+cell+biology&rft.issn=14657392&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-04-14 N1 - Date created - 2002-11-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Nat Cell Biol. 2002 Nov;4(11):E255-6 [12415282] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gene expression after treatment with hydrogen peroxide, menadione, or t-butyl hydroperoxide in breast cancer cells. AN - 72643627; 12414654 AB - Global gene expression patterns in breast cancer cells after treatment with oxidants (hydrogen peroxide, menadione, and t-butyl hydroperoxide) were investigated in three replicate experiments. RNA collected after treatment (at 1, 3, 7, and 24 h) rather than after a single time point, enabled an analysis of gene expression patterns. Using a 17,000 microarray, template-based clustering and multidimensional scaling analysis of the gene expression over the entire time course identified 421 genes as being either up- or down-regulated by the three oxidants. In contrast, only 127 genes were identified for any single time point and a 2-fold change criteria. Surprisingly, the patterns of gene induction were highly similar among the three oxidants; however, differences were observed, particularly with respect to p53, IL-6, and heat-shock related genes. Replicate experiments increased the statistical confidence of the study, whereas changes in gene expression patterns over a time course demonstrated significant additional information versus a single time point. Analyzing the three oxidants simultaneously by template cluster analysis identified genes that heretofore have not been associated with oxidative stress. JF - Cancer research AU - Chuang, Yao-Yu Eric AU - Chen, Yidong AU - Gadisetti AU - Chandramouli, V R AU - Cook, John A AU - Coffin, Deborah AU - Tsai, Mong-Hsun AU - DeGraff, William AU - Yan, Hailing AU - Zhao, Shuping AU - Russo, Angelo AU - Liu, Edison T AU - Mitchell, James B AD - Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 2002/11/01/ PY - 2002 DA - 2002 Nov 01 SP - 6246 EP - 6254 VL - 62 IS - 21 SN - 0008-5472, 0008-5472 KW - Oxidants KW - 0 KW - Vitamin K 3 KW - 723JX6CXY5 KW - tert-Butylhydroperoxide KW - 955VYL842B KW - Hydrogen Peroxide KW - BBX060AN9V KW - Index Medicus KW - Gene Expression Profiling KW - Vitamin K 3 -- pharmacology KW - Tumor Cells, Cultured KW - Reproducibility of Results KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - Hydrogen Peroxide -- pharmacology KW - tert-Butylhydroperoxide -- pharmacology KW - Oxidative Stress -- genetics KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Cluster Analysis KW - Transcriptional Activation KW - Gene Expression -- drug effects KW - Breast Neoplasms -- genetics KW - Oxidants -- pharmacology KW - Breast Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72643627?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Gene+expression+after+treatment+with+hydrogen+peroxide%2C+menadione%2C+or+t-butyl+hydroperoxide+in+breast+cancer+cells.&rft.au=Chuang%2C+Yao-Yu+Eric%3BChen%2C+Yidong%3BGadisetti%3BChandramouli%2C+V+R%3BCook%2C+John+A%3BCoffin%2C+Deborah%3BTsai%2C+Mong-Hsun%3BDeGraff%2C+William%3BYan%2C+Hailing%3BZhao%2C+Shuping%3BRusso%2C+Angelo%3BLiu%2C+Edison+T%3BMitchell%2C+James+B&rft.aulast=Chuang&rft.aufirst=Yao-Yu&rft.date=2002-11-01&rft.volume=62&rft.issue=21&rft.spage=6246&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 - 2002-12-10 N1 - Date created - 2002-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Estrogen receptor breast cancer phenotypes in the Surveillance, Epidemiology, and End Results database. AN - 72643340; 12408373 AB - Researchers question whether estrogen receptor alpha-negative (ERN) and -positive (ERP) represent different stages of one disease or different breast cancer types. To further examine ERalpha phenotypes, we stratified incident tumor characteristics in the Surveillance, Epidemiology, and End Results (SEER) Database (n = 82,488) by ERN and ERP. Study variables included black-white race, age-at-diagnosis, and standard incident tumor characteristics. These characteristics were arbitrarily dichotomized into good versus poor prognostic factor groups, for example, good (tumor size 2.0 cm, positive nodes, and poor grade). Age frequency density plots were generated from the corresponding age-at-diagnosis frequency histograms. Average annual age-specific incidence rates (or risks) were adjusted to the 1970 United States standard female population. Age frequency density plots demonstrated bimodal premenopausal and postmenopausal breast cancer populations. ERN was correlated with premenopausal disease, black race, and poor prognostic factor groups, whereas ERP was associated with postmenopausal disease, white race, and favorable tumor characteristics. ERN rates increased premenopausally and then flattened to a nearly constant level after 50 years of age. ERP risk rose for most of a woman's lifetime with the greatest risk occurring between 75 and 79 years. ERalpha exhibited bimodal age frequency distribution with a dichotomous pattern for age-specific rates, racial, and prognostic factor profiles. Menopause had a greater effect on ERN than ERP. Possible implications for breast carcinogenesis and cancer prevention are discussed in the text. JF - Breast cancer research and treatment AU - Anderson, William F AU - Chatterjee, Nilanjan AU - Ershler, William B AU - Brawley, Otis W AD - NCI/Division of Cancer Prevention, EPN, Bethesda, MD 20892-7317, USA. wanderso@mail.nih.gov Y1 - 2002/11// PY - 2002 DA - November 2002 SP - 27 EP - 36 VL - 76 IS - 1 SN - 0167-6806, 0167-6806 KW - Receptors, Estrogen KW - 0 KW - Index Medicus KW - Age Factors KW - Survival Rate KW - Aged, 80 and over KW - Humans KW - SEER Program KW - Continental Population Groups KW - Adult KW - Aged KW - Middle Aged KW - United States -- epidemiology KW - Female KW - Age Distribution KW - Phenotype KW - Breast Neoplasms -- genetics KW - Breast Neoplasms -- metabolism KW - Receptors, Estrogen -- analysis KW - Breast Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72643340?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Estrogen+receptor+breast+cancer+phenotypes+in+the+Surveillance%2C+Epidemiology%2C+and+End+Results+database.&rft.au=Anderson%2C+William+F%3BChatterjee%2C+Nilanjan%3BErshler%2C+William+B%3BBrawley%2C+Otis+W&rft.aulast=Anderson&rft.aufirst=William&rft.date=2002-11-01&rft.volume=76&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 - 2003-03-06 N1 - Date created - 2002-10-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo lipid-derived free radical formation by NADPH oxidase in acute lung injury induced by lipopolysaccharide: a model for ARDS. AN - 72642496; 12409313 AB - Intratracheal instillation of lipopolysaccharide (LPS) activates alveolar macrophages and infiltration of neutrophils, causing lung injury/acute respiratory distress syndrome. Free radicals are a special focus as the final causative molecules in the pathogenesis of lung injury caused by LPS. Although in vitro investigation has demonstrated radical generation after exposure of cells to LPS, in vivo evidence is lacking. Using electron spin resonance (ESR) and the spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN), we investigated in vivo free radical production by rats treated with intratracheal instillation of LPS. ESR spectroscopy of lipid extract from lungs exposed to LPS for 6 h gave a spectrum consistent with that of a POBN/carbon-centered radical adduct (aN=14.94+/-0.07 G and abetaH=2.42+/-0.06 G) tentatively assigned as a product of lipid peroxidation. To further investigate the mechanism of LPS-initiated free radical generation, rats were pretreated with the phagocytic toxicant GdCl3, which significantly decreased the production of radical adducts with a corresponding decrease in neutrophil infiltration. NADPH oxidase knockout mice completely blocked phagocyte-mediated, ESR-detectable radical production in this model of acute lung injury. Rats treated intratracheally with LPS generate lipid-derived free radicals via activation of NADPH oxidase. JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Sato, Keizo AU - Kadiiska, Maria B AU - Ghio, Andrew J AU - Corbett, Jean AU - Fann, Yang C AU - Holland, Steven M AU - Thurman, Ronald G AU - Mason, Ronald P AD - Free Radical Metabolite Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. sato@niehs.nih.gov Y1 - 2002/11// PY - 2002 DA - November 2002 SP - 1713 EP - 1720 VL - 16 IS - 13 KW - Free Radicals KW - 0 KW - Lipopolysaccharides KW - Nitrogen Oxides KW - Proteins KW - Pyridines KW - alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone KW - Gadolinium KW - AU0V1LM3JT KW - NADPH Oxidase KW - EC 1.6.3.1 KW - gadolinium chloride KW - P7082WY76D KW - Index Medicus KW - Gadolinium -- pharmacology KW - Animals KW - Humans KW - Disease Models, Animal KW - Respiratory Distress Syndrome, Newborn -- chemically induced KW - Mice, Knockout KW - Respiratory Distress Syndrome, Newborn -- pathology KW - Rats KW - Bronchoalveolar Lavage Fluid -- chemistry KW - Nitrogen Oxides -- administration & dosage KW - Nitrogen Oxides -- toxicity KW - Phagocytes -- drug effects KW - Bronchoalveolar Lavage Fluid -- cytology KW - Male KW - Phagocytes -- cytology KW - Infant, Newborn KW - Mice KW - Proteins -- metabolism KW - Proteins -- drug effects KW - Mice, Inbred Strains KW - Rats, Sprague-Dawley KW - Electron Spin Resonance Spectroscopy KW - Respiratory Distress Syndrome, Newborn -- metabolism KW - Mice, Inbred C57BL KW - Female KW - NADPH Oxidase -- metabolism KW - Lipopolysaccharides -- administration & dosage KW - Lung -- drug effects KW - Lipopolysaccharides -- toxicity KW - Lung -- pathology KW - Lung -- metabolism KW - NADPH Oxidase -- genetics KW - Free Radicals -- metabolism KW - Lipid Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72642496?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.atitle=In+vivo+lipid-derived+free+radical+formation+by+NADPH+oxidase+in+acute+lung+injury+induced+by+lipopolysaccharide%3A+a+model+for+ARDS.&rft.au=Sato%2C+Keizo%3BKadiiska%2C+Maria+B%3BGhio%2C+Andrew+J%3BCorbett%2C+Jean%3BFann%2C+Yang+C%3BHolland%2C+Steven+M%3BThurman%2C+Ronald+G%3BMason%2C+Ronald+P&rft.aulast=Sato&rft.aufirst=Keizo&rft.date=2002-11-01&rft.volume=16&rft.issue=13&rft.spage=1713&rft.isbn=&rft.btitle=&rft.title=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.issn=1530-6860&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-12-16 N1 - Date created - 2002-10-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Serine phosphorylation of Stat5 proteins in lymphocytes stimulated with IL-2. AN - 72642069; 12407017 AB - Tyrosine phosphorylation regulates cytokine-induced dimerization of STAT proteins. Serine phosphorylation has also been found to occur in a number of STAT proteins, including Stat1, Sat3, Stat4, Stat5a, Stat5b and Stat6, and was shown to be important for maximal transcriptional activation mediated by Stat1, Stat3 and Stat4, but not for Stat5a or Stat5b. As these latter proteins were studied in transiently transfected COS-7 cells stimulated with prolactin, we sought to further investigate the significance of their serine phosphorylation in a more physiologically based system in response to IL-2. Both Stat5a and Stat5b were rapidly phosphorylated on serine in response to IL-2 and the phosphorylation site in Stat5a was mapped to Ser780, which is not conserved in Stat5b. In vitro studies with reporter constructs, and experiments in which wild-type and mutant Stat5a retroviruses were used to transduce Stat5a-deficient splenocytes revealed that the serine mutant constructs were not diminished in their ability to mediate IL-2 signaling and if anything exhibited augmented proliferative capability. Thus, in contrast to the apparent importance of serine phosphorylation for transcriptional activation by Stat1, Stat3 and Stat4 in response to IFN, IL-6 and IL-12 respectively, serine phosphorylation of Stat5a does not enhance Stat5a-mediated signaling in response to IL-2. JF - International immunology AU - Xue, Hai-Hui AU - Fink, Donald W AU - Zhang, Xiaolong AU - Qin, Jun AU - Turck, Christoph W AU - Leonard, Warren J AD - Laboratories of Molecular Immunology, National Heart, Lung and Blood Institute, NIH, Bethesda, MD 20892 USA. Y1 - 2002/11// PY - 2002 DA - November 2002 SP - 1263 EP - 1271 VL - 14 IS - 11 SN - 0953-8178, 0953-8178 KW - DNA-Binding Proteins KW - 0 KW - Enzyme Activators KW - Interleukin-2 KW - Milk Proteins KW - Phosphorus Radioisotopes KW - STAT5 Transcription Factor KW - STAT5A protein, human KW - STAT5B protein, human KW - Stat5a protein, mouse KW - Stat5b protein, mouse KW - Trans-Activators KW - Tumor Suppressor Proteins KW - Serine KW - 452VLY9402 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Mass Spectrometry KW - Animals KW - Humans KW - Phosphorus Radioisotopes -- metabolism KW - Mice KW - Precipitin Tests KW - Phosphorylation -- drug effects KW - Trans-Activators -- metabolism KW - Interleukin-2 -- pharmacology KW - DNA-Binding Proteins -- genetics KW - Lymphocytes -- metabolism KW - Enzyme Activators -- pharmacology KW - Serine -- metabolism KW - Serine -- drug effects KW - Trans-Activators -- genetics KW - DNA-Binding Proteins -- drug effects KW - Lymphocytes -- drug effects KW - Trans-Activators -- drug effects KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72642069?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+immunology&rft.atitle=Serine+phosphorylation+of+Stat5+proteins+in+lymphocytes+stimulated+with+IL-2.&rft.au=Xue%2C+Hai-Hui%3BFink%2C+Donald+W%3BZhang%2C+Xiaolong%3BQin%2C+Jun%3BTurck%2C+Christoph+W%3BLeonard%2C+Warren+J&rft.aulast=Xue&rft.aufirst=Hai-Hui&rft.date=2002-11-01&rft.volume=14&rft.issue=11&rft.spage=1263&rft.isbn=&rft.btitle=&rft.title=International+immunology&rft.issn=09538178&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-07 N1 - Date created - 2002-10-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of metergoline on symptoms in women with premenstrual dysphoric disorder. AN - 72641266; 12411222 AB - The authors investigated the role of acute serotonergic modulation in the efficacy of selective serotonin reuptake inhibitors (SSRIs) in women with premenstrual dysphoric disorder. Patients with premenstrual dysphoric disorder (whose symptoms had remitted during treatment with fluoxetine) and a group of unmedicated healthy comparison women received the serotonin receptor antagonist metergoline as part of a double-blind, placebo-controlled crossover study. The patients with premenstrual dysphoric disorder experienced a return of symptoms 24 hours after treatment with metergoline but not diphenhydramine (active placebo). The comparison women experienced no changes in mood. These data support the role of altered serotonergic transmission in the efficacy of SSRI treatment for premenstrual dysphoric disorder. JF - The American journal of psychiatry AU - Roca, Catherine A AU - Schmidt, Peter J AU - Smith, Mark J AU - Danaceau, Merry A AU - Murphy, Dennis L AU - Rubinow, David R AD - National Institute of Mental Health, Bethesda, MD 20892-1277, USA. Y1 - 2002/11// PY - 2002 DA - November 2002 SP - 1876 EP - 1881 VL - 159 IS - 11 SN - 0002-953X, 0002-953X KW - Receptors, Serotonin KW - 0 KW - Serotonin Antagonists KW - Serotonin Uptake Inhibitors KW - Fluoxetine KW - 01K63SUP8D KW - Metergoline KW - 1501393LY5 KW - Diphenhydramine KW - 8GTS82S83M KW - Abridged Index Medicus KW - Index Medicus KW - Fluoxetine -- adverse effects KW - Affect -- drug effects KW - Affect -- physiology KW - Double-Blind Method KW - Serotonin Uptake Inhibitors -- therapeutic use KW - Humans KW - Personality Inventory KW - Diphenhydramine -- therapeutic use KW - Serotonin Uptake Inhibitors -- adverse effects KW - Adult KW - Treatment Outcome KW - Fluoxetine -- therapeutic use KW - Diphenhydramine -- adverse effects KW - Female KW - Receptors, Serotonin -- physiology KW - Receptors, Serotonin -- drug effects KW - Depression -- physiopathology KW - Premenstrual Syndrome -- psychology KW - Depression -- psychology KW - Depression -- drug therapy KW - Premenstrual Syndrome -- drug therapy KW - Depression -- diagnosis KW - Premenstrual Syndrome -- diagnosis KW - Premenstrual Syndrome -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72641266?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Effects+of+metergoline+on+symptoms+in+women+with+premenstrual+dysphoric+disorder.&rft.au=Roca%2C+Catherine+A%3BSchmidt%2C+Peter+J%3BSmith%2C+Mark+J%3BDanaceau%2C+Merry+A%3BMurphy%2C+Dennis+L%3BRubinow%2C+David+R&rft.aulast=Roca&rft.aufirst=Catherine&rft.date=2002-11-01&rft.volume=159&rft.issue=11&rft.spage=1876&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 - 2002-12-04 N1 - Date created - 2002-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Organochlorine exposure and age at natural menopause. AN - 72640840; 12410018 AB - The effect of potential endocrine-modulating organochlorines on menopause has not been extensively examined. We evaluated the associations of plasma polychlorinated biphenyls (PCBs) and 1,1-dichloro-2,2-bis( -chlorophenyl)ethylene (DDE) with age at natural menopause. We analyzed data from 1407 women in a population-based, case-control study of breast cancer that was carried out in 1993-1996 in North Carolina. The adjusted hazard ratio estimating the rate of onset of natural menopause was 1.4 (95% confidence interval = 0.9-2.1) for the top decile of DDE compared with values below the median. This association is similar in magnitude to the association between smoking and menopause (hazard ratio = 1.4 [1.1-1.9]). No association was seen with PCBs. The suggested effect of DDE on timing of natural menopause encourages further research to corroborate these findings and evaluate potential mechanisms. Prospective studies, in which exposure measurements are taken before menopause, would be particularly useful. JF - Epidemiology (Cambridge, Mass.) AU - Cooper, Glinda S AU - Savitz, David A AU - Millikan, Robert AU - Chiu Kit, Tse AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, NC, USA. cooper1@niehs.nih.gov Y1 - 2002/11// PY - 2002 DA - November 2002 SP - 729 EP - 733 VL - 13 IS - 6 SN - 1044-3983, 1044-3983 KW - Dichlorodiphenyl Dichloroethylene KW - 4M7FS82U08 KW - Polychlorinated Biphenyls KW - DFC2HB4I0K KW - Index Medicus KW - Risk Factors KW - Humans KW - North Carolina KW - Adult KW - Case-Control Studies KW - Aged KW - Middle Aged KW - Environmental Exposure -- adverse effects KW - Female KW - Age Distribution KW - Menopause -- blood KW - Polychlorinated Biphenyls -- blood KW - Dichlorodiphenyl Dichloroethylene -- adverse effects KW - Dichlorodiphenyl Dichloroethylene -- blood KW - Polychlorinated Biphenyls -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72640840?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Organochlorine+exposure+and+age+at+natural+menopause.&rft.au=Cooper%2C+Glinda+S%3BSavitz%2C+David+A%3BMillikan%2C+Robert%3BChiu+Kit%2C+Tse&rft.aulast=Cooper&rft.aufirst=Glinda&rft.date=2002-11-01&rft.volume=13&rft.issue=6&rft.spage=729&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 - 2003-01-21 N1 - Date created - 2002-10-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evasion of innate immunity by parasitic protozoa. AN - 72638469; 12407413 AB - Parasitic protozoa are a major cause of global infectious disease. These eukaryotic pathogens have evolved with the vertebrate immune system and typically produce long-lasting chronic infections. A critical step in their host interaction is the evasion of innate immune defenses. The ability to avoid attack by humoral effector mechanisms, such as complement lysis, is of particular importance to extracellular parasites, whereas intracellular protozoa must resist killing by lysosomal enzymes and toxic metabolites. They do so by remodeling the phagosomal compartments in which they reside and by interfering with signaling pathways that lead to cellular activation. In addition, there is growing evidence that protozoan pathogens modify the antigen-presenting and immunoregulatory functions of dendritic cells, a process that facilitates their evasion of both innate and adaptive immunity. JF - Nature immunology AU - Sacks, David AU - Sher, Alan AD - Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. dsacks@nih.gov Y1 - 2002/11// PY - 2002 DA - November 2002 SP - 1041 EP - 1047 VL - 3 IS - 11 SN - 1529-2908, 1529-2908 KW - Antigens, Protozoan KW - 0 KW - Interleukin-12 KW - 187348-17-0 KW - Index Medicus KW - Insect Vectors -- parasitology KW - Animals KW - Antigen Presentation KW - Dendritic Cells -- immunology KW - Trypanosoma -- physiology KW - Cattle Diseases -- immunology KW - Humans KW - Toxoplasma -- physiology KW - Mice KW - Child KW - Immunity, Innate KW - Leishmania -- physiology KW - Cattle KW - Interleukin-12 -- physiology KW - Antigens, Protozoan -- immunology KW - Cattle Diseases -- parasitology KW - Protozoan Infections, Animal -- immunology KW - Signal Transduction KW - Protozoan Infections, Animal -- parasitology KW - Protozoan Infections -- parasitology KW - Eukaryota -- immunology KW - Phagosomes -- parasitology KW - Protozoan Infections -- immunology KW - Eukaryota -- physiology KW - Host-Parasite Interactions -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72638469?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+immunology&rft.atitle=Evasion+of+innate+immunity+by+parasitic+protozoa.&rft.au=Sacks%2C+David%3BSher%2C+Alan&rft.aulast=Sacks&rft.aufirst=David&rft.date=2002-11-01&rft.volume=3&rft.issue=11&rft.spage=1041&rft.isbn=&rft.btitle=&rft.title=Nature+immunology&rft.issn=15292908&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-12-04 N1 - Date created - 2002-10-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Serotonin 5-HT(3) receptors in rat CA1 hippocampal interneurons: functional and molecular characterization. AN - 72637421; 12411518 AB - The molecular makeup of the serotonin 5-HT(3) receptor (5-HT(3)R) channel was investigated in rat hippocampal CA1 interneurons in slices using single-cell RT-PCR and patch-clamp recording techniques. We tested for the expression of the 5-HT(3A) (both short and long splice variants) and 5-HT(3B) subunits, as well as the expression of the alpha4 subunit of the neuronal nicotinic ACh receptors (nAChRs), the latter of which has been shown to co-assemble with the 5-HT(3A) subunit in heterologous expression systems. Both the 5-HT(3A)-short and alpha4-nAChR subunits were expressed in these interneurons, but we could not detect any expression of either the 5-HT(3B) or the 5-HT(3A)-long subunits. Furthermore, there was a strong tendency for the 5-HT(3A)-short and alpha4-nAChR subunits to be co-expressed in individual interneurons. To assess whether there was any functional evidence for co-assembly between the 5-HT(3A)-short and alpha4-nAChR subunits, we used the sulphydryl agent 2-aminoethyl methanethiosulphonate (MTSEA), which has previously been shown to modulate expressed 5-HT(3)Rs that contain the alpha4-nAChR subunit. In half of the interneurons examined, MTSEA significantly enhanced the amplitude of the 5-HT(3)R-mediated responses, which is consistent with the notion that the alpha4-nAChR subunit co-assembles with the 5-HT(3A) subunit to form a native heteromeric 5-HT(3)R channel in rat CA1 hippocampal interneurons in vivo. In addition, the single-channel properties of the 5-HT(3)R were investigated in outside-out patches. No resolvable single-channel currents were observed. Using non-stationary fluctuation analysis, we obtained an estimate of the single-channel conductance of 4 pS, which is well below that expected for channels containing both the 5-HT(3A) and 5-HT(3B) subunits. JF - The Journal of physiology AU - Sudweeks, Sterling N AU - Hooft, Johannes A van AU - Yakel, Jerrel L AD - Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, PO Box 12233, Research Triangle Park, NC 27709, USA. Y1 - 2002/11/01/ PY - 2002 DA - 2002 Nov 01 SP - 715 EP - 726 VL - 544 SN - 0022-3751, 0022-3751 KW - Ion Channels KW - 0 KW - Receptors, Serotonin KW - Receptors, Serotonin, 5-HT3 KW - methanethiosulfonate ethylammonium KW - Ethyl Methanesulfonate KW - 9H154DI0UP KW - Index Medicus KW - Rats KW - Animals KW - Patch-Clamp Techniques KW - Artifacts KW - Electric Conductivity KW - Protein Processing, Post-Translational KW - In Vitro Techniques KW - Rats, Wistar KW - Action Potentials KW - Ion Channels -- metabolism KW - Receptors, Serotonin -- physiology KW - Receptors, Serotonin -- drug effects KW - Ethyl Methanesulfonate -- analogs & derivatives KW - Hippocampus -- physiology KW - Ethyl Methanesulfonate -- pharmacology KW - Interneurons -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72637421?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Serotonin+5-HT%283%29+receptors+in+rat+CA1+hippocampal+interneurons%3A+functional+and+molecular+characterization.&rft.au=Sudweeks%2C+Sterling+N%3BHooft%2C+Johannes+A+van%3BYakel%2C+Jerrel+L&rft.aulast=Sudweeks&rft.aufirst=Sterling&rft.date=2002-11-01&rft.volume=544&rft.issue=&rft.spage=715&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 - 2003-05-01 N1 - Date created - 2002-11-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1998 Sep 15;95(19):11456-61 [9736758] Mol Pharmacol. 1995 Dec;48(6):1054-62 [8848005] Nature. 1999 Jan 28;397(6717):359-63 [9950429] J Biol Chem. 1999 Feb 12;274(7):3934-6 [9933581] J Neurosci. 1999 Apr 15;19(8):2887-96 [10191306] Neuroscience. 1999;91(1):107-17 [10336063] Adv Neurol. 1999;79:511-24 [10514839] J Biol Chem. 1999 Oct 22;274(43):30799-810 [10521471] Br J Pharmacol. 1997 Oct;122(4):655-62 [9375961] Neuropharmacology. 2000 Oct;39(13):2681-90 [11044738] Trends Neurosci. 2000 Dec;23(12):605-10 [11137150] Neuropharmacology. 2001 Jul;41(1):79-87 [11445188] Neuropharmacology. 2001 Dec;41(8):1013-6 [11747906] Neurosci Lett. 2002 Feb 1;318(3):163-5 [11803124] Eur J Neurosci. 2002 Feb;15(3):449-57 [11876772] Neuron. 1988 Sep;1(7):615-21 [3272181] Neuron. 1990 Oct;5(4):383-92 [1698394] J Neurophysiol. 1991 Mar;65(3):630-8 [1711105] Neuropharmacology. 1999 Dec;38(12):1913-5 [10608286] J Neurochem. 2000 Jul;75(1):240-7 [10854267] J Physiol. 2000 Sep 15;527 Pt 3:515-28 [10990538] Receptors Channels. 1995;3(1):7-12 [8589995] Br J Pharmacol. 1996 Aug;118(7):1836-40 [8842451] J Neurophysiol. 1997 Jan;77(1):517-21 [9120594] J Neurosci. 1997 May 1;17(9):3157-67 [9096150] J Neurosci. 1997 Nov 1;17(21):8353-62 [9334409] J Neurophysiol. 1997 Nov;78(5):2493-502 [9356400] J Physiol. 1997 Nov 1;504 ( Pt 3):603-10 [9401968] Mol Pharmacol. 1998 Feb;53(2):202-12 [9463477] J Neurochem. 1998 Mar;70(3):1094-103 [9489730] J Physiol. 1998 Mar 15;507 ( Pt 3):653-65 [9508827] Neuron. 1998 May;20(5):983-93 [9620702] Trends Pharmacol Sci. 1998 Jun;19(6):212-5 [9666711] Methods Enzymol. 1998;293:123-45 [9711606] J Physiol. 1998 Jul 15;510 ( Pt 2):361-70 [9705989] J Physiol. 1991 May;436:293-308 [1648131] Science. 1991 Oct 18;254(5030):432-7 [1718042] Eur J Pharmacol. 1993 Apr 15;245(2):187-92 [7683998] J Physiol. 1993 Dec;472:615-63 [7908327] Neurosci Res. 1994 Jan;18(4):277-82 [8190370] Neuron. 1994 Oct;13(4):919-27 [7524560] Neurosci Lett. 1994 Jun 20;174(2):133-6 [7526284] J Neurosci. 1995 Mar;15(3 Pt 2):2445-52 [7891179] J Physiol. 1994 Dec 1;481 ( Pt 2):311-23 [7537814] Annu Rev Physiol. 1995;57:447-68 [7539990] J Neurochem. 1995 Aug;65(2):475-83 [7616200] Mol Pharmacol. 1995 Sep;48(3):407-16 [7565620] J Neurochem. 1995 Nov;65(5):1917-25 [7595474] Neuroreport. 1995 Jul 10;6(10):1464-8 [7488749] Brain Res. 1998 Nov 9;810(1-2):257-63 [9813357] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Computational simulations of peptide binding to proteins: how scorpions sting K+ channels. AN - 72635841; 12414669 JF - Biophysical journal AU - Guy, H Robert AD - Laboratory of Experimental and Computational Biology, National Cancer Institute, National Institutes of Health, Bldg. 12B, Suite B112, 12 South Drive, MSC 5677, Bethesda, MD 20892-5677, USA. bg4y@nih.gov Y1 - 2002/11// PY - 2002 DA - November 2002 SP - 2325 EP - 2326 VL - 83 IS - 5 SN - 0006-3495, 0006-3495 KW - Peptides KW - 0 KW - Potassium Channels KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Computer Simulation KW - Thermodynamics KW - Scorpions KW - Protein Binding KW - Magnetic Resonance Spectroscopy KW - Potassium Channels -- metabolism KW - Potassium Channels -- chemistry KW - Peptides -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72635841?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Computational+simulations+of+peptide+binding+to+proteins%3A+how+scorpions+sting+K%2B+channels.&rft.au=Guy%2C+H+Robert&rft.aulast=Guy&rft.aufirst=H&rft.date=2002-11-01&rft.volume=83&rft.issue=5&rft.spage=2325&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 - 2003-05-19 N1 - Date created - 2002-11-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Biophys J. 2002 Nov;83(5):2595-609 [12414693] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neutropenia during combination therapy of interferon alfa and ribavirin for chronic hepatitis C. AN - 72632202; 12395340 AB - Interferon therapy of hepatitis C causes a decrease in neutrophil counts, and neutropenia is a common reason for dose adjustment or early discontinuation. However, it is unclear whether neutropenia caused by interferon is associated with an increased rate of infection. In this study, we assessed factors associated and clinical consequences of neutropenia before and during interferon therapy of chronic hepatitis C. A total of 119 patients with chronic hepatitis C treated with the combination of interferon alfa and ribavirin were analyzed. In these studies, neutropenia was not used as an exclusion or dose modification criterion. In multivariate analysis, only black race was associated with baseline neutropenia. During treatment, neutrophil counts decreased by an average of 34%. Among 3 blacks with baseline neutropenia without cirrhosis or splenomegaly, there was little or no decrease in neutrophil counts (despite typical decreases in platelet and lymphocyte counts). Documented or suspected bacterial infections developed in 22 patients (18%), but in no patient with neutropenia. United States population estimates suggest that 76,000 blacks with hepatitis C have neutrophil counts below 1,500 cells/microL and might be denied therapy if this exclusion criterion was generally applied. In conclusion, neutropenia is frequent during treatment of hepatitis C with interferon and ribavirin, but it is not usually associated with infection. Constitutional neutropenia, which is common among blacks, should not exclude patients from therapy with interferon as these patients usually have minimal further decreases in neutrophil counts on therapy and are not excessively prone to bacterial infections. JF - Hepatology (Baltimore, Md.) AU - Soza, Alejandro AU - Everhart, James E AU - Ghany, Marc G AU - Doo, Edward AU - Heller, Theo AU - Promrat, Kittichai AU - Park, Yoon AU - Liang, T Jake AU - Hoofnagle, Jay H AD - Liver Diseases Section, Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. soza@nih.gov Y1 - 2002/11// PY - 2002 DA - November 2002 SP - 1273 EP - 1279 VL - 36 IS - 5 SN - 0270-9139, 0270-9139 KW - Antiviral Agents KW - 0 KW - Interferon-alpha KW - Ribavirin KW - 49717AWG6K KW - Index Medicus KW - Neutrophils -- cytology KW - Humans KW - Retrospective Studies KW - Leukocyte Count KW - Drug Therapy, Combination KW - Infection -- etiology KW - European Continental Ancestry Group KW - Adult KW - Middle Aged KW - United States -- epidemiology KW - African Continental Ancestry Group KW - Female KW - Male KW - Prevalence KW - Interferon-alpha -- adverse effects KW - Neutropenia -- epidemiology KW - Hepatitis C, Chronic -- epidemiology KW - Hepatitis C, Chronic -- drug therapy KW - Neutropenia -- chemically induced KW - Antiviral Agents -- adverse effects KW - Ribavirin -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72632202?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Neutropenia+during+combination+therapy+of+interferon+alfa+and+ribavirin+for+chronic+hepatitis+C.&rft.au=Soza%2C+Alejandro%3BEverhart%2C+James+E%3BGhany%2C+Marc+G%3BDoo%2C+Edward%3BHeller%2C+Theo%3BPromrat%2C+Kittichai%3BPark%2C+Yoon%3BLiang%2C+T+Jake%3BHoofnagle%2C+Jay+H&rft.aulast=Soza&rft.aufirst=Alejandro&rft.date=2002-11-01&rft.volume=36&rft.issue=5&rft.spage=1273&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 - 2002-12-09 N1 - Date created - 2002-10-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Hepatology. 2003 Apr;37(4):949-50; author reply 950 [12668993] Hepatology. 2003 Jul;38(1):267 [12830010] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 inhibitors preserve dopamine neurons and motor function in experimental parkinsonism. AN - 72631339; 12402257 AB - Drugs currently used for patients with Parkinson's disease provide temporary relief of symptoms but do not halt or slow the underlying neurodegenerative disease process. Increasing evidence suggests that neurons die in Parkinson's disease by a process called apoptosis, which may be triggered by mitochondrial impairment and oxidative stress. We report that two novel synthetic inhibitors of the tumor suppressor protein p53, pifithrin-alpha (PFT-alpha) and Z-1-117, are highly effective in protecting midbrain dopaminergic neurons and improving behavioral outcome in a mouse model of Parkinson's disease. Mice given intraperitoneal injections of PFT-alpha or Z-1-117 exhibited improved motor function, reduced damage to nigrostriatal dopaminergic neurons and reduced depletion of dopamine and its metabolites after exposure to the toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP caused an increase in the level of the proapoptotic protein Bax, which was prevented by giving mice PFT-alpha and Z-1-117. PFT-alpha and Z-1-117 also suppressed Bax production and apoptosis in cultured dopaminergic cells exposed to MPP(+). Our findings demonstrate a pivotal role for p53 in experimental parkinsonism and identify a novel class of synthetic p53 inhibitors with clinical potential. JF - Annals of neurology AU - Duan, Wenzhen AU - Zhu, Xiaoxiang AU - Ladenheim, Bruce AU - Yu, Qian-sheng AU - Guo, Zhihong AU - Oyler, Jon AU - Cutler, Roy G AU - Cadet, Jean Lud AU - Greig, Nigel H AU - Mattson, Mark P AD - Laboratory of Neurosciences, Gerontology Research Center 4F01, National Institute on Aging/NIH, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2002/11// PY - 2002 DA - November 2002 SP - 597 EP - 606 VL - 52 IS - 5 SN - 0364-5134, 0364-5134 KW - Bax protein, mouse KW - 0 KW - Benzothiazoles KW - Dopamine Agents KW - Neuroprotective Agents KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-bcl-2 KW - Thiazoles KW - Tumor Suppressor Protein p53 KW - Z-1-117 KW - bcl-2-Associated X Protein KW - Toluene KW - 3FPU23BG52 KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - 9P21XSP91P KW - pifithrin KW - D213B92S1Y KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Mice KW - Neuroprotective Agents -- pharmacology KW - Thiazoles -- pharmacology KW - Behavior, Animal -- drug effects KW - Proto-Oncogene Proteins -- antagonists & inhibitors KW - Apoptosis -- drug effects KW - Mice, Inbred C57BL KW - Male KW - Toluene -- analogs & derivatives KW - Tumor Suppressor Protein p53 -- antagonists & inhibitors KW - Toluene -- pharmacology KW - Parkinsonian Disorders -- physiopathology KW - Parkinsonian Disorders -- psychology KW - Neurons -- drug effects KW - Parkinsonian Disorders -- chemically induced KW - Neurons -- physiology KW - Dopamine -- metabolism KW - Motor Activity -- drug effects KW - Parkinsonian Disorders -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72631339?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=p53+inhibitors+preserve+dopamine+neurons+and+motor+function+in+experimental+parkinsonism.&rft.au=Duan%2C+Wenzhen%3BZhu%2C+Xiaoxiang%3BLadenheim%2C+Bruce%3BYu%2C+Qian-sheng%3BGuo%2C+Zhihong%3BOyler%2C+Jon%3BCutler%2C+Roy+G%3BCadet%2C+Jean+Lud%3BGreig%2C+Nigel+H%3BMattson%2C+Mark+P&rft.aulast=Duan&rft.aufirst=Wenzhen&rft.date=2002-11-01&rft.volume=52&rft.issue=5&rft.spage=597&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 - 2002-12-03 N1 - Date created - 2002-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical consequences of marijuana. AN - 72630550; 12412830 AB - As documented in national surveys, for the past several years, marijuana has been the most commonly abused drug in the United States, with approximately 6% of the population 12 years and older having used the drug in the month prior to interview. The use of marijuana is not without significant health hazards. Marijuana is associated with effects on almost every organ system in the body, ranging from the central nervous system to the cardiovascular, endocrine, respiratory/pulmonary, and immune systems. Research presented in this special supplement will show that in addition to marijuana abuse/dependence, marijuana use is associated in some studies with impairment of cognitive function in the young and old, fetal and developmental consequences, cardiovascular effects (heart rate and blood pressure changes), respiratory/pulmonary complications such as chronic cough and emphysema, impaired immune function leading to vulnerability to and increased infections, and the risk of developing head, neck, and/or lung cancer. In general, acute effects are better studied than those of chronic use, and more studies are needed that focus on disentangling effects of marijuana from those of other drugs and adverse environmental conditions. JF - Journal of clinical pharmacology AU - Khalsa, Jag H AU - Genser, Sander AU - Francis, Henry AU - Martin, Billy AD - Center on AIDS and Other Medical Consequences of Drug Abuse, National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/11// PY - 2002 DA - November 2002 SP - 7S EP - 10S VL - 42 IS - 11 Suppl SN - 0091-2700, 0091-2700 KW - Index Medicus KW - Marijuana Smoking -- adverse effects KW - Humans KW - Marijuana Abuse -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72630550?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+pharmacology&rft.atitle=Clinical+consequences+of+marijuana.&rft.au=Khalsa%2C+Jag+H%3BGenser%2C+Sander%3BFrancis%2C+Henry%3BMartin%2C+Billy&rft.aulast=Khalsa&rft.aufirst=Jag&rft.date=2002-11-01&rft.volume=42&rft.issue=11+Suppl&rft.spage=7S&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+pharmacology&rft.issn=00912700&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-12 N1 - Date created - 2002-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Leu-574 of HIF-1alpha is essential for the von Hippel-Lindau (VHL)-mediated degradation pathway. AN - 72625609; 12205091 AB - Oxygen homeostasis is crucial for a myriad of developmental, physiological, and pathophysiological processes. Hypoxia-inducible factor 1alpha (HIF-1alpha) plays a pivotal role in response to hypoxia by transcriptionally activating target genes involving oxygen uptake, transport, delivery, and consumption. HIF-1alpha activity is regulated primarily through the ubiquitin-proteasome degradation pathway, which targets the oxygen-dependent degradation domain (ODD) of HIF-1alpha. In particular, the von Hippel-Lindau (VHL) protein complex, an E3 ubiquitin ligase, binds to the ODD upon hydroxylation of HIF-1alpha Pro-564. Here, we show that in vivo VHL interacts with the N-terminal as well as the C-terminal ODD independently, supporting the notion of functional redundancy within the ODD. Moreover, we demonstrate that Leu-574 of HIF-1alpha is essential for VHL binding to the C-terminal ODD. Despite the presence of Pro-564, deletion or mutation of Leu-574 resulted in a loss of VHL binding and a gain of protein stability. Furthermore, the identification of Leu-574 redefines the N-terminal activation domain of HIF-1alpha to be constitutively active. Taken together, this study provides new insight into the mechanisms underlying VHL-mediated HIF-1alpha degradation and transcriptional activation, and a molecular basis for drug targeting. JF - The Journal of biological chemistry AU - Huang, L Eric AU - Pete, Erin A AU - Schau, Maureen AU - Milligan, Justine AU - Gu, Jie AD - Laboratory of Human Carcinogenesis, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. huange@mail.nih.gov Y1 - 2002/11/01/ PY - 2002 DA - 2002 Nov 01 SP - 41750 EP - 41755 VL - 277 IS - 44 SN - 0021-9258, 0021-9258 KW - Hypoxia-Inducible Factor 1, alpha Subunit KW - 0 KW - Transcription Factors 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 - Leucine KW - GMW67QNF9C KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Oxygen -- pharmacology KW - Transcription, Genetic KW - Transcription Factors -- metabolism KW - Transcription Factors -- chemistry KW - Ligases -- chemistry KW - Ligases -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72625609?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Leu-574+of+HIF-1alpha+is+essential+for+the+von+Hippel-Lindau+%28VHL%29-mediated+degradation+pathway.&rft.au=Huang%2C+L+Eric%3BPete%2C+Erin+A%3BSchau%2C+Maureen%3BMilligan%2C+Justine%3BGu%2C+Jie&rft.aulast=Huang&rft.aufirst=L&rft.date=2002-11-01&rft.volume=277&rft.issue=44&rft.spage=41750&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 - 2003-01-17 N1 - Date created - 2002-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neuronal activity is required for the circadian rhythm of vasopressin gene transcription in the suprachiasmatic nucleus in vitro. AN - 72624244; 12399408 AB - Arginine vasopressin (AVP) is synthesized in and secreted by the suprachiasmatic nucleus (SCN) in a circadian pattern. Transcription of the AVP gene in organotypic cultures of rat SCN was studied by using an intronic in situ hybridization. AVP gene transcription in the cultured SCN maintained a daily rhythm with a peak in the daytime. Inhibition of spontaneous activity by the sodium channel blocker, tetrodotoxin (TTX), dramatically decreased AVP heteronuclear RNA levels and suppressed rhythmicity, indicating that ongoing neural activity was required for the AVP gene transcription. In the presence of TTX, the adenylate cyclase stimulator, forskolin, increased AVP transcription in the SCN. In contrast, the protein kinase C activator, phorbol 12-myristate 13-acetate, greatly increased AVP transcription in the absence of TTX, but this effect was blocked by TTX, indicating that the phorbol 12-myristate 13-acetate acted indirectly via synaptic input. Neither protein kinase A nor protein kinase C pathways appear to be involved in the rhythmicity of AVP transcription in the SCN because selective inhibitors of these protein kinases were without effect. In contrast, the MAPK pathway inhibitor, PD98059, profoundly decreased AVP transcription and abolished its daily rhythm. Hence, a functional MAPK signaling pathway appears to be critical for AVP gene expression in the SCN. JF - Endocrinology AU - Arima, Hiroshi AU - House, Shirley B AU - Gainer, Harold AU - Aguilera, Greti AD - Developmental Endocrinology Brach, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. arima105@med.nagoya-u.ac.jp Y1 - 2002/11// PY - 2002 DA - November 2002 SP - 4165 EP - 4171 VL - 143 IS - 11 SN - 0013-7227, 0013-7227 KW - RNA, Heterogeneous Nuclear KW - 0 KW - RNA, Messenger KW - Sodium Channel Blockers KW - Arginine Vasopressin KW - 113-79-1 KW - Colforsin KW - 1F7A44V6OU KW - Tetrodotoxin KW - 4368-28-9 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Gene Expression -- drug effects KW - Animals KW - Rats, Sprague-Dawley KW - In Situ Hybridization KW - Colforsin -- pharmacology KW - Sodium Channel Blockers -- pharmacology KW - RNA, Messenger -- analysis KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Tetrodotoxin -- pharmacology KW - RNA, Heterogeneous Nuclear -- genetics KW - Organ Culture Techniques KW - Arginine Vasopressin -- genetics KW - Suprachiasmatic Nucleus -- metabolism KW - Circadian Rhythm KW - Neurons -- physiology KW - Transcription, Genetic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72624244?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Neuronal+activity+is+required+for+the+circadian+rhythm+of+vasopressin+gene+transcription+in+the+suprachiasmatic+nucleus+in+vitro.&rft.au=Arima%2C+Hiroshi%3BHouse%2C+Shirley+B%3BGainer%2C+Harold%3BAguilera%2C+Greti&rft.aulast=Arima&rft.aufirst=Hiroshi&rft.date=2002-11-01&rft.volume=143&rft.issue=11&rft.spage=4165&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-19 N1 - Date created - 2002-10-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Association of transient dermal mastocytosis and elevated plasma tryptase levels with development of adverse reactions after treatment of onchocerciasis with ivermectin. AN - 72617361; 12402200 AB - To investigate the role of mast cells in treatment-associated adverse reactions in patients with onchocerciasis, changes in plasma tryptase levels and skin mast cell counts were examined in 2 groups of Onchocerca volvulus-infected subjects after ivermectin treatment. After treatment, an increase in tryptase levels was observed concurrent with the onset of blood eosinopenia and preceding the appearance of plasma eosinophil-derived neurotoxin (EDN) and interleukin-5. Tryptase levels were correlated with development of peripheral eosinopenia and markers of eosinophil activation and degranulation. Dermal mast cell numbers increased transiently at 24 h after treatment, preceding the onset of dermal eosinophil infiltration and the development of clinically apparent inflammation. Local reactions were strongly correlated with levels of plasma tryptase and EDN, and the severity of systemic reactions was correlated with levels of tryptase, EDN, and interleukin-5. The data indicate that mast cells play a role in initiation of tissue inflammatory reactions after ivermectin treatment of onchocerciasis. JF - The Journal of infectious diseases AU - Cooper, Philip J AU - Schwartz, Lawrence B AU - Irani, Anne-Marie AU - Awadzi, Kwablah AU - Guderian, Ronald H AU - Nutman, Thomas B AD - Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. pc102d@hotmail.com Y1 - 2002/11/01/ PY - 2002 DA - 2002 Nov 01 SP - 1307 EP - 1313 VL - 186 IS - 9 SN - 0022-1899, 0022-1899 KW - Anthelmintics KW - 0 KW - Biomarkers KW - Interleukin-5 KW - Ivermectin KW - 70288-86-7 KW - Serine Endopeptidases KW - EC 3.4.21.- KW - Tryptases KW - EC 3.4.21.59 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Mast Cells -- parasitology KW - Humans KW - Eosinophilia -- chemically induced KW - Lymphedema -- chemically induced KW - Mast Cells -- physiology KW - Interleukin-5 -- blood KW - Biomarkers -- blood KW - Onchocerca -- pathogenicity KW - Onchocerciasis -- drug therapy KW - Ivermectin -- adverse effects KW - Anthelmintics -- adverse effects KW - Mastocytosis, Cutaneous -- chemically induced KW - Serine Endopeptidases -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72617361?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Association+of+transient+dermal+mastocytosis+and+elevated+plasma+tryptase+levels+with+development+of+adverse+reactions+after+treatment+of+onchocerciasis+with+ivermectin.&rft.au=Cooper%2C+Philip+J%3BSchwartz%2C+Lawrence+B%3BIrani%2C+Anne-Marie%3BAwadzi%2C+Kwablah%3BGuderian%2C+Ronald+H%3BNutman%2C+Thomas+B&rft.aulast=Cooper&rft.aufirst=Philip&rft.date=2002-11-01&rft.volume=186&rft.issue=9&rft.spage=1307&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 - 2002-12-09 N1 - Date created - 2002-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential expression and estrogen response of lactoferrin gene in the female reproductive tract of mouse, rat, and hamster. AN - 72198372; 12390874 AB - Lactoferrin, an iron-binding glycoprotein, kills bacteria and modulates inflammatory and immune responses. Presence of lactoferrin in the female reproductive tract suggests that the protein may be part of the mucosal immune system and act as the first line of defense against pathogenic organisms. We have discovered that lactoferrin is a major estrogen-inducible protein in the uterus of immature mice and is up-regulated by physiological levels of estrogen during proestrous in mature mice. In the present study, we examined lactoferrin gene expression and its response to estrogen stimulation in the female reproductive tract of several strains of immature mouse, rat, and hamster. The lactoferrin expression in the cycling adult female rat was also evaluated. Lactoferrin gene polymorphism exists among the different mouse strains. In the three inbred mouse strains studied, lactoferrin gene expression is stimulated by estrogen in the immature uterus, although it is less robust than in the outbred CD-1 mouse. We found that the lactoferrin gene is constitutively expressed in the epithelium of the vagina and the isthmus oviduct; however, it is estrogen inducible in the uterus of immature mice and rats. Furthermore, lactoferrin is elevated in the uterine epithelium of the mature rat during the proestrous and estrous stages of the estrous cycle. Estrogen stimulation of lactoferrin gene expression in the reproductive tract of an immature hamster is limited to the vaginal epithelium. The present study demonstrates differential expression and estrogen responsiveness of the lactoferrin gene in different regions of the female rodent reproductive tract and variation among the rodent species studied. JF - Biology of reproduction AU - Teng, Christina T AU - Beard, Clara AU - Gladwell, Wesley AD - Gene Regulation Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. teng@niehs.nih.gov Y1 - 2002/11// PY - 2002 DA - November 2002 SP - 1439 EP - 1449 VL - 67 IS - 5 SN - 0006-3363, 0006-3363 KW - Estrogens KW - 0 KW - Estrogens, Non-Steroidal KW - Transferrin KW - Diethylstilbestrol KW - 731DCA35BT KW - Lactoferrin KW - EC 3.4.21.- KW - Index Medicus KW - Animals KW - Animals, Outbred Strains KW - Age Factors KW - Polymorphism, Genetic KW - Mice KW - Uterus -- drug effects KW - Transferrin -- immunology KW - Cross Reactions KW - Estrous Cycle -- genetics KW - Rats KW - Mice, Inbred Strains KW - Rats, Inbred F344 KW - Uterus -- cytology KW - Uterus -- physiology KW - Diethylstilbestrol -- pharmacology KW - Gene Expression Regulation -- drug effects KW - Estrogens, Non-Steroidal -- pharmacology KW - Species Specificity KW - Female KW - Cricetinae KW - Genitalia, Female -- cytology KW - Lactoferrin -- drug effects KW - Lactoferrin -- genetics KW - Genitalia, Female -- drug effects KW - Estrogens -- pharmacology KW - Lactoferrin -- immunology KW - Lactoferrin -- metabolism KW - Genitalia, Female -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72198372?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biology+of+reproduction&rft.atitle=Differential+expression+and+estrogen+response+of+lactoferrin+gene+in+the+female+reproductive+tract+of+mouse%2C+rat%2C+and+hamster.&rft.au=Teng%2C+Christina+T%3BBeard%2C+Clara%3BGladwell%2C+Wesley&rft.aulast=Teng&rft.aufirst=Christina&rft.date=2002-11-01&rft.volume=67&rft.issue=5&rft.spage=1439&rft.isbn=&rft.btitle=&rft.title=Biology+of+reproduction&rft.issn=00063363&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-21 N1 - Date created - 2002-10-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of dopamine receptor blockade on cerebral blood flow response to somatosensory stimulation in the unanesthetized rat. AN - 72194046; 12388628 AB - Local cerebral blood flow (CBF) was determined in 30 cerebral structures, including four structures of the whisker-to-barrel cortex sensory pathway, by the quantitative autoradiographic [(14)C]iodoantipyrine method during unilateral vibrissal stimulation in rats administered 0.1 or 1.0 mg/kg haloperidol or its control vehicle intravenously. The low dose of haloperidol had no significant effects on resting CBF or its enhancement by vibrissal stimulation. By standard t tests, the high dose statistically significantly lowered baseline CBF in frontal and visual cortex, hippocampus, dentate gyrus, inferior olive, cerebellar cortex, and the ventral posteromedial (VPM) thalamic nucleus on the unstimulated side, and raised baseline CBF in the lateral habenula; however, these changes lost statistical significance after Bonferroni correction for multiple comparisons. Neither dose had any effects on the increases in CBF evoked by vibrissal stimulation in the principal sensory trigeminal nucleus and barrel cortex, but the higher dose statistically significantly enhanced the percent increases in CBF due to the sensory stimulation in the spinal trigeminal nucleus and VPM thalamic nucleus. These results do not support a role for direct dopaminergic vasoactive mechanisms in the increases in CBF associated with neuronal functional activation. JF - The Journal of pharmacology and experimental therapeutics AU - Esaki, Takanori AU - Itoh, Yoshiaki AU - Shimoji, Kazuaki AU - Cook, Michelle AU - Jehle, Jane AU - Sokoloff, Louis AD - Laboratory of Cerebral Metabolism, National Institute of Mental Health/NIH, Building 36, 36 Convent Drive, Bethesda, MD 20892-4030, USA. Y1 - 2002/11// PY - 2002 DA - November 2002 SP - 497 EP - 502 VL - 303 IS - 2 SN - 0022-3565, 0022-3565 KW - Dopamine Antagonists KW - 0 KW - Receptors, Dopamine KW - Haloperidol KW - J6292F8L3D KW - Index Medicus KW - Rats KW - Behavior, Animal -- drug effects KW - Animals KW - Rats, Sprague-Dawley KW - Catalepsy -- chemically induced KW - Catalepsy -- psychology KW - Dose-Response Relationship, Drug KW - Neural Pathways -- physiology KW - Haloperidol -- pharmacology KW - Physical Stimulation KW - Male KW - Receptors, Dopamine -- drug effects KW - Vibrissae -- innervation KW - Somatosensory Cortex -- physiology KW - Dopamine Antagonists -- pharmacology KW - Cerebrovascular Circulation -- drug effects KW - Vibrissae -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72194046?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+dopamine+receptor+blockade+on+cerebral+blood+flow+response+to+somatosensory+stimulation+in+the+unanesthetized+rat.&rft.au=Esaki%2C+Takanori%3BItoh%2C+Yoshiaki%3BShimoji%2C+Kazuaki%3BCook%2C+Michelle%3BJehle%2C+Jane%3BSokoloff%2C+Louis&rft.aulast=Esaki&rft.aufirst=Takanori&rft.date=2002-11-01&rft.volume=303&rft.issue=2&rft.spage=497&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 - 2002-11-22 N1 - Date created - 2002-10-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Purine nucleoside phosphorylase: a fortuitous cytosolic arsenate reductase? AN - 72194013; 12388828 JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Waalkes, Michael P AU - Liu, Jie AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute at NIEHS, 111 Alexander Drive, Research Triangle Park, North Carolina, 27709, USA. waalkes@niehs.nih.gov Y1 - 2002/11// PY - 2002 DA - November 2002 SP - 1 EP - 3 VL - 70 IS - 1 SN - 1096-6080, 1096-6080 KW - Arsenates KW - 0 KW - Arsenites KW - Environmental Pollutants KW - Ion Pumps KW - Multienzyme Complexes KW - Purine-Nucleoside Phosphorylase KW - EC 2.4.2.1 KW - Arsenite Transporting ATPases KW - EC 3.6.3.16 KW - Index Medicus KW - Humans KW - Arsenites -- metabolism KW - Arsenates -- metabolism KW - Multienzyme Complexes -- metabolism KW - Purine-Nucleoside Phosphorylase -- metabolism KW - Environmental Pollutants -- metabolism KW - Ion Pumps -- metabolism KW - Cytosol -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72194013?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Purine+nucleoside+phosphorylase%3A+a+fortuitous+cytosolic+arsenate+reductase%3F&rft.au=Waalkes%2C+Michael+P%3BLiu%2C+Jie&rft.aulast=Waalkes&rft.aufirst=Michael&rft.date=2002-11-01&rft.volume=70&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-08 N1 - Date created - 2002-10-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Toxicol Sci. 2002 Nov;70(1):13-9 [12388830] Toxicol Sci. 2002 Nov;70(1):4-12 [12388829] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I study of weekly gemcitabine as a radiation sensitizer for unresectable pancreatic cancer. AN - 72175140; 12377317 AB - To determine the maximal tolerated dose and dose-limiting toxicities (DLTs) of weekly gemcitabine with concurrent radiotherapy (RT) in patients with unresectable adenocarcinoma of the pancreas. Patients who had locally advanced or recurrent unresectable pancreatic cancer were eligible. Gemcitabine was administered as a 30-min infusion once weekly for a total of five cycles during the course of RT. The starting dose of gemcitabine was 350 mg/m(2)/wk. Doses were escalated by increments of 25% in successive cohorts of 3-6 patients. RT was delivered at 180 cGy/d to a total dose of 5400-5580 cGy to the gross tumor volume. Nineteen patients were entered in this study through three dose levels (350-550 mg/m(2)/wk). The maximal tolerated dose was determined to be 440 mg/m(2)/wk. The DLTs were neutropenia, thrombocytopenia, and failure to receive all five cycles of gemcitabine. Other non-DLTs included 16 Grade III toxicities, which consisted of thrombosis, infection, nausea, vomiting, hypotension, constipation, diarrhea, and fatigue. One patient at each gemcitabine dose level experienced Grade IV vomiting, and the patient at the 550 mg/m(2) dose developed Grade IV anorexia. The maximal tolerated dose of gemcitabine when administered as a 30-min infusion once weekly during RT for unresectable pancreatic cancer was found to be 440 mg/m(2)/wk. The DLTs were neutropenia, thrombocytopenia, and failure to receive all five cycles of chemotherapy. Concurrent gemcitabine and RT is reasonably well tolerated and deserves additional evaluation against the current standard of care. JF - International journal of radiation oncology, biology, physics AU - Poggi, Matthew M AU - Kroog, Glenn S AU - Russo, Angelo AU - Muir, Christine AU - Cook, John AU - Smith, Judith AU - Mitchell, James B AU - Herscher, Laurie L AD - Radiation Oncology Sciences Program, Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. mpoggi@usuhs.mil Y1 - 2002/11/01/ PY - 2002 DA - 2002 Nov 01 SP - 670 EP - 676 VL - 54 IS - 3 SN - 0360-3016, 0360-3016 KW - Radiation-Sensitizing Agents KW - 0 KW - Deoxycytidine KW - 0W860991D6 KW - gemcitabine KW - B76N6SBZ8R KW - Index Medicus KW - Drug Administration Schedule KW - Dose-Response Relationship, Drug KW - Aged, 80 and over KW - Radiotherapy Dosage KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Female KW - Survival Analysis KW - Pancreatic Neoplasms -- radiotherapy KW - Deoxycytidine -- adverse effects KW - Deoxycytidine -- analogs & derivatives KW - Deoxycytidine -- administration & dosage KW - Radiation-Sensitizing Agents -- adverse effects KW - Radiation-Sensitizing Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72175140?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Phase+I+study+of+weekly+gemcitabine+as+a+radiation+sensitizer+for+unresectable+pancreatic+cancer.&rft.au=Poggi%2C+Matthew+M%3BKroog%2C+Glenn+S%3BRusso%2C+Angelo%3BMuir%2C+Christine%3BCook%2C+John%3BSmith%2C+Judith%3BMitchell%2C+James+B%3BHerscher%2C+Laurie+L&rft.aulast=Poggi&rft.aufirst=Matthew&rft.date=2002-11-01&rft.volume=54&rft.issue=3&rft.spage=670&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 - 2002-11-22 N1 - Date created - 2002-10-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Varicella-zoster virus (VZV) ORF17 protein induces RNA cleavage and is critical for replication of VZV at 37 degrees C but not 33 degrees C. AN - 72157710; 12368344 AB - Varicella-zoster virus (VZV) open reading frame 17 (ORF17) is homologous to herpes simplex virus (HSV) UL41, which encodes the viral host shutoff protein (vhs). HSV vhs induces degradation of mRNA and rapid shutoff of host protein synthesis. An antibody to ORF17 protein detected a 46-kDa protein in VZV-infected cells. While HSV vhs is located in virions, VZV ORF17 protein was not detectable in virions. ORF17 protein induced RNA cleavage, but to a substantially lesser extent than HSV-1 vhs. Expression of ORF17 protein did not inhibit expression from a beta-galactosidase reporter plasmid, while HSV type 1 vhs abolished reporter expression. Two VZV ORF17 deletion mutants were constructed to examine the role of ORF17 in virus replication. While the ORF17 VZV mutants grew to peak titers that were similar to those of the parental virus at 33 degrees C, the ORF17 mutants grew to 20- to 35-fold-lower titers than parental virus at 37 degrees C. ORF62 protein was distributed in a different pattern in the nuclei and cytoplasm of cells infected with an ORF17 deletion mutant at 37 degrees C compared to 33 degrees C. Inoculation of cotton rats with the ORF17 deletion mutant resulted in a level of latent infection similar to that produced by inoculation with the parental virus. The importance of ORF17 protein for viral replication at 37 degrees C but not at 33 degrees C suggests that this protein may facilitate the growth of virus in certain tissues in vivo. JF - Journal of virology AU - Sato, Hitoshi AU - Callanan, Lawrence D AU - Pesnicak, Lesley AU - Krogmann, Tammy AU - Cohen, Jeffrey I AD - Medical Virology Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 28092-1888, USA. Y1 - 2002/11// PY - 2002 DA - November 2002 SP - 11012 EP - 11023 VL - 76 IS - 21 SN - 0022-538X, 0022-538X KW - IE62 protein, Human herpesvirus 3 KW - 0 KW - Immediate-Early Proteins KW - ORF17 protein, varicella-zoster virus KW - RNA Caps KW - RNA, Viral KW - Trans-Activators KW - Viral Envelope Proteins KW - Viral Nonstructural Proteins KW - Viral Proteins KW - glycoprotein gp1, varicella-zoster virus KW - virion host shutoff protein, Simplexvirus KW - 118367-50-3 KW - Ribonucleases KW - EC 3.1.- KW - beta-Galactosidase KW - EC 3.2.1.23 KW - Index Medicus KW - Viral Proteins -- genetics KW - Herpesvirus 1, Human -- metabolism KW - Trans-Activators -- metabolism KW - Animals KW - Immediate-Early Proteins -- metabolism KW - Humans KW - Open Reading Frames KW - Temperature KW - Gene Expression KW - RNA Caps -- metabolism KW - Intracellular Fluid -- metabolism KW - Mutagenesis KW - Tumor Cells, Cultured KW - Cercopithecus aethiops KW - Genes, Reporter KW - Viral Proteins -- metabolism KW - beta-Galactosidase -- genetics KW - Vero Cells KW - Viral Envelope Proteins -- metabolism KW - Cell Line KW - Virus Replication KW - Herpesvirus 3, Human -- growth & development KW - Herpesvirus 3, Human -- genetics KW - Viral Nonstructural Proteins -- genetics KW - Herpesvirus 3, Human -- metabolism KW - Viral Nonstructural Proteins -- metabolism KW - RNA, Viral -- metabolism KW - Herpesvirus 3, Human -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72157710?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Varicella-zoster+virus+%28VZV%29+ORF17+protein+induces+RNA+cleavage+and+is+critical+for+replication+of+VZV+at+37+degrees+C+but+not+33+degrees+C.&rft.au=Sato%2C+Hitoshi%3BCallanan%2C+Lawrence+D%3BPesnicak%2C+Lesley%3BKrogmann%2C+Tammy%3BCohen%2C+Jeffrey+I&rft.aulast=Sato&rft.aufirst=Hitoshi&rft.date=2002-11-01&rft.volume=76&rft.issue=21&rft.spage=11012&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 - 2002-11-26 N1 - Date created - 2002-10-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Hum Genet. 1992 Dec;90(4):450-6 [1483704] Virology. 1992 Oct;190(2):682-8 [1325700] Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7376-80 [8394020] J Virol. 1993 Dec;67(12):7149-60 [8230437] Virology. 1994 Apr;200(1):297-300 [8128631] J Virol. 1994 Apr;68(4):2339-46 [8139019] Mol Cell Biol. 1994 Oct;14(10):6896-906 [7935407] J Virol. 1995 Jul;69(7):4274-82 [7769688] J Virol. 1995 Aug;69(8):4693-701 [7609034] J Virol. 1995 Aug;69(8):4863-71 [7609054] Virology. 1995 Aug 20;211(2):491-506 [7645253] J Virol. 1995 Nov;69(11):6779-86 [7474089] J Gen Virol. 1995 Nov;76 ( Pt 11):2875-9 [7595398] J Virol. 1996 Apr;70(4):2124-31 [8642633] J Virol. 1996 Apr;70(4):2411-9 [8642669] EMBO J. 1996 May 15;15(10):2575-81 [8665865] J Virol. 1996 Dec;70(12):8710-8 [8970998] J Virol. 1997 Sep;71(9):6913-20 [9261418] J Infect Dis. 1998 May;177(5):1390-3 [9593031] Vaccine. 1998 Aug;16(13):1263-9 [9682389] J Virol. 1999 Sep;73(9):7153-64 [10438802] J Virol. 2000 Feb;74(4):1900-7 [10644363] J Virol. 2000 Mar;74(5):2265-77 [10666257] Arch Virol. 2000;145(10):2027-46 [11087090] J Virol. 2001 Jan;75(2):1072-6 [11134323] J Virol. 2001 May;75(10):4878-88 [11312359] J Gen Virol. 2001 Sep;82(Pt 9):2071-81 [11514716] J Virol. 2001 Oct;75(19):9106-13 [11533174] J Virol. 1999 Nov;73(11):9222-31 [10516030] J Virol. 2001 Nov;75(21):10272-80 [11581395] Methods Enzymol. 2001;342:440-51 [11586916] J Virol. 2002 Apr;76(7):3575-8 [11884583] Virology. 1971 Dec;46(3):890-9 [5167662] Biken J. 1975 Mar;18(1):25-33 [167707] Biken J. 1980 Sep;23(3):95-106 [6257229] Virology. 1983 Dec;131(2):437-54 [6318440] J Gen Virol. 1986 Sep;67 ( Pt 9):1759-816 [3018124] Proc Natl Acad Sci U S A. 1986 Dec;83(23):9094-8 [3024166] J Virol. 1988 Mar;62(3):912-21 [2828686] J Virol. 1989 May;63(5):1897-906 [2539493] J Gen Virol. 1990 Feb;71 ( Pt 2):411-8 [2155295] J Virol. 1991 Jan;65(1):112-22 [1845879] Nucleic Acids Res. 1991 Aug 25;19(16):4459-65 [1653415] Science. 1991 Dec 6;254(5037):1494-7 [1962209] J Virol. 1992 Jan;66(1):359-66 [1309252] J Gen Virol. 1992 Feb;73 ( Pt 2):467-70 [1311370] J Virol. 1992 Sep;66(9):5298-304 [1323696] Virology. 1993 Apr;193(2):1028-32 [8384744] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Office of rare diseases neuropathologic criteria for corticobasal degeneration AN - 220133477; 12430710 AB - A working group supported by the Office of Rare Diseases of the National Institutes of Health formulated neuropathologic criteria for corticobasal degeneration (CBD) that were subsequently validated by an independent group of neuropathologists. The criteria do not require a specific clinical phenotype, since CBD can have diverse clinical presentations, such as progressive asymmetrical rigidity and apraxia, progressive aphasia, or frontal lobe dementia. Cortical atrophy, ballooned neurons, and degeneration of the substantia nigra have been emphasized in previous descriptions and are present in CBD, but the present criteria emphasize tau-immunoreactive lesions in neurons, glia, and cell processes in the neuropathologic diagnosis of CBD. The minimal pathologic features for CBD are cortical and striatal tau-positive neuronal and glial lesions, especially astrocytic plaques and thread-like lesions in both white matter and gray matter, along with neuronal loss in focal cortical regions and in the substantia nigra. The methods required to make this diagnosis include histologic stains to assess neuronal loss, spongiosis and ballooned neurons, and a method to detect tau-positive neuronal and glial lesions. Use of either the Gallyas silver staining method or immunostains with sensitive tau antibodies is acceptable. In cases where ballooned neurons are sparse or difficult to detect, immunostaining for phospho-neurofilament or alpha-B-crystallin may prove helpful. Methods to assess Alzheimer-type pathology and Lewy body pathology are necessary to rule out other causes of dementia and Parkinsonism. Using these criteria provides good differentiation of CBD from other tauopathies, except frontotemporal dementia and Parkinsonism linked to chromosome 17, where additional clinical or molecular genetic information is required to make an accurate diagnosis. JF - Journal of Neuropathology and Experimental Neurology AU - Dickson, D W AU - Bergeron, C AU - Chin, S S AU - Duyckaerts, C AU - et al Y1 - 2002/11// PY - 2002 DA - Nov 2002 SP - 935 EP - 46 CY - Lawrence PB - Lippincott Williams & Wilkins VL - 61 IS - 11 SN - 00223069 KW - Medical Sciences--Psychiatry And Neurology KW - Brain -- physiopathology KW - Neurodegenerative Diseases -- physiopathology KW - Inclusion Bodies -- pathology KW - Humans KW - Atrophy -- physiopathology KW - Silver Staining KW - Atrophy -- pathology KW - Neurofibrillary Tangles -- pathology KW - Neuroglia -- pathology KW - Brain -- pathology KW - Neurodegenerative Diseases -- pathology KW - Neurons -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/220133477?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=unknown&rft.jtitle=Journal+of+Neuropathology+and+Experimental+Neurology&rft.atitle=Office+of+rare+diseases+neuropathologic+criteria+for+corticobasal+degeneration&rft.au=Dickson%2C+D+W%3BBergeron%2C+C%3BChin%2C+S+S%3BDuyckaerts%2C+C%3Bet+al&rft.aulast=Dickson&rft.aufirst=D&rft.date=2002-11-01&rft.volume=61&rft.issue=11&rft.spage=935&rft.isbn=&rft.btitle=&rft.title=Journal+of+Neuropathology+and+Experimental+Neurology&rft.issn=00223069&rft_id=info:doi/ LA - English DB - ProQuest Central N1 - Copyright - Copyright American Association of Neuropathologists, Inc. Nov 2002 N1 - Last updated - 2013-01-30 N1 - CODEN - JNENAD ER - TY - JOUR T1 - Effects of a red-tide toxin on fish hearing AN - 18844682; 5616949 AB - Red tides are formed from blooms of marine algae. Among them, the dinoflagellate (Karenia brevis) that is responsible for Florida red tides can release many types of natural toxins, which cause massive kills of marine animals, including endangered species, and threaten human health. This study was to investigate whether or not a neurotoxin, brevetoxin-3, purified from Florida red tides affects hearing sensitivity of a teleost fish, the goldfish (Carassius auratus). LD sub(50) of the goldfish that were intraperitoneally injected with brevetoxin-3 was 0.068 mu g g super(-1). Evoked auditory brainstem responses were recorded, and hearing threshold was determined using a correlation method. By comparing thresholds of fish before and after a sublethal-dose injection (0.064 mu g g super(-1)) of the toxin, we found that brevetoxin-3 significantly reduces auditory sensitivity up to 9 dB at low frequencies (100 Hz and 500 Hz), but not at a high frequency (2,000 Hz). Reduction of hearing sensitivity was recovered within 24 h. To our knowledge, this is the first study showing a natural red-tide toxin causes minor hearing loss in vertebrates. Results of the study indicate that brevetoxin-3 could affect hearing capabilities of marine animals that survived exposure to red tides. Mechanisms of the toxin-induced reduction of hearing sensitivity are discussed. JF - Journal of Comparative Physiology, A AU - Lu, Z AU - Tomchik, S M AD - NIEHS Marine and Freshwater Biomedical Science Center, Rosenstiel School of Marine and Atmospheric Science, University of Miami, 4600 Rickenbacker Causeway, Miami, FL 33149-1098, USA, zlu@miami.edu Y1 - 2002/11// PY - 2002 DA - Nov 2002 SP - 807 EP - 813 VL - 188 IS - 10 SN - 0340-7594, 0340-7594 KW - Goldfish KW - brevetoxin-3 KW - ASFA 1: Biological Sciences & Living Resources; ASFA 3: Aquatic Pollution & Environmental Quality; Toxicology Abstracts KW - ASW, USA, Florida KW - Red tides KW - Biological poisons KW - Audition KW - Brain KW - Carassius auratus KW - Toxins KW - Neurophysiology KW - Sublethal effects KW - Karenia brevis KW - Hearing KW - X 24171:Microbial KW - Q1 08346:Physiology, biochemistry, biophysics KW - Q5 08524:Public health, medicines, dangerous organisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18844682?accountid=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+Comparative+Physiology%2C+A&rft.atitle=Effects+of+a+red-tide+toxin+on+fish+hearing&rft.au=Lu%2C+Z%3BTomchik%2C+S+M&rft.aulast=Lu&rft.aufirst=Z&rft.date=2002-11-01&rft.volume=188&rft.issue=10&rft.spage=807&rft.isbn=&rft.btitle=&rft.title=Journal+of+Comparative+Physiology%2C+A&rft.issn=03407594&rft_id=info:doi/10.1007%2Fs00359-002-0369-8 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2014-05-07 N1 - SubjectsTermNotLitGenreText - Red tides; Biological poisons; Sublethal effects; Audition; Brain; Neurophysiology; Hearing; Toxins; Karenia brevis; Carassius auratus; ASW, USA, Florida DO - http://dx.doi.org/10.1007/s00359-002-0369-8 ER - TY - JOUR T1 - An Evaluation of College Online Alcohol-Policy Information AN - 18765188; 5630732 AB - Excessive and underage drinking by US college and university students continues to be a significant problem. Curtailing the misuse of alcohol on college campuses is an important goal of college and university administrators because of the many negative consequences resulting from alcohol misuse. As part of their prevention programs, US colleges and universities are required by law to make information about their alcohol policies available to students. Often the source of this information is the school's Web site. The authors evaluated the alcohol-policy information that is available on the Web sites of the 52 top national universities listed in the 2002 rankings of US News and World Report. In general, they found that the information was difficult to find, was located in many areas of the Web site, and did not provide complete information about the school's alcohol policy. JF - Journal of American College Health AU - Faden, V B AU - Baskin, M L AD - Epidemiology Branch, Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA Y1 - 2002/11// PY - 2002 DA - Nov 2002 SP - 101 EP - 107 VL - 51 IS - 3 SN - 0744-8481, 0744-8481 KW - prevention KW - substance abuse KW - Health & Safety Science Abstracts KW - H 4000:Food and Drugs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18765188?accountid=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+American+College+Health&rft.atitle=An+Evaluation+of+College+Online+Alcohol-Policy+Information&rft.au=Faden%2C+V+B%3BBaskin%2C+M+L&rft.aulast=Faden&rft.aufirst=V&rft.date=2002-11-01&rft.volume=51&rft.issue=3&rft.spage=101&rft.isbn=&rft.btitle=&rft.title=Journal+of+American+College+Health&rft.issn=07448481&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 - Comparison of microarray designs for class comparison and class discovery AN - 18685509; 5579262 AB - Two-color microarray experiments in which an aliquot derived from a common RNA sample is placed on each array are called reference designs. Traditionally, microarray experiments have used reference designs, but designs without a reference have recently been proposed as alternatives. JF - Bioinformatics AU - Dobbin, K AU - Simon, R AD - National Cancer Institute, EPN Mailstop 7434, 6130 Executive Blvd., Bethesda, MD 20892, USA Y1 - 2002/11// PY - 2002 DA - Nov 2002 SP - 1438 EP - 1445 VL - 18 IS - 11 SN - 1367-4803, 1367-4803 KW - DNA microarrays KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18685509?accountid=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=Bioinformatics&rft.atitle=Comparison+of+microarray+designs+for+class+comparison+and+class+discovery&rft.au=Dobbin%2C+K%3BSimon%2C+R&rft.aulast=Dobbin&rft.aufirst=K&rft.date=2002-11-01&rft.volume=18&rft.issue=11&rft.spage=1438&rft.isbn=&rft.btitle=&rft.title=Bioinformatics&rft.issn=13674803&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 - Methods for assessing reproducibility of clustering patterns observed in analyses of microarray data AN - 18684784; 5579265 AB - Recent technological advances such as cDNA microarray technology have made it possible to simultaneously interrogate thousands of genes in a biological specimen. A cDNA microarray experiment produces a gene expression 'profile'. Often interest lies in discovering novel subgroupings, or 'clusters', of specimens based on their profiles, for example identification of new tumor taxonomies. Cluster analysis techniques such as hierarchical clustering and self-organizing maps have frequently been used for investigating structure in microarray data. However, clustering algorithms always detect clusters, even on random data, and it is easy to misinterpret the results without some objective measure of the reproducibility of the clusters. JF - Bioinformatics AU - McShane, L M AU - Radmacher, MD AU - Freidlin, B AU - Yu, R AU - Li, M-C AU - Simon, R AD - National Cancer Institute, Biometric Research Branch, DCTD, NIH, Bethesda, MD 20892-7434 Y1 - 2002/11// PY - 2002 DA - Nov 2002 SP - 1462 EP - 1469 VL - 18 IS - 11 SN - 1367-4803, 1367-4803 KW - DNA microarrays KW - cDNA KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18684784?accountid=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=Bioinformatics&rft.atitle=Methods+for+assessing+reproducibility+of+clustering+patterns+observed+in+analyses+of+microarray+data&rft.au=McShane%2C+L+M%3BRadmacher%2C+MD%3BFreidlin%2C+B%3BYu%2C+R%3BLi%2C+M-C%3BSimon%2C+R&rft.aulast=McShane&rft.aufirst=L&rft.date=2002-11-01&rft.volume=18&rft.issue=11&rft.spage=1462&rft.isbn=&rft.btitle=&rft.title=Bioinformatics&rft.issn=13674803&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 - Frozen protein arrays: A new method for arraying and detecting recombinant and native tissue proteins AN - 18684655; 5575762 AB - DNA microarrays are powerful tools for high throughput analysis of gene expression; however, they do not measure protein expression. Current methods for producing protein arrays require sophisticated equipment or extensive protein modification. We developed a low overhead, customizable assay platform called frozen protein arrays that can detect native proteins in protein lysates. Frozen protein arrays were formed from a block of frozen histologic embedding compound containing an array of wells. The wells were filled with samples, which freeze and bond to the block. Cryosections were cut and transferred to nitrocellulose-coated slides. The reproducibility, linearity, and sensitivity was confirmed using frozen protein arrays filled with prostate specific antigen. Frozen protein arrays could detect native tissue proteins. The alpha 1 subunit of NaK-ATPase was detected in rat kidneys with a coefficient of variation of 4.3-6.6%. Frozen protein array analysis indicated that the protein abundance decreased by 48.7% following renal ischemia, similar to the 40% decrease by Western blotting. We conclude that frozen protein arrays are a low cost, moderate size platform for arraying samples including protein lysates. Production of many identical frozen protein arrays is easy, inexpensive, and requires only small sample volumes. The method is gentle on proteins as they remain frozen during production. JF - Proteomics AU - Miyaji, T AU - Hewitt, S M AU - Liotta, LA AU - Star, R A AD - Renal Diagnostics and Therapeutics Unit, NIDDK, NIH, 10 Center Drive Room 3N108, Bethesda, MD 20892-1268, USA, robert_star@nih.gov Y1 - 2002/11// PY - 2002 DA - Nov 2002 SP - 1489 EP - 1493 VL - 2 IS - 11 SN - 1615-9853, 1615-9853 KW - protein arrays KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Bioengineering Abstracts KW - W4 130:General Biomedical Engineering: Tools & Techniques KW - W 30965:Miscellaneous, Reviews KW - W3 33250:Methods: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18684655?accountid=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=Proteomics&rft.atitle=Frozen+protein+arrays%3A+A+new+method+for+arraying+and+detecting+recombinant+and+native+tissue+proteins&rft.au=Miyaji%2C+T%3BHewitt%2C+S+M%3BLiotta%2C+LA%3BStar%2C+R+A&rft.aulast=Miyaji&rft.aufirst=T&rft.date=2002-11-01&rft.volume=2&rft.issue=11&rft.spage=1489&rft.isbn=&rft.btitle=&rft.title=Proteomics&rft.issn=16159853&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 - Prevalence of exposure to solvents, metals, grain dust, and other hazards among farmers in the Agricultural Health Study AN - 18683406; 5564396 AB - Exposures to multiple chemical, physical, and biological agents in agricultural work environments can result in confounding that may obscure or distort risks observed in epidemiologic studies. The Agricultural Health Study (AHS) is a large epidemiology study being conducted to investigate health risks among pesticide applicators and their families. During enrollment in the AHS, questionnaires were administered to over 52,000 licensed pesticide applicators from North Carolina and Iowa, who were mostly farmers. Questions about the frequency of various farming tasks were used to estimate the prevalence of exposure to solvents (25%), metals (68%), grain dusts (65%), diesel exhaust fumes (93%), and other hazards, including exposure to pesticides. Most of the farmers in the AHS reported performing routine maintenance tasks at least once a month, such as painting (63%), welding (64%), and repair of pesticide equipment (58%). The majority of farmers (74% in North Carolina; 59% in Iowa) reported holding nonfarm jobs, of which the most frequent were construction and transportation. The majority of the farmers enrolled in the AHS (55%) also reported that they mixed or applied pesticides on 10 or more days per year. The associations between the use of pesticides and the frequency with which the farmers in the AHS reported performing various types of specific farming activities were assessed to evaluate potential confounding. Confounding risk ratios calculated for these activities suggest that the magnitude of bias due to confounding is likely to be minimal. JF - Journal of Exposure Analysis and Environmental Epidemiology AU - Coble, J AU - Hoppin, JA AU - Engel, L AU - Elci, O C AU - Dosemeci, M AU - Lynch, C F AU - Alavanja, M AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Occupational Epidemiology Branch, 6120 Executive Boulevard, EPS8110, Rockville, MD 20892-7240, USA, jcoble@mail.nih.gov Y1 - 2002/11// PY - 2002 DA - Nov 2002 SP - 418 EP - 426 VL - 12 IS - 6 SN - 1053-4245, 1053-4245 KW - man KW - Pollution Abstracts; Health & Safety Science Abstracts; Toxicology Abstracts KW - X 24240:Miscellaneous KW - H 1000:Occupational Safety and Health KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18683406?accountid=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+Exposure+Analysis+and+Environmental+Epidemiology&rft.atitle=Prevalence+of+exposure+to+solvents%2C+metals%2C+grain+dust%2C+and+other+hazards+among+farmers+in+the+Agricultural+Health+Study&rft.au=Coble%2C+J%3BHoppin%2C+JA%3BEngel%2C+L%3BElci%2C+O+C%3BDosemeci%2C+M%3BLynch%2C+C+F%3BAlavanja%2C+M&rft.aulast=Coble&rft.aufirst=J&rft.date=2002-11-01&rft.volume=12&rft.issue=6&rft.spage=418&rft.isbn=&rft.btitle=&rft.title=Journal+of+Exposure+Analysis+and+Environmental+Epidemiology&rft.issn=10534245&rft_id=info:doi/10.1038%2Fsj.jea.7500248 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1038/sj.jea.7500248 ER - TY - JOUR T1 - The Origin, Fate, and Health Effects of Combustion By-Products: A Research Framework AN - 18637574; 5537439 AB - Incomplete combustion processes can emit organic pollutants, metals, and fine particles. Combustion by-products represent global human and environmental health challenges that are relevant not only in heavily industrialized nations, but also in developing nations where up to 90% of rural households rely on unprocessed biomass fuels for cooking, warmth, and light. These issues were addressed at the Seventh International Congress on Combustion By-Products, which convened 4-6 June 2001 in Research Triangle Park, North Carolina. This congress included a diverse group of multidisciplinary researchers and practitioners who discussed recent developments and future goals in the control of combustion by-products and their effects of exposure on human and ecologic health. Participants recommended that interdisciplinary, coordinated research efforts should be focused to capitalize on the important potential synergisms between efforts to reduce the adverse human health effects linked to exposures to combustion by-products and broader efforts to reduce greenhouse gas emissions and save energy through efficiency. In this article we summarize the principal findings and recommendations for research focus and direction. JF - Environmental Health Perspectives AU - Avakian, MD AU - Dellinger, B AU - Fiedler, H AU - Gullet, B AU - Koshland, C AU - Marklund, S AU - Oberdoerster, G AU - Safe, S AU - Sarofim, A AU - Smith, K R AU - Schwartz, D AU - Suk, WA AD - Division of Extramural Research and Training, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709, USA, suk@niehs.nih.gov Y1 - 2002/11// PY - 2002 DA - Nov 2002 SP - 1155 EP - 1162 VL - 110 IS - 11 SN - 0091-6765, 0091-6765 KW - fate KW - origin KW - Toxicology Abstracts KW - X 24250:Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18637574?accountid=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=The+Origin%2C+Fate%2C+and+Health+Effects+of+Combustion+By-Products%3A+A+Research+Framework&rft.au=Avakian%2C+MD%3BDellinger%2C+B%3BFiedler%2C+H%3BGullet%2C+B%3BKoshland%2C+C%3BMarklund%2C+S%3BOberdoerster%2C+G%3BSafe%2C+S%3BSarofim%2C+A%3BSmith%2C+K+R%3BSchwartz%2C+D%3BSuk%2C+WA&rft.aulast=Avakian&rft.aufirst=MD&rft.date=2002-11-01&rft.volume=110&rft.issue=11&rft.spage=1155&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 ER - TY - JOUR T1 - Shortening of RNA:DNA Hybrid in the Elongation Complex of RNA Polymerase Is a Prerequisite for Transcription Termination AN - 18634963; 5531646 AB - Passage of E. coli RNA polymerase through an intrinsic transcription terminator, which encodes an RNA hairpin followed by a stretch of uridine residues, results in quick dissociation of the elongation complex. We show that folding of the hairpin disrupts the three upstream base pairs of the 8 bp RNA:DNA hybrid, a major stability determinant in the complex. Shortening the weak rU:dA hybrid from 8 nt to 5 nt causes dissociation of the complex. During termination, the hairpin does not directly compete for base pairing with the 8 bp hybrid. Thus, melting of the hybrid seems to result from spatial restrictions in RNA polymerase that couple the hairpin formation with the disruption of the hybrid immediately downstream from the stem. Our results suggest that a similar mechanism disrupts elongation complexes of yeast RNA polymerase II in vitro. JF - Molecular Cell AU - Komissarova, N AU - Becker, J AU - Solter, S AU - Kireeva, M AU - Kashlev, M AD - NCI Center for Cancer Research, Frederick Cancer Research and Development Center, Frederick, MD 21702 USA, natkom@mail.ncifcrf.gov Y1 - 2002/11// PY - 2002 DA - Nov 2002 SP - 1151 EP - 1162 VL - 10 IS - 5 SN - 1097-2765, 1097-2765 KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - J 02726:RNA and ribosomes KW - N 14553:Transcription initiation, elongation & termination UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18634963?accountid=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+Cell&rft.atitle=Shortening+of+RNA%3ADNA+Hybrid+in+the+Elongation+Complex+of+RNA+Polymerase+Is+a+Prerequisite+for+Transcription+Termination&rft.au=Komissarova%2C+N%3BBecker%2C+J%3BSolter%2C+S%3BKireeva%2C+M%3BKashlev%2C+M&rft.aulast=Komissarova&rft.aufirst=N&rft.date=2002-11-01&rft.volume=10&rft.issue=5&rft.spage=1151&rft.isbn=&rft.btitle=&rft.title=Molecular+Cell&rft.issn=10972765&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 Hepatic Endothelial Carcinogen Riddelliine Induces Endothelial Apoptosis, Mitosis, S Phase, and p53 and Hepatocytic Vascular Endothelial Growth Factor Expression after Short-Term Exposure AN - 18634650; 5539404 AB - Riddelliineis a naturally occurring pyrrolizidine alkaloid found in certain poisonous rangeland plants of the western United States. In National Toxicology Program 2-year studies, riddelliine induced high incidences of hemangiosarcoma in the liver of F344/N rats (both sexes) and B6C3F1 mice (males). To understand this pathogenesis, we tested short-term effects of riddelliine. Three groups (control; 1.0 mg/kg/day, high dose used in the 2-year study; and 2.5 mg/kg/day) of seven male F344/N rats per group were terminated after 8 consecutive doses and 30 doses (6 weeks, excluding weekends). Serum vascular endothelial growth factor (VEGF), histological, immunohistochemical [factor VIII-related antigen/von Willebrand factor (fVIII-ra/vWf)], VEGF, VEGF receptor-2 (VEGFR2), glutathione S-transferase- pi , S-phase (BrdU), p53, apoptosis, and ultrastructural evaluations were performed on the liver. Following 8 doses of 1.0 and 2.5 mg/kg/day, increased numbers of apoptotic and S-phase nuclei appeared in hepatocytes and endothelial cells. Following 30 doses of 1.0 and 2.5 mg/kg/day, hepatocytes exhibited reduced mitosis, fewer S-phase nuclei, increased hypertrophy, and fatty degeneration, while endothelial cells showed karyomegaly, cytomegaly, decreased apoptosis, more S-phase nuclei, and p53 positivity. Hepatocytes of treated animals expressed higher VEGF immunopositivity. That altered endothelial cells were fVIII-ra/vWf and VEGFR2 positive confirmed their identity. These changes may have promoted hemangiosarcoma development upon long-term exposure through endothelial adduct formation, apoptosis, proliferation of endothelial cells having undamaged and/or damaged DNA, and mutation. Endothelial proliferation may also have been promoted through endothelial arrest at S phase, which was associated with endothelial karyo- and cytomegaly, resulting in hepatocytic hypoxia, triggering VEGF induction. [copy ] 2002 Elsevier Science (USA). JF - Toxicology and Applied Pharmacology AU - Nyska, A AU - Moomaw, C R AU - Foley, J F AU - Maronpot, R R AU - Malarkey, DE AU - Cummings, CA AU - Peddada, S AU - Moyer, C F AU - Allen, D G AU - Travlos, G AU - Chan, P C AD - Laboratory of Experimental Pathology, MD B3-06, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709, nyska@niehs.nih.gov Y1 - 2002/11/01/ PY - 2002 DA - 2002 Nov 01 SP - 153 EP - 164 PB - Academic Press VL - 184 IS - 3 SN - 0041-008X, 0041-008X KW - Riddelliine KW - p53 protein KW - rats KW - vascular endothelial growth factor KW - Toxicology Abstracts KW - X 24112:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18634650?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+Applied+Pharmacology&rft.atitle=The+Hepatic+Endothelial+Carcinogen+Riddelliine+Induces+Endothelial+Apoptosis%2C+Mitosis%2C+S+Phase%2C+and+p53+and+Hepatocytic+Vascular+Endothelial+Growth+Factor+Expression+after+Short-Term+Exposure&rft.au=Nyska%2C+A%3BMoomaw%2C+C+R%3BFoley%2C+J+F%3BMaronpot%2C+R+R%3BMalarkey%2C+DE%3BCummings%2C+CA%3BPeddada%2C+S%3BMoyer%2C+C+F%3BAllen%2C+D+G%3BTravlos%2C+G%3BChan%2C+P+C&rft.aulast=Nyska&rft.aufirst=A&rft.date=2002-11-01&rft.volume=184&rft.issue=3&rft.spage=153&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+Applied+Pharmacology&rft.issn=0041008X&rft_id=info:doi/10.1006%2Ftaap.2002.9485 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1006/taap.2002.9485 ER - TY - JOUR T1 - MHC class I and class II presentation of tumor antigen in retrovirally and adenovirally transduced dendritic cells AN - 18628411; 5527416 AB - The unique antigen-presenting capabilities of dendritic cells (DCs) make them an attractive means with which to initiate an antitumor immune response. Using DCs transduced with tumor antigens for immunotherapy has several theoretical advantages over peptidepulsed DCs including the possibility that transduced DCs are capable of presenting epitopes on both class I and class II MHC molecules. To test this theory, we inserted the human tumor antigen gp100 into mouse DCs transgenic for HLA-DR beta 1*0401 using either adenoviral vector or a VSV-G pseudotyped retroviral vector. DCs transduced with tumor antigen were able to be recognized by both a murine CD8 super(+) T-cell clone and a murine CD4 super(+) T-cell line in a cytokine release assay, thereby demonstrating presentation of both MHC class I and class II gp100 epitopes. This study describes the simultaneous presentation of a tumor-associated antigen to both CD4 super(+) and CD8 super(+) T cells and lends support to the use of gene-modified DCs as a means to initiate both CD4 super(+) and CD8 super(+) antitumor responses. JF - Cancer Gene Therapy AU - Sloan, J M AU - Kershaw, M H AU - Touloukian, CE AU - Lapointe, R AU - Robbins, P F AU - Restifo, N P AU - Hwu, P AD - Room 2B42 Building 10, National Institutes of Health, Bethesda, MD 20892, USA, patrick_hwu@nih.gov Y1 - 2002/11// PY - 2002 DA - Nov 2002 SP - 946 EP - 950 VL - 9 IS - 11 SN - 0929-1903, 0929-1903 KW - CD4 antigen KW - CD8 antigen KW - DR determinant KW - class I molecules KW - class II molecules KW - histocompatibility antigen HLA KW - man KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33170:Cellular based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18628411?accountid=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+Gene+Therapy&rft.atitle=MHC+class+I+and+class+II+presentation+of+tumor+antigen+in+retrovirally+and+adenovirally+transduced+dendritic+cells&rft.au=Sloan%2C+J+M%3BKershaw%2C+M+H%3BTouloukian%2C+CE%3BLapointe%2C+R%3BRobbins%2C+P+F%3BRestifo%2C+N+P%3BHwu%2C+P&rft.aulast=Sloan&rft.aufirst=J&rft.date=2002-11-01&rft.volume=9&rft.issue=11&rft.spage=946&rft.isbn=&rft.btitle=&rft.title=Cancer+Gene+Therapy&rft.issn=09291903&rft_id=info:doi/10.1038%2Fsj.cgt.7700509 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1038/sj.cgt.7700509 ER - TY - JOUR T1 - The P1 plasmid in action: time-lapse photomicroscopy reveals some unexpected aspects of plasmid partition AN - 18623839; 5539568 AB - The prophage of bacteriophage P1 is a low copy number plasmid in Escherichia coli and is segregated to daughter cells by an active partition system. The dynamics of the partition process have now been successfully followed by time-lapse photomicroscopy. The process appears to be fundamentally different from that previously inferred from statistical analysis of fixed cells. A focus containing several plasmid copies is captured at the cell center. Immediately before cell division, the copies eject bi-directionally along the long axis of the cell. Cell division traps one or more plasmid copies in each daughter cell. These copies are free to move, associate, and disassociate. Later, they are captured to the new cell center to re-start the cycle. Studies with mutants suggest that the ability to segregate accurately at a very late stage in the cell cycle is dependent on a novel ability of the plasmid to control cell division. Should segregation be delayed, cell division is also delayed until segregation is successfully completed. [copy ] 2002 Elsevier Science (USA) JF - Plasmid AU - Li, Y AU - Austin, S AD - Gene Regulation and Chromosome Biology Laboratory, Division of Basic Sciences, NCI-Frederick, Frederick, MD 21702-1201, USA Y1 - 2002/11// PY - 2002 DA - Nov 2002 SP - 174 EP - 178 PB - Academic Press VL - 48 IS - 3 SN - 0147-619X, 0147-619X KW - plasmid P1 KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - J 02760:Plasmids KW - G 07320:Bacterial genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18623839?accountid=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=Plasmid&rft.atitle=The+P1+plasmid+in+action%3A+time-lapse+photomicroscopy+reveals+some+unexpected+aspects+of+plasmid+partition&rft.au=Li%2C+Y%3BAustin%2C+S&rft.aulast=Li&rft.aufirst=Y&rft.date=2002-11-01&rft.volume=48&rft.issue=3&rft.spage=174&rft.isbn=&rft.btitle=&rft.title=Plasmid&rft.issn=0147619X&rft_id=info:doi/10.1016%2FS0147-619X%2802%2900104-X LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0147-619X(02)00104-X ER - TY - JOUR T1 - Redirecting Migration of T Cells to Chemokine Secreted from Tumors by Genetic Modification with CXCR2 AN - 18620633; 5528707 AB - T-cell-based immunotherapies provide a promising means of cancer treatment although durable antitumor responses are infrequent. A potential reason for these shortcomings may lie in the observed lack of trafficking of specific T cells to tumor. Our increasing knowledge of the process of trafficking involving adhesion molecules and chemokines affords us the opportunity to intervene and correct deficiencies in this process. Chemokines can be expressed by a range of tumors and may serve as suitable targets for directing specific T cells toward tumor. We initially sought to identify which chemokines were produced by a range of human tumor cell lines, and which chemokines and chemokine receptors were expressed by cultured T cells. We identified two chemokines: Growth-Regulated Oncogene- alpha (Gro- alpha ; CXCL1) and Regulated on Activation Normal T Cell-Expressed and Secreted (RANTES; CCL5), to be secreted by several human tumor cell lines. Expression was also detected in fine-needle aspirates of melanoma from patients. In addition, we determined the expression of several chemokine receptors on cultured human T cells including CCR1, CCR2, CCR4, CCR5, CXCR3, and CXCR4. Cultured, activated human T cells expressed the chemokines lymphotactin (XCL1), RANTES, macrophage inflammatory protein-1 alpha (MIP-1 alpha ; CCL3) and MIP-1 beta (CCL4), but no appreciable Gro- alpha . In a strategy to direct T cells toward chemokines expressed by tumors we chose Gro- alpha as the target chemokine because it was produced by tumor and not by T cells themselves. However, T cells did not express the receptor for Gro- alpha , CXCR2, and therefore, T cells were transduced with a retroviral vector encoding CXCR2. Calcium ion mobilization, an important first step in chemokine receptor signaling, was subsequently demonstrated in transduced T cells in response to Gro- alpha . In addition, Gro- alpha was chemotactic for T cells expressing CXCR2 in vitro toward both recombinant protein and tumor-derived chemokine. Interestingly we demonstrate, for the first time, that Gro- alpha was able to induce interferon- gamma (IFN- gamma ) secretion from transduced T cells, thereby extending our knowledge of other potential functions of CXCR2. This study demonstrates the feasibility of redirecting the migration properties of T cells toward chemokines secreted by tumors. JF - Human Gene Therapy AU - Kershaw, M H AU - Wang, Gang AU - Westwood, JA AU - Pachynski, R K AU - Tiffany, H L AU - Marincola, F M AU - Wang, Ena AU - Young, HA AU - Murphy, P M AU - Hwu, P AD - Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, Room 2B42, Bethesda, MD 20892, USA, Patrick_Hwu@nih.gov Y1 - 2002/11/01/ PY - 2002 DA - 2002 Nov 01 SP - 1971 EP - 1980 VL - 13 IS - 16 SN - 1043-0342, 1043-0342 KW - CXCR2 protein KW - gamma -Interferon KW - man KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18620633?accountid=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=Redirecting+Migration+of+T+Cells+to+Chemokine+Secreted+from+Tumors+by+Genetic+Modification+with+CXCR2&rft.au=Kershaw%2C+M+H%3BWang%2C+Gang%3BWestwood%2C+JA%3BPachynski%2C+R+K%3BTiffany%2C+H+L%3BMarincola%2C+F+M%3BWang%2C+Ena%3BYoung%2C+HA%3BMurphy%2C+P+M%3BHwu%2C+P&rft.aulast=Kershaw&rft.aufirst=M&rft.date=2002-11-01&rft.volume=13&rft.issue=16&rft.spage=1971&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Insect Cells as a Factory to Produce Adeno-Associated Virus Type 2 Vectors AN - 18616503; 5528704 AB - Recombinant adeno-associated viruses (rAAV) are produced transiently in mammalian cells usually by co-transfecting two or three plasmids containing AAV genes, adenovirus helper genes, and a vector genome. Expansion and transfection of adherent cells limit the scale of rAAV production. Efficient transfection is performed with cells on solid support media such as tissue culture plates. A large animal study or a human clinical trial may require 10 super(15) particles of vector, depending on dose. To generate this quantity of rAAV by transfection, more than 10 super(11) HEK293 cells may be needed, which would require about 5000 x 175 cm super(2) flasks. The ability to scale up rAAV production by these methods severely restricts the commercialization and use of AAV vectors. A recombinant baculovirus derived from the Autographa californica nuclear polyhedrosis virus is widely employed for large-scale production of heterologous proteins in cultured insect cells and may provide an attractive alternative. Toward this goal, we have explored the production of rAAV in invertebrate cells. Sf9 cells may be coinfected in suspension cultures with three recombinant baculoviruses (a Rep-baculovirus, a VP-baculovirus, and an AAV ITR vector genome baculovirus) and, 3 days later, rAAV is recovered. The particles produced are indistinguishable from 293 cell-produced rAAV, as determined on the basis of physical properties and biologic activities. Particles produced by either method were composed of similar proteins and nucleic acid. The yield of genome-containing particles produced per Sf9 cell approached 5 x 10 super(4), thus, 1000 ml of cultured Sf9 cells produced the equivalent of between 500 to 1000 x 175 cm super(2) flasks of 293 cells. This robust system provides a simple, cost-effective method for AAV vector production. JF - Human Gene Therapy AU - Urabe, M AU - Ding, C AU - Kotin, R M AD - Laboratory of Biochemical Genetics, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10, Room 7N264, 10 Center Drive, MSC 1654, Bethesda, MD 20892-1654, USA, kotinr@nhlbi.nih.gov Y1 - 2002/11/01/ PY - 2002 DA - 2002 Nov 01 SP - 1935 EP - 1943 VL - 13 IS - 16 SN - 1043-0342, 1043-0342 KW - Alfalfa looper KW - Insects KW - Sf9 cells KW - man KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Entomology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Z 05161:Cell & tissue culture KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews KW - W4 120:Genetic Engineering in Medicine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18616503?accountid=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=Insect+Cells+as+a+Factory+to+Produce+Adeno-Associated+Virus+Type+2+Vectors&rft.au=Urabe%2C+M%3BDing%2C+C%3BKotin%2C+R+M&rft.aulast=Urabe&rft.aufirst=M&rft.date=2002-11-01&rft.volume=13&rft.issue=16&rft.spage=1935&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Distribution and licensing of drug discovery tools - NIH perspectives AN - 18610825; 5513154 AB - Now, more than ever, drug discovery conducted at industrial or academic facilities requires rapid access to state-of-the-art research tools. Unreasonable restrictions or delays in the distribution or use of such tools can stifle new discoveries, thus limiting the development of future biomedical products. In grants and its own research programs the National Institutes of Health (NIH) is implementing its new policy to facilitate the exchanges of these tools for research discoveries and product development. JF - Drug Discovery Today AU - Ferguson, S M AU - Kim, J P AD - Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville MD 20852, USA Y1 - 2002/11/01/ PY - 2002 DA - 2002 Nov 01 SP - 1102 EP - 1106 PB - Elsevier Science Ltd VL - 7 IS - 21 SN - 1359-6446, 1359-6446 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W 30965:Miscellaneous, Reviews KW - W3 33000:General topics and reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18610825?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+Discovery+Today&rft.atitle=Distribution+and+licensing+of+drug+discovery+tools+-+NIH+perspectives&rft.au=Ferguson%2C+S+M%3BKim%2C+J+P&rft.aulast=Ferguson&rft.aufirst=S&rft.date=2002-11-01&rft.volume=7&rft.issue=21&rft.spage=1102&rft.isbn=&rft.btitle=&rft.title=Drug+Discovery+Today&rft.issn=13596446&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - The fundamental contribution of phages to GAS evolution, genome diversification and strain emergence AN - 18609635; 5513644 AB - The human bacterial pathogen group A Streptococcus (GAS) causes many different diseases including pharyngitis, tonsillitis, impetigo, scarlet fever, streptococcal toxic shock syndrome, necrotizing fasciitis and myositis, and the post-infection sequelae glomerulonephritis and rheumatic fever. The frequency and severity of GAS infections increased in the 1980s and 1990s, but the cause of this increase is unknown. Recently, genome sequencing of serotype M1, M3 and M18 strains revealed many new proven or putative virulence factors that are encoded by phages or phage-like elements. Importantly, these genetic elements account for an unexpectedly large proportion of the difference in gene content between the three strains. These new genome-sequencing studies have provided evidence that temporally and geographically distinct epidemics, and the complex array of GAS clinical presentations, might be related in part to the acquisition or evolution of phage-encoded virulence factors. We anticipate that new phage-encoded virulence factors will be identified by sequencing the genomes of additional GAS strains, including organisms non-randomly associated with particular clinical syndromes. JF - Trends in Microbiology AU - Banks, D J AU - Beres, S B AU - Musser, J M AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT 59840, USA Y1 - 2002/11/01/ PY - 2002 DA - 2002 Nov 01 SP - 515 EP - 521 PB - Elsevier Science Ltd VL - 10 IS - 11 SN - 0966-842X, 0966-842X KW - streptococci KW - Microbiology Abstracts B: Bacteriology KW - J 02832:Antigenic properties and virulence UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18609635?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Trends+in+Microbiology&rft.atitle=The+fundamental+contribution+of+phages+to+GAS+evolution%2C+genome+diversification+and+strain+emergence&rft.au=Banks%2C+D+J%3BBeres%2C+S+B%3BMusser%2C+J+M&rft.aulast=Banks&rft.aufirst=D&rft.date=2002-11-01&rft.volume=10&rft.issue=11&rft.spage=515&rft.isbn=&rft.btitle=&rft.title=Trends+in+Microbiology&rft.issn=0966842X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Solution Structure of the Phosphoryl Transfer Complex between the Cytoplasmic A Domain of the Mannitol Transporter II super(Mannitol) and HPr of the Escherichia coli Phosphotransferase System AN - 18608780; 5470923 AB - The solution structure of the complex between the cytoplasmic A domain (IIA super(Mtl)) of the mannitol transporter II super(Mannitol) and the histidine-containing phosphocarrier protein (HPr) of the Escherichia coli phosphotransferase system has been solved by NMR, including the use of conjoined rigid body/torsion angle dynamics, and residual dipolar couplings, coupled with cross-validation, to permit accurate orientation of the two proteins. A convex surface on HPr, formed by helices 1 and 2, interacts with a complementary concave depression on the surface of IIA super(Mtl) formed by helix 3, portions of helices 2 and 4, and [beta]-strands 2 and 3. The majority of intermolecular contacts are hydrophobic, with a small number of electrostatic interactions at the periphery of the interface. The active site histidines, His-15 of HPr and His-65 of IIA super(Mtl), are in close spatial proximity, and a pentacoordinate phosphoryl transition state can be readily accommodated with no change in protein-protein orientation and only minimal perturbations of the backbone immediately adjacent to the histidines. Comparison with two previously solved structures of complexes of HPr with partner proteins of the phosphotransferase system, the N-terminal domain of enzyme I (EIN) and enzyme IIA super(Glucose) (IIA super(Glc)), reveals a number of common features despite the fact that EIN, IIA super(Glc), and IIA super(Mtl) bear no structural resemblance to one another. Thus, entirely different underlying structural elements can form binding surfaces for HPr that are similar in terms of both shape and residue composition. These structural comparisons illustrate the roles of surface and residue complementarity, redundancy, incremental build-up of specificity and conformational side chain plasticity in the formation of transient specific protein-protein complexes in signal transduction pathways. JF - Journal of Biological Chemistry AU - Cornilescu, G AU - Lee, B R AU - Cornilescu, C C AU - Wang, G AU - Peterkofsky, A AU - Clore, G M AD - Laboratory of Chemical Physics, NIDDK, and Laboratories of Cell Biology and Biophysical Chemistry, NHLBI, National Institutes of Health, Bethesda, Maryland, mariusc@intra.niddk.nih.gov. Y1 - 2002/11/01/ PY - 2002 DA - 2002 Nov 01 SP - 42289 EP - 42298 VL - 277 IS - 44 SN - 0021-9258, 0021-9258 KW - HPr protein KW - histidine KW - mannitol KW - phosphotransferase KW - Microbiology Abstracts B: Bacteriology KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18608780?accountid=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=Solution+Structure+of+the+Phosphoryl+Transfer+Complex+between+the+Cytoplasmic+A+Domain+of+the+Mannitol+Transporter+II+super%28Mannitol%29+and+HPr+of+the+Escherichia+coli+Phosphotransferase+System&rft.au=Cornilescu%2C+G%3BLee%2C+B+R%3BCornilescu%2C+C+C%3BWang%2C+G%3BPeterkofsky%2C+A%3BClore%2C+G+M&rft.aulast=Cornilescu&rft.aufirst=G&rft.date=2002-11-01&rft.volume=277&rft.issue=44&rft.spage=42289&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 - Postgenomic Analysis of Four Novel Antigens of Group A Streptococcus: Growth Phase-Dependent Gene Transcription and Human Serologic Response AN - 18603135; 5470126 AB - Analysis of three group A Streptococcus genomes (serotypes M1, M3, and M18) recently identified four previously undescribed genes that encode extracellular proteins. Each of these genes encode proteins with an LPXTG amino acid motif that covalently links many virulence factors produced by gram- positive bacteria to the cell surface. Western immunoblot analysis of serum samples obtained from 80 patients with invasive infections, noninvasive soft tissue infections, pharyngitis, and rheumatic fever indicated that these four proteins are expressed in vivo. However, the level of gene transcript and the time of maximal gene transcription varied in representative serotype M1, M3, and M18 strains. Surface expression of two proteins was confirmed by flow cytometry. Studies using a mouse infection model suggest that antibodies specific for one of the proteins (Spy0843) may contribute to a protective host immune response against a serotype M1 infection. These results are additional evidence that postgenomic strategies provide new ways to identify and investigate novel bacterial proteins that may participate in host-pathogen interactions or serve as targets for therapeutics research. JF - Journal of Bacteriology AU - Reid, S D AU - Green, N M AU - Sylva, G L AU - Voyich, J M AU - Stenseth, E T AU - DeLeo AU - Palzkill, T AU - Low, DE AU - Hill, H R AU - Musser, J M AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th St., Hamilton, MT 59840, jmusser@niaid.nih.gov Y1 - 2002/11// PY - 2002 DA - Nov 2002 SP - 6316 EP - 6324 VL - 184 IS - 22 SN - 0021-9193, 0021-9193 KW - Spy0843 protein KW - streptococci KW - Microbiology Abstracts B: Bacteriology KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18603135?accountid=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=Postgenomic+Analysis+of+Four+Novel+Antigens+of+Group+A+Streptococcus%3A+Growth+Phase-Dependent+Gene+Transcription+and+Human+Serologic+Response&rft.au=Reid%2C+S+D%3BGreen%2C+N+M%3BSylva%2C+G+L%3BVoyich%2C+J+M%3BStenseth%2C+E+T%3BDeLeo%3BPalzkill%2C+T%3BLow%2C+DE%3BHill%2C+H+R%3BMusser%2C+J+M&rft.aulast=Reid&rft.aufirst=S&rft.date=2002-11-01&rft.volume=184&rft.issue=22&rft.spage=6316&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.184.22.6316-6324.2002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/JB.184.22.6316-6324.2002 ER - TY - JOUR T1 - Analysis of methamphetamine-induced changes in the expression of integrin family members in the cortex of wild-type and c-fos knockout mice. AN - 1859406578; 12709300 AB - Methamphetamine (METH) is an illicit drug that is also neurotoxic. Recent studies suggest that in addition to dopamine terminal degeneration in the striatum, METH causes apoptosis in cortical neurons. Earlier, we showed that c-fos knockout mice are more susceptible to the toxic effects of the drug. In order to identify possible pathways related to these differences, we have used cDNA array that provided us with a comprehensive catalog of METH affected genes. In the present study, we report on the effects of METH on the integrin family members that were shown to be involved in intracellular signaling cascades effecting cell survival. We found that, in comparison to wild type animals, c-fos knockout mice have lower baseline levels of the integrins in the cortex. Moreover, METH caused time-dependent decreases in their transcripts in both strains of mice. Quantitative RT-PCR confirmed the changes obtained in cDNA array. These findings are discussed in view of the possible role of integrins in METH-induced toxic effects on the cortical neurons. JF - Neurotoxicity research AU - Betts, Elizabeth S. AU - Krasnova, Irina N. AU - McCoy, Michael T. AU - Ladenheim, Bruce AU - Cadet, Jean Lud AD - Molecular Neuropsychiatry Section, National Institute on Drug Abuse, Intramural Research Program, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. PY - 2002 SP - 617 EP - 623 VL - 4 IS - 7-8 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859406578?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurotoxicity+research&rft.atitle=Analysis+of+methamphetamine-induced+changes+in+the+expression+of+integrin+family+members+in+the+cortex+of+wild-type+and+c-fos+knockout+mice.&rft.au=Betts%2C+Elizabeth+S.%3BKrasnova%2C+Irina+N.%3BMcCoy%2C+Michael+T.%3BLadenheim%2C+Bruce%3BCadet%2C+Jean+Lud&rft.aulast=Betts&rft.aufirst=Elizabeth&rft.date=2002-11-01&rft.volume=4&rft.issue=7-8&rft.spage=617&rft.isbn=&rft.btitle=&rft.title=Neurotoxicity+research&rft.issn=1476-3524&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2003-04-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation and mode of action of the second small RNA activator of RpoS translation, RprA AN - 18567637; 5529009 AB - Translation of the stationary phase sigma factor RpoS is stimulated by at least two small RNAs, DsrA and RprA. DsrA disrupts an inhibitory secondary structure in the rpoS leader mRNA by pairing with the upstream RNA. Mutations in rprA and compensating mutations in the rpoS leader demonstrate that RprA interacts with the same region of the RpoS leader as DsrA. This is the first example of two different small RNAs regulating a common target. Regulation of these RNAs differs. DsrA synthesis is increased at low temperature. We find that RprA synthesis is regulated by the RcsC/RcsB phosphorelay system, previously found to regulate capsule synthesis and promoters of ftsZ and osmC. An rcsB null mutation abolishes the basal level, whereas mutations in rcsC that activate capsule synthesis also activate expression of the rprA promoter. An essential site with similarity to other RcsB-regulated promoters was defined in the rprA promoter. Activation of the RcsC/RcsB system leads to increased RpoS synthesis, in an RprA-dependent fashion. This work suggests a new signal for RpoS translation and extends the global regulation effected by the RcsC /RcsB system to coregulation of RpoS with capsule and FtsZ. JF - Molecular Microbiology AU - Majdalani, N AU - Hernandez, D AU - Gottesman, S AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4264, USA., susang@helix.nih.gov Y1 - 2002/11// PY - 2002 DA - Nov 2002 SP - 813 EP - 826 PB - Blackwell Science Ltd VL - 46 IS - 3 SN - 0950-382X, 0950-382X KW - RpoS protein KW - ftsZ gene KW - osmC gene KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - J 02726:RNA and ribosomes KW - N 14400:General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18567637?accountid=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=Regulation+and+mode+of+action+of+the+second+small+RNA+activator+of+RpoS+translation%2C+RprA&rft.au=Majdalani%2C+N%3BHernandez%2C+D%3BGottesman%2C+S&rft.aulast=Majdalani&rft.aufirst=N&rft.date=2002-11-01&rft.volume=46&rft.issue=3&rft.spage=813&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1046%2Fj.1365-2958.2002.03203.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1046/j.1365-2958.2002.03203.x ER - TY - JOUR T1 - The segregation of the Escherichia coli origin and terminus of replication AN - 18562920; 5529039 AB - Escherichia coli chromosome replication forks are tethered to the cell centre. Two opposing models describe how the chromosomes segregate. In the extrusion-capture model, newly replicated DNA is fed bi-directionally from the forks toward the cell poles, forming new chromosomes in each cell half. Starting with the origins, chromosomal regions segregate away from their sisters progressively as they are replicated. The termini segregate last. In the sister chromosome cohesion model, replication produces sister chromosomes that are paired along much of their length. The origins and most other chromosomal regions remain paired until late in the replication cycle, and all segregate together. We use a combination of microscopy and flow cytometry to determine the relationship of origin and terminus segregation to the cell cycle. Origin segregation frequently follows closely after initiation, in strong support of the extrusion-capture model. The spatial disposition of the origin and terminus sequences also fits this model. Terminus segregation occurs extremely late in the cell cycle as the daughter cells separate. As the septum begins to invaginate, the termini of the completed sister chromosomes are transiently held apart at the cell centre, on opposite sides of the cell. This may facilitate the resolution of topological linkages between the chromosomes. JF - Molecular Microbiology AU - Li, Y AU - Sergueev, K AU - Austin, S AD - Gene Regulation and Chromosome Biology Laboratory, Center for Cancer Research, NCI-Frederick, Frederick, Maryland 21702-1201, USA., austin@ncifcrf.gov Y1 - 2002/11// PY - 2002 DA - Nov 2002 SP - 985 EP - 996 PB - Blackwell Science Ltd VL - 46 IS - 4 SN - 0950-382X, 0950-382X KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - J 02725:DNA KW - N 14650:General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18562920?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Microbiology&rft.atitle=The+segregation+of+the+Escherichia+coli+origin+and+terminus+of+replication&rft.au=Li%2C+Y%3BSergueev%2C+K%3BAustin%2C+S&rft.aulast=Li&rft.aufirst=Y&rft.date=2002-11-01&rft.volume=46&rft.issue=4&rft.spage=985&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1046%2Fj.1365-2958.2002.03234.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1046/j.1365-2958.2002.03234.x ER - TY - JOUR T1 - Insights into negative modulation of E. coli replication initiation from the structure of SeqA-hemimethylated DNA complex AN - 18552471; 5524419 AB - The SeqA protein binds clusters of fully methylated or hemimethylated GATC sequences at oriC and negatively modulates the initiation of DNA replication. We find that SeqA can be proteolytically cleaved into an N-terminal multimerization and a C-terminal DNA-binding domain and have determined the crystal structure of the C-terminal domain in complex with a hemimethylated GATC site. SeqA makes direct hydrogen bonds and van der Waals contacts with the hemimethylated A-T base pair in addition to interactions with the surrounding bases and DNA backbone. The tetrameric protein-DNA complex found in the crystal suggests that SeqA binds multiple GATC sites on separate DNA duplexes, altering the overall DNA topology and sequestering oriC from replication initiation. JF - Nature Structural Biology AU - Guarne, A AU - Zhao, Q AU - Ghirlando, R AU - Yang, W AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA, wei.yang@nih.gov Y1 - 2002/11// PY - 2002 DA - Nov 2002 SP - 839 EP - 843 VL - 9 IS - 11 SN - 1072-8368, 1072-8368 KW - SeqA protein KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - J 02725:DNA KW - N 14650:General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18552471?accountid=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=Nature+Structural+Biology&rft.atitle=Insights+into+negative+modulation+of+E.+coli+replication+initiation+from+the+structure+of+SeqA-hemimethylated+DNA+complex&rft.au=Guarne%2C+A%3BZhao%2C+Q%3BGhirlando%2C+R%3BYang%2C+W&rft.aulast=Guarne&rft.aufirst=A&rft.date=2002-11-01&rft.volume=9&rft.issue=11&rft.spage=839&rft.isbn=&rft.btitle=&rft.title=Nature+Structural+Biology&rft.issn=10728368&rft_id=info:doi/10.1038%2Fnsb857 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1038/nsb857 ER - TY - JOUR T1 - Confirmation by 16S rRNA PCR of the COBAS AMPLICOR CT/NG Test for Diagnosis of Neisseria gonorrhoeae Infection in a Low-Prevalence Population AN - 18510177; 5472412 AB - The COBAS AMPLICOR CT/NG test is widely used for the diagnosis of Neisseria gonorrhoeae infection using genital swabs or urine samples. Although highly specific, cross-reactivity occurs with some nonpathogenic strains of Neisseria and Lactobacillus species. In low-prevalence populations, even highly specific assays may require confirmatory testing of positive results. We assessed the positive predictive value (PPV) of this test in a low-prevalence (0.5%) setting. Genital and urine specimens testing positive using the COBAS AMPLICOR NG test were retested using an investigational 16S rRNA PCR assay. Additionally, 737 specimens were tested in parallel by both culture and the above PCR protocol. Of 9,772 specimens tested in-house, 168 were positive by the AMPLICOR test; in addition, 62 AMPLICOR-positive specimens were referred to our laboratory for confirmatory testing, yielding 230 positive specimens. Of these, 72 were confirmed positive by 16S rRNA PCR, yielding a specificity of 98.7% and a PPV of 31.3%. Specificity was similar for all specimen types, whereas PPV varied with prevalence: specimens from males, females, urine specimens, and genital swabs had PPVs of 70.8, 13.3, 51.9, and 20.1%, respectively. The PPV was higher when the initial AMPLICOR optical density (OD) was [>=]3.5 versus initial and repeat OD readings in an equivocal zone of [>=]0.2 to =]0.2 and =]2.0 and =]3.5, with 3.7, 20, and 33.3% confirmed positive, respectively (P = 0.004). Comparing PCR to culture as the "gold standard," specificity increased from 96.8 to 99.9% when 16S rRNA PCR was performed on specimens positive by the COBAS AMPLICOR NG test. Confirmatory testing with a more specific method such as 16S rRNA PCR should be considered in low-prevalence populations, especially for specimens with an OD in the equivocal zone. JF - Journal of Clinical Microbiology AU - Diemert, D J AU - Libman, MD AU - Lebel, P AD - Malaria Vaccine Development Unit, National Institute of Allergy and Infectious Diseases, Twinbrook I, Room 1123, 5640 Fishers Ln., Rockville, MD 20852, ddiemert@niaid.nih.gov Y1 - 2002/11// PY - 2002 DA - Nov 2002 SP - 4056 EP - 4059 VL - 40 IS - 11 SN - 0095-1137, 0095-1137 KW - COBAS AMPLICOR CT/NG test KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Microbiology Abstracts B: Bacteriology KW - W4 130:General Biomedical Engineering: Tools & Techniques KW - J 02704:Enumeration KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18510177?accountid=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=Confirmation+by+16S+rRNA+PCR+of+the+COBAS+AMPLICOR+CT%2FNG+Test+for+Diagnosis+of+Neisseria+gonorrhoeae+Infection+in+a+Low-Prevalence+Population&rft.au=Diemert%2C+D+J%3BLibman%2C+MD%3BLebel%2C+P&rft.aulast=Diemert&rft.aufirst=D&rft.date=2002-11-01&rft.volume=40&rft.issue=11&rft.spage=4056&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Microbiology&rft.issn=00951137&rft_id=info:doi/10.1128%2FJCM.40.11.4056-4059.2002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/JCM.40.11.4056-4059.2002 ER - TY - JOUR T1 - Toll-Like Receptor 4-Dependent Activation of Dendritic Cells by beta -Defensin 2 AN - 18506127; 5476459 AB - beta -Defensins are small antimicrobial peptides of the innate immune system produced in response to microbial infection of mucosal tissue and skin. We demonstrate that murine beta -defensin 2 (mDF2 beta ) acts directly on immature dendritic cells as an endogenous ligand for Toll-like receptor 4 (TLR-4), inducing up-regulation of costimulatory molecules and dendritic cell maturation. These events, in turn, trigger robust, type 1 polarized adaptive immune responses in vivo, suggesting that mDF2 beta may play an important role in immunosurveillance against pathogens and, possibly, self antigens or tumor antigens. JF - Science (Washington) AU - Biragyn, A AU - Ruffini, P A AU - Leifer, CA AU - Klyushnenkova, E AU - Shakhov, A AU - Chertov, O AU - Shirakawa, A K AU - Farber, J M AU - Segal, D M AU - Oppenheim, J J AU - Kwak, L W AD - Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, MD 20892, USA, arya@mail.ncifcrf.gov Y1 - 2002/11/01/ PY - 2002 DA - 2002 Nov 01 SP - 1025 EP - 1029 PB - American Association for the Advancement of Science VL - 298 IS - 5595 SN - 0036-8075, 0036-8075 KW - TLR4 protein KW - Toll-like receptors KW - mice KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - F 06801:Bacteria KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18506127?accountid=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=Toll-Like+Receptor+4-Dependent+Activation+of+Dendritic+Cells+by+beta+-Defensin+2&rft.au=Biragyn%2C+A%3BRuffini%2C+P+A%3BLeifer%2C+CA%3BKlyushnenkova%2C+E%3BShakhov%2C+A%3BChertov%2C+O%3BShirakawa%2C+A+K%3BFarber%2C+J+M%3BSegal%2C+D+M%3BOppenheim%2C+J+J%3BKwak%2C+L+W&rft.aulast=Biragyn&rft.aufirst=A&rft.date=2002-11-01&rft.volume=&rft.issue=&rft.spage=2953&rft.isbn=&rft.btitle=&rft.title=Electronics+Newsweekly&rft.issn=19441630&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 - Specific Immune Responses and Enhancement of Murine Pulmonary Clearance of Moraxella catarrhalis by Intranasal Immunization with a Detoxified Lipooligosaccharide Conjugate Vaccine AN - 18500239; 5464249 AB - Moraxella catarrhalis is an important human mucosal pathogen. This study investigated the effect of intranasal immunization with a detoxified- lipooligosaccharide-cross-reactive mutant of diphtheria toxin (dLOS-CRM) vaccine candidate on pulmonary clearance following an aerosol challenge of mice with M. catarrhalis. Intranasal immunization with dLOS-CRM plus cholera toxin induced a significantly dose-dependent increase of immunoglobulin A (IgA) and IgG in the nasal wash, lung lavage fluid, saliva, and fecal extract. In addition, serum IgG, IgM, and IgA against LOS of M. catarrhalis were detected. LOS-specific antibody-forming cells were found in the nasal passages, spleens, nasally associated lymphoid tissues, cervical lymph nodes, lungs, and Peyer's patches using an enzyme-linked immunospot assay. The dLOS-CRM vaccine induced a significant bacterial clearance (70 to 90%) of both homologous and heterologous strains in the lungs compared to that observed in the controls (P < 0.01). Intriguingly, intranasal immunization with dLOS-CRM showed a higher level of bacterial clearance compared with subcutaneous injections with dLOS-CRM. These data indicate that dLOS-CRM induces specific mucosal and systemic immunity through intranasal immunization and also provides effective bacterial clearance. On the basis of these results, we believe that dLOS-CRM should undergo continued testing to determine whether it would induce protective immune response in humans. JF - Infection and Immunity AU - Jiao, X AU - Hirano, T AU - Hou, Y AU - Gu, X AD - 5 Research Court, Rockville, MD 20850, guxx@nidcd.nih.gov Y1 - 2002/11// PY - 2002 DA - Nov 2002 SP - 5982 EP - 5989 VL - 70 IS - 11 SN - 0019-9567, 0019-9567 KW - lipooligosaccharides KW - mice KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - J 02834:Vaccination and immunization KW - F 06807:Active immunization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18500239?accountid=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=Specific+Immune+Responses+and+Enhancement+of+Murine+Pulmonary+Clearance+of+Moraxella+catarrhalis+by+Intranasal+Immunization+with+a+Detoxified+Lipooligosaccharide+Conjugate+Vaccine&rft.au=Jiao%2C+X%3BHirano%2C+T%3BHou%2C+Y%3BGu%2C+X&rft.aulast=Jiao&rft.aufirst=X&rft.date=2002-11-01&rft.volume=70&rft.issue=11&rft.spage=5982&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.70.11.5982-5989.2002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/IAI.70.11.5982-5989.2002 ER - TY - JOUR T1 - Enhanced Interleukin-12 and CD40 Ligand Activities but Reduced Staphylococcus aureus Cowan 1-Induced Responses Suggest a Generalized and Progressively Impaired Type 1 Cytokine Pattern for Human Schistosomiasis AN - 18499842; 5464233 AB - Whole-blood-cell cultures from schistosomiasis patients were stimulated with a variety of T-cell-dependent and T-cell-independent stimuli to determine whether the defect in type 1 cytokine expression observed following helminth infection is associated with alterations in interleukin-12 (IL-12) or CD40 ligand (CD40L) responsiveness. Cultures from uninfected individuals produced abundant gamma interferon in response to Staphylococcus aureus Cowan 1 (SAC), while patients with intestinal and hepatosplenic disease displayed intermediate and weak responses, respectively. Importantly, the decrease in type 1 cytokine expression was not attributed to defects in IL-12- or CD40L-induced activity. Indeed, schistosomiasis patients displayed heightened responses and even produced more biologically active IL-12 when stimulated with SAC and CD40L than did uninfected controls. Finally, additional studies suggested only a partial role for IL-10, since intestinal patients were the only group that overproduced this downregulatory cytokine. Together, these studies demonstrate that the type 1 deficiency in chronic hepatosplenic schistosomiasis is not related to specific defects in IL-12, IL-10, or CD40L activity, although changes in the functional status of antigen-presenting cells appear to be involved. JF - Infection and Immunity AU - Montenegro, SML AU - Abath, FGC AU - Domingues, ALC AU - Melo, W G AU - Morais, CNL AU - Coutinho, E M AU - Mahanty, S AU - Wynn, T A AD - Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, MSC 8003, Room 6154, 50 South Dr., Bethesda, MD 20892, twynn@niaid.nih.gov Y1 - 2002/11// PY - 2002 DA - Nov 2002 SP - 5903 EP - 5912 VL - 70 IS - 11 SN - 0019-9567, 0019-9567 KW - CD40L protein KW - gamma -Interferon KW - man KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - F 06774:Other cytokines (TNF, GM-CSF) KW - J 02833:Immune response and immune mechanisms KW - F 06804:Helminths UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18499842?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Enhanced+Interleukin-12+and+CD40+Ligand+Activities+but+Reduced+Staphylococcus+aureus+Cowan+1-Induced+Responses+Suggest+a+Generalized+and+Progressively+Impaired+Type+1+Cytokine+Pattern+for+Human+Schistosomiasis&rft.au=Montenegro%2C+SML%3BAbath%2C+FGC%3BDomingues%2C+ALC%3BMelo%2C+W+G%3BMorais%2C+CNL%3BCoutinho%2C+E+M%3BMahanty%2C+S%3BWynn%2C+T+A&rft.aulast=Montenegro&rft.aufirst=SML&rft.date=2002-11-01&rft.volume=70&rft.issue=11&rft.spage=5903&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.70.11.5903-5912.2002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/IAI.70.11.5903-5912.2002 ER - TY - JOUR T1 - Blood lead levels of primary-school children in Penghu County, Taiwan: distribution and influencing factors AN - 18498935; 5468483 AB - Objectives. The purpose of this study was to investigate the blood lead levels (BLLs) of primary-school children aged 7 to 12 in Penghu island and to determine the factors affecting their BLLs.Methods. A total of 1,885 participants were recruited and BLLs were measured with a flameless atomic absorption spectrophotometer. A questionnaire was used to collect personal information.Results. The results indicated that the mean BLL of primary-school children in Penghu was 6.0 plus or minus 2.4 mu g/dl (1.0~29.3 mu g /dl). The mean BLL of schoolboys (n=1,046) was 6.3 plus or minus 2.6 mu g/dl, with a maximum of 29.3 mu g/dl, while the mean BLL of schoolgirls (n=839) was 5.7 plus or minus 2.2 mu g/dl, with a maximum of 23.4 mu g/dl. Risk-factor analysis showed that personal characteristics (i.e., gender, frequency of milk consumption, grade levels) and geographic factors (i.e., levels of urbanization) significantly influence the BLLs. However, there was no significant impact on BLLs from drinking water, residential distance from a major road, and living close to lead-emitting sources.Conclusions. Geographical factors were highly associated with BLLs. The BLLs of the primary-school children living in the main Penghu island were lower than those in the other small islands. JF - International Archives of Occupational and Environmental Health AU - Yang, T AU - Wu, T N AU - Hsu, S W AU - Lai, CH AU - Ko, K N AU - Liou, SH AD - School of Public Health, National Defense Medical Center, Nei-Hu, Taipei, Taiwan, yang@ndmctsgh.edu.t Y1 - 2002/11// PY - 2002 DA - Nov 2002 SP - 528 EP - 534 PB - Springer-Verlag, [URL:http://link.springer.de/link/service/journals/00420/bibs/2075 008/20750528.htm] VL - 75 IS - 8 SN - 0340-0131, 0340-0131 KW - man KW - Toxicology Abstracts; Health & Safety Science Abstracts; Pollution Abstracts KW - X 24166:Environmental impact KW - H 12000:Epidemiology and Public Health KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18498935?accountid=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+Archives+of+Occupational+and+Environmental+Health&rft.atitle=Blood+lead+levels+of+primary-school+children+in+Penghu+County%2C+Taiwan%3A+distribution+and+influencing+factors&rft.au=Yang%2C+T%3BWu%2C+T+N%3BHsu%2C+S+W%3BLai%2C+CH%3BKo%2C+K+N%3BLiou%2C+SH&rft.aulast=Yang&rft.aufirst=T&rft.date=2002-11-01&rft.volume=75&rft.issue=8&rft.spage=528&rft.isbn=&rft.btitle=&rft.title=International+Archives+of+Occupational+and+Environmental+Health&rft.issn=03400131&rft_id=info:doi/10.1007%2Fs00420-002-0360-2 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1007/s00420-002-0360-2 ER - TY - JOUR T1 - Staphylococcus aureus Aconitase Inactivation Unexpectedly Inhibits Post-Exponential-Phase Growth and Enhances Stationary-Phase Survival AN - 18498609; 5464214 AB - Staphylococcus aureus preferentially catabolizes glucose, generating pyruvate, which is subsequently oxidized to acetate under aerobic growth conditions. Catabolite repression of the tricarboxylic acid (TCA) cycle results in the accumulation of acetate. TCA cycle derepression coincides with exit from the exponential growth phase, the onset of acetate catabolism, and the maximal expression of secreted virulence factors. These data suggest that carbon and energy for post-exponential-phase growth and virulence factor production are derived from the catabolism of acetate mediated by the TCA cycle. To test this hypothesis, the aconitase gene was genetically inactivated in a human isolate of S. aureus, and the effects on physiology, morphology, virulence factor production, virulence for mice, and stationary-phase survival were examined. TCA cycle inactivation prevented the post-exponential growth phase catabolism of acetate, resulting in premature entry into the stationary phase. This phenotype was accompanied by a significant reduction in the production of several virulence factors and alteration in host-pathogen interaction. Unexpectedly, aconitase inactivation enhanced stationary-phase survival relative to the wild- type strain. Aconitase is an iron-sulfur cluster-containing enzyme that is highly susceptible to oxidative inactivation. We speculate that reversible loss of the iron-sulfur cluster in wild-type organisms is a survival strategy used to circumvent oxidative stress induced during host-pathogen interactions. Taken together, these data demonstrate the importance of the TCA cycle in the life cycle of this medically important pathogen. JF - Infection and Immunity AU - Somerville, G A AU - Chaussee AU - Morgan, C I AU - Fitzgerald, J R AU - Dorward, D W AU - Reitzer, L J AU - Musser, J M AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th St., Hamilton, MT 59840, jmusser@niaid.nih.gov Y1 - 2002/11// PY - 2002 DA - Nov 2002 SP - 6373 EP - 6382 VL - 70 IS - 11 SN - 0019-9567, 0019-9567 KW - Microbiology Abstracts B: Bacteriology KW - J 02722:Biodegradation, growth, nutrition and leaching UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18498609?accountid=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=Staphylococcus+aureus+Aconitase+Inactivation+Unexpectedly+Inhibits+Post-Exponential-Phase+Growth+and+Enhances+Stationary-Phase+Survival&rft.au=Somerville%2C+G+A%3BChaussee%3BMorgan%2C+C+I%3BFitzgerald%2C+J+R%3BDorward%2C+D+W%3BReitzer%2C+L+J%3BMusser%2C+J+M&rft.aulast=Somerville&rft.aufirst=G&rft.date=2002-11-01&rft.volume=70&rft.issue=11&rft.spage=6373&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.70.11.6373-6382.2002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/IAI.70.11.6373-6382.2002 ER - TY - JOUR T1 - Optimization of DNA vaccination against cutaneous leishmaniasis AN - 1500776020; 19045450 AB - The present studies were designed to examine the requirements of dose, route of inoculation and constituent antigens for the maintenance of complete and long lasting protection against cutaneous leishmaniasis due to conferred by a cocktail DNA vaccine encoding the antigens LACK, LmST11 and TSA. Vaccination of C57Bl/6 mice with LACK DNA alone resulted in partial protection, whereas the combination of LmST11 and TSA provided stronger, though still incomplete protection compared to the combination of all three Ag DNAs. When intradermal (i.d), intramuscular (i.m.), and subcutaneous (s.c.) vaccination routes were compared, i.d. immunization reduced by five-fold the dose necessary to maintain complete protection. In vivo depletion of CD4+ or CD8+ T cells provided direct evidence that both populations are necessary to mediate complete protection. These results establish intradermal vaccination using DNA encoding multiple antigens as a way to optimize priming of CD4+ and CD8+ T cells necessary for potent and durable protection against cutaneous leishmaniasis. JF - Vaccine AU - Mendez, Susana AU - Belkaid, Yasmine AU - Seder, Robert A AU - Sacks, David AD - Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Room 126, Building 4, Center Dr. MSC 0425, Bethesda, MD 20892-0425, USA Y1 - 2002/11// PY - 2002 DA - November 2002 SP - 3702 EP - 3708 PB - Elsevier B.V., The Boulevard Kidlington Oxford OX5 1GB United Kingdom VL - 20 IS - 31 SN - 0264-410X, 0264-410X KW - ASFA 3: Aquatic Pollution & Environmental Quality; ASFA 1: Biological Sciences & Living Resources; Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts C: Algology, Mycology & Protozoology; Immunology Abstracts KW - DNA vaccines KW - CD8+ T cells KW - Disease control KW - CD8 antigen KW - Vaccination KW - Immunization KW - CD4 antigen KW - Antigens KW - Lymphocytes T KW - Inoculation KW - DNA KW - Vaccines KW - Cutaneous leishmaniasis KW - K 03350:Immunology KW - F 06905:Vaccines KW - Q1 08484:Species interactions: parasites and diseases KW - N 14845:Miscellaneous KW - Q5 08524:Public health, medicines, dangerous organisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1500776020?accountid=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=Vaccine&rft.atitle=Optimization+of+DNA+vaccination+against+cutaneous+leishmaniasis&rft.au=Mendez%2C+Susana%3BBelkaid%2C+Yasmine%3BSeder%2C+Robert+A%3BSacks%2C+David&rft.aulast=Mendez&rft.aufirst=Susana&rft.date=2002-11-01&rft.volume=20&rft.issue=31&rft.spage=3702&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/10.1016%2FS0264-410X%2802%2900376-6 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2014-02-01 N1 - Last updated - 2016-02-04 N1 - SubjectsTermNotLitGenreText - Antigens; Disease control; DNA; Vaccines; Vaccination; Immunization; CD4 antigen; DNA vaccines; Inoculation; Lymphocytes T; CD8 antigen; Cutaneous leishmaniasis DO - http://dx.doi.org/10.1016/S0264-410X(02)00376-6 ER - TY - JOUR T1 - Chromosome and gene alterations in breast cancer as markers for diagnosis and prognosis as well as pathogenetic targets for therapy. AN - 72641784; 12407694 AB - Chromosomal abnormalities have been implicated in cancer development since the turn of the last century. Only during the past two decades, with advances in cytogenetics and molecular biology, has the genetic basis of neoplasia been firmly established, however, with chromosomal alterations being recognized as critical in the pathogenesis of human cancer. Recurrent chromosomal alterations provide cytological and molecular markers for the diagnosis and prognosis of disease. They also facilitate the identification of genes that are important in carcinogenesis and, ultimately, may lead to the development of targeted therapy. In breast cancer, the most prevalent malignancy among females, substantial progress has been achieved in identifying genes located at sites of recurrent chromosomal alterations and in profiling gene expression through the application of powerful cytogenetic and functional genomic techniques. Characterization of the molecular pathologic characteristics and gene-expression profiles of breast cancer should provide new clinical tools for the accurate diagnosis and prediction of prognosis as well as new targets for the development of therapeutic agents. Published 2002 Wiley-Liss, Inc. JF - American journal of medical genetics AU - Popescu, Nicholas C AU - Zimonjic, Drazen B AD - Molecular Cytogenetics Section, Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, Building 37, Room 3C05, 37 Convent Drive MSC 4258, Bethesda, MD 20892-4258, USA. popescun@dc37.nci.nih.gov Y1 - 2002/10/30/ PY - 2002 DA - 2002 Oct 30 SP - 142 EP - 149 VL - 115 IS - 3 SN - 0148-7299, 0148-7299 KW - BRCA1 Protein KW - 0 KW - BRCA2 Protein KW - Neoplasm Proteins KW - fragile histidine triad protein KW - Acid Anhydride Hydrolases KW - EC 3.6.- KW - Index Medicus KW - Gene Expression Profiling KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - Neoplasm Proteins -- genetics KW - Prognosis KW - Chromosome Aberrations KW - BRCA2 Protein -- metabolism KW - BRCA1 Protein -- metabolism KW - Neoplasm Proteins -- metabolism KW - Female KW - Breast Neoplasms -- genetics KW - Breast Neoplasms -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72641784?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chromosome+and+gene+alterations+in+breast+cancer+as+markers+for+diagnosis+and+prognosis+as+well+as+pathogenetic+targets+for+therapy.&rft.au=Popescu%2C+Nicholas+C%3BZimonjic%2C+Drazen+B&rft.aulast=Popescu&rft.aufirst=Nicholas&rft.date=2002-10-30&rft.volume=115&rft.issue=3&rft.spage=142&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 - 2003-05-09 N1 - Date created - 2002-10-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutations that permit efficient replication of hepatitis C virus RNA in Huh-7 cells prevent productive replication in chimpanzees. AN - 72633967; 12391335 AB - The development of a subgenomic replicon derived from the hepatitis C virus (HCV) strain Con1 enabled the study of viral RNA replication in Huh-7 cells. The level of replication of replicons, as well as full-length Con1 genomes, increased significantly by a combination of two adaptive mutations in NS3 (E1202G and T1280I) and a single mutation in NS5A (S2197P). However, these cell culture-adaptive mutations influenced in vivo infectivity. After intrahepatic transfection of chimpanzees, the wild-type Con1 genome was infectious and produced viral titers similar to those produced by other infectious HCV clones. Repeated independent transfections with RNA transcripts of a Con1 genome containing the three adaptive mutations failed to achieve active HCV infection. Furthermore, although a chimpanzee transfected with RNA transcripts of a Con1 genome with only the NS5A mutation became infected, this mutation was detected only in virus genomes recovered from serum at day 4; viruses recovered at day 7 had a reversion back to the original Con1 sequence. Our study demonstrates that mutations that are adaptive for replication of HCV in cell culture may be highly attenuating in vivo. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Bukh, Jens AU - Pietschmann, Thomas AU - Lohmann, Volker AU - Krieger, Nicole AU - Faulk, Kristina AU - Engle, Ronald E AU - Govindarajan, Sugantha AU - Shapiro, Max AU - St Claire, Marisa AU - Bartenschlager, Ralf AD - Hepatitis Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. jbukh@niaid.nih.gov Y1 - 2002/10/29/ PY - 2002 DA - 2002 Oct 29 SP - 14416 EP - 14421 VL - 99 IS - 22 SN - 0027-8424, 0027-8424 KW - NS-5 protein, hepatitis C virus KW - 0 KW - NS3 protein, hepatitis C virus KW - RNA, Viral KW - Viral Nonstructural Proteins KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured KW - Replicon KW - RNA, Viral -- biosynthesis KW - Humans KW - Genome, Viral KW - Pan troglodytes KW - Mutagenesis KW - Hepacivirus -- physiology KW - Virus Replication -- genetics KW - Viral Nonstructural Proteins -- genetics KW - Adaptation, Physiological -- physiology KW - Hepacivirus -- genetics KW - Adaptation, Physiological -- genetics KW - Viral Nonstructural Proteins -- physiology KW - Virus Replication -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72633967?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutations+that+permit+efficient+replication+of+hepatitis+C+virus+RNA+in+Huh-7+cells+prevent+productive+replication+in+chimpanzees.&rft.au=Bukh%2C+Jens%3BPietschmann%2C+Thomas%3BLohmann%2C+Volker%3BKrieger%2C+Nicole%3BFaulk%2C+Kristina%3BEngle%2C+Ronald+E%3BGovindarajan%2C+Sugantha%3BShapiro%2C+Max%3BSt+Claire%2C+Marisa%3BBartenschlager%2C+Ralf&rft.aulast=Bukh&rft.aufirst=Jens&rft.date=2002-10-29&rft.volume=99&rft.issue=22&rft.spage=14416&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 - 2002-12-09 N1 - Date created - 2002-10-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2291-5 [10051634] Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8738-43 [9238047] Virology. 1999 Mar 30;256(1):36-44 [10087224] Vox Sang. 1999;76(3):149-58 [10341329] Hepatology. 1999 Jul;30(1):316-24 [10385673] Science. 1999 Jul 2;285(5424):110-3 [10390360] Science. 1999 Jul 2;285(5424):26-30 [10428695] Virology. 1999 Sep 15;262(1):250-63 [10489358] J Virol. 2001 May;75(10):4614-24 [11312331] Curr Top Microbiol Immunol. 2000;242:55-84 [10592656] J Virol. 2000 Feb;74(4):2046-51 [10644379] J Gen Virol. 2000 Jul;81(Pt 7):1631-48 [10859368] Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13318-23 [11078521] Virology. 1998 Apr 25;244(1):161-72 [9581788] Mol Cell Biol. 1998 Sep;18(9):5208-18 [9710605] J Infect Dis. 1998 Oct;178(4):1193-7 [9806059] Lancet. 1998 Oct 31;352(9138):1426-32 [9807989] N Engl J Med. 1998 Nov 19;339(21):1485-92 [9819446] Science. 2000 Dec 8;290(5498):1972-4 [11110665] J Virol. 2001 Feb;75(3):1252-64 [11152498] J Virol. 2001 Feb;75(3):1437-49 [11152517] J Gen Virol. 2001 Jun;82(Pt 6):1291-7 [11369872] J Virol. 2001 Sep;75(18):8516-23 [11507197] Antiviral Res. 2001 Oct;52(1):1-17 [11530183] Gastroenterology. 2001 Nov;121(5):1226-33 [11677216] Immunity. 2001 Dec;15(6):883-95 [11754811] J Virol. 2002 Feb;76(3):1171-80 [11773393] J Virol. 2002 Mar;76(6):2997-3006 [11861865] J Virol. 2002 Apr;76(8):4008-21 [11907240] J Virol. 2002 Jun;76(12):5974-84 [12021330] J Virol. 2002 Sep;76(17):8551-9 [12163575] Lancet. 1978 Mar 4;1(8062):459-63 [76017] Biochem Biophys Res Commun. 1991 Feb 28;175(1):220-8 [1847805] Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):187-91 [1309604] J Virol. 1992 Nov;66(11):6649-54 [1328684] Virology. 1993 Jun;194(2):475-80 [8389072] Semin Liver Dis. 1995 Feb;15(1):41-63 [7597443] N Engl J Med. 1996 Jan 11;334(2):77-81 [8531962] Hepatology. 1997 Jun;25(6):1527-38 [9185778] Science. 1997 Jul 25;277(5325):570-4 [9228008] J Virol. 1999 Apr;73(4):3317-25 [10074186] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bioactive alkaloids of frog skin: Combinatorial bioprospecting reveals that pumiliotoxins have an arthropod source AN - 18605647; 5472198 AB - Nearly 500 alkaloids have been detected in skin extracts from frogs of the family Dendrobatidae. All seem to have been sequestered unchanged into skin glands from alkaloid-containing arthropods. Ants, beetles, and millipedes seem to be the source of decahydroquinolines, certain izidines, coccinellines, and spiropyrrolizidine oximes. But the dietary source for a major group of frog-skin alkaloids, namely the pumiliotoxins (PTXs), alloPTXs, and homoPTXs, remained a mystery. In hopes of revealing an arthropod source for the PTX group, small arthropods were collected from eight different sites on a Panamanian island, where the dendrobatid frog (Dendrobates pumilio) was known to contain high levels of two PTXs. The mixed arthropod collections from several sites, each representing up to 20 arthropod taxa, contained PTX 307A and/or alloPTX 323B. In addition, the mixed arthropod collections from several sites contained a 5,8-disubstituted indolizidine (205A or 235B), representing another class of alkaloids previously unknown from an arthropod. An ant alkaloid, decahydroquinoline 195A, was detected in the mixed arthropod collections from several sites. Thus, "combinatorial bioprospecting" demonstrates that further collection and analysis of individual taxa of leaf-litter arthropods should reveal the taxa from which PTXs, alloPTXs, and 5,8-disubstituted indolizidines are derived. JF - Proceedings of the National Academy of Sciences, USA AU - Daly, J W AU - Kaneko, T AU - Wilham, J AU - Garraffo, H M AU - Spande, T F AU - Espinosa, A AU - Donnelly, MA AD - Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, jdaly@nih.gov Y1 - 2002/10/29/ PY - 2002 DA - 2002 Oct 29 SP - 13996 EP - 14001 VL - 99 IS - 22 SN - 0027-8424, 0027-8424 KW - Ants KW - Dendrobatids KW - Poison frogs KW - Poison-dart frogs KW - alkaloids KW - pumiliotoxins KW - Ecology Abstracts; ASFA 1: Biological Sciences & Living Resources; Entomology Abstracts; Toxicology Abstracts KW - Panama KW - Diets KW - Food organisms KW - Skin KW - Chemical composition KW - Allelochemicals KW - Formicidae KW - Metabolites KW - Dendrobatidae KW - Freshwater KW - Dendrobates pumilio KW - Defence mechanisms KW - Chemical defence KW - Toxins KW - Alkaloids KW - Arthropoda KW - Q1 08306:Physiology, biochemistry, biophysics KW - Q1 08483:Species interactions: general KW - Q1 08326:Physiology, biochemistry, biophysics KW - Q1 08625:Non-edible products KW - Z 05198:Defense & offense KW - X 24173:Animals KW - D 04669:Amphibians UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18605647?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Bioactive+alkaloids+of+frog+skin%3A+Combinatorial+bioprospecting+reveals+that+pumiliotoxins+have+an+arthropod+source&rft.au=Daly%2C+J+W%3BKaneko%2C+T%3BWilham%2C+J%3BGarraffo%2C+H+M%3BSpande%2C+T+F%3BEspinosa%2C+A%3BDonnelly%2C+MA&rft.aulast=Daly&rft.aufirst=J&rft.date=2002-10-29&rft.volume=99&rft.issue=22&rft.spage=13996&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.222551599 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2014-05-07 N1 - SubjectsTermNotLitGenreText - Diets; Food organisms; Alkaloids; Chemical composition; Skin; Metabolites; Defence mechanisms; Chemical defence; Allelochemicals; Toxins; Arthropoda; Formicidae; Dendrobatidae; Dendrobates pumilio; Panama; Freshwater DO - http://dx.doi.org/10.1073/pnas.222551599 ER - TY - JOUR T1 - Beta-cell dysfunction and insulin resistance in type 2 diabetes: role of metabolic and genetic abnormalities. AN - 72663978; 12431757 AB - Defects in insulin action and insulin secretion are both present in type 2 diabetes, and both are believed to be genetically predetermined. In the absence of a defect in beta-cell function, individuals can compensate indefinitely for insulin resistance with appropriate hyperinsulinemia, as observed even in obese populations such as the Pima Indians of Arizona. However, loss of beta-cell function leads eventually to the postprandial and fasting hyperglycemia that characterizes type 2 diabetes. This progression occurs despite initially effective antidiabetic therapies, a situation clearly demonstrated by the United Kingdom Prospective Diabetes Study (UKPDS). External factors (access to high-calorie foods, lack of exercise, weight gain), the increased insulin requirements imposed by insulin resistance, and toxicities from hyperglycemia and elevated free fatty acids may all contribute to beta-cell deterioration. Free fatty acids, resistin, and tumor necrosis factor (TNF)-alpha potentially worsen the insulin resistance. beta-Cell dysfunction resulting from glucose toxicity and lipotoxicity is potentially reversible with restoration of metabolic control. Therefore, attention to these toxicities may delay the deterioration of beta-cell function and suggest new approaches to the management of type 2 diabetes. JF - The American journal of medicine AU - LeRoith, Derek AD - Clinical Endocrinology Branch of the National Institutes of Health, Bethesda, Maryland, USA. leroith@comcast.net Y1 - 2002/10/28/ PY - 2002 DA - 2002 Oct 28 SP - 3S EP - 11S VL - 113 Suppl 6A SN - 0002-9343, 0002-9343 KW - Blood Glucose KW - 0 KW - Insulin KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Liver -- physiopathology KW - Muscle, Skeletal -- cytology KW - Humans KW - Disease Progression KW - Muscle, Skeletal -- physiopathology KW - Insulin -- secretion KW - Genetic Predisposition to Disease KW - Blood Glucose -- analysis KW - Homeostasis -- physiology KW - Hyperglycemia -- physiopathology KW - Adipose Tissue -- physiopathology KW - Islets of Langerhans -- physiology KW - Diabetes Mellitus, Type 2 -- metabolism KW - Diabetes Mellitus, Type 2 -- genetics KW - Diabetes Mellitus, Type 2 -- physiopathology KW - Insulin Resistance -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72663978?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+medicine&rft.atitle=Beta-cell+dysfunction+and+insulin+resistance+in+type+2+diabetes%3A+role+of+metabolic+and+genetic+abnormalities.&rft.au=LeRoith%2C+Derek&rft.aulast=LeRoith&rft.aufirst=Derek&rft.date=2002-10-28&rft.volume=113+Suppl+6A&rft.issue=&rft.spage=3S&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+medicine&rft.issn=00029343&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-27 N1 - Date created - 2002-11-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Opposing effects of 15-lipoxygenase-1 and -2 metabolites on MAPK signaling in prostate. Alteration in peroxisome proliferator-activated receptor gamma. AN - 72637635; 12189136 AB - Human prostate tumors have elevated levels of 15-lipoxygenase-1 (15-LOX-1) and data suggest that 15-LOX-1 may play a role in the development of prostate cancer. In contrast, 15-LOX-2 expression is higher in normal rather than in tumor prostate tissue and appears to suppress cancer development. We recently reported that 13-(S)-HODE, the 15-LOX-1 metabolite, up-regulates the MAP kinase signaling pathway and subsequently down-regulates PPARgamma in human colorectal carcinoma cells. To determine whether this mechanism is applicable to prostate cancer and what the effects of 15-LOX-2 are, we investigated the effect of 15-LOX-1, 15-LOX-2, and their metabolites on epidermal growth factor (EGF)- and insulin-like growth factor (IGF)-1 signaling in prostate carcinoma cells. In PC3 cells, 13-(S)-HODE, a 15-LOX-1 metabolite, up-regulated MAP kinase while in contrast 15-(S)-HETE, a 15-LOX-2 metabolite, down-regulated MAP kinase. As a result, 13-(S)-HODE increased PPARgamma phosphorylation while a subsequent decrease in PPARgamma phosphorylation was observed with 15-(S)-HETE. Thus, 15-LOX metabolites have opposing effects on the regulation of the MAP kinase signaling pathway and a downstream target of MAP kinase signaling like PPARgamma. In addition to the EGF signaling pathway, the IGF signaling pathway appears to be linked to prostate cancer. 13-(S)-HODE and 15-(S)-HETE up-regulate or down-regulate, respectively, both the MAPK and Akt pathways after activation with IGF-1. Thus, the effect of these lipid metabolites is not solely restricted to EGF signaling and not solely restricted to MAPK signaling. These results provide a plausible mechanism to explain the apparent opposing effects 15-LOX-1 and 15-LOX-2 play in prostate cancer. JF - The Journal of biological chemistry AU - Hsi, Linda C AU - Wilson, Leigh C AU - Eling, Thomas E AD - Eicosanoid Biochemistry Section, Laboratory of Molecular Carcinogenesis, NIEHS/National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 2002/10/25/ PY - 2002 DA - 2002 Oct 25 SP - 40549 EP - 40556 VL - 277 IS - 43 SN - 0021-9258, 0021-9258 KW - Hydroxyeicosatetraenoic Acids KW - 0 KW - Isoenzymes KW - Linoleic Acids KW - Receptors, Cytoplasmic and Nuclear KW - Transcription Factors KW - 13-hydroxy-9,11-octadecadienoic acid KW - 5204-88-6 KW - Epidermal Growth Factor KW - 62229-50-9 KW - 15-hydroxy-5,8,11,13-eicosatetraenoic acid KW - 73945-47-8 KW - Arachidonate 15-Lipoxygenase KW - EC 1.13.11.33 KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Index Medicus KW - Tumor Cells, Cultured KW - Phosphorylation KW - Humans KW - Linoleic Acids -- pharmacology KW - Hydroxyeicosatetraenoic Acids -- pharmacology KW - Epidermal Growth Factor -- metabolism KW - Male KW - Prostatic Neoplasms -- metabolism KW - Prostatic Neoplasms -- pathology KW - Arachidonate 15-Lipoxygenase -- metabolism KW - Transcription Factors -- metabolism KW - Mitogen-Activated Protein Kinases -- metabolism KW - Receptors, Cytoplasmic and Nuclear -- metabolism KW - Prostate -- metabolism KW - Prostate -- enzymology KW - Prostatic Neoplasms -- enzymology KW - Signal Transduction KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72637635?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Opposing+effects+of+15-lipoxygenase-1+and+-2+metabolites+on+MAPK+signaling+in+prostate.+Alteration+in+peroxisome+proliferator-activated+receptor+gamma.&rft.au=Hsi%2C+Linda+C%3BWilson%2C+Leigh+C%3BEling%2C+Thomas+E&rft.aulast=Hsi&rft.aufirst=Linda&rft.date=2002-10-25&rft.volume=277&rft.issue=43&rft.spage=40549&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 - 2002-12-09 N1 - Date created - 2002-10-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intakes of fruits and vegetables, carotenoids and vitamins A, E, C in relation to the risk of bladder cancer in the ATBC cohort study AN - 954574588; 13759187 AB - We examined the relation between dietary fruit and vegetables, carotenoids and vitamin intakes and the risk of bladder cancer among male smokers in a prospective cohort study. Over a median of 11 years, we followed 27111 male smokers aged 50-69 years who were initially enrolled in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study. During this period, 344 men developed bladder cancer. All of these men had completed a 276-food item dietary questionnaire at baseline. Cox proportional hazards models were used to estimate the relative risks and 95% confidence intervals and to simultaneously adjust for age, smoking history, energy intake and intervention group. Consumption of fruits and vegetables was not associated with the risk of bladder cancer (relative risk=1.28; 95% confidence intervals CI: 0.89-1.84, for highest vs lowest quintile). Similarly, no associations were observed for groups of fruits or vegetables (berries and cruciferous vegetables), or for specific fruits and vegetables. Dietary intakes of alpha-carotene, beta-carotene, lycopene, lutein/zeaxanthin, beta-cryptoxanthin, vitamins A, E, and C, and folate were not related to the risk of bladder cancer. These findings suggest that fruit and vegetable intakes are not likely to be associated with bladder cancer risk. However, these results may not be generalisable to non-smokers.BRITISH JOURNAL OF CANCER: (2002) 87, 960-965. doi:10.1038/sj.bjc.6600604 www.bjcancer.com[copy 2002 Cancer Research UK JF - British Journal of Cancer AU - Michaud, D S AU - Pietinen, P AU - Taylor, P R AU - Virtanen, M AU - Virtamo, J AU - Albanes, D AD - Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20852, USA Y1 - 2002/10/21/ PY - 2002 DA - 2002 Oct 21 SP - 960 EP - 965 PB - Nature Publishing Group, The Macmillan Building London N1 9XW UK VL - 87 IS - 9 SN - 0007-0920, 0007-0920 KW - Risk Abstracts KW - British Isles KW - Diets KW - Historical account KW - fruits KW - Ingestion KW - Cancer KW - urinary bladder KW - vitamins KW - intervention KW - prevention KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/954574588?accountid=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=British+Journal+of+Cancer&rft.atitle=Intakes+of+fruits+and+vegetables%2C+carotenoids+and+vitamins+A%2C+E%2C+C+in+relation+to+the+risk+of+bladder+cancer+in+the+ATBC+cohort+study&rft.au=Michaud%2C+D+S%3BPietinen%2C+P%3BTaylor%2C+P+R%3BVirtanen%2C+M%3BVirtamo%2C+J%3BAlbanes%2C+D&rft.aulast=Michaud&rft.aufirst=D&rft.date=2002-10-21&rft.volume=87&rft.issue=9&rft.spage=960&rft.isbn=&rft.btitle=&rft.title=British+Journal+of+Cancer&rft.issn=00070920&rft_id=info:doi/10.1038%2Fsj.bjc.6600604 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2012-03-01 N1 - Last updated - 2012-03-30 N1 - SubjectsTermNotLitGenreText - Diets; Historical account; urinary bladder; vitamins; intervention; fruits; prevention; Ingestion; Cancer; British Isles DO - http://dx.doi.org/10.1038/sj.bjc.6600604 ER - TY - JOUR T1 - Biologic damage resulting from exposure to tobacco smoke and from radon: implication for preventive interventions AN - 18610973; 5508879 AB - Cigarette smoking and residential radon are, respectively, the first and second leading cause of lung cancer in the United States today. Of the approximately 157 000 lung deaths occurring in 2000, approximately 90% can be attributed to cigarette smoking and 30% of the lung cancer deaths among non-smokers can be attributed to residential radon exposure. Although dwarfed by cigarette related lung cancer, lung cancer among lifetime non-smokers is a leading cause of death in the United States, and many other countries, accounting for approximately 16 000 deaths per year in the US. Laboratory studies and epidemiological investigations, particularly those conducted in the past decade, are yielding evidence that tobacco smoke and radon may share important elements of lung cancer's pathologic mechanism(s). Lung cancer prevention among smokers, ex-smokers and lifetime nonsmokers can be enhanced as we learn more about the etiologic mechanism(s) of lung cancer resulting from these and other exposures including diet, non-malignant respiratory diseases, occupational exposures, and susceptibility-gene. In this article we review both laboratory and epidemiologic data that gives insight into the biologic damage done to the lung from these exposures. JF - Oncogene AU - Alavanja, MCR AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd., Room 8000, Rockville, Maryland, MD 20892, USA, alavanjm@mail.nih.gov Y1 - 2002/10/21/ PY - 2002 DA - 2002 Oct 21 SP - 7365 EP - 7375 VL - 21 IS - 48 SN - 0950-9232, 0950-9232 KW - damage KW - epidemiology KW - man KW - Oncogenes & Growth Factors Abstracts; Toxicology Abstracts KW - X 24250:Reviews KW - B 26000:ONCOGENES AND GROWTH FACTORS: GENERAL UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18610973?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Biologic+damage+resulting+from+exposure+to+tobacco+smoke+and+from+radon%3A+implication+for+preventive+interventions&rft.au=Alavanja%2C+MCR&rft.aulast=Alavanja&rft.aufirst=MCR&rft.date=2002-10-21&rft.volume=21&rft.issue=48&rft.spage=7365&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/10.1038%2Fsj.onc.1205798 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1038/sj.onc.1205798 ER - TY - JOUR T1 - Redesign of a four-helix bundle protein by phage display coupled with proteolysis and structural characterization by NMR and X-ray crystallography. AN - 72178290; 12381319 AB - To test whether it is practical to use phage display coupled with proteolysis for protein design, we used this approach to convert a partially unfolded four-helix bundle protein, apocytochrome b(562), to a stably folded four-helix bundle protein. Four residues expected to form a hydrophobic core were mutated. One residue was changed to Trp to provide a fluorescence probe for studying the protein's physical properties and to partially fill the void left by the heme. The other three positions were randomly mutated. In addition, another residue in the region to be redesigned was substituted with Arg to provide a specific cutting site for protease Arg-c. This library of mutants was displayed on the surface of phage and challenged with protease Arg-c to select stably folded proteins. The consensus sequence that emerged from the selection included hydrophobic residues at only one of the three positions and non-hydrophobic residues at the other two. Nevertheless, the selected proteins were thermodynamically very stable. The structure of a selected protein was characterized using multi-dimensional NMR. All four helices were formed in the structure. Further, site-directed mutagenesis was used to change one of the two non-hydrophobic residues to a hydrophobic residue, which increased the stability of the protein, indicating that the selection result was not based solely on the protein's global stability and that local structural characteristics may also govern the selection. This conclusion is supported by the crystal structure of another mutant that has two hydrophobic residues substituted for the two non-hydrophobic residues. These results suggest that the hydrophobic interactions in the core are not sufficient to dictate the selection and that the location of the cutting site of the protease also influences the selection of structures. JF - Journal of molecular biology AU - Chu, Ruiai AU - Takei, Jiro AU - Knowlton, J Randolph AU - Andrykovitch, Michelle AU - Pei, Wuhong AU - Kajava, Andrey V AU - Steinbach, Peter J AU - Ji, Xinhua AU - Bai, Yawen AD - Laboratory of Biochemistry, Building 37, Room 6114E, National Cancer Institute, NIH, Bethesda, MD 20892-4255, USA. Y1 - 2002/10/18/ PY - 2002 DA - 2002 Oct 18 SP - 253 EP - 262 VL - 323 IS - 2 SN - 0022-2836, 0022-2836 KW - Apoproteins KW - 0 KW - Cytochrome b Group KW - Escherichia coli Proteins KW - Fluorescent Dyes KW - Peptide Library KW - Hydrogen KW - 7YNJ3PO35Z KW - cytochrome b562, E coli KW - 9064-79-3 KW - Index Medicus KW - Fluorescent Dyes -- metabolism KW - Thermodynamics KW - Models, Molecular KW - Humans KW - Protein Denaturation KW - Amino Acid Sequence KW - Magnetic Resonance Spectroscopy KW - Mutagenesis, Site-Directed KW - Hydrogen -- chemistry KW - Molecular Sequence Data KW - Crystallography, X-Ray KW - Protein Structure, Tertiary KW - Protein Conformation KW - Cytochrome b Group -- metabolism KW - Cytochrome b Group -- genetics KW - Apoproteins -- chemistry KW - Protein Folding KW - Apoproteins -- genetics KW - Cytochrome b Group -- chemistry KW - Apoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72178290?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Redesign+of+a+four-helix+bundle+protein+by+phage+display+coupled+with+proteolysis+and+structural+characterization+by+NMR+and+X-ray+crystallography.&rft.au=Chu%2C+Ruiai%3BTakei%2C+Jiro%3BKnowlton%2C+J+Randolph%3BAndrykovitch%2C+Michelle%3BPei%2C+Wuhong%3BKajava%2C+Andrey+V%3BSteinbach%2C+Peter+J%3BJi%2C+Xinhua%3BBai%2C+Yawen&rft.aulast=Chu&rft.aufirst=Ruiai&rft.date=2002-10-18&rft.volume=323&rft.issue=2&rft.spage=253&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 - 2002-11-26 N1 - Date created - 2002-10-16 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 1M6T; PDB N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genomic instability in mouse Burkitt lymphoma is dominated by illegitimate genetic recombinations, not point mutations. AN - 72163573; 12370814 AB - lambda-MYC-induced mouse Burkitt lymphoma (BL) harboring the shuttle vector pUR288, which includes a lacZ reporter gene to study mutagenesis, was employed to assess genomic instability associated with MYC deregulation. The frequency of lacZ mutations in lymphomas was elevated only 1.75-fold above that in normal tissue, indicating that mouse BL does not exhibit a phenotype of hypermutability. However, the nature of lacZ mutations was strikingly different in normal tissues and lymphomas. While point mutations comprised approximately 75% of the mutations found in normal tissues, apparent translocations, deletions and inversions constituted the majority of mutations ( approximately 65%) in lymphomas. Genomic instability in mouse BL thus seems characterized by a preponderance of illegitimate genetic rearrangements in the context of near-background mutant frequencies. SKY analyses of cell lines from primary BL tumors revealed substantial changes in chromosomal structure, confirming the lacZ studies. Bi-allelic deletions of the tumor suppressor p16(Ink4a) were detected in six out of 16 cell lines, illustrating cellular selection of advantageous mutations. Together, these approaches indicate that MYC may contribute to lymphomagenesis through the dominant mutator effect of inducing chromosomal instability. The results further suggest that a phenotype of hypermutability (elevated mutant frequency) may not always be required for oncogenesis to occur. JF - Oncogene AU - Rockwood, Lynne D AU - Torrey, Ted A AU - Kim, Joong Su AU - Coleman, Allen E AU - Kovalchuk, Alexander L AU - Xiang, Shao AU - Ried, Thomas AU - Morse, Herbert C AU - Janz, Siegfried AD - Laboratory of Genetics, Center for Cancer Research (CCR), NCI, Bethesda, Maryland, MD 20892, USA. Y1 - 2002/10/17/ PY - 2002 DA - 2002 Oct 17 SP - 7235 EP - 7240 VL - 21 IS - 47 SN - 0950-9232, 0950-9232 KW - Index Medicus KW - Animals KW - Point Mutation KW - Genes, Reporter KW - Genes, Immunoglobulin KW - Mice KW - Mice, Transgenic KW - Genes, p16 KW - Lac Operon KW - Cell Line KW - Recombination, Genetic KW - Burkitt Lymphoma -- genetics KW - Genes, myc -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72163573?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Genomic+instability+in+mouse+Burkitt+lymphoma+is+dominated+by+illegitimate+genetic+recombinations%2C+not+point+mutations.&rft.au=Rockwood%2C+Lynne+D%3BTorrey%2C+Ted+A%3BKim%2C+Joong+Su%3BColeman%2C+Allen+E%3BKovalchuk%2C+Alexander+L%3BXiang%2C+Shao%3BRied%2C+Thomas%3BMorse%2C+Herbert+C%3BJanz%2C+Siegfried&rft.aulast=Rockwood&rft.aufirst=Lynne&rft.date=2002-10-17&rft.volume=21&rft.issue=47&rft.spage=7235&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-04 N1 - Date created - 2002-10-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In situ GABAergic modulation of synchronous gonadotropin releasing hormone-1 neuronal activity. AN - 72190494; 12388600 AB - Evidence indicates that gonadotropin releasing hormone-1 [GnRH-1, also known as luteinizing hormone releasing hormone (LHRH)] neurons can exhibit synchronized neuroendocrine secretory activity before entrance into the CNS. In this study, we used calcium imaging to evaluate patterns of activity in individual, embryonic, GnRH-1 neurons as well as population dynamics of GnRH-1 neurons in mouse nasal explants maintained for 1 versus 3 weeks. Independent of age, GnRH-1 neurons displayed significant calcium peaks that synchronized at an interval of approximately 20 min across multiple GnRH-1 cells within an explant. Acute tetrodotoxin treatment decreased the amplitude of calcium peaks in individual GnRH-1 neurons and the duration but not the frequency of synchronized activity in the population of GnRH-1 neurons. Acute GABA(B) receptor antagonism increased the frequency of synchronized neuronal activity at both ages, whereas acute GABA(A) receptor antagonism decreased calcium oscillations in individual GNRH-1 cells as well as synchronization of the calcium pulses within the GnRH-1 population at the 1 week time point to background non-GNRH-1 cell levels. These results indicate that developing GnRH-1 neurons rely heavily on GABAergic signaling to initiate synchronized bouts of activity but thereafter, possess an innate capacity for synchronized activity patterns that are modulated by, but not completely dependent on GABAergic signaling. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Moore, Joseph Patrick AU - Shang, Eric AU - Wray, Susan AD - Cellular and Developmental Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/10/15/ PY - 2002 DA - 2002 Oct 15 SP - 8932 EP - 8941 VL - 22 IS - 20 KW - Fluorescent Dyes KW - 0 KW - GABA Antagonists KW - GABA-A Receptor Antagonists KW - GABA-B Receptor Antagonists KW - Receptors, GABA-B KW - Gonadotropin-Releasing Hormone KW - 33515-09-2 KW - Tetrodotoxin KW - 4368-28-9 KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Nose -- innervation KW - Cell Division -- physiology KW - Membrane Potentials -- physiology KW - Mice KW - GABA Antagonists -- pharmacology KW - Receptors, GABA-B -- genetics KW - Calcium -- metabolism KW - Signal Transduction -- physiology KW - Cells, Cultured KW - Signal Transduction -- drug effects KW - Neurosecretory Systems -- cytology KW - Nose -- embryology KW - Tetrodotoxin -- pharmacology KW - Nose -- metabolism KW - Time Factors KW - Gonadotropin-Releasing Hormone -- metabolism KW - Neurons -- metabolism KW - Calcium Signaling -- physiology KW - Neurons -- drug effects KW - Neurons -- cytology KW - gamma-Aminobutyric Acid -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72190494?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=In+situ+GABAergic+modulation+of+synchronous+gonadotropin+releasing+hormone-1+neuronal+activity.&rft.au=Moore%2C+Joseph+Patrick%3BShang%2C+Eric%3BWray%2C+Susan&rft.aulast=Moore&rft.aufirst=Joseph&rft.date=2002-10-15&rft.volume=22&rft.issue=20&rft.spage=8932&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=1529-2401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-25 N1 - Date created - 2002-10-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synergistic engagement of an ineffective endogenous anti-tumor immune response and induction of IFN-gamma and Fas-ligand-dependent tumor eradication by combined administration of IL-18 and IL-2. AN - 72161313; 12370382 AB - IFN-gamma is a critical component of the endogenous and many cytokine-induced antitumor immune responses. In this study we have shown that the combination of IL-18 and IL-2 (IL-18/IL-2) synergistically enhances IFN-gamma production both in vitro and in vivo, and synergizes in vivo to induce complete durable regression of well-established 3LL tumors in >80% of treated mice. We have observed a nascent, but ineffective, host immune response against 3LL that depends on endogenous IFN-gamma and IL-12 production and the Fas/Fas ligand (Fas-L) pathway. The combined administration of IL-18/IL-2 engages this endogenous response to induce tumor regression via a mechanism that is independent of NK and NKT cells or IL-12, but is critically dependent on CD8(+) T cells, IFN-gamma, and the Fas/Fas-L pathway. These studies demonstrate the importance of IFN-gamma as well as the Fas/Fas-L pathway in both endogenous and cytokine-driven antitumor immune responses engaged by IL-18/IL-2 and provide preclinical impetus for clinical investigation of this potent anti-tumor combination. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Wigginton, Jon M AU - Lee, Jong-Keuk AU - Wiltrout, Theresa A AU - Alvord, W Gregory AU - Hixon, Julie A AU - Subleski, Jeffrey AU - Back, Timothy C AU - Wiltrout, Robert H AD - Pediatric Oncology Branch, National Cancer Institute-Center for Cancer Research, Building 560, Room 31-93, Bethesda, MD 20892, USA. jw121b@nih.gov Y1 - 2002/10/15/ PY - 2002 DA - 2002 Oct 15 SP - 4467 EP - 4474 VL - 169 IS - 8 SN - 0022-1767, 0022-1767 KW - Adjuvants, Immunologic KW - 0 KW - Antigens, CD95 KW - Fas Ligand Protein KW - Fasl protein, mouse KW - Interleukin-18 KW - Interleukin-2 KW - Ligands KW - Membrane Glycoproteins KW - Interleukin-12 KW - 187348-17-0 KW - Interferon-gamma KW - 82115-62-6 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Interleukin-2 -- administration & dosage KW - Mice, Knockout KW - Interleukin-18 -- administration & dosage KW - Adjuvants, Immunologic -- administration & dosage KW - T-Lymphocyte Subsets -- immunology KW - Signal Transduction -- immunology KW - Spleen -- immunology KW - Adjuvants, Immunologic -- pharmacology KW - Drug Synergism KW - Injections, Intraperitoneal KW - Interleukin-2 -- pharmacology KW - Interleukin-18 -- pharmacology KW - Spleen -- cytology KW - Spleen -- metabolism KW - B-Lymphocytes -- immunology KW - Mice KW - Cells, Cultured KW - Interleukin-12 -- physiology KW - Mice, Inbred C57BL KW - Mice, SCID KW - Killer Cells, Natural -- immunology KW - Remission Induction KW - Carcinoma, Lewis Lung -- prevention & control KW - Antigens, CD95 -- metabolism KW - Membrane Glycoproteins -- physiology KW - Carcinoma, Lewis Lung -- immunology KW - Antigens, CD95 -- physiology KW - Apoptosis -- immunology KW - Interferon-gamma -- biosynthesis KW - Carcinoma, Lewis Lung -- pathology KW - Interferon-gamma -- physiology KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72161313?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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+engagement+of+an+ineffective+endogenous+anti-tumor+immune+response+and+induction+of+IFN-gamma+and+Fas-ligand-dependent+tumor+eradication+by+combined+administration+of+IL-18+and+IL-2.&rft.au=Wigginton%2C+Jon+M%3BLee%2C+Jong-Keuk%3BWiltrout%2C+Theresa+A%3BAlvord%2C+W+Gregory%3BHixon%2C+Julie+A%3BSubleski%2C+Jeffrey%3BBack%2C+Timothy+C%3BWiltrout%2C+Robert+H&rft.aulast=Wigginton&rft.aufirst=Jon&rft.date=2002-10-15&rft.volume=169&rft.issue=8&rft.spage=4467&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 - 2002-11-27 N1 - Date created - 2002-10-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Populating partially unfolded forms by hydrogen exchange-directed protein engineering. AN - 72158041; 12369818 AB - The native-state hydrogen exchange of a redesigned apocytochrome b(562) suggests that at least two partially unfolded forms (PUFs) exist for this four-helix bundle protein under native conditions. The more stable PUF has the N-terminal helix unfolded. To verify the conclusion further and obtain more detailed structural information about this PUF, five hydrophobic core residues in the N-terminal helix were mutated to Gly and Asp to destabilize the native state selectively and populate the PUF for structural studies. The secondary structure and the backbone dynamics of this mutant were characterized using multidimensional NMR. Consistent with the prediction, the N-terminal region of the mutant was found to be unfolded while other parts of the proteins remained folded. These results suggest that native-state hydrogen exchange-directed protein engineering can be a useful approach to populating partially unfolded forms for detailed structural studies. JF - Biochemistry AU - Takei, Jiro AU - Pei, Wuhong AU - Vu, Diep AU - Bai, Yawen AD - Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Building 37, Room 6114E, Bethesda, Maryland 20892, USA. Y1 - 2002/10/15/ PY - 2002 DA - 2002 Oct 15 SP - 12308 EP - 12312 VL - 41 IS - 41 SN - 0006-2960, 0006-2960 KW - Amyloid KW - 0 KW - Apoproteins KW - Cytochrome b Group KW - Hydrogen KW - 7YNJ3PO35Z KW - Glycine KW - TE7660XO1C KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Glycine -- genetics KW - Apoproteins -- chemistry KW - Thermodynamics KW - Hydrogen -- chemistry KW - Nuclear Magnetic Resonance, Biomolecular KW - Amyloid -- chemistry KW - Circular Dichroism KW - Protein Structure, Secondary -- genetics KW - Cytochrome b Group -- chemistry KW - Amyloid -- metabolism KW - Protein Conformation KW - Protein Folding KW - Protein Engineering -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72158041?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Populating+partially+unfolded+forms+by+hydrogen+exchange-directed+protein+engineering.&rft.au=Takei%2C+Jiro%3BPei%2C+Wuhong%3BVu%2C+Diep%3BBai%2C+Yawen&rft.aulast=Takei&rft.aufirst=Jiro&rft.date=2002-10-15&rft.volume=41&rft.issue=41&rft.spage=12308&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-12-04 N1 - Date created - 2002-10-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunization with a cannabinoid receptor type 1 peptide results in experimental allergic meningocerebellitis in the Lewis rat: a model for cell-mediated autoimmune neuropathology. AN - 72124194; 12271464 AB - Neuronal elements are increasingly suggested as primary targets of an autoimmune attack in certain neurological and neuropsychiatric diseases. Type 1 cannabinoid receptors (CB1) were selected as autoimmune targets because they are predominantly expressed on neuronal surfaces in brain and display strikingly high protein levels in striatum, hippocampus, and cerebellum. Female Lewis rats were immunized with N-terminally acetylated peptides (50 or 400 microg per rat) of the extracellular domains of the rat CB1 and killed at various time points. Subsequent evaluation using immunohistochemistry and in situ hybridization showed dense infiltration of immune cells exclusively within the cerebellum, peaking 12-16 days after immunization with the CB1 peptide containing amino acids 9-25. The infiltrates clustered in meninges and perivascular locations in molecular and granular cell layers and were also scattered throughout the CB1-rich neuropil. They consisted primarily of CD4(+) and ED1(+) cells, suggestive of cell-mediated autoimmune pathology. There were no inflammatory infiltrates elsewhere in the brain or spinal cord. The results show that neuronal elements, such as neuronal cell-surface receptors, may be recognized as antigenic targets in a cell-mediated autoimmune attack and, therefore, support the hypothesis of cell-mediated antineuronal autoimmune pathology in certain brain disorders. JF - Journal of neuroscience research AU - Proescholdt, Margit G AU - Quigley, Laura AU - Martin, Roland AU - Herkenham, Miles AD - Section on Functional Neuroanatomy, National Institute of Mental Health, Bethesda, Maryland 20892-4070, USA. Y1 - 2002/10/15/ PY - 2002 DA - 2002 Oct 15 SP - 150 EP - 160 VL - 70 IS - 2 SN - 0360-4012, 0360-4012 KW - Peptide Fragments KW - 0 KW - RNA, Messenger KW - Receptors, Cannabinoid KW - Receptors, Drug KW - Index Medicus KW - Animals KW - Rats, Inbred Lew KW - Apoptosis KW - Reproducibility of Results KW - Cerebellar Diseases -- immunology KW - Cerebellar Diseases -- pathology KW - Lymph Nodes -- pathology KW - Disease Progression KW - Disease Models, Animal KW - Amino Acid Sequence KW - Immunity, Cellular -- immunology KW - RNA, Messenger -- biosynthesis KW - Behavior, Animal KW - Rats KW - In Situ Nick-End Labeling KW - Autoimmunity -- immunology KW - Cerebellar Diseases -- complications KW - In Situ Hybridization KW - Molecular Sequence Data KW - Immunohistochemistry KW - Female KW - Receptors, Drug -- genetics KW - Encephalitis -- pathology KW - Receptors, Drug -- immunology KW - Nervous System Autoimmune Disease, Experimental -- pathology KW - Meningitis -- complications KW - Peptide Fragments -- immunology KW - Nervous System Autoimmune Disease, Experimental -- immunology KW - Receptors, Drug -- metabolism KW - Nervous System Autoimmune Disease, Experimental -- complications KW - Meningitis -- pathology KW - Nervous System Autoimmune Disease, Experimental -- chemically induced KW - Encephalitis -- immunology KW - Meningitis -- immunology KW - Peptide Fragments -- administration & dosage KW - Encephalitis -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72124194?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Immunization+with+a+cannabinoid+receptor+type+1+peptide+results+in+experimental+allergic+meningocerebellitis+in+the+Lewis+rat%3A+a+model+for+cell-mediated+autoimmune+neuropathology.&rft.au=Proescholdt%2C+Margit+G%3BQuigley%2C+Laura%3BMartin%2C+Roland%3BHerkenham%2C+Miles&rft.aulast=Proescholdt&rft.aufirst=Margit&rft.date=2002-10-15&rft.volume=70&rft.issue=2&rft.spage=150&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 - 2002-11-12 N1 - Date created - 2002-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vasoactive intestinal peptide mRNA and immunoreactivity are decreased in fetal alcohol syndrome model. AN - 72076675; 12220738 AB - Vasoactive intestinal peptide (VIP) regulates growth in the early post-implantation embryo. Previous work has demonstrated that peptide agonists (SALLRSIPA and NAPVSIPQ) from downstream mediators that are regulated by VIP were able to prevent the alcohol-induced fetal death, growth restriction and microcephaly associated with fetal alcohol syndrome. Here we evaluated the role of VIP in this mouse model of fetal alcohol syndrome, to determine if fetal or maternal levels of VIP are altered. In addition, we evaluated whether peptide treatment would alter the effects of alcohol on VIP levels. Treatment groups included control, alcohol, and alcohol+peptides. VIP levels were measured with enzyme immunoassay [EIA] (Peninsula Laboratories, Belmont, CA). Quantitation of VIP expression was measured with rt-PCR using mimic cDNA primers. Embryo/decidual VIP levels were similar in control and alcohol-treated groups 6 h after treatment. However, in the embryo/deciduas at 12 and 24 h, VIP levels were below the EIA's detection limit in the alcohol-treated groups, and significantly lower than the control or peptide-pretreated groups (p<0.05). Maternal cortex VIP levels were undetectable and significantly lower in the alcohol-treated group than control or peptide+alcohol group at 6 and 12 h (p<0.001). VIP mRNA expression was quantitated in the embryo and deciduas, with a significant decline noted at 6 h to 58% of control levels (p=0.02). Pretreatment with the peptides attenuated the alcohol-induced decrease in VIP mRNA. These studies demonstrate that treatment with alcohol can decrease the expression and immunoreactivity of VIP in both maternal and fetal tissues. This alcohol-induced loss of a recognized regulator of embryonic growth and differentiation may contribute to the sequelae of toxicity observed in fetal alcohol syndrome. JF - Regulatory peptides AU - Spong, Catherine Y AU - Auth, Jonathan AU - Vink, Joy AU - Goodwin, Katie AU - Abebe, Daniel T AU - Hill, Joanna M AU - Brenneman, Douglas E AD - Section on Developmental and Molecular Pharmacology, Laboratory of Developmental Neurobiology, NICHD, NIH, Building 49, Room 5A-38, MSC 4480, 9000 Rockville Pike, Bethesda, MD 20892, USA. spongc@exchange.nih.gov Y1 - 2002/10/15/ PY - 2002 DA - 2002 Oct 15 SP - 143 EP - 147 VL - 108 IS - 2-3 SN - 0167-0115, 0167-0115 KW - RNA, Messenger KW - 0 KW - Vasoactive Intestinal Peptide KW - 37221-79-7 KW - Index Medicus KW - Maternal-Fetal Exchange KW - Animals KW - Gestational Age KW - Disease Models, Animal KW - Mice KW - RNA, Messenger -- genetics KW - Female KW - Pregnancy KW - Fetal Death KW - Gene Expression Regulation, Developmental -- physiology KW - Vasoactive Intestinal Peptide -- metabolism KW - Fetal Alcohol Spectrum Disorders -- genetics KW - Transcription, Genetic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72076675?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+peptides&rft.atitle=Vasoactive+intestinal+peptide+mRNA+and+immunoreactivity+are+decreased+in+fetal+alcohol+syndrome+model.&rft.au=Spong%2C+Catherine+Y%3BAuth%2C+Jonathan%3BVink%2C+Joy%3BGoodwin%2C+Katie%3BAbebe%2C+Daniel+T%3BHill%2C+Joanna+M%3BBrenneman%2C+Douglas+E&rft.aulast=Spong&rft.aufirst=Catherine&rft.date=2002-10-15&rft.volume=108&rft.issue=2-3&rft.spage=143&rft.isbn=&rft.btitle=&rft.title=Regulatory+peptides&rft.issn=01670115&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-10 N1 - Date created - 2002-09-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Radioimmunotherapy of A431 Xenografted Mice with Pretargeted B3 Antibody-Streptavidin and super(90)Y-labeled 1,4,7,10-Tetraazacyclododecane-N,N',N",N"'-tetraacetic Acid (DOTA)-Biotin AN - 18950015; 5730942 AB - We investigated the biodistribution of super(88)Y/ super(111)In-labeled 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA)-biotin and therapy with super(90)Y-labeled DOTA-biotin in tumor-bearing mice after B3-streptavidin antibody conjugate (B3-SA) pretargeting. B3 antibody, recognizing Lewis super(y) antigen, was conjugated to streptavidin (B3-SA). For pretargeting, 400 mu g of the B3-SA was injected i.v. into mice bearing A431 tumor xenografts. After tumor localization of B3-SA, 100 mu g of synthetic clearing agent was injected i.v. to clear the unbound B3-SA from the circulation. Four h later, 1 mu g of radiolabeled DOTA-biotin was injected i.v. Radioimmunotherapy was performed with doses of 9.25 to 37 MBq of super(90)Y-labeled DOTA-biotin. As a result, radiolabeled DOTA-biotin cleared rapidly. All of the normal tissues had 163 days in the 37 MBq super(90)Y group (P 180 days after therapy, compared with control groups, with less than or equal to 29.2 days mean survival time (P < 0.001). Tumor pretargeting with B3-SA and radiolabeled DOTA-biotin has shown favorable, specific, and fast targeting that has resulted in good tumor responses and, thus, serves as a rationale for human studies with the B3-SA pretargeting approach. JF - Cancer Research AU - Yao, Z AU - Zhang, M AU - Axworthy, D B AU - Wong, K J AU - Garmestani, K AU - Park, L AU - Park, C W AU - Mallett, R W AU - Theodore, L J AU - Yau, E K AU - Waldmann, T A AU - Brechbiel, M W AU - Paik, CH AU - Pastan, I AU - Carrasquillo, JA AD - Nuclear Medicine Department of the Warren G. Magnuson Clinical Center, Metabolism Branch, Radiation Oncology Branch, and Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA Y1 - 2002/10/15/ PY - 2002 DA - 2002 Oct 15 SP - 5755 EP - 5760 VL - 62 IS - 20 SN - 0008-5472, 0008-5472 KW - mice KW - biotin KW - streptavidin KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Antibodies KW - Immunotherapy KW - Radiotherapy KW - Xenografts KW - W3 33160:Antibody based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18950015?accountid=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=Radioimmunotherapy+of+A431+Xenografted+Mice+with+Pretargeted+B3+Antibody-Streptavidin+and+super%2890%29Y-labeled+1%2C4%2C7%2C10-Tetraazacyclododecane-N%2CN%27%2CN%22%2CN%22%27-tetraacetic+Acid+%28DOTA%29-Biotin&rft.au=Yao%2C+Z%3BZhang%2C+M%3BAxworthy%2C+D+B%3BWong%2C+K+J%3BGarmestani%2C+K%3BPark%2C+L%3BPark%2C+C+W%3BMallett%2C+R+W%3BTheodore%2C+L+J%3BYau%2C+E+K%3BWaldmann%2C+T+A%3BBrechbiel%2C+M+W%3BPaik%2C+CH%3BPastan%2C+I%3BCarrasquillo%2C+JA&rft.aulast=Yao&rft.aufirst=Z&rft.date=2002-10-15&rft.volume=62&rft.issue=20&rft.spage=5755&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 - Xenografts; Immunotherapy; Radiotherapy; Antibodies ER - TY - JOUR T1 - Vector-based Vaccine/Cytokine Combination Therapy to Enhance Induction of Immune Responses to a Self-Antigen and Antitumor Activity AN - 18947014; 5730943 AB - Many antigens associated with human tumors are overexpressed in tumor cells as compared with normal tissues; these "self" tumor-associated antigens are also expressed during fetal development, and it is, thus, not surprising that they are either weakly immunogenic or functionally nonimmunogenic in the tumor-bearing host. In the studies reported here, we have used different vaccines and vaccine strategies in an attempt to develop antitumor immunity in a stringent animal model. The tumor antigen used was human carcinoembryonic antigen (CEA). The model used was CEA transgenic mice, in which the human CEA transgene is under the control of the endogenous CEA promoter; CEA is expressed in fetal tissues and normal gastrointestinal tissues, and CEA protein is found in sera. Previous studies have shown these CEA transgenic mice to be tolerant to the induction of CEA immunity using CEA protein in adjuvant as an immunogen. CEA-expressing tumor cells were implanted 14 days before vaccine therapy. The vaccines used were recombinant vaccinia virus containing the transgenes for CEA and three T-cell costimulatory molecules [B7-1, ICAM-1, and LFA-3, designated recombinant vaccinia (rV)-CEA/TRICOM], with each transgene under the control of individual poxvirus promoters, and a replication-defective avipox virus (fowlpox; rF) containing the same four transgenes (designated rF-CEA/TRICOM). The results demonstrate that (a) continued boosting with vaccine is required to maintain CEA-specific T-cell responses, and boosting with rF-CEA/TRICOM is superior to boosting with rF-CEA; (b) a diversified vaccination protocol consisting of primary vaccination with rV-CEA/TRICOM followed by boosting with rF-CEA/TRICOM is more efficacious than homogeneous vaccination with rF-CEA/TRICOM in the induction of both CEA-specific T-cell responses and antitumor activity; and (c) the use of cytokines, local granulocyte macrophage colony-stimulating factor (GM-CSF) and low-dose systemic interleukin 2, in combination with vaccine is essential in inducing antitumor activity, as compared with the use of cytokines alone, or the use of vaccines without cytokine. Both GM-CSF and interleukin 2 were shown to contribute to the induction of CEA-specific T-cell responses. These studies thus provide a "proof of concept" that potent vaccines and vaccine strategies, in combination with cytokines, may be essential to obtain the level of T-cell responses directed against a self-antigen that is necessary to achieve antitumor responses. JF - Cancer Research AU - Aarts, WM AU - Schlom, J AU - Hodge, J W AD - Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA Y1 - 2002/10/15/ PY - 2002 DA - 2002 Oct 15 SP - 5770 EP - 5777 VL - 62 IS - 20 SN - 0008-5472, 0008-5472 KW - transgenic mice KW - man KW - carcinoembryonic antigen KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Granulocyte-macrophage colony-stimulating factor KW - Lymphocytes T KW - Cytokines KW - Xenografts KW - Vaccines KW - W3 33350:Cancer vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18947014?accountid=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=Vector-based+Vaccine%2FCytokine+Combination+Therapy+to+Enhance+Induction+of+Immune+Responses+to+a+Self-Antigen+and+Antitumor+Activity&rft.au=Aarts%2C+WM%3BSchlom%2C+J%3BHodge%2C+J+W&rft.aulast=Aarts&rft.aufirst=WM&rft.date=2002-10-15&rft.volume=62&rft.issue=20&rft.spage=5770&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 - Cytokines; Vaccines; Lymphocytes T; Granulocyte-macrophage colony-stimulating factor; Xenografts ER - TY - JOUR T1 - Virulence control in group A Streptococcus by a two-component gene regulatory system: Global expression profiling and in vivo infection modeling AN - 18598529; 5465545 AB - Two-component gene regulatory systems composed of a membrane-bound sensor and cytoplasmic response regulator are important mechanisms used by bacteria to sense and respond to environmental stimuli. Group A Streptococcus, the causative agent of mild infections and life-threatening invasive diseases, produces many virulence factors that promote survival in humans. A two-component regulatory system, designated covRS (cov, control of virulence; csrRS), negatively controls expression of five proven or putative virulence factors (capsule, cysteine protease, streptokinase, streptolysin S, and streptodornase). Inactivation of covRS results in enhanced virulence in mouse models of invasive disease. Using DNA microarrays and quantitative RT-PCR, we found that CovR influences transcription of 15% (n = 271) of all chromosomal genes, including many that encode surface and secreted proteins mediating host-pathogen interactions. CovR also plays a central role in gene regulatory networks by influencing expression of genes encoding transcriptional regulators, including other two-component systems. Differential transcription of genes influenced by covR also was identified in mouse soft-tissue infection. This analysis provides a genome-scale overview of a virulence gene network in an important human pathogen and adds insight into the molecular mechanisms used by group A Streptococcus to interact with the host, promote survival, and cause disease. JF - Proceedings of the National Academy of Sciences, USA AU - Graham, M R AU - Smoot, L M AU - Migliaccio, CAL AU - Virtaneva, K AU - Sturdevant, DE AU - Porcella, S F AU - Federle, MJ AU - Adams, G J AU - Scott, J R AU - Musser, J M AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, jmusser@niaid.nih.gov Y1 - 2002/10/15/ PY - 2002 DA - 2002 Oct 15 SP - 13855 EP - 13860 VL - 99 IS - 21 SN - 0027-8424, 0027-8424 KW - CovR protein KW - covRS gene KW - csrRS gene KW - streptococci KW - streptodornase KW - streptokinase KW - streptolysin S KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18598529?accountid=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=Virulence+control+in+group+A+Streptococcus+by+a+two-component+gene+regulatory+system%3A+Global+expression+profiling+and+in+vivo+infection+modeling&rft.au=Graham%2C+M+R%3BSmoot%2C+L+M%3BMigliaccio%2C+CAL%3BVirtaneva%2C+K%3BSturdevant%2C+DE%3BPorcella%2C+S+F%3BFederle%2C+MJ%3BAdams%2C+G+J%3BScott%2C+J+R%3BMusser%2C+J+M&rft.aulast=Graham&rft.aufirst=M&rft.date=2002-10-15&rft.volume=99&rft.issue=21&rft.spage=13855&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.202353699 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1073/pnas.202353699 ER - TY - JOUR T1 - Surface plasmon resonance-based competition assay to assess the sera reactivity of variants of humanized antibodies AN - 18483427; 5441055 AB - While clinical trials are the only way to evaluate the immunogenicity, in patients, of murine or genetically engineered humanized variants of a potentially therapeutic or diagnostic monoclonal antibody (MAb), ethical and logistical considerations of clinical trials do not permit the evaluation of variants of a given MAb that are generated to minimize its immunogenicity. The most promising variant could be identified by comparing the reactivities of the parental antibody (Ab) and its variants to the sera of patients containing anti-variable region (anti-VR) Abs to the administered parental Ab. We have developed a surface plasmon resonance (SPR) biosensor-based assay to monitor the binding of the sera anti-VR Abs to the parental Ab and the inhibition of this binding by the variants. SPR biosensors allow the real-time detection and monitoring of the binding between an immobilized protein and its soluble ligand without the need for prior purification and labeling of the mobile analyte. This new assay requires no radiolabeling, is relatively less time-consuming, and uses only small amounts of serum (5-20 mu l of diluted serum) through a new microfluidic sample handling technique. To validate the assay, we have tested the relative reactivities of the CDR-grafted anti-carcinoma Ab, HuCC49, and its two variants, designated V5 and V10, to the sera of patients who were earlier administered radiolabeled murine CC49 in a clinical trial. A comparison of IC50s (the concentrations of the competitor Abs required for 50% inhibition of the binding of sera to immobilized HuCC49) showed that V5 and V10 were less reactive than HuCC49 to the three patients' sera tested. We have also demonstrated, for the first time, the specific detection and comparison of relative amounts of anti-VR Abs present in the sera of different patients without prior removal of anti-murine Fc Abs and/or circulating antigen. This may facilitate the rapid screening, for the presence of anti-VR Abs, of the sera of patients undergoing clinical trials. JF - Journal of Immunological Methods AU - Gonzales, N R AU - Schuck, P AU - Schlom, J AU - Kashmiri, S V AD - Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Room 8B09, Bethesda, MD 20892, USA, js141c@nih.gov Y1 - 2002/10/15/ PY - 2002 DA - 2002 Oct 15 SP - 197 EP - 210 PB - Elsevier Science B.V. VL - 268 IS - 2 SN - 0022-1759, 0022-1759 KW - surface plasmon resonance KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - F 06713:Physicochemical methods KW - W4 230:Biosensors, Bioelectronics & Bioindicators KW - W 30965:Miscellaneous, Reviews KW - W3 33250:Methods: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18483427?accountid=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=Surface+plasmon+resonance-based+competition+assay+to+assess+the+sera+reactivity+of+variants+of+humanized+antibodies&rft.au=Gonzales%2C+N+R%3BSchuck%2C+P%3BSchlom%2C+J%3BKashmiri%2C+S+V&rft.aulast=Gonzales&rft.aufirst=N&rft.date=2002-10-15&rft.volume=268&rft.issue=2&rft.spage=197&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunological+Methods&rft.issn=00221759&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Inactivation of human peroxiredoxin I during catalysis as the result of the oxidation of the catalytic site cysteine to cysteine-sulfinic acid. AN - 72158084; 12161445 AB - By following peroxiredoxin I (Prx I)-dependent NADPH oxidation spectrophotometrically, we observed that Prx I activity decreased gradually with time. The decay in activity was coincident with the conversion of Prx I to a more acidic species as assessed by two-dimensional gel electrophoresis. Mass spectral analysis and studies with Cys mutants determined that this shift in pI was due to selective oxidation of the catalytic site Cys(51)-SH to Cys(51)-SO(2)H. Thus, Cys(51)-SOH generated as an intermediate during catalysis appeared to undergo occasional further oxidation to Cys(51)-SO(2)H, which cannot be reversed by thioredoxin. The presence of H(2)O(2) alone was not sufficient to cause oxidation of Cys(51) to Cys(51)-SO(2)H. Rather, the presence of complete catalytic components (H(2)O(2), thioredoxin, thioredoxin reductase, and NADPH) was necessary, indicating that such hyperoxidation occurs only when Prx I is engaged in the catalytic cycle. Likewise, hyperoxidation of Cys(172)/Ser(172) mutant Prx I required not only H(2)O(2), but also a catalysis-supporting thiol (dithiothreitol). Kinetic analysis of Prx I inactivation in the presence of a low steady-state level (<1 microm) of H(2)O(2) indicated that Prx I was hyperoxidized at a rate of 0.072% per turnover at 30 degrees C. Hyperoxidation of Prx I was also detected in HeLa cells treated with H(2)O(2). JF - The Journal of biological chemistry AU - Yang, Kap-Seok AU - Kang, Sang Won AU - Woo, Hyun Ae AU - Hwang, Sung Chul AU - Chae, Ho Zoon AU - Kim, Kanghwa AU - Rhee, Sue Goo AD - Laboratory of Cell Signaling, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/10/11/ PY - 2002 DA - 2002 Oct 11 SP - 38029 EP - 38036 VL - 277 IS - 41 SN - 0021-9258, 0021-9258 KW - Antioxidants KW - 0 KW - Oxidants KW - Peptides KW - Recombinant Proteins KW - Thioredoxins KW - 52500-60-4 KW - NADP KW - 53-59-8 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Peroxidases KW - EC 1.11.1.- KW - Peroxiredoxins KW - EC 1.11.1.15 KW - Thioredoxin-Disulfide Reductase KW - EC 1.8.1.9 KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Spectrometry, Mass, Electrospray Ionization KW - HeLa Cells KW - Humans KW - Hydrogen Peroxide -- metabolism KW - Hydrogen-Ion Concentration KW - Thioredoxins -- metabolism KW - Peptides -- metabolism KW - Amino Acid Sequence KW - Recombinant Proteins -- genetics KW - Oxidation-Reduction KW - Antioxidants -- metabolism KW - Recombinant Proteins -- metabolism KW - Thioredoxin-Disulfide Reductase -- metabolism KW - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization KW - Molecular Sequence Data KW - Oxidants -- metabolism KW - Recombinant Proteins -- chemistry KW - Antioxidants -- chemistry KW - Mutation KW - Catalysis KW - Cysteine -- metabolism KW - Cysteine -- chemistry KW - Peroxidases -- genetics KW - Peroxidases -- chemistry KW - Catalytic Domain KW - NADP -- metabolism KW - Cysteine -- analogs & derivatives KW - Peroxidases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72158084?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Inactivation+of+human+peroxiredoxin+I+during+catalysis+as+the+result+of+the+oxidation+of+the+catalytic+site+cysteine+to+cysteine-sulfinic+acid.&rft.au=Yang%2C+Kap-Seok%3BKang%2C+Sang+Won%3BWoo%2C+Hyun+Ae%3BHwang%2C+Sung+Chul%3BChae%2C+Ho+Zoon%3BKim%2C+Kanghwa%3BRhee%2C+Sue+Goo&rft.aulast=Yang&rft.aufirst=Kap-Seok&rft.date=2002-10-11&rft.volume=277&rft.issue=41&rft.spage=38029&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 - 2002-11-25 N1 - Date created - 2002-10-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The human papilloma virus E7 oncoprotein inhibits transforming growth factor-beta signaling by blocking binding of the Smad complex to its target sequence. AN - 72156707; 12145312 AB - The human papillomavirus (HPV) oncoprotein E7 is implicated in the etiology of cervical cancer associated with infection by HPV. HPV-positive cells develop resistance to TGF-beta growth inhibitory activity through the inhibition of hypophosphorylation of pRb by papillomavirus type 16 E7 oncoprotein. In this study, we examined whether E7, in addition to its well known effects on pRb, might directly target the Smad proteins that mediate TGF-beta signaling. Here, we show that E7 significantly blocks both Smad transcriptional activity and the ability of TGF-beta to inhibit DNA synthesis. We found that E7 interacts constitutively with Smad2, Smad3, and Smad4. Confocal microscopic studies confirm that E7 and Smads co-localize in vivo. Using a canonical Smad DNA binding sequence, we found that E7 blocks Smad3 binding to its target sequence on DNA. These results suggest that suppression of Smad-mediated signaling by E7 may contribute to HPV-associated carcinogenesis. JF - The Journal of biological chemistry AU - Lee, Dug Keun AU - Kim, Byung-Chul AU - Kim, Isaac Yi AU - Cho, Eun-ah AU - Satterwhite, Daniel J AU - Kim, Seong-Jin AD - Laboratory of Cell Regulation and Carcinogenesis, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/10/11/ PY - 2002 DA - 2002 Oct 11 SP - 38557 EP - 38564 VL - 277 IS - 41 SN - 0021-9258, 0021-9258 KW - DNA-Binding Proteins KW - 0 KW - Oncogene Proteins, Viral KW - Smad Proteins KW - TGFB1 protein, human KW - Trans-Activators KW - Transforming Growth Factor beta KW - Transforming Growth Factor beta1 KW - DNA KW - 9007-49-2 KW - Cyclin-Dependent Kinases KW - EC 2.7.11.22 KW - Index Medicus KW - Cyclin-Dependent Kinases -- metabolism KW - Animals KW - Humans KW - DNA -- metabolism KW - Genes, Reporter KW - Transcription, Genetic KW - Protein Binding KW - Female KW - Cell Line KW - Uterine Cervical Neoplasms -- virology KW - Trans-Activators -- metabolism KW - Signal Transduction -- physiology KW - Papillomaviridae -- metabolism KW - Papillomaviridae -- genetics KW - Transforming Growth Factor beta -- metabolism KW - Oncogene Proteins, Viral -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72156707?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=The+human+papilloma+virus+E7+oncoprotein+inhibits+transforming+growth+factor-beta+signaling+by+blocking+binding+of+the+Smad+complex+to+its+target+sequence.&rft.au=Lee%2C+Dug+Keun%3BKim%2C+Byung-Chul%3BKim%2C+Isaac+Yi%3BCho%2C+Eun-ah%3BSatterwhite%2C+Daniel+J%3BKim%2C+Seong-Jin&rft.aulast=Lee&rft.aufirst=Dug&rft.date=2002-10-11&rft.volume=277&rft.issue=41&rft.spage=38557&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 - 2002-11-25 N1 - Date created - 2002-10-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The p53 network in lung carcinogenesis. AN - 72146723; 12362272 AB - The p53 tumor suppressor gene lies at the crossroads of multiple cellular response pathways that control a cell's fate in response to endogenous or exogenous stresses. Positive and negative regulatory loops both upstream and downstream of p53 cooperate to finely tune its functions as a transcription factor, a DNA damage sensor, and possibly, a protein-assembly scaffold. Through this plethora of activities, p53 is a major determinant of cell survival and a safeguard against genetic instability. Functional inactivation of p53 pathways through genetic and epigenetic events affecting the p53 gene itself and/or its interacting partners occur with a high frequency in lung cancer. The p53 mutational spectrum provides molecular evidence of the etiology of lung cancer and supports abundant epidemiological data indicating the role of tobacco smoke in the causation of this disease. JF - Oncogene AU - Robles, Ana I AU - Linke, Steven P AU - Harris, Curtis C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/10/07/ PY - 2002 DA - 2002 Oct 07 SP - 6898 EP - 6907 VL - 21 IS - 45 SN - 0950-9232, 0950-9232 KW - Codon KW - 0 KW - Index Medicus KW - Polymorphism, Genetic KW - Humans KW - Mutation KW - Genes, p53 KW - Lung Neoplasms -- genetics KW - Cell Transformation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72146723?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=The+p53+network+in+lung+carcinogenesis.&rft.au=Robles%2C+Ana+I%3BLinke%2C+Steven+P%3BHarris%2C+Curtis+C&rft.aulast=Robles&rft.aufirst=Ana&rft.date=2002-10-07&rft.volume=21&rft.issue=45&rft.spage=6898&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-05 N1 - Date created - 2002-10-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - RB and cyclin dependent kinase pathways: defining a distinction between RB and p16 loss in lung cancer. AN - 72144981; 12362273 AB - The genetic components of the RB:CDK:cyclin:p16 tumor suppressor pathway undergo mutational and epigenetic alterations in a wide range of human cancers and serve as critical targets for inactivation by the transforming oncoproteins of several DNA tumor viruses. Lung cancer has been a useful model system for these studies as it was the first tumor to demonstrate an important role for RB in the genesis of a common adult malignancy and was also the first human cancer to demonstrate genetic evidence for a multi-component RB:p16 tumor suppressor pathway. Lung tumorigenesis, however, is a complex disease process that requires longstanding carcinogen exposure in order to acquire somatic alterations at many distinct genetic loci. Understanding the multifunctional properties of RB to regulate cell proliferation, differentiation, and apoptosis and how they relate to the sequential accumulation of other clonal gene defects will be essential in order to understand the specific patterns of gene inactivation observed in different subtypes of lung cancer and to fulfill the promise of 'molecular target' therapeutics. JF - Oncogene AU - Kaye, Frederic J AD - Genetics Branch, Center for Cancer Research, NCI, NIH and National Naval Medical Center, Bethesda, Maryland 20889, USA. fkaye@helix.nih.gov Y1 - 2002/10/07/ PY - 2002 DA - 2002 Oct 07 SP - 6908 EP - 6914 VL - 21 IS - 45 SN - 0950-9232, 0950-9232 KW - Proto-Oncogene Proteins KW - 0 KW - CDK4 protein, human KW - EC 2.7.11.22 KW - Cyclin-Dependent Kinase 4 KW - Cyclin-Dependent Kinases KW - Index Medicus KW - Humans KW - Cyclin-Dependent Kinases -- metabolism KW - Cyclin-Dependent Kinases -- genetics KW - Genes, Retinoblastoma KW - Lung Neoplasms -- genetics KW - Genes, p16 KW - Carcinoma, Small Cell -- genetics KW - Gene Deletion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72144981?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=RB+and+cyclin+dependent+kinase+pathways%3A+defining+a+distinction+between+RB+and+p16+loss+in+lung+cancer.&rft.au=Kaye%2C+Frederic+J&rft.aulast=Kaye&rft.aufirst=Frederic&rft.date=2002-10-07&rft.volume=21&rft.issue=45&rft.spage=6908&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-05 N1 - Date created - 2002-10-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Towards a Synthetic Glycoconjugate Vaccine Against Neisseria meningitidis A AN - 21150376; 11371001 AB - Albumin conjugates of synthetic fragments of the capsular polysaccharide of the Gram-negative bacterium Neisseria meningitidis serogroup A were prepared. The fragments include monosaccharides 1 [-D-ManpNAc-(1O)-(CH2)2NH2] and 2 [6-O-P(O)(O-)2-D-ManpNAc-(1O)-(CH2)2NH2], disaccharide 3 {-D-ManpNAc-[1O-P(O)(O-)6]-D-ManpNAc-(1O)-(CH2)2NH2}, and trisaccharide 4 {-D-ManpNAc-[1O-P(O)(O-)6]-D-ManpNAc-[1O-P(O)(O-)6]-D-ManpNAc-(1O) - (CH2)2NH2}. Two monosaccharide blocks were employed as key intermediates. The reducing-end mannose unit featured the NHAc group at C-2, and contained the aminoethyl spacer as the aglycon for the final bioconjugation. The interresidual phosphodiester linkages were fashioned from an anomerically positioned H-phosphonate group in a 2-azido-mannose building block. The spacer-linked saccharides 1-4 were N-acylated with hepta-4,6-dienoic acid and the resulting conjugated diene-equipped saccharides were subjected to Diels-Alder-type addition with maleimidobutyryl-group functionalized human serum albumin to form covalent conjugates containing up to 26 saccharide haptens per albumin molecule. Complete 1H, 13C, and 31P NMR assignments for 1-4 are given. Antigenicity of the neoglycoconjugates containing 1-4 was demonstrated by a double immunodiffusion assay which indicated that a fragment as small as a monosaccharide is recognized by a polyclonal meningococcus group A antiserum and that the O-acetyl group(s) present in the natural capsular material is not essential for antigenicity. JF - Chemistry: A European Journal AU - Berkin, Ali AU - Coxon, Bruce AU - Pozsgay, Vince AD - Laboratory of Developmental and Molecular Immunity National Institute of Child Health and Human Development National Institutes of Health, 6 Center Dr., MSC 2720 Bethesda, MD 20892-2720 (USA), vipo@helix.nih.gov Y1 - 2002/10/04/ PY - 2002 DA - 2002 Oct 04 SP - 4424 EP - 4433 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 USA VL - 8 IS - 19 SN - 0947-6539, 0947-6539 KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts; CSA Neurosciences Abstracts KW - Immunodiffusion KW - Antigenicity KW - Haptens KW - Mannose KW - human serum albumin KW - Spacer KW - Neisseria meningitidis KW - monosaccharides KW - Disaccharides KW - glycoconjugates KW - Albumin KW - phosphodiesters KW - N.M.R. KW - Vaccines KW - Capsular polysaccharides KW - F 06905:Vaccines KW - J 02350:Immunology KW - N3 11150:General and miscellaneous topics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21150376?accountid=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=Chemistry%3A+A+European+Journal&rft.atitle=Towards+a+Synthetic+Glycoconjugate+Vaccine+Against+Neisseria+meningitidis+A&rft.au=Berkin%2C+Ali%3BCoxon%2C+Bruce%3BPozsgay%2C+Vince&rft.aulast=Berkin&rft.aufirst=Ali&rft.date=2002-10-04&rft.volume=8&rft.issue=19&rft.spage=4424&rft.isbn=&rft.btitle=&rft.title=Chemistry%3A+A+European+Journal&rft.issn=09476539&rft_id=info:doi/10.1002%2F1521-3765%2820021004%298%3A193.0.CO%3B2-1 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-01-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Antigenicity; Immunodiffusion; Mannose; Haptens; human serum albumin; Spacer; monosaccharides; Disaccharides; glycoconjugates; Albumin; N.M.R.; phosphodiesters; Vaccines; Capsular polysaccharides; Neisseria meningitidis DO - http://dx.doi.org/10.1002/1521-3765(20021004)8:19<4424::AID-CHEM4424>3.0.CO;2-1 ER - TY - JOUR T1 - Mouse methionine sulfoxide reductase B: effect of selenocysteine incorporation on its activity and expression of the seleno-containing enzyme in bacterial and mammalian cells AN - 20194581; 5464895 AB - The mammalian methionine sulfoxide reductase B (MsrB) has been found to be a selenoprotein which can reduce R form of both free and protein-incorporated methionine sulfoxide to methionine. Together with MsrA, which reduces specifically the S form of methionine sulfoxide, the living cell can repair methionine-damaged proteins and salvage free methionine under oxidative stress conditions. Here, we report about the pivotal role of the selenocysteine residue in the protein putative active site by site-directed mutagenesis directed to the selenocysteine codon. Using theEscherichia coli SECIS (selenocysteine insertion sequence) element, needed for the recognition of the UGA codon as a selenocysteine codon in E. coli, we expressed the seleno-MsrB as a recombinant selenoprotein inE. coli . The recombinant seleno-MsrB has been shown to be much more active than the cysteine mutant, whereas the mutations to alanine and serine rendered the protein inactive. Although the yields of expression of the full-length N-terminus and C-terminus His-tagged seleno-MsrB were only 3% (of the total MsrB expressed), the C-terminus His-tagged protein enabled us to get a pure preparation of the seleno-MsrB. Using both recombinant selenoproteins, the N-terminus His-tagged and the C-terminus His-tagged proteins, we were able to determine the specific activities of the recombinant seleno-MsrB, which were found to be much higher than the cysteine mutant homologue. This finding confirmed our suggestion that the selenocysteine is essential for maintaining high reducing activity of MsrB. In addition, using radioactive selenium we were able to determine the in vivo presence of MsrB as a selenoprotein in mammalian cell cultures. [copy ] 2002 Elsevier Science (USA) JF - Biochemical and Biophysical Research Communications AU - Bar-Noy, S AU - Moskovitz, J AD - Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 2002/10/04/ PY - 2002 DA - 2002 Oct 04 SP - 956 EP - 961 PB - Academic Press VL - 297 IS - 4 SN - 0006-291X, 0006-291X KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts B: Bacteriology KW - Site-directed mutagenesis KW - selenoproteins KW - Alanine KW - C-Terminus KW - Selenocysteine KW - Enzymes KW - Cell culture KW - R form KW - Insertion sequences KW - Methionine KW - N-Terminus KW - Selenium KW - reductase KW - Mammalian cells KW - Oxidative stress KW - Cysteine KW - S form KW - Escherichia coli KW - Codons KW - Mutation KW - Serine KW - J 02410:Animal Diseases KW - A 01490:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20194581?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+Biophysical+Research+Communications&rft.atitle=Mouse+methionine+sulfoxide+reductase+B%3A+effect+of+selenocysteine+incorporation+on+its+activity+and+expression+of+the+seleno-containing+enzyme+in+bacterial+and+mammalian+cells&rft.au=Bar-Noy%2C+S%3BMoskovitz%2C+J&rft.aulast=Bar-Noy&rft.aufirst=S&rft.date=2002-10-04&rft.volume=297&rft.issue=4&rft.spage=956&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+Biophysical+Research+Communications&rft.issn=0006291X&rft_id=info:doi/10.1016%2FS0006-291X%2802%2902314-8 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-05-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Site-directed mutagenesis; selenoproteins; Alanine; C-Terminus; Selenocysteine; Enzymes; Cell culture; R form; Insertion sequences; Methionine; N-Terminus; Selenium; reductase; Mammalian cells; S form; Cysteine; Oxidative stress; Codons; Mutation; Serine; Escherichia coli DO - http://dx.doi.org/10.1016/S0006-291X(02)02314-8 ER - TY - JOUR T1 - Plasmodium Chloroquine Resistance and the Search for a Replacement Antimalarial Drug AN - 18496280; 5463382 AB - Genetic and biochemical research is providing new information on the mechanism of chloroquine resistance. Drug discovery initiatives are finding new leads that have favorable pharmaceutical properties and efficacy against chloroquine-resistant malaria. JF - Science (Washington) AU - Wellems, TE AD - Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA, tew@helix.nih.gov Y1 - 2002/10/04/ PY - 2002 DA - 2002 Oct 04 SP - 124 EP - 126 PB - American Association for the Advancement of Science VL - 298 IS - 5591 SN - 0036-8075, 0036-8075 KW - Chloroquine KW - Mosquitoes KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; ASFA 3: Aquatic Pollution & Environmental Quality KW - Q5 01524:Public health, medicines, dangerous organisms KW - K 03090:Protozoa: human UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18496280?accountid=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=Science+%28Washington%29&rft.atitle=Plasmodium+Chloroquine+Resistance+and+the+Search+for+a+Replacement+Antimalarial+Drug&rft.au=Wellems%2C+TE&rft.aulast=Wellems&rft.aufirst=TE&rft.date=2002-10-04&rft.volume=298&rft.issue=5591&rft.spage=124&rft.isbn=&rft.btitle=&rft.title=Science+%28Washington%29&rft.issn=00368075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Malaria--A Shadow over Africa AN - 18493964; 5463380 AB - Reduction in severe disease and death from falciparum malaria in Africa requires new, more effective and inexpensive public health measures. The completed genomes of Plasmodium falciparum and its vector Anopheles gambiae represent a big step toward the discovery of these needed tools. JF - Science (Washington) AU - Miller, L H AU - Greenwood, B AD - Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA Y1 - 2002/10/04/ PY - 2002 DA - 2002 Oct 04 SP - 121 EP - 122 PB - American Association for the Advancement of Science VL - 298 IS - 5591 SN - 0036-8075, 0036-8075 KW - Mosquitoes KW - aquatic insects KW - ASFA 1: Biological Sciences & Living Resources; Entomology Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology; ASFA 3: Aquatic Pollution & Environmental Quality KW - Freshwater KW - Q5 01524:Public health, medicines, dangerous organisms KW - K 03090:Protozoa: human KW - Z 05206:Medical & veterinary entomology KW - Q1 01305:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18493964?accountid=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=Science+%28Washington%29&rft.atitle=Malaria--A+Shadow+over+Africa&rft.au=Miller%2C+L+H%3BGreenwood%2C+B&rft.aulast=Miller&rft.aufirst=L&rft.date=2002-10-04&rft.volume=298&rft.issue=5591&rft.spage=121&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 - Freshwater ER - TY - JOUR T1 - Mismatch negativity of the color modality during a selective attention task to auditory stimuli in children with mental retardation. AN - 85362221; pmid-12427518 AB - Event-related potentials (ERPs) in response to a stimulus change in the visual color modality were recorded in normal subjects and children with mental retardation (MR) under selective attention conditions with auditory stimuli. The paradigm included the presentation of a standard (blue color screen, B) or deviant (red, R, or greenish blue color screen, GB) visual stimulus, and a target or non-target tone burst stimulus. In Experiment 1, negativity of the subtracted waveform in response to visual stimuli with a latency of 250-280 ms was clearly observed in the ERPs of normal adults. These potentials prominently appeared at posterior sites in one condition, for which the deviant was GB, but were frontal site-dominant for the other condition. A P300 response to visual deviance was not observed in the GB-B paradigm and the subtracted negativity for this paradigm seemed to be more evident than that for the R-B paradigm. The subtracted negativities could be detected in the range of 180-400 ms after the stimulus onset in control children for the GB-B paradigm. The grand average waves of subtracted ERPs in normal children showed a similar distribution to that in normal adults. Similar subtracted potentials could be recorded with the same paradigm in children with MR, however, the negativities were different in waveform and spatial distribution than in controls. Therefore, the subtracted negativity of the present visual modality represented the analogue of the auditory mismatch negativity (MMN), and so-called 'visual MMN' was detectable in children and even in MR patients when the selective attention was directed to other stimuli.Copyright 2002 Elsevier Science B.V. JF - Brain & development AU - Horimoto, Reiko AU - Inagaki, Masumi AU - Yano, Takemi AU - Sata, Yoshimi AU - Kaga, Makiko AD - Department of Developmental Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, 1-7-3 Kohnodai, Ichikawa 272-0827, Japan. Y1 - 2002/10// PY - 2002 DA - Oct 2002 SP - 703 EP - 709 VL - 24 IS - 7 SN - 0387-7604, 0387-7604 KW - Index Medicus KW - National Library of Medicine KW - Acoustic Stimulation KW - Adolescent KW - Adult KW - Attention: physiology KW - Child KW - Color Perception KW - Event-Related Potentials, P300: physiology KW - *Evoked Potentials: physiology KW - *Evoked Potentials, Visual: physiology KW - Female KW - Humans KW - *Intellectual Disability: physiopathology KW - Male KW - Photic Stimulation KW - Visual Perception: physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85362221?accountid=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+%26+development&rft.atitle=Mismatch+negativity+of+the+color+modality+during+a+selective+attention+task+to+auditory+stimuli+in+children+with+mental+retardation.&rft.au=Horimoto%2C+Reiko%3BInagaki%2C+Masumi%3BYano%2C+Takemi%3BSata%2C+Yoshimi%3BKaga%2C+Makiko&rft.aulast=Horimoto&rft.aufirst=Reiko&rft.date=2002-10-01&rft.volume=24&rft.issue=7&rft.spage=703&rft.isbn=&rft.btitle=&rft.title=Brain+%26+development&rft.issn=03877604&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Immortalization of rat eustachian tube epithelial cells by adenovirus 12-simian virus 40 hybrid virus. AN - 85359296; pmid-12389862 AB - The eustachian tube epithelial cells play an important role in the initial pathogenesis of otitis media. In order to study the role of the eustachian tube epithelial cells in the pathogenesis of otitis media, we have established a rat eustachian tube epithelial cell line. The cell line was derived by infecting primary cultures of eustachian tube epithelial cells with the adenovirus 12-simian virus 40 (Adl2-SV40) hybrid virus. The immortalized cells have retained the morphological characteristics of the parental cells and show positive staining with anti-cytokeratin antibodies (a marker for epithelial cells), but not with anti-vimentin antibodies (a fibroblast marker). The cells have been in continuous culture for more than 10 months and have undergone 38 passages. Western blotting and cell staining have confirmed the expression of the SV40 T antigen and p53. Chromosomal analysis indicates that the cell line is aneuploid and derived from male rat epithelial cells. Together, our results suggest that the cell line originated from eustachian tube epithelial cells from a male rat and was successfully immortalized by the Ad12-SV40 virus. JF - The Annals of otology, rhinology, and laryngology AU - Jin, Sunji AU - Moon, Sung-Kyun AU - Gu, Xin-Xing AU - Ueyama, Shigehiro AU - Rhim, Johng S AU - Lim, David J AD - Laboratory of Immunology, National Institute on Deafness and Other Communication Disorders, Bethesda, Maryland, USA. Y1 - 2002/10// PY - 2002 DA - Oct 2002 SP - 919 EP - 925 VL - 111 IS - 10 SN - 0003-4894, 0003-4894 KW - National Library of Medicine KW - *Adenoviridae: genetics KW - Animals KW - Blotting, Western KW - Cell Culture Techniques KW - Cell Line: virology KW - Cell Line, Transformed KW - *Cell Transformation, Viral KW - Culture Media KW - *Epithelial Cells KW - *Eustachian Tube: cytology KW - Hybridization, Genetic KW - Immunohistochemistry KW - Karyotyping KW - Male KW - Otitis Media: etiology KW - Rats KW - Rats, Inbred WKY KW - *Simian virus 40: genetics KW - Time Factors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85359296?accountid=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+Annals+of+otology%2C+rhinology%2C+and+laryngology&rft.atitle=Immortalization+of+rat+eustachian+tube+epithelial+cells+by+adenovirus+12-simian+virus+40+hybrid+virus.&rft.au=Jin%2C+Sunji%3BMoon%2C+Sung-Kyun%3BGu%2C+Xin-Xing%3BUeyama%2C+Shigehiro%3BRhim%2C+Johng+S%3BLim%2C+David+J&rft.aulast=Jin&rft.aufirst=Sunji&rft.date=2002-10-01&rft.volume=111&rft.issue=10&rft.spage=919&rft.isbn=&rft.btitle=&rft.title=The+Annals+of+otology%2C+rhinology%2C+and+laryngology&rft.issn=00034894&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Toward Dynamic Assessment of Reading: Applying Metacognitive Awareness Guidance to Reading Assessment Tasks AN - 85352395; llba-200304785 AB - This paper focuses on research that aimed to provide a theoretical-practical framework to link literacy assessment practices with learning theory. An experimental study was designed with reference to three theoretical axes: metacognitive awareness theory, schema theory & the Vygotskian zone of proximal development. The study tested the effect of using written metacognitive awareness guidance (MCAG) as a tool for activating & engaging learners' habits of mind while processing authentic reading assessment tasks taken from Israeli kits of assessment tasks (Guterman, 2000). The study on grade 4 pupils (N = 300) used three modalities: a control group, which received no treatment; a placebo group, which received content instructions; & a treatment group, which was given written MCAG. The findings confirmed that applying metacognitive awareness guidance to reading assessment tasks makes a difference in the learners' levels of performance & achievement on those tasks, & also increases learners' chances of internalizing the guidance components. 7 Tables, 1 Figure, 28 References. Adapted from the source document JF - Journal of Research in Reading AU - Guterman, Eva AD - Section Social & Emotional Development, National Instit Child Health & Human Development, Bethesda, MD guterman@mail.nih.gov Y1 - 2002/10// PY - 2002 DA - Oct 2002 SP - 283 EP - 298 VL - 25 IS - 3 SN - 0141-0423, 0141-0423 KW - *Literacy (48550) KW - *Reading Acquisition (70650) KW - *Children (11850) KW - *Metalinguistic Awareness (53180) KW - *Metacognition (53100) KW - *Diagnostic Tests (18550) KW - *Learning Theories (46100) KW - article KW - 4120: applied linguistics; reading testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85352395?accountid=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+Research+in+Reading&rft.atitle=Toward+Dynamic+Assessment+of+Reading%3A+Applying+Metacognitive+Awareness+Guidance+to+Reading+Assessment+Tasks&rft.au=Guterman%2C+Eva&rft.aulast=Guterman&rft.aufirst=Eva&rft.date=2002-10-01&rft.volume=25&rft.issue=3&rft.spage=283&rft.isbn=&rft.btitle=&rft.title=Journal+of+Research+in+Reading&rft.issn=01410423&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2003-10-01 N1 - Last updated - 2014-06-17 N1 - CODEN - JRREDE N1 - SubjectsTermNotLitGenreText - *Metacognition (53100); *Reading Acquisition (70650); *Metalinguistic Awareness (53180); *Learning Theories (46100); *Literacy (48550); *Children (11850); *Diagnostic Tests (18550) ER - TY - JOUR T1 - Strategies to improve neuroreceptor parameter estimation by linear regression analysis. AN - 85278428; pmid-12368666 AB - In an attempt to improve neuroreceptor distribution volume (V) estimates, the authors evaluated three alternative linear methods to Logan graphical analysis (GA): GA using total least squares (TLS), and two multilinear analyses, MA1 and MA2, based on mathematical rearrangement of GA equation and two-tissue compartments, respectively, using simulated and actual PET data of two receptor tracers, [(18)F]FCWAY and [(11)C]MDL 100,907. For simulations, all three methods decreased the noise-induced GA bias (up to 30%) at the expense of increased variability. The bias reduction was most pronounced for MA1, moderate to large for MA2, and modest to moderate for TLS. In addition, GA, TLS, and MA1, methods that used only a portion of the data (T > t*, chosen by an automatic process), showed a small underestimation for [(11)C]MDL 100,907 with its slow kinetics, due to selection of t* before the true point of linearity. These noniterative methods are computationally simple, allowing efficient pixelwise parameter estimation. For tracers with kinetics that permit t* to be accurately identified within the study duration, MA1 appears to be the best. For tracers with slow kinetics and low to moderate noise, however, MA2 may provide the lowest bias while maintaining computational ease for pixelwise parameter estimation. JF - Journal of Cerebral Blood Flow and Metabolism AU - Ichise Masanori AU - Toyama, Hiroshi AU - Innis, Robert B AU - Carson, Richard E AD - Molecular Imaging Branch, National Institutes of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 2002 SP - 1271 EP - 1281 VL - 22 IS - 10 SN - 0271-678X, 0271-678X KW - Regression Analysis KW - Reproducibility of Results KW - Human KW - Brain KW - Raphe Nuclei KW - Basal Ganglia KW - Mathematics KW - Kinetics KW - Fluorine Radioisotopes KW - Tomography, Emission-Computed KW - Models, Neurological KW - Observer Variation KW - Receptors, Sensory UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85278428?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Cerebral+Blood+Flow+and+Metabolism&rft.atitle=Strategies+to+improve+neuroreceptor+parameter+estimation+by+linear+regression+analysis.&rft.au=Ichise+Masanori%3BToyama%2C+Hiroshi%3BInnis%2C+Robert+B%3BCarson%2C+Richard+E&rft.aulast=Ichise+Masanori&rft.aufirst=&rft.date=2002-10-01&rft.volume=22&rft.issue=10&rft.spage=1271&rft.isbn=&rft.btitle=&rft.title=Journal+of+Cerebral+Blood+Flow+and+Metabolism&rft.issn=0271678X&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Epidemiology and prevention of colorectal cancer. AN - 72803120; 12507200 AB - CRC, the second-leading cause of cancer death in the United States, is a highly preventable disease. Ironically, available and effective screening technologies are not consistently applied, even as new ones are developed. This discordance between preventive opportunity and practice conveys a sobering message regarding nontechnologic issues that must be addressed if the promise of CRC prevention is to be realized. Our response to this message will determine the public health impact of cancer prevention. In the 1980s, cancer chemoprevention was regarded as scientific speculation. Within the last decade, however, cancer has been recognized as a late, nonobligate stage of carcinogenesis, a chronic process that provides time and targets for preventive intervention. Further advances are emerging out of rigorous clinical testing, which remains the limiting factor in transforming ingenious concepts into useful tools for the prevention of CRC. The challenges and rewards of participation in chemoprevention research--both as patients and health care providers-have never been greater. JF - The Surgical clinics of North America AU - Hawk, Ernest T AU - Limburg, Paul J AU - Viner, Jaye L AD - Gastrointestinal and Other Cancers Research Group, National Cancer Institute, Division of Cancer Prevention, EPN, Suite 2141, 6130 Executive Boulevard, Bethesda, MD 20892-7317, USA. eh51p@nih.gov Y1 - 2002/10// PY - 2002 DA - October 2002 SP - 905 EP - 941 VL - 82 IS - 5 SN - 0039-6109, 0039-6109 KW - Biomarkers, Tumor KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Physical Fitness KW - SEER Program KW - Chemoprevention -- methods KW - Smoking -- adverse effects KW - Life Style KW - Primary Prevention KW - Risk Factors KW - Biomarkers, Tumor -- analysis KW - Incidence KW - Diet KW - United States -- epidemiology KW - Emigration and Immigration KW - Colorectal Neoplasms -- epidemiology KW - Colorectal Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72803120?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Epidemiology+and+prevention+of+colorectal+cancer.&rft.au=Hawk%2C+Ernest+T%3BLimburg%2C+Paul+J%3BViner%2C+Jaye+L&rft.aulast=Hawk&rft.aufirst=Ernest&rft.date=2002-10-01&rft.volume=82&rft.issue=5&rft.spage=905&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 - 2003-01-29 N1 - Date created - 2002-12-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Acute ethanol binge followed by withdrawal regulates production of reactive oxygen species and cytokine-induced neutrophil chemoattractant and liver injury during reperfusion after hepatic ischemia. AN - 72759211; 12470499 AB - This work tests the hypothesis that withdrawal from an acute ethanol binge regulates the production of reactive oxygen species (ROS) and chemokines by Kupffer cells, and as a result compromises or protects the liver from injury. Male Sprague-Dawley rats received an intravenous ethanol bolus (1.75 g/kg), followed by an intravenous infusion of 200-300 mg/kg/h for 12 h. At 12 h, ethanol infusion was stopped and replaced by saline. At 18 h, rats were subjected to 45 min of partial hepatic ischemia, followed by 0-24 h of reperfusion (I/R). At specific time points, Kupffer cells were isolated for superoxide anion assay and CINC (cytokine-induced neutrophil chemoattractant) and MIP-2 (macrophage inflammatory protein-2) production in vitro. Alanine transferase (ALT) activity, endotoxin, CINC, and MIP-2 were measured in serum samples taken at appropriate intervals. Results show that at 3 h post reperfusion, serum ALT was significantly elevated in the ethanol-treated group + I/R, compared with the saline + I/R group. ROS production by Kupffer cells at this time was also significantly increased compared with the saline + I/R group. However, ethanol withdrawal + I/R did not significantly alter CINC and MIP-2 production at 3 h of reperfusion. After 24 h, serum ALT was lower in the ethanol + I/R group than in the saline + I/R group. Superoxide anion and MIP-2 releases by Kupffer cells were not statistically significantly different between these two groups at this time. CINC production by Kupffer cells from the ethanol-treated + I/R group was significantly lower than in the saline + I/R group. Concomitantly, CINC and nuclear factor-kappaB (NF-kappaB) mRNAs and NF-kappaB translocation and binding in Kupffer cells in this treatment group were down-regulated. Moreover, the number of polymorphonuclear neutrophils (PMNs) sequestered in the liver was significantly lower in the ethanol + I/R group than in the saline-treated group. ROS and chemokine productions in sham animals with or without ethanol were lower than in the I/R group. These data suggest that acute ethanol binge followed by withdrawal may compromise the liver to injury during the early phase, whereas in the later phase it may be protective. Furthermore, these results support the notion that Kupffer cells are involved in hepatic injury in the early phase, whereas PMNs participate more actively during the later phase of reperfusion. JF - Antioxidants & redox signaling AU - Bautista, Abraham P AD - Department of Physiology and National Institute on Alcohol Abuse and Alcoholism-Sponsored Alcohol Research Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA. abauti123@cs.com Y1 - 2002/10// PY - 2002 DA - October 2002 SP - 721 EP - 731 VL - 4 IS - 5 SN - 1523-0864, 1523-0864 KW - NF-kappa B KW - 0 KW - Reactive Oxygen Species KW - Tumor Necrosis Factor-alpha KW - Superoxides KW - 11062-77-4 KW - Ethanol KW - 3K9958V90M KW - Alanine Transaminase KW - EC 2.6.1.2 KW - Index Medicus KW - Animals KW - Substance Withdrawal Syndrome KW - Infusions, Intravenous KW - Injections, Intravenous KW - Disease Models, Animal KW - Reverse Transcriptase Polymerase Chain Reaction KW - Tumor Necrosis Factor-alpha -- genetics KW - NF-kappa B -- genetics KW - Rats KW - Reperfusion KW - Superoxides -- metabolism KW - Alanine Transaminase -- blood KW - Rats, Sprague-Dawley KW - Cells, Cultured KW - Gene Expression Regulation -- drug effects KW - Male KW - Reactive Oxygen Species -- metabolism KW - Liver -- blood supply KW - Alcoholic Intoxication -- physiopathology KW - Ethanol -- pharmacology KW - Kupffer Cells -- physiology KW - Ischemia -- physiopathology KW - Ethanol -- administration & dosage KW - Kupffer Cells -- drug effects KW - Liver -- physiology KW - Alcoholic Intoxication -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72759211?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antioxidants+%26+redox+signaling&rft.atitle=Acute+ethanol+binge+followed+by+withdrawal+regulates+production+of+reactive+oxygen+species+and+cytokine-induced+neutrophil+chemoattractant+and+liver+injury+during+reperfusion+after+hepatic+ischemia.&rft.au=Bautista%2C+Abraham+P&rft.aulast=Bautista&rft.aufirst=Abraham&rft.date=2002-10-01&rft.volume=4&rft.issue=5&rft.spage=721&rft.isbn=&rft.btitle=&rft.title=Antioxidants+%26+redox+signaling&rft.issn=15230864&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-17 N1 - Date created - 2002-12-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Specific up-regulation of CRH or AVP secretion by acetylcholine or lipopolysaccharide in inflammatory susceptible Lewis rat fetal hypothalamic cells. AN - 72721164; 12458034 AB - Lewis (LEW/N) rats, compared to Fischer (F344/N) rats, are susceptible to inflammatory/autoimmune diseases, in part, as a result of their blunted hypothalamic-pituitary-adrenal (HPA) axis responses. We examined regulation of LEW/N and F344/N fetal hypothalamic cell secretion of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP), two major HPA axis mediators, by inflammatory and neurotransmitter stimuli. Interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and protein kinase A (PKA) and protein kinase C (PKC) activators did not affect LEW/N basal secretion. Compared to F344/N, LEW/N cells were hyporesponsive to lipopolysaccharide (LPS), serotonin (5-HT), and acetylcholine chloride (ACh). However, LPS-induced AVP release and ACh-evoked CRH secretion in LEW/N were comparable with those of F344/N. Our findings suggest that the blunted LEW/N neuropeptide response was more likely related to components of second messenger systems, rather than to any one specific stimulus. JF - Journal of neuroimmunology AU - Wei, Rongtai AU - Phillips, Terry M AU - Sternberg, Esther M AD - Integrative Neural Immune Program, NIMH, NIH, 36 Convent Drive, Room 1A23, Bethesda, MD 20892-4020, USA. Y1 - 2002/10// PY - 2002 DA - October 2002 SP - 31 EP - 40 VL - 131 IS - 1-2 SN - 0165-5728, 0165-5728 KW - Interleukin-1 KW - 0 KW - Interleukin-6 KW - Lipopolysaccharides KW - Tumor Necrosis Factor-alpha KW - Arginine Vasopressin KW - 113-79-1 KW - Colforsin KW - 1F7A44V6OU KW - Serotonin KW - 333DO1RDJY KW - Corticotropin-Releasing Hormone KW - 9015-71-8 KW - Acetylcholine KW - N9YNS0M02X KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Serotonin -- pharmacology KW - Interleukin-1 -- pharmacology KW - Rats, Inbred Lew KW - Dose-Response Relationship, Drug KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Interleukin-6 -- pharmacology KW - Rats KW - Colforsin -- pharmacology KW - Rats, Inbred F344 KW - Cells, Cultured KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Inflammation -- metabolism KW - Up-Regulation KW - Species Specificity KW - Hypothalamus -- secretion KW - Hypothalamus -- drug effects KW - Corticotropin-Releasing Hormone -- biosynthesis KW - Lipopolysaccharides -- pharmacology KW - Arginine Vasopressin -- secretion KW - Hypothalamus -- embryology KW - Acetylcholine -- pharmacology KW - Corticotropin-Releasing Hormone -- secretion KW - Arginine Vasopressin -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72721164?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Specific+up-regulation+of+CRH+or+AVP+secretion+by+acetylcholine+or+lipopolysaccharide+in+inflammatory+susceptible+Lewis+rat+fetal+hypothalamic+cells.&rft.au=Wei%2C+Rongtai%3BPhillips%2C+Terry+M%3BSternberg%2C+Esther+M&rft.aulast=Wei&rft.aufirst=Rongtai&rft.date=2002-10-01&rft.volume=131&rft.issue=1-2&rft.spage=31&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 - 2002-12-09 N1 - Date created - 2002-11-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Update on hematopoietic stem cell gene transfer using non-human primate models. AN - 72692324; 12435050 AB - Gene transfer into hematopoietic stem cells (HSCs) using integrating vectors is an attractive treatment strategy for many genetic and hematological diseases. The preclinical testing of gene transfer approaches in non-human primates and other large animal models will be invaluable in order to assess toxicity and efficacy, as their HSC biology is much more closely related to humans than murine models. Gene transfer studies targeting HSCs in non-human primates have focused on optimizing gene transfer efficiency, and significant advances have been achieved using standard retroviral vectors. Utilization of lentiviral and other alternative vector system are still very preliminary in large animal models. Further development of post-transduction selection and/or expansion strategies using drug-resistance or amplifier genes will most likely be necessary for clinical applications. JF - Current opinion in molecular therapeutics AU - Hu, Jiong AU - Dunbar, Cynthia E AD - Molecular Hematopoiesis Hematology Branch, National Heart Lung and Blood Institutes, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2002/10// PY - 2002 DA - October 2002 SP - 482 EP - 490 VL - 4 IS - 5 SN - 1464-8431, 1464-8431 KW - Index Medicus KW - Animals KW - Genetic Vectors KW - Transduction, Genetic KW - Retroviridae -- genetics KW - Primates KW - Transfection KW - Hematopoietic Stem Cells UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72692324?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+molecular+therapeutics&rft.atitle=Update+on+hematopoietic+stem+cell+gene+transfer+using+non-human+primate+models.&rft.au=Hu%2C+Jiong%3BDunbar%2C+Cynthia+E&rft.aulast=Hu&rft.aufirst=Jiong&rft.date=2002-10-01&rft.volume=4&rft.issue=5&rft.spage=482&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+molecular+therapeutics&rft.issn=14648431&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-01 N1 - Date created - 2002-11-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of protein kinases in neuropeptide gene regulation by PACAP in chromaffin cells: a pharmacological and bioinformatic analysis. AN - 72688845; 12438168 AB - Pituitary adenylate cyclase-activating polypeptide (PACAP) is an adrenomedullary cotransmitter that along with acetylcholine is responsible for driving catecholamine and neuropeptide biosynthesis and secretion from chromaffin cells in response to stimulation of the splanchnic nerve. Two neuropeptides whose biosynthesis is regulated by PACAP include enkephalin and vasoactive intestinal polypeptide (VIP). Occupancy of PAC1 PACAP receptors on chromaffin cells can result in elevation of cyclic AMP, inositol phosphates, and intracellular calcium. The proenkephalin A and VIP genes are transcriptionally responsive to signals generated within all three pathways, and potentially by combinatorial activation of these pathways as well. The characteristics of PACAP regulation of enkephalin and VIP biosynthesis were examined pharmacologically for evidence of involvement of several serine/threonine protein kinases activated by cAMP, IP3, and/or calcium, including calmodulin kinase II, protein kinase A, and protein kinase C. Evidence is presented for the differential involvement of these protein kinases in regulation of enkephalin and VIP biosynthesis in chromaffin cells, and for a prominent role of the mixed-function (tyrosine and serine/threonine) MAP kinase family in mediating transcriptional activation of neuropeptide genes by PACAP. JF - Annals of the New York Academy of Sciences AU - Hamelink, Carol AU - Lee, Hyeon-Woo AU - Hsu, Chang-Mei AU - Eiden, Lee E AD - Section on Molecular Neuroscience, NIMH Intramural Research Program, Bethesda, Maryland 20892, USA. Y1 - 2002/10// PY - 2002 DA - October 2002 SP - 474 EP - 490 VL - 971 SN - 0077-8923, 0077-8923 KW - Enkephalins KW - 0 KW - Neuropeptides KW - Pituitary Adenylate Cyclase-Activating Polypeptide KW - Protein Precursors KW - RNA, Messenger KW - proenkephalin KW - Cyclic AMP KW - E0399OZS9N KW - Protein Kinases KW - EC 2.7.- KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Software KW - Animals KW - Databases as Topic KW - Transcription, Genetic KW - Computational Biology KW - Transcriptional Activation KW - Calcium -- metabolism KW - Protein Kinase C -- metabolism KW - Cattle KW - Enkephalins -- biosynthesis KW - RNA, Messenger -- metabolism KW - Cells, Cultured KW - Protein Precursors -- biosynthesis KW - Cyclic AMP -- metabolism KW - Gene Expression Regulation KW - Neuropeptides -- metabolism KW - Neuropeptides -- physiology KW - Protein Kinases -- physiology KW - Chromaffin Cells -- metabolism KW - Neuropeptides -- biosynthesis KW - Neuropeptides -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72688845?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Role+of+protein+kinases+in+neuropeptide+gene+regulation+by+PACAP+in+chromaffin+cells%3A+a+pharmacological+and+bioinformatic+analysis.&rft.au=Hamelink%2C+Carol%3BLee%2C+Hyeon-Woo%3BHsu%2C+Chang-Mei%3BEiden%2C+Lee+E&rft.aulast=Hamelink&rft.aufirst=Carol&rft.date=2002-10-01&rft.volume=971&rft.issue=&rft.spage=474&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 - 2002-12-16 N1 - Date created - 2002-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Partnership for Parkinson's disease research: patient-researcher-clinician-sponsor. AN - 72681723; 12428716 AB - Parkinson's disease (PD) appears to arise from the interaction of three events-an individual's inherited genetic susceptibility, their subsequent environmental exposures, and their age. We clearly need to intensify efforts to understand the environmental triggers of PD, the importance of the timing of exposure to these triggers, and the interplay between these exposures and a persons underlying genetic constitution and susceptibilities. This knowledge, once generated, will lead to better detection of the earliest stages of PD, to improved therapeutics, and most importantly, to viable prevention strategies so that people need not suffer from environmentally-caused PD. Many promising lines of investigation are already supported by the National Institute of Environmental Health Sciences (NIEHS), National Institute of Neurological Disorders and Stroke (NINDS), and the National Institute of Aging (NIA) and other public and private organizations. In order to accelerate the pace of progress in this field, the NIEHS is developing a Consortium Centers Program that will provide a formal mechanism for "cross-talk" between PD clinicians, basic research scientists, and patient advocates. The Consortium will seek to identify and support novel approaches and research ventures that might not otherwise be pursued by scientists working in isolation. The NIEHS will also continue to explore ways to promote more mechanism-based research to understand putative environmental triggers for PD in concert with defined genetic susceptibilities. JF - Neurotoxicology AU - Olden, Kenneth AU - Guthrie, Janet AU - Lawler, Cindy AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. olden@niehs.nih.gov Y1 - 2002/10// PY - 2002 DA - October 2002 SP - 451 EP - 456 VL - 23 IS - 4-5 SN - 0161-813X, 0161-813X KW - Index Medicus KW - Humans KW - Patients KW - Research KW - Research Support as Topic KW - Parkinson Disease -- etiology KW - Parkinson Disease -- physiopathology KW - Parkinson Disease -- genetics KW - Parkinson Disease -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72681723?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurotoxicology&rft.atitle=Partnership+for+Parkinson%27s+disease+research%3A+patient-researcher-clinician-sponsor.&rft.au=Olden%2C+Kenneth%3BGuthrie%2C+Janet%3BLawler%2C+Cindy&rft.aulast=Olden&rft.aufirst=Kenneth&rft.date=2002-10-01&rft.volume=23&rft.issue=4-5&rft.spage=451&rft.isbn=&rft.btitle=&rft.title=Neurotoxicology&rft.issn=0161813X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-12-16 N1 - Date created - 2002-11-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gene therapy-based treatment for HIV-positive patients with malignancies. AN - 72681426; 12427287 AB - Gene therapy for the treatment of HIV has long been a goal of many investigators. The majority of trials have involved the use of lymphocytes transduced with vectors promoting resistance to HIV infection or replication. Unfortunately, the results have been less than encouraging with low-level marking and, more importantly, clearance of these lymphocytes from the circulation. Conversely, gene-modified hematopoietic stem cells appear able to introduce foreign transgenes while avoiding immunologic clearance. Furthermore, the use of less toxic conditioning regimens for allogeneic transplantation provides an attractive approach to conferring HIV resistance while allowing treatment of HIV-related disorders such as malignancies. This combination of nonmyeloablative allogeneic transplantation using gene-modified hematopoietic stem cell theoretically overcomes the high transplant mortality associated with traditional conditioning regimens in patients with HIV as well as providing a self-renewing source of HIV-resistant cells. To assess the safety and feasibility of such an approach, a clinical protocol was initiated in those patients infected with HIV with a hematologic malignancy meeting the standard indications for allogeneic transplantation and provided here is an update to the previously published original report. Only patient 1 received genetically modified cells. Both patients tolerated the procedure with no effect on viral load and improved CD4 counts, and patient 1 remains in complete remission from acute myelogenous leukemia 3 years post transplant. Patient 2 also achieved clinical remission from chemorefractory Hodgkin's disease but died of relapsed disease 12 months after transplantation. Vector-transduced cells remain detectable at low levels more than 3 years post-transplantation, suggesting the potential for gene therapy as a reasonable goal for the treatment of HIV. JF - Journal of hematotherapy & stem cell research AU - Kang, Elizabeth M AU - De Witte, Moniek AU - Malech, Harry AU - Morgan, Richard A AU - Carter, Charles AU - Leitman, Susan F AU - Childs, Richard AU - Barrett, A John AU - Little, Richard AU - Tisdale, John F AD - Molecular and Clinical Hematology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA. ElizabethK@intra.niddk.nih.gov Y1 - 2002/10// PY - 2002 DA - October 2002 SP - 809 EP - 816 VL - 11 IS - 5 SN - 1525-8165, 1525-8165 KW - CYBB protein, human KW - 0 KW - Gene Products, rev KW - Membrane Glycoproteins KW - rev Gene Products, Human Immunodeficiency Virus KW - NADPH Oxidase KW - EC 1.6.3.1 KW - Index Medicus KW - Cell Lineage KW - Humans KW - Transgenes KW - Clinical Trials as Topic KW - Genes, gag -- genetics KW - Transplantation, Homologous KW - Hodgkin Disease -- therapy KW - CD4-Positive T-Lymphocytes -- metabolism KW - Gene Products, rev -- genetics KW - Genetic Vectors KW - Treatment Outcome KW - Retroviridae -- genetics KW - Time Factors KW - Membrane Glycoproteins -- genetics KW - Neoplasms -- virology KW - HIV Infections -- complications KW - HIV Infections -- therapy KW - Genetic Therapy -- methods KW - Neoplasms -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72681426?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+hematotherapy+%26+stem+cell+research&rft.atitle=Gene+therapy-based+treatment+for+HIV-positive+patients+with+malignancies.&rft.au=Kang%2C+Elizabeth+M%3BDe+Witte%2C+Moniek%3BMalech%2C+Harry%3BMorgan%2C+Richard+A%3BCarter%2C+Charles%3BLeitman%2C+Susan+F%3BChilds%2C+Richard%3BBarrett%2C+A+John%3BLittle%2C+Richard%3BTisdale%2C+John+F&rft.aulast=Kang&rft.aufirst=Elizabeth&rft.date=2002-10-01&rft.volume=11&rft.issue=5&rft.spage=809&rft.isbn=&rft.btitle=&rft.title=Journal+of+hematotherapy+%26+stem+cell+research&rft.issn=15258165&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-26 N1 - Date created - 2002-11-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Correlation between pharmacological effects and plasma cocaine concentrations after smoked administration. AN - 72660255; 12422990 AB - The relationship between blood cocaine concentrations and pharmacological effects is of both theoretical and practical interest. This study utilized a computer-assisted smoking device for the delivery of three active doses (10, 20, and 40 mg) of cocaine base to seven human volunteers. Doses were administered in an ascending dose design with random placement of placebo. Physiological, subjective, and performance measures were collected concurrently with blood samples. Mean peak plasma cocaine concentrations were achieved at 2 min after the 20-mg and 40-mg doses and at 5 min after the 10-mg dose. Maximal responses in systolic and diastolic blood pressure, "feel", "good" drug, and drug "liking" subjective effects were also achieved immediately after drug administration. Pupil diameter and heart rate increases demonstrated a modest counter-clockwise hysteresis in relation to plasma cocaine concentrations shortly after dosing. Systolic and diastolic blood pressure, heart rate, and some subjective and performance measures of drug effect demonstrated a biphasic response after smoked cocaine. Initial increases above baseline levels were followed by an apparent compensatory decrease below baseline levels at a later time after smoked cocaine. Despite evidence of hysteresis and biphasic responses for some measures, linear correlation was obtained between mean plasma cocaine concentrations and several pharmacological effects over a period of 4 h after dosing. Several subjective and cardiovascular measures returned to baseline levels in the presence of detectable concentrations of cocaine. JF - Journal of analytical toxicology AU - Jenkins, Amanda J AU - Keenan, Robert M AU - Henningfield, Jack E AU - Cone, Edward J AD - Addiction Research Center, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, Maryland 21224, USA. cccotox@inetmail.att.net Y1 - 2002/10// PY - 2002 DA - October 2002 SP - 382 EP - 392 VL - 26 IS - 7 SN - 0146-4760, 0146-4760 KW - Crack Cocaine KW - 0 KW - Index Medicus KW - Heart Rate -- drug effects KW - Psychomotor Performance -- drug effects KW - Double-Blind Method KW - Dose-Response Relationship, Drug KW - Humans KW - Adult KW - Blood Pressure -- drug effects KW - Administration, Inhalation KW - Male KW - Emotions -- drug effects KW - Smoking KW - Crack Cocaine -- administration & dosage KW - Crack Cocaine -- pharmacokinetics KW - Cocaine-Related Disorders -- physiopathology KW - Cocaine-Related Disorders -- blood KW - Crack Cocaine -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72660255?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Correlation+between+pharmacological+effects+and+plasma+cocaine+concentrations+after+smoked+administration.&rft.au=Jenkins%2C+Amanda+J%3BKeenan%2C+Robert+M%3BHenningfield%2C+Jack+E%3BCone%2C+Edward+J&rft.aulast=Jenkins&rft.aufirst=Amanda&rft.date=2002-10-01&rft.volume=26&rft.issue=7&rft.spage=382&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 - 2003-04-01 N1 - Date created - 2002-11-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Medical radiation, family history of cancer, and benign breast disease in relation to breast cancer risk in young women, USA. AN - 72660121; 12420949 AB - In previous studies breast cancer risk has been increased among women who received high doses (above 100-200 cGy) of ionizing radiation or those exposed to lower doses prior to age 20. Some evidence suggests that such risk may be distinctly elevated among women with a family history of breast or ovarian cancer (probably only carriers of specific gene mutations) and women with benign breast disease (BBD). A population-based case-control study in Los Angeles County obtained interview data from 744 women who were aged 40 or younger and diagnosed with breast cancer during 1983-1988, and from 744 matched controls. Women with a positive family history of breast or ovarian cancer reported cancer in a mother, sister, or grandmother. Women with BBD reported a physician diagnosis. Radiation exposure was defined as a history of either radiation therapy or moderate exposure to medical radiography. Breast cancer risk was elevated among women exposed to medical radiation prior to age 20 years (odds ratio (OR) = 1.4, 95% confidence interval (CI) = 1.2-1.8), relative to unexposed women. This increased risk was observed only among women with a history of BBD (OR = 2.4, 95% CI = 1.6-3.7). Overall, risk was not associated with exposure to medical radiation after age 20 years, although among women with a positive family history of breast or ovarian cancer, exposed women had an increased risk (OR= 1.8, 95% CI = 1.0-3.1). Breast cancer risk was not increased among women with a family history of breast/ovarian cancer exposed to medical radiation before age 20 years or those with BBD exposed to medical radiation after age 20 years. Study participants may have received radiation doses that are no longer common, hampering study generalizability. Although differences in recall between cases and controls cannot be completely excluded, women with BBD or a family history of breast cancer appear to have greater breast cancer risk following relatively low ionizing radiation exposure than other women in this study. JF - Cancer causes & control : CCC AU - Hill, Deirdre A AU - Preston-Martin, Susan AU - Ross, Ronald K AU - Bernstein, Leslie AD - Department of Preventive Medicine, University of Southern California, Keck School of Medicine, Norris Comprehensive Cancer Center, Los Angeles 90033, USA. dhill@mail.nih.gov Y1 - 2002/10// PY - 2002 DA - October 2002 SP - 711 EP - 718 VL - 13 IS - 8 SN - 0957-5243, 0957-5243 KW - Index Medicus KW - Breast -- radiation effects KW - Radiation Dosage KW - Ovarian Neoplasms -- genetics KW - Risk Factors KW - Humans KW - Adult KW - Case-Control Studies KW - Radiography -- adverse effects KW - Genetic Predisposition to Disease KW - Female KW - Radiotherapy -- adverse effects KW - Breast Neoplasms -- genetics KW - Neoplasms, Radiation-Induced -- etiology KW - Breast Neoplasms -- etiology KW - Breast Diseases -- complications KW - Neoplasms, Radiation-Induced -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72660121?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+causes+%26+control+%3A+CCC&rft.atitle=Medical+radiation%2C+family+history+of+cancer%2C+and+benign+breast+disease+in+relation+to+breast+cancer+risk+in+young+women%2C+USA.&rft.au=Hill%2C+Deirdre+A%3BPreston-Martin%2C+Susan%3BRoss%2C+Ronald+K%3BBernstein%2C+Leslie&rft.aulast=Hill&rft.aufirst=Deirdre&rft.date=2002-10-01&rft.volume=13&rft.issue=8&rft.spage=711&rft.isbn=&rft.btitle=&rft.title=Cancer+causes+%26+control+%3A+CCC&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-06 N1 - Date created - 2002-11-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Urinary elimination of cocaine metabolites in chronic cocaine users during cessation. AN - 72653191; 12422991 AB - We previously showed that chronic cocaine use by active illicit users produced a longer plasma half-life than expected based on acute low-dose cocaine studies. Here we report urinary excretion patterns of cocaine metabolites as benzoylecgonine (BE) equivalents from 18 of the same individuals, housed for up to 14 days on a closed research unit. In addition, we evaluated whether creatinine normalization of BE equivalents increased mean detection time and reduced mean within-subject variability. All urine voids (N = 953) were individually assayed; BE equivalents were determined semi-quantitatively by FPIA. Compared to concentration in first void after admission, BE equivalents decreased to approximately 33%, 8%, and 4% at 24, 48, and 72 h, respectively. Mean +/- SD (range) time to first negative specimen (BE equivalents < 300 ng/mL) was 43.6 +/- 17.1 (16-66) h. BE equivalents fluctuated considerably across successive specimens; 69% of participants tested positive at least once after testing negative, and the mean time to last positive specimen was 57.5 +/- 31.6 (11-147) h after the first specimen. Thus, mean cocaine metabolite detection times were consistent with prolonged elimination, with 63% of participants testing positive longer than the expected 48-h window of detection after admission to the unit. Mean time to last positive after last use of cocaine, known by self-report only, was approximately 81 +/- 34 (34-162) h. Creatinine normalization, with the cut-off of 300 ng BE equivalents/mg creatinine, increased detection time: mean time to first negative specimen was 54.8 +/- 20.7 (20-100) h, and mean time to last positive specimen was 88.4 +/- 51.0 (35.6-235) h. Compared with the concentration in the first void after admission, BE equivalents/creatinine decreased to approximately 56%, 6%, and 5% at 24, 48, and 72 h. However, creatinine normalization did not reduce the fluctuation of BE equivalents across successive specimens. Thus, creatinine normalized values may be useful when the goal is to maximize the probability or duration of cocaine metabolite detection, but may be less useful in determining whether an individual has used cocaine since a previous specimen collection. JF - Journal of analytical toxicology AU - Preston, Kenzie L AU - Epstein, David H AU - Cone, Edward J AU - Wtsadik, Abraham T AU - Huestis, Marilyn A AU - Moolchan, Eric T AD - Clinical Pharmacology and Therapeutics Research Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA. kpreston@intra.nida.nih.gov Y1 - 2002/10// PY - 2002 DA - October 2002 SP - 393 EP - 400 VL - 26 IS - 7 SN - 0146-4760, 0146-4760 KW - Crack Cocaine KW - 0 KW - benzoylecgonine KW - 5353I8I6YS KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Fluorescence Polarization Immunoassay KW - Half-Life KW - Substance Abuse Detection KW - Humans KW - Adult KW - Gas Chromatography-Mass Spectrometry KW - Male KW - Female KW - Crack Cocaine -- urine KW - Cocaine -- analogs & derivatives KW - Cocaine -- urine KW - Crack Cocaine -- analogs & derivatives KW - Cocaine-Related Disorders -- rehabilitation KW - Cocaine-Related Disorders -- urine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72653191?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Urinary+elimination+of+cocaine+metabolites+in+chronic+cocaine+users+during+cessation.&rft.au=Preston%2C+Kenzie+L%3BEpstein%2C+David+H%3BCone%2C+Edward+J%3BWtsadik%2C+Abraham+T%3BHuestis%2C+Marilyn+A%3BMoolchan%2C+Eric+T&rft.aulast=Preston&rft.aufirst=Kenzie&rft.date=2002-10-01&rft.volume=26&rft.issue=7&rft.spage=393&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 - 2003-04-01 N1 - Date created - 2002-11-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A longitudinal view of triggers and thresholds of suicidal behavior in depression. AN - 72649104; 12416595 AB - Recurrent brief depressive disorder (RBD) and major depressive disorder (MDD) share the same diagnostic picture of full-blown depression and are both associated with increased suicide attempt rates. However, longitudinal diagnostic shifts from RBD to MDD or vice versa, called "combined depression" (CD), have demonstrated a substantially higher risk of suicide attempts in epidemiologic and clinical studies. Following the stress-diathesis model of suicidal behavior, we compared possible triggers and thresholds for suicidal behavior among patients with RBD, MDD, and CD. RBD and MDD diagnoses were based on DSM-IV criteria. Furthermore, the goal of this study was to determine if impulsivity as an underlying factor could explain high suicide attempt rates in CD. A structured clinical interview evaluating comorbid Axis I and II disorders and RBD and a battery of instruments assessing suicidal behavior were administered to 101 patients with RBD (N = 27), MDD (N = 33), or CD (N = 41). Patients with CD showed significantly higher (p < .05) scores on measures of suicidal behavior in comparison with RBD and MDD patients. Together with comorbid substance abuse and marital status, CD was among the highest-ranking risk factors for suicide attempts. Impulsivity was identified as a major underlying factor, predicting 80.7% of suicide attempts. CD seems to be an important clinical risk factor for the prediction of suicide attempts, similar to risk factors such as substance use disorders and borderline personality disorder. All of these factors share the same diathesis for increased impulsivity and suicidal ideation, which could explain comorbidity and suicidal behavior. The coexistence of a greater propensity for suicidal ideation and impulsivity in RBD might also explain why such patients are more prone to attempt suicide, even if they do not, in the case of RBD, meet the duration criteria for MDD. JF - The Journal of clinical psychiatry AU - Pezawas, Lukas AU - Stamenkovic, Mara AU - Jagsch, Reinhold AU - Ackerl, Sandra AU - Putz, Christine AU - Stelzer, Barbara AU - Moffat, Rebecca R AU - Schindler, Shird AU - Aschauer, Harald AU - Kasper, Siegfried AD - Department of General Psychiatry, University of Vienna, Austria. pezawas@nariya.nimh.nih.gov Y1 - 2002/10// PY - 2002 DA - October 2002 SP - 866 EP - 873 VL - 63 IS - 10 SN - 0160-6689, 0160-6689 KW - Index Medicus KW - Models, Psychological KW - Age of Onset KW - Suicide, Attempted -- psychology KW - Humans KW - Aged KW - Substance-Related Disorders -- psychology KW - Longitudinal Studies KW - Recurrence KW - Comorbidity KW - Personality Disorders -- epidemiology KW - Austria -- epidemiology KW - Personality Disorders -- diagnosis KW - Factor Analysis, Statistical KW - Psychiatric Status Rating Scales KW - Suicide, Attempted -- statistics & numerical data KW - Adult KW - Middle Aged KW - Stress, Psychological -- epidemiology KW - Female KW - Male KW - Substance-Related Disorders -- epidemiology KW - Stress, Psychological -- psychology KW - Depressive Disorder -- epidemiology KW - Depressive Disorder -- psychology KW - Depressive Disorder -- diagnosis KW - Suicide -- statistics & numerical data KW - Suicide -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72649104?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+psychiatry&rft.atitle=A+longitudinal+view+of+triggers+and+thresholds+of+suicidal+behavior+in+depression.&rft.au=Pezawas%2C+Lukas%3BStamenkovic%2C+Mara%3BJagsch%2C+Reinhold%3BAckerl%2C+Sandra%3BPutz%2C+Christine%3BStelzer%2C+Barbara%3BMoffat%2C+Rebecca+R%3BSchindler%2C+Shird%3BAschauer%2C+Harald%3BKasper%2C+Siegfried&rft.aulast=Pezawas&rft.aufirst=Lukas&rft.date=2002-10-01&rft.volume=63&rft.issue=10&rft.spage=866&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+psychiatry&rft.issn=01606689&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-15 N1 - Date created - 2002-11-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Successful and safe perfusion of the primate brainstem: in vivo magnetic resonance imaging of macromolecular distribution during infusion. AN - 72633286; 12405380 AB - Intrinsic disease processes of the brainstem (gliomas, neurodegenerative disease, and others) have remained difficult or impossible to treat effectively because of limited drug penetration across the blood-brainstem barrier with conventional delivery methods. The authors used convection-enhanced delivery (CED) of a macromolecular tracer visible on magnetic resonance (MR) imaging to examine the utility of CED for safe perfusion of the brainstem. Three primates (Macaca mulatta) underwent CED of various volumes of infusion ([Vis]; 85, 110, and 120 microl) of Gd-bound albumin (72 kD) in the pontine region of the brainstem during serial MR imaging. Infusate volume of distribution (Vd), homogeneity, and anatomical distribution were visualized and quantified using MR imaging. Neurological function was observed and recorded up to 35 days postinfusion. Histological analysis was performed in all animals. Large regions of the pons and midbrain were successfully and safely perfused with the macromolecular protein. The Vd was linearly proportional to the Vi (R2 = 0.94), with a Vd/Vi ratio of 8.7 +/- 1.2 (mean +/- standard deviation). Furthermore, the concentration across the perfused region was homogeneous. The Vd increased slightly at 24 hours after completion of the infusion, and remained larger until the intensity of infusion faded (by Day 7). No animal exhibited a neurological deficit after infusion. Histological analysis revealed normal tissue architecture and minimal gliosis that was limited to the region immediately surrounding the cannula track. First, CED can be used to perfuse the brainstem safely and effectively with macromolecules. Second, a large-molecular-weight imaging tracer can be used successfully to deliver, monitor in vivo, and control the distribution of small- and large-molecular-weight putative therapeutic agents for treatment of intrinsic brainstem processes. JF - Journal of neurosurgery AU - Lonser, Russell R AU - Walbridge, Stuart AU - Garmestani, Kayhan AU - Butman, John A AU - Walters, Hugh A AU - Vortmeyer, Alexander O AU - Morrison, Paul F AU - Brechbiel, Martin W AU - Oldfield, Edward H AD - Surgical Neurology Branch and Biomedical Engineering and Instrumentation Program, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. lonserr@ninds.nih.gov Y1 - 2002/10// PY - 2002 DA - October 2002 SP - 905 EP - 913 VL - 97 IS - 4 SN - 0022-3085, 0022-3085 KW - Albumins KW - 0 KW - Contrast Media KW - Gadolinium KW - AU0V1LM3JT KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Convection KW - Animals KW - Rats, Sprague-Dawley KW - Macaca mulatta KW - Male KW - Blood-Brain Barrier KW - Gadolinium -- pharmacokinetics KW - Contrast Media -- pharmacokinetics KW - Brain Stem -- blood supply KW - Magnetic Resonance Imaging -- methods KW - Albumins -- toxicity KW - Albumins -- pharmacokinetics KW - Contrast Media -- toxicity KW - Gadolinium -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72633286?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Successful+and+safe+perfusion+of+the+primate+brainstem%3A+in+vivo+magnetic+resonance+imaging+of+macromolecular+distribution+during+infusion.&rft.au=Lonser%2C+Russell+R%3BWalbridge%2C+Stuart%3BGarmestani%2C+Kayhan%3BButman%2C+John+A%3BWalters%2C+Hugh+A%3BVortmeyer%2C+Alexander+O%3BMorrison%2C+Paul+F%3BBrechbiel%2C+Martin+W%3BOldfield%2C+Edward+H&rft.aulast=Lonser&rft.aufirst=Russell&rft.date=2002-10-01&rft.volume=97&rft.issue=4&rft.spage=905&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 - 2002-11-14 N1 - Date created - 2002-10-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Calcium dysregulation and neuronal apoptosis by the HIV-1 proteins Tat and gp120. AN - 72529644; 12394783 AB - Patients with AIDS often develop cognitive and motor dysfunction that results from damage to synapses and death of neurons in brain regions such as the hippocampus and basal ganglia. This brain syndrome, called AIDS dementia or HIV encephalitis, is believed to result from the infection of one or more populations of mitotic brain cells with HIV-1, which then release viral proteins that are toxic to neurons. Two neurotoxic HIV-1 proteins have been identified, the viral coat protein gp120 and the transcription regulator Tat. Each of these proteins can induce apoptosis of cultured neurons and can render neurons vulnerable to excitotoxicity and oxidative stress. Gp120 and Tat also cause neuronal dysfunction and death in rodents in vivo. Both gp120 and Tat disrupt neuronal calcium homeostasis by perturbing calcium-regulating systems in the plasma membrane and endoplasmic reticulum. Accordingly, drugs that stabilize cellular calcium homeostasis can protect neurons against the toxic effects of gp120 and Tat. By altering voltage-dependent calcium channels, glutamate receptor channels, and membrane transporters, the HIV-1 proteins promote calcium overload, oxyradical production, and mitochondrial dysfunction. A better understanding of how gp120 and Tat disrupt neuronal calcium homeostasis may lead to the development of novel treatments for AIDS patients. JF - Journal of acquired immune deficiency syndromes (1999) AU - Haughey, Norman J AU - Mattson, Mark P AD - Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, Baltimore, Maryland 21224, USA. Y1 - 2002/10/01/ PY - 2002 DA - 2002 Oct 01 SP - S55 EP - S61 VL - 31 Suppl 2 SN - 1525-4135, 1525-4135 KW - Gene Products, tat KW - 0 KW - HIV Envelope Protein gp120 KW - tat Gene Products, Human Immunodeficiency Virus KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - AIDS/HIV KW - Cells, Cultured KW - Humans KW - AIDS Dementia Complex -- physiopathology KW - Homeostasis KW - Gene Products, tat -- physiology KW - Calcium -- metabolism KW - HIV Envelope Protein gp120 -- physiology KW - Apoptosis KW - HIV-1 -- pathogenicity KW - Neurons -- cytology KW - Neurons -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72529644?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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+%281999%29&rft.atitle=Calcium+dysregulation+and+neuronal+apoptosis+by+the+HIV-1+proteins+Tat+and+gp120.&rft.au=Haughey%2C+Norman+J%3BMattson%2C+Mark+P&rft.aulast=Haughey&rft.aufirst=Norman&rft.date=2002-10-01&rft.volume=31+Suppl+2&rft.issue=&rft.spage=S55&rft.isbn=&rft.btitle=&rft.title=Journal+of+acquired+immune+deficiency+syndromes+%281999%29&rft.issn=15254135&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-12 N1 - Date created - 2002-10-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Epidemic anthrax in the eighteenth century, the Americas. AN - 72517488; 12396933 AB - Anthrax has been described as a veterinary disease of minor importance to clinical medicine, causing occasional occupational infections in single cases or clusters. Its potential for rapid and widespread epidemic transmission under natural circumstances has not been widely appreciated. A little-known 1770 epidemic that killed 15,000 people in Saint-Domingue (modern Haiti) was probably intestinal anthrax. The epidemic spread rapidly throughout the colony in association with consumption of uncooked beef. Large-scale, highly fatal epidemics of anthrax may occur under unusual but natural circumstances. Historical information may not only provide important clues about epidemic development but may also raise awareness about bioterrorism potential. JF - Emerging infectious diseases AU - Morens, David M AD - National Institutes of Health, Bethesda, Maryland, USA. dm270q@nih.gov Y1 - 2002/10// PY - 2002 DA - October 2002 SP - 1160 EP - 1162 VL - 8 IS - 10 SN - 1080-6040, 1080-6040 KW - Index Medicus KW - Animals KW - Haiti -- epidemiology KW - Cattle KW - Food Microbiology KW - Humans KW - History, 18th Century KW - Meat -- microbiology KW - African Continental Ancestry Group KW - Anthrax -- epidemiology KW - Intestinal Diseases -- history KW - Anthrax -- transmission KW - Intestinal Diseases -- microbiology KW - Intestinal Diseases -- epidemiology KW - Anthrax -- history KW - Disease Outbreaks -- history KW - Anthrax -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72517488?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Emerging+infectious+diseases&rft.atitle=Epidemic+anthrax+in+the+eighteenth+century%2C+the+Americas.&rft.au=Morens%2C+David+M&rft.aulast=Morens&rft.aufirst=David&rft.date=2002-10-01&rft.volume=8&rft.issue=10&rft.spage=1160&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 completed - 2002-12-27 N1 - Date created - 2002-10-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Clin Infect Dis. 1992 Jan;14(1):298-307 [1571445] J Am Vet Med Assoc. 1959 Nov 1;135:458-62 [14409786] Bull Hist Med. 1951 Jul-Aug;25(4):324-41 [14859018] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Accelerated hyperfractionated radiotherapy and concurrent protracted venous infusion chemotherapy in locally advanced head and neck cancer. AN - 72517458; 12393978 AB - Concurrent radiotherapy and chemotherapy result in a significant benefit with respect to induction chemotherapy followed by radiotherapy or radiotherapy alone, although with a significant increase of toxicity. To discover a more tolerated and effective chemoradiation regimen, the feasibility and efficacy of a hyperfractionated accelerated irradiation with concurrent protracted venous infusion chemotherapy was investigated. Sixty-five patients with advanced head and neck cancer underwent a definitive (53 patients) or a postoperative adjuvant (12 patients) chemoradiation treatment. Chemotherapy consisted of an intravenous protracted infusion of 5 and 200 mg/m /d cisplatin and 5-fluorouracil, respectively. Radiotherapy consisted of a split-course accelerated hyperfractionation of two 150-cGy (split twice a day) or three 100-cGy fractions per day (split three times a day) at more than 6-hour intervals, for 2 weeks followed, after a 1-week interruption, by 2-to-3-week treatment, with the same fractionation schedule, to a total dose of 60 Gy to 69 Gy. Confluent mucositis was tolerable and was the cause of treatment delay of more than 10 days in only 20% of patients. Grade 3 or greater systemic toxicity occurred only in 9 of 65 (14%) patients and was never the cause of drug dose reduction. Complete responses were observed in 69% of patients with gross diseases. At a median follow-up of 43.5 months, 45% of patients were alive and free of disease and 38% died of cancer. The 5-year actuarial local regional failure was 35%. The 5-year actuarial disease-specific survival was 50%. Preservation of larynx function was achieved in 47% of living patients and in 74% of all patients, with advanced tumors of the laryngopharynx. The long-term results of this study suggest that this chemoradiation regimen has the potential of achieving a significant improvement over standard therapy while avoiding significant toxicity. JF - American journal of clinical oncology AU - Arcangeli, Giorgio AU - Saracino, Biancamaria AU - Danesi, Donatella Tirindelli AU - De Campora, Enrico AU - Giovinazzo, Giuseppe AU - Cognetti, Francesco AU - Carlini, Paolo AU - Arcangeli, Stefano AU - Mecozzi, Antonella AD - Regina Elena National Cancer Institute, Division of Radiation Oncology, Rome, Italy. Y1 - 2002/10// PY - 2002 DA - October 2002 SP - 431 EP - 437 VL - 25 IS - 5 SN - 0277-3732, 0277-3732 KW - Cisplatin KW - Q20Q21Q62J KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Infusions, Intravenous KW - Mouth Neoplasms -- radiotherapy KW - Combined Modality Therapy KW - Dose Fractionation KW - Pharyngeal Neoplasms -- radiotherapy KW - Humans KW - Infusion Pumps, Implantable KW - Laryngeal Neoplasms -- radiotherapy KW - Aged KW - Pilot Projects KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Laryngeal Neoplasms -- drug therapy KW - Cisplatin -- administration & dosage KW - Fluorouracil -- administration & dosage KW - Pharyngeal Neoplasms -- drug therapy KW - Adult KW - Middle Aged KW - Mouth Neoplasms -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Male KW - Female KW - Survival Analysis KW - Head and Neck Neoplasms -- radiotherapy KW - Head and Neck Neoplasms -- drug therapy KW - Carcinoma, Squamous Cell -- radiotherapy KW - Carcinoma, Squamous Cell -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72517458?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+clinical+oncology&rft.atitle=Accelerated+hyperfractionated+radiotherapy+and+concurrent+protracted+venous+infusion+chemotherapy+in+locally+advanced+head+and+neck+cancer.&rft.au=Arcangeli%2C+Giorgio%3BSaracino%2C+Biancamaria%3BDanesi%2C+Donatella+Tirindelli%3BDe+Campora%2C+Enrico%3BGiovinazzo%2C+Giuseppe%3BCognetti%2C+Francesco%3BCarlini%2C+Paolo%3BArcangeli%2C+Stefano%3BMecozzi%2C+Antonella&rft.aulast=Arcangeli&rft.aufirst=Giorgio&rft.date=2002-10-01&rft.volume=25&rft.issue=5&rft.spage=431&rft.isbn=&rft.btitle=&rft.title=American+journal+of+clinical+oncology&rft.issn=02773732&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-05 N1 - Date created - 2002-10-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential toxicogenomic responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin in malignant and nonmalignant human airway epithelial cells. AN - 72175799; 12377990 AB - In humans, exposure to high levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is associated with chronic obstructive pulmonary disease and lung cancer. While several studies have shown that the lung is a target organ for TCDD toxicity, little is known on the specific biological pathways altered by TCDD. Studies have shown that the transcriptional response of TCDD (in vivo and in vitro) is complex, and exhibits cell type and tissue specificity. Thus, the purpose of this study was to look at global and concentration-dependent effects of TCDD on gene expression in human lung cells. Gene expression profiling of both a nontumorigenic (HPL1A) and a malignant, tumorigenic lung cell line (A549) was performed by microarray dual fluorescence hybridizations in cells treated with increasing concentrations of TCDD (0, 0.1, 1, 10 nM) for 24 h. Real time RT-PCR was used to verify alterations in specific genes. Results showed that 68 out of 2091 genes were changed in each cell line, and 15 of those genes were found altered in both cell lines. Common gene responses altered by TCDD were identified and included known xenobiotic metabolizing genes, genes known to alter cell cycle, as well as genes that are involved with cell signaling and that mediate cell motility or communication. Cell line specific differences in gene expression were found that indicate the nonmalignant HPL1A cells are retinoic acid responsive. In addition, TCDD altered specific immunomodulatory genes in the HPL1A cells. These data show that TCDD alters multiple integrated networks of signaling pathways associated with pulmonary disease, particularly that of lung cancer. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Martinez, Jeanelle M AU - Afshari, Cynthia A AU - Bushel, Pierre R AU - Masuda, Akira AU - Takahashi, Takashi AU - Walker, Nigel J AD - National Institute of Environmental Health Sciences, Rall Building 101, 111 Alexander Drive, Research Triangle Park, NC 27709, USA. Y1 - 2002/10// PY - 2002 DA - October 2002 SP - 409 EP - 423 VL - 69 IS - 2 SN - 1096-6080, 1096-6080 KW - Carcinogens KW - 0 KW - DNA, Complementary KW - Fluorescent Dyes KW - Mutagens KW - Polychlorinated Dibenzodioxins KW - Receptors, Aryl Hydrocarbon KW - RNA KW - 63231-63-0 KW - Index Medicus KW - Receptors, Aryl Hydrocarbon -- drug effects KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - Lung Neoplasms -- drug therapy KW - Algorithms KW - In Situ Hybridization, Fluorescence KW - Reverse Transcriptase Polymerase Chain Reaction KW - RNA -- biosynthesis KW - Immune System -- drug effects KW - Tumor Cells, Cultured KW - DNA, Complementary -- metabolism KW - Signal Transduction -- drug effects KW - RNA -- isolation & purification KW - Receptors, Aryl Hydrocarbon -- genetics KW - Cell Differentiation -- drug effects KW - Cell Line KW - Lung Neoplasms -- pathology KW - Epithelial Cells -- drug effects KW - Carcinoma -- pathology KW - Polychlorinated Dibenzodioxins -- toxicity KW - Carcinogens -- toxicity KW - Mutagens -- toxicity KW - Gene Expression Regulation -- drug effects KW - Gene Expression Regulation, Neoplastic -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72175799?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Differential+toxicogenomic+responses+to+2%2C3%2C7%2C8-tetrachlorodibenzo-p-dioxin+in+malignant+and+nonmalignant+human+airway+epithelial+cells.&rft.au=Martinez%2C+Jeanelle+M%3BAfshari%2C+Cynthia+A%3BBushel%2C+Pierre+R%3BMasuda%2C+Akira%3BTakahashi%2C+Takashi%3BWalker%2C+Nigel+J&rft.aulast=Martinez&rft.aufirst=Jeanelle&rft.date=2002-10-01&rft.volume=69&rft.issue=2&rft.spage=409&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-24 N1 - Date created - 2002-10-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Map kinase activation correlates with K-ras mutation and loss of heterozygosity on chromosome 6 in alveolar bronchiolar carcinomas from B6C3F1 mice exposed to vanadium pentoxide for 2 years. AN - 72173495; 12376484 AB - Previous work showed a correlation between K-ras mutation and loss of heterozygosity (LOH) on chromosome 6 in the region of K-ras in lung carcinomas from B6C3F1 mice. We hypothesized that mitogen-activated protein kinase (MAPK) would be activated only in those lung neoplasms with both K-ras mutation and LOH. As MAPK activity can be correlated directly with signal detection using antibodies to phosphorylated MAPK, we were able to analyze lung carcinomas from B6C3F1 mice for the presence or absence of MAPK activity by western analysis. Vanadium pentoxide-induced mouse lung carcinomas, which had been shown to have a high frequency of K-ras mutations and LOH on chromosome 6 and for which frozen tumor tissue was available, were used for this study. Total MAPK expression levels were similar between normal lung and lung carcinomas. Phospho-MAPK was elevated in five of six lung carcinoma samples examined in which K-ras mutations and chromosome 6 LOH were identified and in four of five carcinomas with K-ras mutations that lacked LOH. Phospho-MAPK was undetectable or weakly expressed in seven carcinomas examined without K-ras mutations and in normal lung. By immunohistochemistry three K-ras positive/LOH negative samples exhibited multifocal areas of nuclear and cytoplasmic staining for phospho-MAPK. Large amounts of non-staining fibroblasts, lymphocytes and macrophages were also observed in these tumors. Two of these lung carcinomas were microdissected and chromosome 6 LOH was detected in regions of phospho-MAPK positive cells. These results suggest that MAPK is activated during vanadium pentoxide-induced B6C3F1 mouse lung tumorigenesis following K-ras mutation and loss of the wild-type K-ras allele. JF - Carcinogenesis AU - Devereux, Theodora R AU - Holliday, Wanda AU - Anna, Colleen AU - Ress, Nancy AU - Roycroft, Joseph AU - Sills, Robert C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, PO Box 12233, National Institutes of Health, Research Triangle Park, NC 27709, USA. devereux@niehs.nih.gov Y1 - 2002/10// PY - 2002 DA - October 2002 SP - 1737 EP - 1743 VL - 23 IS - 10 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - Vanadium Compounds KW - vanadium pentoxide KW - BVG363OH7A KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Index Medicus KW - Mice, Inbred Strains KW - Animals KW - Phosphorylation KW - Enzyme Activation -- drug effects KW - Mice KW - Lung -- pathology KW - Male KW - Female KW - Mutagenesis KW - Loss of Heterozygosity KW - Genes, ras -- genetics KW - Adenocarcinoma, Bronchiolo-Alveolar -- chemically induced KW - Mitogen-Activated Protein Kinases -- metabolism KW - Adenocarcinoma, Bronchiolo-Alveolar -- pathology KW - Vanadium Compounds -- toxicity KW - Carcinogens -- toxicity KW - Lung Neoplasms -- genetics KW - Lung Neoplasms -- chemically induced KW - Chromosome Mapping KW - Adenocarcinoma, Bronchiolo-Alveolar -- genetics KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72173495?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Map+kinase+activation+correlates+with+K-ras+mutation+and+loss+of+heterozygosity+on+chromosome+6+in+alveolar+bronchiolar+carcinomas+from+B6C3F1+mice+exposed+to+vanadium+pentoxide+for+2+years.&rft.au=Devereux%2C+Theodora+R%3BHolliday%2C+Wanda%3BAnna%2C+Colleen%3BRess%2C+Nancy%3BRoycroft%2C+Joseph%3BSills%2C+Robert+C&rft.aulast=Devereux&rft.aufirst=Theodora&rft.date=2002-10-01&rft.volume=23&rft.issue=10&rft.spage=1737&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-22 N1 - Date created - 2002-10-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - cDNA microarray profiling of rat mammary gland carcinomas induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 7,12-dimethylbenz[a]anthracene. AN - 72173410; 12376462 AB - cDNA microarray analysis was used to examine gene expression profiles in normal female Sprague-Dawley rat mammary gland and in carcinomas induced by the cooked meat-derived carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and the potent experimental carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). Nine tubulopapillary carcinomas (five from PhIP-treated rats and four from DMBA-treated rats) and normal mammary gland from virgin, pregnant and lactating rats were examined on a rat 6.9k cDNA microarray. Although histologically identical, PhIP- and DMBA-induced carcinomas could be distinguished by hierarchical clustering and multi-dimensional scaling analyses of cDNA expression. In addition, the expression of 21 clones was statistically different between PhIP- and DMBA-induced carcinomas (F-test, P < 0.05). The data indicate that distinct chemical carcinogens induce unique gene expression patterns in mammary gland carcinomas. The specific chemical carcinogen-associated cDNA array profiles found in carcinomas may ultimately be applicable to better understanding cancer etiology. PhIP- and DMBA-induced carcinomas also shared similarities in cDNA expression profiles. By comparing the expression in carcinomas (PhIP plus DMBA induced) with normal rat mammary gland (at any stage of differentiation), 172 clones were found to be differentially expressed. Genes showing increased expression in carcinomas by cDNA microarray analysis (and further validated by immunohistochemistry and western blot analysis) include cyclin D1, PDGF-A chain, retinol binding protein 1, prohibitin and the transcription factor STAT5A. The similarities in gene expression between PhIP- and DMBA-induced carcinomas raise the possibility that several molecular pathways for rat mammary gland transformation are maintained irrespective of the carcinogenic initiating agent. JF - Carcinogenesis AU - Shan, Liang AU - He, Mei AU - Yu, Minshu AU - Qiu, Cunping AU - Lee, Norman H AU - Liu, Edison T AU - Snyderwine, Elizabeth G AD - Chemical Carcinogenesis Section, Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 2002/10// PY - 2002 DA - October 2002 SP - 1561 EP - 1568 VL - 23 IS - 10 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - DNA, Complementary KW - Imidazoles KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - Index Medicus KW - Rats KW - Animals KW - DNA, Complementary -- genetics KW - Female KW - Pregnancy KW - Lactation KW - Mammary Neoplasms, Experimental -- chemically induced KW - Mammary Neoplasms, Experimental -- classification KW - Oligonucleotide Array Sequence Analysis KW - Pregnancy Complications -- chemically induced KW - Mammary Neoplasms, Experimental -- genetics KW - Mammary Neoplasms, Experimental -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72173410?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=cDNA+microarray+profiling+of+rat+mammary+gland+carcinomas+induced+by+2-amino-1-methyl-6-phenylimidazo%5B4%2C5-b%5Dpyridine+and+7%2C12-dimethylbenz%5Ba%5Danthracene.&rft.au=Shan%2C+Liang%3BHe%2C+Mei%3BYu%2C+Minshu%3BQiu%2C+Cunping%3BLee%2C+Norman+H%3BLiu%2C+Edison+T%3BSnyderwine%2C+Elizabeth+G&rft.aulast=Shan&rft.aufirst=Liang&rft.date=2002-10-01&rft.volume=23&rft.issue=10&rft.spage=1561&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-22 N1 - Date created - 2002-10-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Coordination of altered DNA repair and damage pathways in arsenite-exposed keratinocytes. AN - 72172040; 12377979 AB - Human exposure to arsenic, a ubiquitous and toxic environmental pollutant, is associated with an increased incidence of skin cancer. However, the mechanism(s) associated with AsIII-mediated toxicity and carcinogenesis at low levels of exposure remains elusive. Aberrations in cell proliferation, oxidative damage, and DNA-repair fidelity have been implicated in sodium arsenite (AsIII)-mediated carcinogenicity and toxicity, but these events have been examined in isolation in the majority of biological models of arsenic exposure. We hypothesized that the simultaneous interaction of these effects may be important in arsenic-mediated neoplasia in the skin. To evaluate this, normal human epidermal keratinocytes (NHEK) were exposed to nontoxic doses (0.005-5 micro M) of AsIII and monitored for several physiological endpoints at the times when cells were harvested for gene expression measurements (1-24 h). Two-fluor cDNA microarray analyses indicated that AsIII treatment decreased the expression of genes associated with DNA repair (e.g., p53 and Damage-specific DNA-binding protein 2) and increased the expression of genes indicative of the cellular response to oxidative stress (e.g., Superoxide dismutase 1, NAD(P)H quinone oxidoreductase, and Serine/threonine kinase 25). AsIII also modulated the expression of certain transcripts associated with increased cell proliferation (e.g., Cyclin G1, Protein kinase C delta), oncogenes, and genes associated with cellular transformation (e.g., Gro-1 and V-yes). These observations correlated with measurements of cell proliferation and mitotic measurements as AsIII treatment resulted in a dose-dependent increase in cellular mitoses at 24 h and an increase in cell proliferation at 48 h of exposure. Data in this manuscript demonstrates that AsIII exposure simultaneously modulates DNA repair, cell proliferation, and redox-related gene expression in nontransformed, normal NHEK. It is anticipated that data in this report will serve as a foundation for furthering our knowledge of AsIII-regulated gene expression in skin and other tissues and contribute to a better understanding of arsenic toxicity and carcinogenesis. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Hamadeh, Hisham K AU - Trouba, Kevin J AU - Amin, Rupesh P AU - Afshari, Cynthia A AU - Germolec, Dori AD - Intramural Microarray Center, Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences/NIH, Research Triangle Park, NC 27709, USA. Y1 - 2002/10// PY - 2002 DA - October 2002 SP - 306 EP - 316 VL - 69 IS - 2 SN - 1096-6080, 1096-6080 KW - Arsenites KW - 0 KW - DNA, Complementary KW - Free Radical Scavengers KW - arsenite KW - N5509X556J KW - Thymidine KW - VC2W18DGKR KW - Acetylcysteine KW - WYQ7N0BPYC KW - Index Medicus KW - Gene Expression -- drug effects KW - Transcription, Genetic -- drug effects KW - Blotting, Northern KW - DNA, Complementary -- genetics KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - Acetylcysteine -- pharmacology KW - Thymidine -- metabolism KW - Skin -- drug effects KW - Cell Survival -- drug effects KW - Skin -- cytology KW - Mitotic Index KW - Cell Line KW - DNA, Complementary -- biosynthesis KW - Free Radical Scavengers -- pharmacology KW - DNA Damage KW - Keratinocytes -- drug effects KW - Arsenites -- toxicity KW - Keratinocytes -- metabolism KW - DNA Repair -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72172040?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Coordination+of+altered+DNA+repair+and+damage+pathways+in+arsenite-exposed+keratinocytes.&rft.au=Hamadeh%2C+Hisham+K%3BTrouba%2C+Kevin+J%3BAmin%2C+Rupesh+P%3BAfshari%2C+Cynthia+A%3BGermolec%2C+Dori&rft.aulast=Hamadeh&rft.aufirst=Hisham&rft.date=2002-10-01&rft.volume=69&rft.issue=2&rft.spage=306&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-24 N1 - Date created - 2002-10-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - XPD codon 751 polymorphism, metabolism genes, smoking, and bladder cancer risk. AN - 72170732; 12376500 AB - Cigarette smoking is the main risk factor for bladder cancer, accounting for at least 50% of bladder cancer in men. Cigarette smoke is a rich source of arylamines, which are detoxified by the NAT2 enzyme and activated by the NAT1 enzyme to highly reactive species that can form bulky adducts on DNA. DNA damage from such adducts is mainly repaired by the nucleotide excision repair pathway, in which the XPD protein functions in opening the DNA helix. We hypothesized that an XPD codon 751 polymorphism (Lys-to-Gln amino acid change) could affect the repair of smoking-induced DNA damage and could be associated with bladder-cancer risk. We also hypothesized that allelic variants of the NAT1 and NAT2 genes might modify the effect of the XPD codon 751 polymorphism on smoking-associated bladder-cancer risk. We determined the XPD codon 751 genotype for 228 bladder-cancer cases and 210 controls who were frequency-matched to cases by age, sex, and ethnicity, and we used our previously published data on the NAT1 and NAT2 genotypes for these same individuals (J. A. Taylor et al., Cancer Res., 58: 3603-3610, 1998). We found a slight decrease in risk for the XPD codon 751 Gln/Gln genotype (adjusted odds ratio: 0.8; 95% confidence interval: 0.4-1.3) compared with subjects with the Lys/Lys or Lys/Gln genotypes. The analysis with smoking showed that smokers with the Lys/Lys or Lys/Gln genotypes were twice as likely to have bladder cancer than smokers with the Gln/Gln genotype (test of interaction P = 0.03). The combined presence of the NAT1/NAT2 high-risk genotype and the XPD Lys/Lys or Lys/Gln genotypes ignoring smoking had an odds ratio that was only slightly higher than expected, assuming no genotype-genotype interaction (P = 0.52). We found little evidence for a gene-gene-exposure, three-way interaction among the XPD codon 751 genotype, smoking, and the NAT1/NAT2 genotype. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Stern, Mariana C AU - Johnson, Laura R AU - Bell, Douglas A AU - Taylor, Jack A AD - Molecular and Genetic Epidemiology Section, Laboratory of Molecular Carcinogenesis and the National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina, 27709, USA. Y1 - 2002/10// PY - 2002 DA - October 2002 SP - 1004 EP - 1011 VL - 11 IS - 10 Pt 1 SN - 1055-9965, 1055-9965 KW - DNA Adducts KW - 0 KW - DNA-Binding Proteins KW - Isoenzymes KW - Proteins KW - Transcription Factors KW - Arylamine N-Acetyltransferase KW - EC 2.3.1.5 KW - N-acetyltransferase 1 KW - NAT2 protein, human KW - DNA Helicases KW - EC 3.6.4.- KW - Xeroderma Pigmentosum Group D Protein KW - EC 3.6.4.12 KW - ERCC2 protein, human KW - EC 5.99.- KW - Index Medicus KW - Odds Ratio KW - Humans KW - Aged KW - Isoenzymes -- genetics KW - Genotype KW - Risk Factors KW - Case-Control Studies KW - Arylamine N-Acetyltransferase -- pharmacology KW - Middle Aged KW - Female KW - Isoenzymes -- pharmacology KW - Male KW - Arylamine N-Acetyltransferase -- genetics KW - Proteins -- pharmacology KW - Urinary Bladder Neoplasms -- etiology KW - DNA Repair KW - Polymorphism, Genetic KW - DNA Helicases -- pharmacology KW - DNA Damage KW - Urinary Bladder Neoplasms -- genetics KW - Smoking -- adverse effects KW - Genetic Predisposition to Disease UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72170732?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=XPD+codon+751+polymorphism%2C+metabolism+genes%2C+smoking%2C+and+bladder+cancer+risk.&rft.au=Stern%2C+Mariana+C%3BJohnson%2C+Laura+R%3BBell%2C+Douglas+A%3BTaylor%2C+Jack+A&rft.aulast=Stern&rft.aufirst=Mariana&rft.date=2002-10-01&rft.volume=11&rft.issue=10+Pt+1&rft.spage=1004&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 - 2002-12-24 N1 - Date created - 2002-10-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - SAGE transcript profiles of normal primary human hepatocytes expressing oncogenic hepatitis B virus X protein. AN - 72159179; 12207007 AB - Hepatitis B virus (HBV) is a major risk factor for hepatocellular carcinoma (HCC). HBV encodes an oncogenic HBx gene that functions as a transcriptional coactivator of multiple cellular genes. To understand the role(s) of HBx in the early genesis of HCC, we systematically analyzed gene expression profiles by serial analysis of gene expression (SAGE) in freshly isolated human primary hepatocytes infected with a replication-defective adenovirus containing HBx. A total of 19,501 sequence tags (representing 1443 unique transcripts) were analyzed, which provide a distribution of a transcriptome characteristic of normal hepatocytes and a profile associated with HBx expression. Examples of the targeted genes were confirmed by the Megarray analysis with a significant correlation between quantitative SAGE and Megarray (r = 0.8, P < 0.005). In HBx-expressing hepatocytes, a total of 57 transcripts (3.9%) were induced, and 46 transcripts (3.3%) were repressed by more than fivefold. Interestingly, most of the HBx-up-regulated transcripts can be clustered into three major classes, including genes that encode ribosomal proteins, transcription factors with zinc-finger motifs, and proteins associated with protein degradation pathways. These results suggest that HBx may function as a major regulator in common cellular pathways that, in turn, regulate protein synthesis, gene transcription, and protein degradation. JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Wu, Chuan-Ging AU - Forgues, Marshonna AU - Siddique, Shabina AU - Farnsworth, Julie AU - Valerie, Kristoffer AU - Wang, Xin Wei AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 2002/10// PY - 2002 DA - October 2002 SP - 1665 EP - 1667 VL - 16 IS - 12 KW - Proteins KW - 0 KW - Trans-Activators KW - hepatitis B virus X protein KW - Index Medicus KW - Transfection KW - Nucleic Acid Hybridization -- methods KW - Humans KW - Gene Expression KW - Transcription, Genetic -- genetics KW - Protein Biosynthesis -- genetics KW - Gene Expression Regulation KW - Proteins -- metabolism KW - Proteins -- genetics KW - Adenoviridae -- genetics KW - Gene Expression Profiling KW - Trans-Activators -- genetics KW - Trans-Activators -- physiology KW - Hepatocytes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72159179?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.atitle=SAGE+transcript+profiles+of+normal+primary+human+hepatocytes+expressing+oncogenic+hepatitis+B+virus+X+protein.&rft.au=Wu%2C+Chuan-Ging%3BForgues%2C+Marshonna%3BSiddique%2C+Shabina%3BFarnsworth%2C+Julie%3BValerie%2C+Kristoffer%3BWang%2C+Xin+Wei&rft.aulast=Wu&rft.aufirst=Chuan-Ging&rft.date=2002-10-01&rft.volume=16&rft.issue=12&rft.spage=1665&rft.isbn=&rft.btitle=&rft.title=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.issn=1530-6860&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-12-17 N1 - Date created - 2002-10-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Second-order schedules of drug self-administration in animals. AN - 72158363; 12373434 AB - On a second-order schedule, a subject responds according to one schedule (the unit schedule) for a brief presentation of a stimulus such as a light. Responding by the subject on this unit schedule is then reinforced according to another schedule of reinforcement. Second-order schedules of drug injection allow the study of more complex behavioral sequences than do simple schedules and may more accurately reflect the human drug-abuse situation. Much of the early work in this area used primates as subjects and focused on the behavioral variables controlling responding. It was shown that long sequences of behavior could be maintained on second-order schedules with relatively infrequent injections of drug and that the second-order, brief-stimulus presentations were critical to the acquisition and maintenance of responding. Also, the continued presentation of the brief stimulus in extinction often led to prolonged extinction behavior. These studies clearly showed that environmental stimuli greatly influence drug self-administration behavior under second-order schedules. The focus of much of the more recent work with second-order schedules has been on the evaluation of pharmacological treatments for drug addiction, both as antagonist and substitution therapies. Both types of potential therapies have shown promise in these preclinical models of addictive behavior. The recent extension of second-order self-administration studies to rats as subjects has facilitated the investigation of neural mechanisms involved in this behavior. While this use of second-order schedules is a relatively recent phenomenon, significant contributions have already been made in identifying neural mechanisms critical to second-order schedule drug self-administration. This active area of research holds great promise for delineating specific brain regions critical to different aspects of drug addiction. JF - Psychopharmacology AU - Schindler, Charles W AU - Panlilio, Leigh V AU - Goldberg, Steven R AD - Preclinical Pharmacology Section, Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. cschindl@helix.nih.gov Y1 - 2002/10// PY - 2002 DA - October 2002 SP - 327 EP - 344 VL - 163 IS - 3-4 SN - 0033-3158, 0033-3158 KW - BP 897 KW - 0 KW - Piperazines KW - Morphine KW - 76I7G6D29C KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Animals KW - Drug Administration Schedule KW - Drug Interactions KW - Dose-Response Relationship, Drug KW - Food KW - Piperazines -- pharmacology KW - Cocaine -- administration & dosage KW - Morphine -- pharmacology KW - Photic Stimulation KW - Self Administration KW - Extinction, Psychological -- drug effects KW - Cocaine -- pharmacology KW - Drug Evaluation, Preclinical -- methods KW - Morphine -- administration & dosage KW - Time Factors KW - Conditioning, Operant -- drug effects KW - Behavior, Animal -- drug effects KW - Reinforcement Schedule UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72158363?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Second-order+schedules+of+drug+self-administration+in+animals.&rft.au=Schindler%2C+Charles+W%3BPanlilio%2C+Leigh+V%3BGoldberg%2C+Steven+R&rft.aulast=Schindler&rft.aufirst=Charles&rft.date=2002-10-01&rft.volume=163&rft.issue=3-4&rft.spage=327&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-20 N1 - Date created - 2002-10-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Co-surfactant of ethoxylated sorbitan ester and sorbitan monooleate for enhanced flushing of tetrachloroethylene. AN - 72149123; 12365839 AB - This work evaluated the flushing efficiency of tetrachloroethylene (PCE) using the co-surfactant of non-ionic ethoxylated sorbitan ester (Tween) and oilphilic sorbitan monooleate (Span 80), which formed more hydrophobic micelles than Tween alone. The flushing efficiency was evaluated with laboratory columns filled with silica and aquifer sand. Results from column flushing were also compared to those of batch solubility experiments to study the removal mechanism by the co-surfactant solution. Compared to Tween 80 alone, the molar solubilization ratio and the affinity between the micelles and PCE increased 84% and 90%, respectively, by the co-surfactant solution of Tween 80 and Span 80 mixed at a 4:1 ratio. Flushing with 1% Tween 80 solution yielded a steady PCE recovery of 7% for both silica and aquifer sand in each pore volume (PV). Flushing with co-surfactant of 1% Tween 80 + Span 80 (4:1) further increased PCE recovery to 10% for silica sand and 13% for aquifer sand per PV. A comparison of results from column flushing and batch solubility tests indicated that the primary flushing mechanism of PCE using the co-surfactant solution of Tween 80 + Span 80 (4:1) was micellar solubilization. JF - Chemosphere AU - Yeh, Carol Kuei-Jyum AU - Peng, Su-Lan AU - Hsu, I-Yuang AD - Department of Environmental Science and Engineering, National Pingtung University of Science and Technology, Nei Pu, Taiwan, ROC. kjyeh@mail.npust.edu.tw Y1 - 2002/10// PY - 2002 DA - October 2002 SP - 421 EP - 430 VL - 49 IS - 4 SN - 0045-6535, 0045-6535 KW - Hexoses KW - 0 KW - Polysorbates KW - Solvents KW - Surface-Active Agents KW - sorbitan monooleate KW - 06XEA2VD56 KW - Silicon Dioxide KW - 7631-86-9 KW - Tetrachloroethylene KW - TJ904HH8SN KW - Index Medicus KW - Solvents -- chemistry KW - Solubility KW - Chromatography, Liquid -- methods KW - Hexoses -- chemistry KW - Tetrachloroethylene -- chemistry KW - Surface-Active Agents -- chemistry KW - Tetrachloroethylene -- isolation & purification KW - Polysorbates -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72149123?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemosphere&rft.atitle=Co-surfactant+of+ethoxylated+sorbitan+ester+and+sorbitan+monooleate+for+enhanced+flushing+of+tetrachloroethylene.&rft.au=Yeh%2C+Carol+Kuei-Jyum%3BPeng%2C+Su-Lan%3BHsu%2C+I-Yuang&rft.aulast=Yeh&rft.aufirst=Carol&rft.date=2002-10-01&rft.volume=49&rft.issue=4&rft.spage=421&rft.isbn=&rft.btitle=&rft.title=Chemosphere&rft.issn=00456535&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-05 N1 - Date created - 2002-10-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synergistic effect of influenza a virus on endotoxin-induced mortality in rat pups: a potential model for sudden infant death syndrome. AN - 72140317; 12357040 AB - Sudden infant death syndrome is the most common cause of postneonatal infant mortality in the developed world. It is a diagnosis of exclusion with peak age of incidence between 2 and 6 mo. Fifty to 63% of these infants have a preexisting upper respiratory tract infection before death. We hypothesized that the immature immune system may be altered by a primary infection, preventing a protective response after secondary challenge. To mimic dual infection, we used a nonlethal strain of a rat-adapted influenza A virus and a sublethal dose of endotoxin to establish a model that results in pathology and death in 12-d-old rat pups similar to that seen in infants dying of sudden infant death syndrome. Mortality only occurred when specific criteria such as timing between infectious insults and developmental age of the pup were met. Results suggest that mortality is caused by a rapid systemic shock event rather than lung-specific damage. Gross pathologic findings such as lung petechiae and liquid blood around the heart on necropsy were consistent with those seen in infants dying of sudden infant death syndrome. Histopathologic lesions including subendocardial hemorrhage and mild cortical thymocyte necrosis were found with greater severity and frequency in dually challenged animals. Macrophage subpopulation in rat-adapted influenza A virus-inoculated animals was significantly elevated in the spleen at the time of death. Our model suggests that the developing immune system can be primed to respond in an exaggerated way to a second immune challenge resulting in unexpected death. JF - Pediatric research AU - Blood-Siegfried, Jane AU - Nyska, Abraham AU - Lieder, Holly AU - Joe, Mijeom AU - Vega, Libia AU - Patterson, Rachel AU - Germolec, Dori AD - Environmental Immunology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. blood002@mc.duke.edu Y1 - 2002/10// PY - 2002 DA - October 2002 SP - 481 EP - 490 VL - 52 IS - 4 SN - 0031-3998, 0031-3998 KW - Cytokines KW - 0 KW - Endotoxins KW - Index Medicus KW - Rats KW - Infant KW - Cytokines -- blood KW - Animals KW - Rats, Inbred F344 KW - Humans KW - Bronchoalveolar Lavage Fluid KW - Spleen -- pathology KW - Enzyme-Linked Immunosorbent Assay KW - Lung -- pathology KW - Female KW - Pregnancy KW - Influenza A virus -- physiology KW - Survival Rate KW - Disease Models, Animal KW - Sudden Infant Death -- pathology KW - Endotoxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72140317?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Synergistic+effect+of+influenza+a+virus+on+endotoxin-induced+mortality+in+rat+pups%3A+a+potential+model+for+sudden+infant+death+syndrome.&rft.au=Blood-Siegfried%2C+Jane%3BNyska%2C+Abraham%3BLieder%2C+Holly%3BJoe%2C+Mijeom%3BVega%2C+Libia%3BPatterson%2C+Rachel%3BGermolec%2C+Dori&rft.aulast=Blood-Siegfried&rft.aufirst=Jane&rft.date=2002-10-01&rft.volume=52&rft.issue=4&rft.spage=481&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 - 2003-03-04 N1 - Date created - 2002-10-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Do children with falling blood lead levels have improved cognition? AN - 72139791; 12359796 AB - Exposure to lead at levels encountered by urban children impairs cognitive development. An observational study suggested improvement in IQ when blood lead level fell, but the only randomized trial of chelation showed no benefit in IQ. We did a new analysis of the data from the clinical trial using change in blood lead level as the independent variable. The 741 children began with blood lead levels between 20 and 44 microg/dL, and were 13 to 33 months old at randomization to chelation or placebo. Blood lead levels were measured repeatedly, and cognitive tests were given at baseline, 6 months, and 36 months follow-up. By 6 months after randomization, blood lead levels had fallen by similar amounts in both chelated and placebo children, despite the immediate drops in the chelated group; there was no association between change in blood lead level and change in cognitive test score. Blood lead levels continued to fall. At 36 months follow-up, in the placebo group only, cognitive test scores had increased 4.0 points per 10 microg/dL fall in blood lead level from baseline to 36 months follow-up and 5.1 points from 6 to 36 months. The improvement in scores in the placebo group only implies that factors other than declining blood lead levels per se are responsible for cognitive improvement; it is possible but less likely that succimer, the active drug, impairs cognition. JF - Pediatrics AU - Liu, Xianchen AU - Dietrich, Kim N AU - Radcliffe, Jerilynn AU - Ragan, N Beth AU - Rhoads, George G AU - Rogan, Walter J AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2002/10// PY - 2002 DA - October 2002 SP - 787 EP - 791 VL - 110 IS - 4 KW - Chelating Agents KW - 0 KW - Placebos KW - Lead KW - 2P299V784P KW - Succimer KW - DX1U2629QE KW - Abridged Index Medicus KW - Index Medicus KW - Neuropsychological Tests -- statistics & numerical data KW - Infant KW - Double-Blind Method KW - Humans KW - Treatment Outcome KW - Child Development -- drug effects KW - Child Development -- physiology KW - Male KW - Female KW - Child, Preschool KW - Lead -- adverse effects KW - Cognition Disorders -- diagnosis KW - Lead Poisoning -- drug therapy KW - Chelating Agents -- therapeutic use KW - Succimer -- therapeutic use KW - Lead Poisoning -- blood KW - Lead Poisoning -- complications KW - Cognition Disorders -- chemically induced KW - Lead -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72139791?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatrics&rft.atitle=Do+children+with+falling+blood+lead+levels+have+improved+cognition%3F&rft.au=Liu%2C+Xianchen%3BDietrich%2C+Kim+N%3BRadcliffe%2C+Jerilynn%3BRagan%2C+N+Beth%3BRhoads%2C+George+G%3BRogan%2C+Walter+J&rft.aulast=Liu&rft.aufirst=Xianchen&rft.date=2002-10-01&rft.volume=110&rft.issue=4&rft.spage=787&rft.isbn=&rft.btitle=&rft.title=Pediatrics&rft.issn=1098-4275&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-12-23 N1 - Date created - 2002-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thioltransferase (glutaredoxin) mediates recovery of motor neurons from excitotoxic mitochondrial injury. AN - 72124809; 12351714 AB - Mitochondrial dysfunction involving electron transport components is implicated in the pathogenesis of several neurodegenerative disorders and is a critical event in excitotoxicity. Excitatory amino acid L-beta-N-oxalylamino-L-alanine (L-BOAA), causes progressive corticospinal neurodegeneration in humans. In mice, L-BOAA triggers glutathione loss and protein thiol oxidation that disrupts mitochondrial complex I selectively in motor cortex and lumbosacral cord, the regions affected in humans. We examined the factors regulating postinjury recovery of complex I in CNS regions after a single dose of L-BOAA. The expression of thioltransferase (glutaredoxin), a protein disulfide oxidoreductase regulated through AP1 transcription factor was upregulated within 30 min of L-BOAA administration, providing the first evidence for functional regulation of thioltransferase during restoration of mitochondrial function. Regeneration of complex I activity in motor cortex was concurrent with increase in thioltransferase protein and activity, 1 hr after the excitotoxic insult. Pretreatment with alpha-lipoic acid, a thiol delivery agent that protects motor neurons from L-BOAA-mediated toxicity prevented the upregulation of thioltransferase and AP1 activation, presumably by maintaining thiol homeostasis. Downregulation of thioltransferase using antisense oligonucleotides prevented the recovery of complex I in motor cortex and exacerbated the mitochondrial dysfunction in lumbosacral cord, providing support for the critical role for thioltransferase in maintenance of mitochondrial function in the CNS. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Kenchappa, Rajappa S AU - Diwakar, Latha AU - Boyd, Michael R AU - Ravindranath, Vijayalakshmi AD - Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Bangalore 560 029, India. Y1 - 2002/10/01/ PY - 2002 DA - 2002 Oct 01 SP - 8402 EP - 8410 VL - 22 IS - 19 KW - Glutaredoxins KW - 0 KW - Neuroprotective Agents KW - Neurotoxins KW - Oligonucleotides, Antisense KW - Thioctic Acid KW - 73Y7P0K73Y KW - Oxidoreductases KW - EC 1.- KW - NADH, NADPH Oxidoreductases KW - EC 1.6.- KW - Electron Transport Complex I KW - EC 1.6.5.3 KW - Protein Disulfide Reductase (Glutathione) KW - EC 1.8.4.2 KW - Index Medicus KW - Animals KW - Motor Cortex -- cytology KW - Spinal Cord -- metabolism KW - Recovery of Function -- physiology KW - Oligonucleotides, Antisense -- pharmacology KW - Mice KW - Recovery of Function -- drug effects KW - Motor Cortex -- metabolism KW - Neurotoxins -- toxicity KW - Motor Cortex -- drug effects KW - Neuroprotective Agents -- pharmacology KW - Lumbosacral Region KW - Up-Regulation -- drug effects KW - Spinal Cord -- drug effects KW - Thioctic Acid -- pharmacology KW - Oxidative Stress -- drug effects KW - NADH, NADPH Oxidoreductases -- metabolism KW - Male KW - Spinal Cord -- cytology KW - Motor Neurons -- metabolism KW - Oxidoreductases -- genetics KW - Oxidoreductases -- metabolism KW - Mitochondria -- drug effects KW - Motor Neurons -- cytology KW - Mitochondria -- metabolism KW - Oxidoreductases -- antagonists & inhibitors KW - Motor Neurons -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72124809?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Thioltransferase+%28glutaredoxin%29+mediates+recovery+of+motor+neurons+from+excitotoxic+mitochondrial+injury.&rft.au=Kenchappa%2C+Rajappa+S%3BDiwakar%2C+Latha%3BBoyd%2C+Michael+R%3BRavindranath%2C+Vijayalakshmi&rft.aulast=Kenchappa&rft.aufirst=Rajappa&rft.date=2002-10-01&rft.volume=22&rft.issue=19&rft.spage=8402&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=1529-2401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-10-24 N1 - Date created - 2002-09-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I clinical and pharmacokinetic study of flavopiridol administered as a daily 1-hour infusion in patients with advanced neoplasms. AN - 72124802; 12351605 AB - To define the maximum-tolerated dose (MTD), dose-limiting toxicity, and pharmacokinetics of the cyclin-dependent kinase inhibitor flavopiridol administered as a daily 1-hour infusion every 3 weeks. Fifty-five patients with advanced neoplasms were treated with flavopiridol at doses of 12, 17, 24, 30, 37.5, and 52.5 mg/m(2)/d for 5 days; doses of 50 and 62.5 mg/m(2)/d for 3 days; and doses of 62.5 and 78 mg/m(2)/d for 1 day. Plasma sampling was performed to characterize the pharmacokinetics of flavopiridol with these schedules. Dose-limiting neutropenia developed at doses >/= 52.5 mg/m(2)/d. Nonhematologic toxicities included nausea, vomiting, diarrhea, hypotension, and a proinflammatory syndrome characterized by anorexia, fatigue, fever, and tumor pain. The median peak concentrations of flavopiridol achieved at the MTDs on the 5-day, 3-day, and 1-day schedule were 1.7 micro mol/L (range, 1.3 to 4.2 micro mol/L), 3.2 micro mol/L (range, 1.7 to 4.8 micro mol/L), and 3.9 micro mol/L (1.8 to 5.1 micro mol/L), respectively. Twelve patients had stable disease for >/= 3 months, with a median duration of 6 months (range, 3 to 11 months). The recommended phase II doses of flavopiridol as a 1-hour infusion are 37.5 mg/m(2)/d for 5 days, 50 mg/m(2)/d for 3 days, and 62.5 mg/m(2)/d for 1 day. Flavopiridol as a daily 1-hour infusion can be safely administered and can achieve concentrations in the micromolar range, sufficient to inhibit cyclin-dependent kinases in preclinical models. Further studies to determine the optimal schedule of flavopiridol as a single agent and in combination with chemotherapeutic agents are underway. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Tan, Antoinette R AU - Headlee, Donna AU - Messmann, Richard AU - Sausville, Edward A AU - Arbuck, Susan G AU - Murgo, Anthony J AU - Melillo, Giovanni AU - Zhai, Suoping AU - Figg, William D AU - Swain, Sandra M AU - Senderowicz, Adrian M AD - Center for Cancer Research, Developmental Therapeutics Program, and Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2002/10/01/ PY - 2002 DA - 2002 Oct 01 SP - 4074 EP - 4082 VL - 20 IS - 19 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents KW - 0 KW - Flavonoids KW - Piperidines KW - alvocidib KW - 45AD6X575G KW - Index Medicus KW - Drug Administration Schedule KW - Infusions, Intravenous KW - Area Under Curve KW - Dose-Response Relationship, Drug KW - Humans KW - Adult KW - Treatment Outcome KW - Neutropenia -- chemically induced KW - Aged KW - Middle Aged KW - Maximum Tolerated Dose KW - Male KW - Female KW - Neoplasms -- drug therapy KW - Antineoplastic Agents -- administration & dosage KW - Antineoplastic Agents -- pharmacokinetics KW - Piperidines -- pharmacokinetics KW - Flavonoids -- adverse effects KW - Piperidines -- administration & dosage KW - Flavonoids -- pharmacokinetics KW - Piperidines -- adverse effects KW - Flavonoids -- administration & dosage KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72124802?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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+clinical+and+pharmacokinetic+study+of+flavopiridol+administered+as+a+daily+1-hour+infusion+in+patients+with+advanced+neoplasms.&rft.au=Tan%2C+Antoinette+R%3BHeadlee%2C+Donna%3BMessmann%2C+Richard%3BSausville%2C+Edward+A%3BArbuck%2C+Susan+G%3BMurgo%2C+Anthony+J%3BMelillo%2C+Giovanni%3BZhai%2C+Suoping%3BFigg%2C+William+D%3BSwain%2C+Sandra+M%3BSenderowicz%2C+Adrian+M&rft.aulast=Tan&rft.aufirst=Antoinette&rft.date=2002-10-01&rft.volume=20&rft.issue=19&rft.spage=4074&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 - 2002-11-08 N1 - Date created - 2002-09-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neonatal exposure to genistein induces estrogen receptor (ER)alpha expression and multioocyte follicles in the maturing mouse ovary: evidence for ERbeta-mediated and nonestrogenic actions. AN - 72117925; 12297547 AB - Outbred CD-1 mice were treated neonatally on Days 1-5 with the phytoestrogen, genistein (1, 10, or 100 micro g per pup per day), and ovaries were collected on Days 5, 12, and 19. Ribonuclease protection assay analysis of ovarian mRNA showed that estrogen receptor beta (ERbeta) predominated over ERalpha in controls and increased with age. Genistein treatment did not alter ERbeta expression, however, ERalpha expression was higher on Days 5 and 12. ERbeta was immunolocalized in granulosa cells, whereas ERalpha was immunolocalized in interstitial and thecal cells. Genistein treatment caused a dramatic increase in ERalpha in granulosa cells. Genistein-treated ERbeta knockout mice showed a similar induction of ERalpha, which is seen in CD-1 mice, suggesting that ERbeta does not mediate this effect. Similar ERalpha induction in granulosa cells was seen in CD-1 mice treated with lavendustin A, a tyrosine kinase inhibitor that has no known estrogenic actions, which suggests that this property of genistein may be responsible. As a functional analysis, genistein-treated mice were superovulated and the number of oocytes was counted. A statistically significant increase in the number of ovulated oocytes was observed with the lowest dose, whereas a decrease was observed with the two higher doses. This increase in ovulatory capacity with the low dose coincided with higher ERalpha expression. Histological evaluations on Day 19 revealed a dose-related increase in multioocyte follicles (MOFs) in genistein-treated mice. Tyrosine kinase inhibition was apparently not responsible for MOFs because they were not present in mice that had been treated with lavendustin; however, ERbeta must play a role, because mice lacking ERbeta showed no MOFs. These data taken together demonstrate alterations in the ovary following neonatal exposure to genistein. Given that human infants are exposed to high levels of genistein in soy-based foods, this study indicates that the effects of such exposure on the developing reproductive tract warrant further investigation. JF - Biology of reproduction AU - Jefferson, Wendy N AU - Couse, John F AU - Padilla-Banks, Elizabeth AU - Korach, Kenneth S AU - Newbold, Retha R AD - Developmental Endocrinology Section, Laboratory of Molecular Toxicology, Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2002/10// PY - 2002 DA - October 2002 SP - 1285 EP - 1296 VL - 67 IS - 4 SN - 0006-3363, 0006-3363 KW - Enzyme Inhibitors KW - 0 KW - Estrogen Receptor alpha KW - Estrogen Receptor beta KW - Phenols KW - RNA, Messenger KW - Receptors, Estrogen KW - lavendustin A KW - 3Y0G32G2RV KW - Genistein KW - DH2M523P0H KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Ribonucleases KW - EC 3.1.- KW - Index Medicus KW - Gene Expression -- drug effects KW - Animals KW - Phenols -- pharmacology KW - RNA, Messenger -- analysis KW - Mice KW - Granulosa Cells -- chemistry KW - Ribonucleases -- metabolism KW - Mice, Knockout KW - Protein-Tyrosine Kinases -- antagonists & inhibitors KW - Mice, Inbred C57BL KW - Enzyme Inhibitors -- pharmacology KW - Oocytes KW - Superovulation KW - Female KW - Ovary -- growth & development KW - Animals, Newborn KW - Ovary -- chemistry KW - Receptors, Estrogen -- genetics KW - Genistein -- pharmacology KW - Genistein -- adverse effects KW - Receptors, Estrogen -- deficiency KW - Receptors, Estrogen -- analysis KW - Receptors, Estrogen -- physiology KW - Ovary -- physiology KW - Ovarian Follicle -- drug effects KW - Ovarian Follicle -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72117925?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biology+of+reproduction&rft.atitle=Neonatal+exposure+to+genistein+induces+estrogen+receptor+%28ER%29alpha+expression+and+multioocyte+follicles+in+the+maturing+mouse+ovary%3A+evidence+for+ERbeta-mediated+and+nonestrogenic+actions.&rft.au=Jefferson%2C+Wendy+N%3BCouse%2C+John+F%3BPadilla-Banks%2C+Elizabeth%3BKorach%2C+Kenneth+S%3BNewbold%2C+Retha+R&rft.aulast=Jefferson&rft.aufirst=Wendy&rft.date=2002-10-01&rft.volume=67&rft.issue=4&rft.spage=1285&rft.isbn=&rft.btitle=&rft.title=Biology+of+reproduction&rft.issn=00063363&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-11 N1 - Date created - 2002-09-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Let's not relive the past: a review of cancer risk after diagnostic or therapeutic irradiation. AN - 72116725; 12244466 JF - Pediatric radiology AU - Ron, Elaine AD - Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH - MS 7238, Room 7048, 6120 Executive Boulevard, Bethesda, MD 20892, USA. eron@mail.nih.gov Y1 - 2002/10// PY - 2002 DA - October 2002 SP - 739 EP - 44; discussion 751-4 VL - 32 IS - 10 SN - 0301-0449, 0301-0449 KW - Index Medicus KW - Infant KW - Radiation Dosage KW - Humans KW - Adult KW - Child KW - Adolescent KW - Male KW - Female KW - Risk Assessment KW - Child, Preschool KW - Neoplasms, Radiation-Induced -- etiology KW - Neoplasms, Radiation-Induced -- epidemiology KW - Radiography -- adverse effects KW - Radiotherapy -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72116725?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+radiology&rft.atitle=Let%27s+not+relive+the+past%3A+a+review+of+cancer+risk+after+diagnostic+or+therapeutic+irradiation.&rft.au=Ron%2C+Elaine&rft.aulast=Ron&rft.aufirst=Elaine&rft.date=2002-10-01&rft.volume=32&rft.issue=10&rft.spage=739&rft.isbn=&rft.btitle=&rft.title=Pediatric+radiology&rft.issn=03010449&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-16 N1 - Date created - 2002-09-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I study of a vaccine using recombinant vaccinia virus expressing PSA (rV-PSA) in patients with metastatic androgen-independent prostate cancer. AN - 72115897; 12242725 AB - A Phase I trial of recombinant vaccinia prostate specific antigen (rV-PSA) in patients with advanced metastatic prostate cancer was conducted. This report describes 42 patients who were treated with up to three monthly vaccinations. All patients were entered on a dose-escalation phase I study of recombinant vaccinia containing the gene for PSA (rV-PSA). The primary objective of this study was to determine the safety of this vaccine in metastatic androgen-independent prostate cancer patients. A secondary objective was to assess evidence of anti-tumor activity by PSA measurements, radiologic findings, and immunologic methods. There was no significant treatment-related toxicity apart from erythema, tenderness, and vesicle formation that lasted several days at the site of injection in some patients. There were immunologic responses, in selected patients, as evidenced by an increase in the proportion of PSA-specific T cells after vaccination. Furthermore, we show that these patients' T cells can lyse PSA-expressing tumor cells in vitro. Given the low toxicity profile and the evidence of immunologic activity, we believe future study is warranted with PSA-based vaccines in prostate cancer. New PSA-based vaccines and vaccine strategies are currently being evaluated. Copyright 2002 Wiley-Liss, Inc. JF - The Prostate AU - Gulley, James AU - Chen, Alice P AU - Dahut, William AU - Arlen, Philip M AU - Bastian, Anne AU - Steinberg, Seth M AU - Tsang, Kwong AU - Panicali, Dennis AU - Poole, Diane AU - Schlom, Jeffrey AU - Michael Hamilton, J AD - Medical Oncology Clinical Research Unit, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/10/01/ PY - 2002 DA - 2002 Oct 01 SP - 109 EP - 117 VL - 53 IS - 2 SN - 0270-4137, 0270-4137 KW - Cancer Vaccines KW - 0 KW - Recombinant Proteins KW - Interferon-gamma KW - 82115-62-6 KW - Prostate-Specific Antigen KW - EC 3.4.21.77 KW - Index Medicus KW - Vaccinia virus -- genetics KW - Vaccinia virus -- immunology KW - Aged, 80 and over KW - Humans KW - Adult KW - Recombinant Proteins -- immunology KW - Recombinant Proteins -- adverse effects KW - Disease Progression KW - Aged KW - Middle Aged KW - Interferon-gamma -- blood KW - Recombinant Proteins -- therapeutic use KW - Male KW - Prostatic Neoplasms -- immunology KW - Bone Neoplasms -- secretion KW - Cancer Vaccines -- adverse effects KW - Prostate-Specific Antigen -- genetics KW - Prostate-Specific Antigen -- immunology KW - Cancer Vaccines -- therapeutic use KW - Adenocarcinoma -- therapy KW - Cancer Vaccines -- immunology KW - Adenocarcinoma -- secondary KW - Bone Neoplasms -- therapy KW - Prostatic Neoplasms -- therapy KW - Prostate-Specific Antigen -- therapeutic use KW - Immunotherapy, Active -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72115897?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Prostate&rft.atitle=Phase+I+study+of+a+vaccine+using+recombinant+vaccinia+virus+expressing+PSA+%28rV-PSA%29+in+patients+with+metastatic+androgen-independent+prostate+cancer.&rft.au=Gulley%2C+James%3BChen%2C+Alice+P%3BDahut%2C+William%3BArlen%2C+Philip+M%3BBastian%2C+Anne%3BSteinberg%2C+Seth+M%3BTsang%2C+Kwong%3BPanicali%2C+Dennis%3BPoole%2C+Diane%3BSchlom%2C+Jeffrey%3BMichael+Hamilton%2C+J&rft.aulast=Gulley&rft.aufirst=James&rft.date=2002-10-01&rft.volume=53&rft.issue=2&rft.spage=109&rft.isbn=&rft.btitle=&rft.title=The+Prostate&rft.issn=02704137&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-10-29 N1 - Date created - 2002-09-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The crystal structure of mitochondrial cytochrome bc1 in complex with famoxadone: the role of aromatic-aromatic interaction in inhibition. AN - 72115330; 12269811 AB - Ubiquinol cytochrome c oxido-reductase (EC. 1.10.2.2, bc1) is an integral membrane protein complex essential to cellular respiration. Structures of the 11-subunit mitochondrial bc1 complex were determined with and without the fungicide famoxadone. Specific inhibition by famoxadone is achieved through a coordinated optimization of aromatic-aromatic interactions where conformational rearrangements in famoxadone and in residues lining the inhibitor-binding pocket produce a network of aromatic-aromatic interactions that mimic the crystal lattice of benzene. The profound aromatic-aromatic interactions as supported by prior mutagenesis provide a structural basis for specific protein-ligand interaction in a hydrophobic environment. Dramatic conformational changes, both in cyt. b and ISP subunits in the inhibitor-protein complex, confer experimental evidence for a functional role of cytochrome b in the induced conformational arrest of ISP and allow the identification of a possible intrasubunit signal transduction pathway that controls the movement of ISP. These results support an inhibitory mechanism that is consistent with the requirement for ISP movement in the electron transfer of this complex. JF - Biochemistry AU - Gao, Xiugong AU - Wen, Xiaolin AU - Yu, ChangAn AU - Esser, Lothar AU - Tsao, Scott AU - Quinn, Byron AU - Zhang, Li AU - Yu, Linda AU - Xia, Di AD - Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2002/10/01/ PY - 2002 DA - 2002 Oct 01 SP - 11692 EP - 11702 VL - 41 IS - 39 SN - 0006-2960, 0006-2960 KW - Cytochrome b Group KW - 0 KW - Enzyme Inhibitors KW - Hydroquinones KW - Macromolecular Substances KW - Methacrylates KW - Oxazoles KW - Protein Subunits KW - famoxadon KW - Electron Transport Complex III KW - EC 1.10.2.2 KW - Index Medicus KW - Crystallization KW - Animals KW - Electron Transport KW - Amino Acid Sequence KW - Cytochrome b Group -- chemistry KW - Protein Binding KW - Oxidation-Reduction KW - Cattle KW - Molecular Sequence Data KW - Crystallography, X-Ray KW - Inhibitory Concentration 50 KW - Hydroquinones -- chemistry KW - Protein Conformation KW - Enzyme Inhibitors -- chemistry KW - Mitochondria, Heart -- enzymology KW - Oxazoles -- chemistry KW - Electron Transport Complex III -- chemistry KW - Electron Transport Complex III -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72115330?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+crystal+structure+of+mitochondrial+cytochrome+bc1+in+complex+with+famoxadone%3A+the+role+of+aromatic-aromatic+interaction+in+inhibition.&rft.au=Gao%2C+Xiugong%3BWen%2C+Xiaolin%3BYu%2C+ChangAn%3BEsser%2C+Lothar%3BTsao%2C+Scott%3BQuinn%2C+Byron%3BZhang%2C+Li%3BYu%2C+Linda%3BXia%2C+Di&rft.aulast=Gao&rft.aufirst=Xiugong&rft.date=2002-10-01&rft.volume=41&rft.issue=39&rft.spage=11692&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-19 N1 - Date created - 2002-09-24 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 1LOL; PDB; 1LON N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of polymerase eta in somatic hypermutation determined by analysis of mutations in a patient with xeroderma pigmentosum variant. AN - 72111951; 12244178 AB - To determine the possible role of polymerase eta (pol eta) in somatic hypermutation of B cells, a mutational analysis of 24 nonproductive rearrangements from a patient with xeroderma pigmentosum variant with a defect in pol eta was conducted. Although the mutational frequency of A and T bases decreased in WA (A/T, A) motifs, regardless of their RGYW (purine, G; pyrimidine, A/T) context, the overall mutational frequency of A or T bases was not affected. Moreover, the overall mutational frequency of the sequences examined was not decreased. There was an apparent increase in the number of insertions and deletions. The results are consistent with the conclusion that pol eta specifically targets WA motifs. However, its overall contribution to the somatic hypermutational process does not appear to be indispensable and in its absence other mechanisms maintain mutational activity. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Yavuz, Sule AU - Yavuz, Akif S AU - Kraemer, Kenneth H AU - Lipsky, Peter E AD - Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892, USA. Y1 - 2002/10/01/ PY - 2002 DA - 2002 Oct 01 SP - 3825 EP - 3830 VL - 169 IS - 7 SN - 0022-1767, 0022-1767 KW - Immunoglobulin Heavy Chains KW - 0 KW - Immunoglobulin Variable Region KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Rad30 protein KW - Abridged Index Medicus KW - Index Medicus KW - Immunoglobulin Variable Region -- genetics KW - Humans KW - Gene Rearrangement, B-Lymphocyte, Heavy Chain KW - Middle Aged KW - Repetitive Sequences, Nucleic Acid -- genetics KW - Germ-Line Mutation KW - Base Pair Mismatch -- genetics KW - Immunoglobulin Heavy Chains -- genetics KW - Mutagenesis, Insertional KW - Male KW - Sequence Deletion KW - Genetic Variation KW - Sequence Analysis, DNA -- methods KW - DNA-Directed DNA Polymerase -- analysis KW - Xeroderma Pigmentosum -- enzymology KW - DNA-Directed DNA Polymerase -- physiology KW - Somatic Hypermutation, Immunoglobulin -- genetics KW - Xeroderma Pigmentosum -- genetics KW - DNA-Directed DNA Polymerase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72111951?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=The+role+of+polymerase+eta+in+somatic+hypermutation+determined+by+analysis+of+mutations+in+a+patient+with+xeroderma+pigmentosum+variant.&rft.au=Yavuz%2C+Sule%3BYavuz%2C+Akif+S%3BKraemer%2C+Kenneth+H%3BLipsky%2C+Peter+E&rft.aulast=Yavuz&rft.aufirst=Sule&rft.date=2002-10-01&rft.volume=169&rft.issue=7&rft.spage=3825&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 - 2002-11-12 N1 - Date created - 2002-09-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interleukin 7 worsens graft-versus-host disease. AN - 72104952; 12239180 AB - Impaired immune reconstitution has moved to the forefront of clinical problems limiting progress in allogeneic bone marrow transplantation (BMT). The identification of therapies that can enhance immune reconstitution by increasing thymopoiesis is critical to solving this problem. Interleukin 7 (IL-7) is the most potent thymopoietic cytokine identified thus far. To study the effects of IL-7 on immune reconstitution and graft-versus-host disease (GVHD) following allogeneic BMT, we administered recombinant human IL-7 (rhIL-7) in a murine parent into an F1 model. Results showed that rhIL-7 therapy lowered the "threshold" T-cell dose required to induce both clinical signs of GVHD as well as lethal GVHD. Histologic analysis of GVHD target tissues revealed that rhIL-7 increased the degree of inflammation and tissue damage observed at all T-cell doses studied, but did not change the pattern of organs affected or the histologic appearance of the GVHD within target organs. In addition, we evaluated the capacity for rhIL-7 to enhance thymopoiesis in the setting of allogeneic T cell-depleted (TCD) and T-cell-replete BMT. We observed that rhIL-7 therapy enhanced thymic function in TCD allogeneic BM transplant recipients, but not in animals that received even modest doses of T cells presumably due to thymic toxicity of the graft-versus-host reaction. Thus, caution must be exercised as IL-7 is developed clinically as an immunorestorative agent for use in the setting of allogeneic BMT. These results suggest that use of IL-7 should be limited to the setting of TCD BMT to obtain the greatest benefit on immune competence with the least toxicity. JF - Blood AU - Sinha, Manoj L AU - Fry, Terry J AU - Fowler, Daniel H AU - Miller, Georgina AU - Mackall, Crystal L AD - Pediatric Oncology Branch, Experimental Transplantation and Immunology Branch, National Cancer Institute, and Veterinary Resources Program, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2002/10/01/ PY - 2002 DA - 2002 Oct 01 SP - 2642 EP - 2649 VL - 100 IS - 7 SN - 0006-4971, 0006-4971 KW - Interleukin-7 KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Liver -- pathology KW - Colon -- pathology KW - Body Weight -- drug effects KW - Mice, Inbred C57BL KW - Disease Progression KW - Mice KW - Bone Marrow Transplantation -- pathology KW - Bone Marrow Transplantation -- immunology KW - Interleukin-7 -- toxicity KW - Graft vs Host Disease -- pathology KW - Weight Loss UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72104952?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+7+worsens+graft-versus-host+disease.&rft.au=Sinha%2C+Manoj+L%3BFry%2C+Terry+J%3BFowler%2C+Daniel+H%3BMiller%2C+Georgina%3BMackall%2C+Crystal+L&rft.aulast=Sinha&rft.aufirst=Manoj&rft.date=2002-10-01&rft.volume=100&rft.issue=7&rft.spage=2642&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-12-05 N1 - Date created - 2002-09-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Preliminary experience with an ampakine (CX516) as a single agent for the treatment of schizophrenia: a case series. AN - 72075170; 12223253 AB - We used L-(quinoxalin-6-ylcarbonyl)piperidine (CX516) (a modulator of the alpha-amino-3-hydroxy-5-methyl-4-isoxasole propionic acid (AMPA) receptor) as a sole agent in a double blind placebo-controlled design in a small series of patients with schizophrenia who were partially refractory to treatment with traditional neuroleptics. The study entailed weekly increments in doses of CX516, from 300 mg tid for week 1 up to 900 mg tid on week 4. Patients were followed with clinical ratings, neuropsychological testing, and were monitored for adverse events. Four patients received 2 to 4 weeks of CX516, two received placebo and two withdrew during the placebo phase. Adverse events associated with drug administration were transient and included leukopenia in one patient and elevation in liver enzymes in another. No clear improvement in psychosis or in cognition was observed over the course of the study. CX516 at the doses tested did not appear to yield dramatic effects as a sole agent, but inference from this study is limited. JF - Schizophrenia research AU - Marenco, Stefano AU - Egan, Michael F AU - Goldberg, Terry E AU - Knable, Michael B AU - McClure, Robert K AU - Winterer, Georg AU - Weinberger, Daniel R AD - Intramural Research Program, Clinical Brain Disorders Branch, National Institute of Mental Health, Building 10, Room 4S235, Bethesda, MD 20892, USA. marenco@intra.nimh.nih.gov Y1 - 2002/10/01/ PY - 2002 DA - 2002 Oct 01 SP - 221 EP - 226 VL - 57 IS - 2-3 SN - 0920-9964, 0920-9964 KW - 1-(quinoxalin-6-ylcarbonyl)piperidine KW - 0 KW - Antipsychotic Agents KW - Dioxoles KW - Piperidines KW - Index Medicus KW - Double-Blind Method KW - Humans KW - Adult KW - Middle Aged KW - Male KW - Female KW - Piperidines -- therapeutic use KW - Dioxoles -- adverse effects KW - Antipsychotic Agents -- therapeutic use KW - Schizophrenia -- drug therapy KW - Antipsychotic Agents -- adverse effects KW - Dioxoles -- therapeutic use KW - Piperidines -- adverse effects KW - Psychotic Disorders -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72075170?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Preliminary+experience+with+an+ampakine+%28CX516%29+as+a+single+agent+for+the+treatment+of+schizophrenia%3A+a+case+series.&rft.au=Marenco%2C+Stefano%3BEgan%2C+Michael+F%3BGoldberg%2C+Terry+E%3BKnable%2C+Michael+B%3BMcClure%2C+Robert+K%3BWinterer%2C+Georg%3BWeinberger%2C+Daniel+R&rft.aulast=Marenco&rft.aufirst=Stefano&rft.date=2002-10-01&rft.volume=57&rft.issue=2-3&rft.spage=221&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 - 2002-11-08 N1 - Date created - 2002-09-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Extrapyramidal symptom profiles in Japanese patients with schizophrenia treated with olanzapine or haloperidol. AN - 72074655; 12223254 AB - Previous clinical trials have clearly shown the superiority of olanzapine to haloperidol in the improvement of extrapyramidal symptoms (EPS) in schizophrenic patients. The primary purpose of this study was to compare EPS profiles in Japanese schizophrenic patients treated with an atypical antipsychotic, olanzapine, or a typical antipsychotic, haloperidol, as measured by the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). The DIEPSS, which consists of eight individual parameters and one global assessment (overall severity), was used to evaluate 182 patients enrolled in this 8-week study. The primary safety analysis was maximum change (that could be either a decrease or increase) from baseline in DIEPSS total score. Secondary analyses included change from baseline to maximum in DIEPSS total score, change from baseline to endpoint (LOCF) in DIEPSS total score, and the rank sum of the maximum change (that could be either a decrease or increase) from baseline in the DIEPSS individual items. Incidence of treatment-emergent EPS adverse events using the DIEPSS scale was also analyzed. The olanzapine group showed statistically significant superiority to the haloperidol group on the primary analysis (p<0.001). Secondary analyses also demonstrated olanzapine's superiority in DIEPSS total, parkinsonism, akathisia and overall severity scores (all p< or =0.014). Categorical analysis of treatment-emergent akathisia and parkinsonism syndromes at endpoint showed improvement in the olanzapine group but worsening in the haloperidol group. The results from this study suggest that olanzapine, as in Caucasian populations, is a safe treatment in Japanese patients chronically ill with schizophrenia. JF - Schizophrenia research AU - Inada, Toshiya AU - Yagi, Gohei AU - Miura, Sadanori AD - Department of Geriatric Mental Health, National Institute of Mental Health, National Center of Neurology and Psychiatry, Ichikawa, Japan. inada@ncnp-k.go.jp Y1 - 2002/10/01/ PY - 2002 DA - 2002 Oct 01 SP - 227 EP - 238 VL - 57 IS - 2-3 SN - 0920-9964, 0920-9964 KW - Antipsychotic Agents KW - 0 KW - Benzodiazepines KW - 12794-10-4 KW - Pirenzepine KW - 3G0285N20N KW - Haloperidol KW - J6292F8L3D KW - olanzapine KW - N7U69T4SZR KW - Index Medicus KW - Japan -- epidemiology KW - Double-Blind Method KW - Humans KW - Adult KW - Incidence KW - Middle Aged KW - Statistics, Nonparametric KW - Male KW - Female KW - Haloperidol -- adverse effects KW - Pirenzepine -- analogs & derivatives KW - Schizophrenia -- drug therapy KW - Antipsychotic Agents -- adverse effects KW - Pirenzepine -- adverse effects KW - Basal Ganglia Diseases -- epidemiology KW - Basal Ganglia Diseases -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72074655?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Extrapyramidal+symptom+profiles+in+Japanese+patients+with+schizophrenia+treated+with+olanzapine+or+haloperidol.&rft.au=Inada%2C+Toshiya%3BYagi%2C+Gohei%3BMiura%2C+Sadanori&rft.aulast=Inada&rft.aufirst=Toshiya&rft.date=2002-10-01&rft.volume=57&rft.issue=2-3&rft.spage=227&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 - 2002-11-08 N1 - Date created - 2002-09-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A Dose Response Study of Cognitive Behavioral Therapy in Cocaine Abusers AN - 61496753; 200303402 AB - In order to evaluate the effect of frequency of counseling sessions, we studied retention, cocaine use & craving, & psychiatric symptoms of 68 cocaine-dependent outpatients randomly assigned to twice weekly, once weekly, or biweekly sessions in a 12-week treatment program that utilized manual-based, individual cognitive behavioral psychotherapy. All participants were tested & monitored twice a week. Retention was comparable among treatment groups, & improvement was found regardless of counseling frequency. Cocaine use (urine toxicology & self-report), cocaine craving (VAS), & total psychiatric symptoms (SCL-90) decreased by modest but statistically significant (p < 0.05) amounts in all treatment groups. Findings suggest that cognitive behavioral therapy is effective in reducing cocaine use even if a less intensive schedule is used. 3 Tables, 2 Figures, 24 References. Adapted from the source document. JF - Journal of Substance Abuse Treatment AU - Covi, Lino AU - Hess, Judith M AU - Schroeder, Jennifer R AU - Preston, Kenzie L AD - National Instit Drug Abuse Intramural Research Program, Baltimore, MD lcovi@intra.nida.nih.gov Y1 - 2002/10// PY - 2002 DA - October 2002 SP - 191 EP - 197 VL - 23 IS - 3 SN - 0740-5472, 0740-5472 KW - Treatment Programs KW - Psychotherapy KW - Behavior Modification KW - Program Evaluation KW - Cocaine KW - Drug Abuse KW - article KW - 6129: addiction KW - 6121: therapeutic interventions UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61496753?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocialservices&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Substance+Abuse+Treatment&rft.atitle=A+Dose+Response+Study+of+Cognitive+Behavioral+Therapy+in+Cocaine+Abusers&rft.au=Covi%2C+Lino%3BHess%2C+Judith+M%3BSchroeder%2C+Jennifer+R%3BPreston%2C+Kenzie+L&rft.aulast=Covi&rft.aufirst=Lino&rft.date=2002-10-01&rft.volume=23&rft.issue=3&rft.spage=191&rft.isbn=&rft.btitle=&rft.title=Journal+of+Substance+Abuse+Treatment&rft.issn=07405472&rft_id=info:doi/ LA - English DB - Social Services Abstracts N1 - Date revised - 2007-05-01 N1 - Last updated - 2016-09-28 N1 - CODEN - JSATEG N1 - SubjectsTermNotLitGenreText - Drug Abuse; Cocaine; Treatment Programs; Program Evaluation; Behavior Modification; Psychotherapy ER - TY - JOUR T1 - Catastrophic failures of freezing bags for cellular therapy products: description, cause, and consequences AN - 21344549; 7347576 AB - Background Container integrity is critical for maintaining sterility of cryopreserved cellular therapy products. We investigated a series of catastrophic bag failures, first noticed in early 2001. Methods Process records were reviewed for all PBPC and lymphocyte products cryopreserved in bags from January 2000 through April 2002. Patient charts were also reviewed. Results One thousand two hundred and four bags were removed from storage for infusion to 261 patients. All products had been cryopreserved in Cryocyte poly(ethylene co-vinyl acetate) (EVA) bags in either 10% DMSO or 5% DMSO and 6% pentastarch. Product volumes were 25-75 mL, and bags were stored with overwrap bags in a liquid nitrogen tank. From January 2000 to April 2001, failure occurred in 10 of 599 (1.7%) bags. From May 2001 to April 2002, 58 of 605 (9.6%) bags failed, typically with extensive fractures that were visible before thaw. Of the 58 that failed, 24 were salvaged by aseptic methods and infused to patients under antibiotic coverage; 10 of those 24 (42%) had positive bacterial cultures. Bag failures were not related to product type, cryoprotectant solution, liquid versus vapor storage, or freezer location. Failures were linked to use of four Cryocyte bag lots manufactured in 2000 and 2001. After replacing these lots with a 1999 Cryocyte lot and with KryoSafe polyfluoroethylene polyfluoropropylene (FEP) bags, no more failures occurred in 75 and 102 bags, respectively, thawed through April 2002. Discussion High rates of bag failure were associated with four Cryocyte bag lots. No serious adverse patient effects occurred, but bag failures led to microbial contamination, increased product preparation time, increased antibiotic use, and increased resource expenditure to replace products. JF - Cytotherapy AU - Khuu, H M AU - Cowley, H AU - David-Ocampo, V AU - Carter, C S AU - Kasten-Sportes, C AU - Wayne, A S AU - Solomon, S R AU - Bishop, M R AU - Childs, R M AU - Read, E J AD - Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD, USA Y1 - 2002/10// PY - 2002 DA - Oct 2002 SP - 539 EP - 549 PB - Taylor & Francis Ltd., 11 New Fetter Lane London EC4P 4EE UK, [mailto:info@tandf.co.uk], [URL:http://www.tandf.co.uk] VL - 4 IS - 6 SN - 1465-3249, 1465-3249 KW - Microbiology Abstracts B: Bacteriology KW - CRYOPRESERVATION KW - CELLULAR THERAPY PRODUCT KW - ASEPTIC METHODS KW - PLASTIC BAGS KW - BACTERIAL KW - CONTAMINATION KW - Contamination KW - Sterility KW - Freezing KW - Fractures KW - Antibiotics KW - Cell culture KW - Lymphocytes KW - Cryopreservation KW - Acetic acid KW - Vapors KW - Cryoprotectors KW - Nitrogen KW - J 02400:Human Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21344549?accountid=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=Cytotherapy&rft.atitle=Catastrophic+failures+of+freezing+bags+for+cellular+therapy+products%3A+description%2C+cause%2C+and+consequences&rft.au=Khuu%2C+H+M%3BCowley%2C+H%3BDavid-Ocampo%2C+V%3BCarter%2C+C+S%3BKasten-Sportes%2C+C%3BWayne%2C+A+S%3BSolomon%2C+S+R%3BBishop%2C+M+R%3BChilds%2C+R+M%3BRead%2C+E+J&rft.aulast=Khuu&rft.aufirst=H&rft.date=2002-10-01&rft.volume=4&rft.issue=6&rft.spage=539&rft.isbn=&rft.btitle=&rft.title=Cytotherapy&rft.issn=14653249&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-02-01 N1 - SuppNotes - 12 references N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Vapors; Contamination; Fractures; Freezing; Sterility; Cryoprotectors; Cell culture; Antibiotics; Lymphocytes; Acetic acid; Cryopreservation; Nitrogen ER - TY - JOUR T1 - Adult BM stem cells regenerate mouse myocardium AN - 21298674; 7347573 JF - Cytotherapy AU - Orlic, D AD - Genetics and Molecular Biology Branch, National Human Genome Research Institute, NIH, Bethesda, MD, USA Y1 - 2002/10// PY - 2002 DA - Oct 2002 SP - 521 EP - 525 PB - Taylor & Francis Ltd., 11 New Fetter Lane London EC4P 4EE UK, [mailto:info@tandf.co.uk], [URL:http://www.tandf.co.uk] VL - 4 IS - 6 SN - 1465-3249, 1465-3249 KW - Biotechnology and Bioengineering Abstracts KW - Stem cells KW - Myocardium KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21298674?accountid=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=Cytotherapy&rft.atitle=Adult+BM+stem+cells+regenerate+mouse+myocardium&rft.au=Orlic%2C+D&rft.aulast=Orlic&rft.aufirst=D&rft.date=2002-10-01&rft.volume=4&rft.issue=6&rft.spage=521&rft.isbn=&rft.btitle=&rft.title=Cytotherapy&rft.issn=14653249&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-03-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Stem cells; Myocardium ER - TY - JOUR T1 - Cerebrovascular Disease in HIV-Infected Pediatric Patients: Neuroimaging Findings AN - 20871864; 9433219 AB - OBJECTIVE. The goal of our study was to report on the prevalence and the neuroradiologic manifestations of cerebrovascular complications in children infected with HIV. We also elucidate the types of vascular involvement, identify their anatomic distribution, and discuss possible causes. MATERIALS AND METHODS. We conducted a retrospective study of 567 patients (age range, 1 month-29 years; median age, 5.47 years) who acquired HIV as children. Of these, 426 patients (75%) were evaluated with neuroimaging studies. We reviewed these studies to identify the cerebrovascular abnormalities and classify them by type, anatomic location, and shape. RESULTS. Eleven children (2.6%) were found to have cerebrovascular lesions. Only one had focal neurologic symptoms at the time of diagnosis. Twenty-six aneurysms were found in seven patients, and 27 infarctions were found in eight patients. In four of the patients with infarctions, fusiform aneurysms of the cerebral arteries were also identified. Most patients had advanced HIV disease. Nine of the 11 patients were infected by a vertical transmission route or during blood transfusion early in the neonatal period. In this group of patients, the diagnosis of cerebrovascular disease was made earlier (mean age at diagnosis, 8.2 years) than in the two patients who were infected later in life (mean age at diagnosis, 14.9 years). CONCLUSION. HIV-infected children have an increased incidence of cerebrovascular disease that is associated with severe immune suppression and with vertically acquired HIV infection or exposure to the virus in the neonatal period. Despite extensive lesions, most children in our study were asymptomatic. Screening with MR imaging should be considered for high-risk children and is advisable when evidence of neurologic symptoms or neurocognitive dysfunction is noted. JF - American Journal of Roentgenology AU - Patsalides, AD AU - Wood, LV AU - Atac, G K AU - Sandifer, E AU - Butman, JA AU - Patronas, N J AD - Diagnostic Radiology Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, 10 Center Dr., Bldg. 10, Rm. 1C-660, Bethesda, MD 20892-1182, USA Y1 - 2002/10// PY - 2002 DA - Oct 2002 SP - 999 EP - 1003 VL - 179 IS - 4 SN - 0361-803X, 0361-803X KW - Virology & AIDS Abstracts; CSA Neurosciences Abstracts; Biotechnology and Bioengineering Abstracts KW - Neuroimaging KW - Age KW - Aneurysm KW - Pediatrics KW - Cerebrovascular diseases KW - Arteries KW - Magnetic resonance imaging KW - Infection KW - Children KW - Cognition KW - Disease transmission KW - Blood transfusion KW - Human immunodeficiency virus KW - Risk groups KW - Neonates KW - Infarction KW - Vascular system KW - V 22360:AIDS and HIV KW - W 30910:Imaging KW - N3 11024:Neuroimmunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20871864?accountid=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+Roentgenology&rft.atitle=Cerebrovascular+Disease+in+HIV-Infected+Pediatric+Patients%3A+Neuroimaging+Findings&rft.au=Patsalides%2C+AD%3BWood%2C+LV%3BAtac%2C+G+K%3BSandifer%2C+E%3BButman%2C+JA%3BPatronas%2C+N+J&rft.aulast=Patsalides&rft.aufirst=AD&rft.date=2002-10-01&rft.volume=179&rft.issue=4&rft.spage=999&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Roentgenology&rft.issn=0361803X&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 - Age; Neuroimaging; Aneurysm; Cerebrovascular diseases; Pediatrics; Arteries; Magnetic resonance imaging; Children; Infection; Cognition; Disease transmission; Blood transfusion; Risk groups; Neonates; Infarction; Vascular system; Human immunodeficiency virus ER - TY - JOUR T1 - Plasmodium malariae infection boosts Plasmodium falciparum gametocyte production AN - 18922371; 5617245 AB - We analyzed records of malariotherapy patients sequentially or simultaneously inoculated with Plasmodium falciparum and Plasmodium malariae. Gametocyte production was enhanced in P. falciparum by prior or concurrent P. malariae infection but diminished or unaffected in P. malariae by P. falciparum. Conversely, asexual-form production was diminished in P. malariae but unaffected in P. falciparum. JF - American Journal of Tropical Medicine and Hygiene AU - McKenzie, F E AU - Jeffery, G M AU - Collins, W E AD - Fogarty International Center, National Institutes of Health, Bethesda, MD, USA Y1 - 2002/10// PY - 2002 DA - October 2002 SP - 411 EP - 414 VL - 67 IS - 4 SN - 0002-9637, 0002-9637 KW - Gametocytes KW - gametocytes KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; ASFA 3: Aquatic Pollution & Environmental Quality; ASFA 1: Biological Sciences & Living Resources KW - Human diseases KW - Protozoan diseases KW - Therapy KW - Malaria KW - Plasmodium falciparum KW - Pathogens KW - Sexual cells KW - Freshwater KW - Interspecific relationships KW - Plasmodium malariae KW - Reproduction KW - K 03090:Protozoa: human KW - Q1 08484:Species interactions: parasites and diseases KW - Q5 08524:Public health, medicines, dangerous organisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18922371?accountid=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=American+Journal+of+Tropical+Medicine+and+Hygiene&rft.atitle=Plasmodium+malariae+infection+boosts+Plasmodium+falciparum+gametocyte+production&rft.au=McKenzie%2C+F+E%3BJeffery%2C+G+M%3BCollins%2C+W+E&rft.aulast=McKenzie&rft.aufirst=F&rft.date=2002-10-01&rft.volume=67&rft.issue=4&rft.spage=411&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 - Last updated - 2016-12-21 N1 - SubjectsTermNotLitGenreText - Human diseases; Protozoan diseases; Interspecific relationships; Reproduction; Malaria; Sexual cells; Pathogens; Therapy; Plasmodium malariae; Plasmodium falciparum; Freshwater ER - TY - JOUR T1 - Respiratory cancer and exposure to man-made vitreous fibers: A systematic review AN - 18834374; 5729103 AB - Man-made vitreous fibers (MMVF's) have some structural features similar to those found in asbestos. This has lead to concern that exposure to MMVF's could increase the risk of respiratory cancer. Bibliographic resources were used to identify 10 case-control and 10 cohort studies, which analyzed the relationship between exposure to MMVF's and cancer of the respiratory system. Standardized mortality ratio's (SMR's) were extracted from the cohort studies for a meta-analysis. A significant increase in SMR was observed for workers exposed to rock and glass wool, but not in workers exposed to glass filament. Meta-analysis of SMR's after stratification by fiber type resulted in aggregate estimates of risk of 1.23 (95% CI = 1.10-1.38), 1.08 (95% CI = 0.93-1.26), and 1.32 (95% CI = 1.15-1.52) for exposure to glass wool, glass filament, and rock wool, respectively. Some or all of the increased mortality could be attributed to tobacco use. The results highlight the difficulty of assessing small increases in risk of respiratory cancer potentially caused by occupational exposure in populations with high prevalence of tobacco use. JF - American Journal of Industrial Medicine AU - Berrigan, D AD - Applied Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Executive Plaza North, MSC 7344, Room 4009A, 6130 Executive Blvd., Bethesda, MD 20892-7344, USA, berrigad@mail.nih.gov Y1 - 2002/10// PY - 2002 DA - Oct 2002 SP - 354 EP - 362 VL - 42 IS - 4 SN - 0271-3586, 0271-3586 KW - man-made vitreous fibers KW - Health & Safety Science Abstracts KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18834374?accountid=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+Industrial+Medicine&rft.atitle=Respiratory+cancer+and+exposure+to+man-made+vitreous+fibers%3A+A+systematic+review&rft.au=Berrigan%2C+D&rft.aulast=Berrigan&rft.aufirst=D&rft.date=2002-10-01&rft.volume=42&rft.issue=4&rft.spage=354&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Industrial+Medicine&rft.issn=02713586&rft_id=info:doi/10.1002%2Fajim.10111 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1002/ajim.10111 ER - TY - JOUR T1 - Absence of Tight Junction Formation in an Allogeneic Graft Cell Line Used for Developing an Engineered Artificial Salivary Gland AN - 18676090; 5574080 AB - An essential structural feature of fluid-secreting epithelial tissues is the presence of tight junctions. To develop a tissue-engineered organ capable of fluid secretion, the cellular component must establish these structures. As part of efforts to create an engineered artificial salivary gland, we have examined the ability of a candidate allogeneic graft cell line, HSG, to produce several key tight junction proteins, as well as to exhibit functional activities consistent with effective tight junction strand formation. In contrast to results obtained with a control kidney cell line, MDCK-II, HSG cells were unable to synthesize four important tight junction-associated proteins: ZO-1, occludin, claudin-1, and claudin-2. In addition, unlike MDCK-II cells, HSG cell monolayers could not restrict paracellular permeability. HSG cells were, thus, unable to generate significant transepithelial electrical resistance or serve as an effective barrier to osmotically imposed fluid movement. Furthermore, these two functional activities could not be reconstituted via the stable transfection of HSG cells with cDNAs encoding either claudin-1 or claudin-2. We conclude that because of their inability to form tight junctions, HSG cells are unsuitable for use as an allogeneic graft cell in an artificial salivary fluid secretory device. These studies also emphasize the importance of graft cell selection in artificial organ development, as certain required characteristics may be difficult to reengineer. JF - Tissue Engineering AU - Aframian, D J AU - Tran, S D AU - Cukierman, E AU - Yamada, K M AU - Baum, B J AD - GTTB, NIDCR, NIH Bldg. 10, Rm. 1N113, MSC-1190, Bethesda, MD 20892, USA, bbaum@dir.nidcr.nih.gov Y1 - 2002/10// PY - 2002 DA - Oct 2002 SP - 871 EP - 878 VL - 8 IS - 5 SN - 1076-3279, 1076-3279 KW - ZO-1 protein KW - claudin-1 KW - claudin-2 KW - tight junction-associated proteins KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W 30965:Miscellaneous, Reviews KW - W3 33220:Cell culture KW - W4 110:Biomedical Materials & Tissue Engineering UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18676090?accountid=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=Tissue+Engineering&rft.atitle=Absence+of+Tight+Junction+Formation+in+an+Allogeneic+Graft+Cell+Line+Used+for+Developing+an+Engineered+Artificial+Salivary+Gland&rft.au=Aframian%2C+D+J%3BTran%2C+S+D%3BCukierman%2C+E%3BYamada%2C+K+M%3BBaum%2C+B+J&rft.aulast=Aframian&rft.aufirst=D&rft.date=2002-10-01&rft.volume=8&rft.issue=5&rft.spage=871&rft.isbn=&rft.btitle=&rft.title=Tissue+Engineering&rft.issn=10763279&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 Role of Hypoxia-Inducible Signaling Pathway in Nickel Carcinogenesis AN - 18650141; 5550824 AB - Using human and rodent cells in vitro, we characterized a hypoxia-inducible signaling pathway as one of the pathways affected by carcinogenic nickel compounds. Acute exposure to nickel activates hypoxia-inducible transcription factor-1 (HIF-1), which strongly induces hypoxia-inducible genes, including the recently discovered tumor marker Cap43. This gene has been cloned based on its nickel inducibility and was found to be highly inducible by hypoxia. To identify other HIF-1-dependent/independent nickel-inducible genes, we used cells obtained from HIF-1 alpha null mouse embryos and analyzed gene expression changes using the microarray technique. We found that genes coding for glycolytic enzymes, known to be regulated by HIF-1, were also induced in nickel-exposed cells. In addition, we identified a number of new genes highly induced by nickel in an HIF-dependent manner. Elevated HIF-1 activity after acute nickel exposure might be selectively advantageous because nickel-transformed rodent and human cells possess increased HIF-1 transcriptional activity. Hypoxia plays an important role in tumor progression. It selects for cells with enhanced glycolytic activity, causing production of large amounts of lactic acid, one of the most common features of tumor cells (Warburg effect). Here, we hypothesize that exposure to nickel activates the hypoxia-inducible pathway and facilitates selection of cells with increased transcriptional activity of hypoxia-inducible genes, which may be important in the nickel-induced carcinogenic process. JF - Environmental Health Perspectives AU - Salnikow, K AU - Davidson, T AU - Costa, M AD - Dept. of Environmental Medicine, NIEHS and Kaplan Comprehensive Cancer Centers, New York University, 550 First Ave, New York, NY 10016 USA, salnikow@env.med.nyu.edu Y1 - 2002/10// PY - 2002 DA - Oct 2002 SP - 831 EP - 834 VL - 110 SN - 0091-6765, 0091-6765 KW - signaling pathways KW - Toxicology Abstracts KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18650141?accountid=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=The+Role+of+Hypoxia-Inducible+Signaling+Pathway+in+Nickel+Carcinogenesis&rft.au=Salnikow%2C+K%3BDavidson%2C+T%3BCosta%2C+M&rft.aulast=Salnikow&rft.aufirst=K&rft.date=2002-10-01&rft.volume=110&rft.issue=&rft.spage=831&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 ER - TY - JOUR T1 - Sodium Arsenite-Induced Stress-Related Gene Expression in Normal Human Epidermal, HaCaT, and HEL30 Keratinocytes AN - 18643662; 5550810 AB - Arsenic is a carcinogen that poses a significant health risk in humans. Based on evidence that arsenic has differential effects on human, rodent, normal, and transformed cells, these studies addressed the relative merits of using normal human epidermal keratinocytes (NHEK) and immortalized human (HaCaT) and mouse (HEL30) keratinocytes when examining stress-induced gene expression that may contribute to carcinogenesis. We hypothesize that redox-related gene expression is differentially modulated by arsenic in normal versus immortalized keratinocytes. To test the hypothesis, we exposed keratinocytes to sodium arsenite for 4 or 24 hr, at which time serine threonine kinase-25 (stk25) and nicotine adenine dinucleotide phosphate [nad(p)h] quinone oxidoreductase gene expression were measured. The effect of glutathione reduction on arsenite-induced cytotoxicity and gene expression in NHEK also was evaluated by addition of L-buthionine-[S,R]-sulfoximine (BSO) to culture media. Results indicate the term LC sub(50) for arsenite is approximately 10-15 mu M in NHEK and HEL30 keratinocytes and 30 mu M in HaCaT keratinocytes. Compared with HaCaT and HEL30 keratinocytes, a nontoxic concentration of arsenite (2.5 mu M) increases stk25 and nad(p)h quinone oxidoreductase gene expression in NHEK, an effect partially attenuated by BSO. These data indicate that NHEK and HaCaT/HEL30 keratinocytes have similar sensitivities toward arsenite-induced cytotoxicity but unique gene expression responses. They also suggest that arsenite modulates gene expression in NHEK involved in cellular signaling and other aspects of intermediary metabolism that may contribute to the carcinogenic process. JF - Environmental Health Perspectives AU - Trouba, K J AU - Geisenhoffer, K M AU - Germolec AD - Environmental Immunology, NIEHS, PO Box 12233, Research Triangle Park, NC 27709 USA, germolec@niehs.nih.gov Y1 - 2002/10// PY - 2002 DA - Oct 2002 SP - 761 EP - 766 VL - 110 SN - 0091-6765, 0091-6765 KW - HEL30 cells KW - HaCaT cells KW - man KW - mice KW - Toxicology Abstracts KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18643662?accountid=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=Sodium+Arsenite-Induced+Stress-Related+Gene+Expression+in+Normal+Human+Epidermal%2C+HaCaT%2C+and+HEL30+Keratinocytes&rft.au=Trouba%2C+K+J%3BGeisenhoffer%2C+K+M%3BGermolec&rft.aulast=Trouba&rft.aufirst=K&rft.date=2002-10-01&rft.volume=110&rft.issue=&rft.spage=761&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - High-frequency conjugative transfer of antibiotic resistance genes to Yersinia pestis in the flea midgut AN - 18627009; 5528969 AB - The acquisition of foreign DNA by horizontal transfer from unrelated organisms is a major source of variation leading to new strains of bacterial pathogens. The extent to which this occurs varies widely, due in part to lifestyle factors that determine exposure to potential donors. Yersinia pestis, the plague bacillus, infects normally sterile sites in its mammalian host, but forms dense aggregates in the non-sterile digestive tract of its flea vector to produce a transmissible infection. Here we show that unrelated co-infecting bacteria in the flea midgut are readily incorporated into these aggregates, and that this close physical contact leads to high-frequency conjugative genetic exchange. Transfer of an antibiotic resistance plasmid from an Escherichia coli donor to Y. pestis occurred in the flea midgut at a frequency of 10 super(-3) after only 3 days of co-infection, and after 4 weeks 95% of co-infected fleas contained an average of 10 super(3) antibiotic-resistant Y. pestis transconjugants. Thus, transit in its arthropod vector exposes Y. pestis to favourable conditions for efficient genetic exchange with microbial flora of the flea gut. Horizontal gene transfer in the flea may be the source of antibiotic-resistant Y. pestis strains recently isolated from plague patients in Madagascar. JF - Molecular Microbiology AU - Hinnebusch, B J AU - Rosso, M AU - Schwan, T G AU - Carniel, E AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 S 4th St., Hamilton, MT 59840, USA., jhinnebusch@niaid.nih.gov Y1 - 2002/10// PY - 2002 DA - Oct 2002 SP - 349 EP - 354 PB - Blackwell Science Ltd VL - 46 IS - 2 SN - 0950-382X, 0950-382X KW - Fleas KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - G 07320:Bacterial genetics KW - J 02795:Antibiotic resistance UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18627009?accountid=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=High-frequency+conjugative+transfer+of+antibiotic+resistance+genes+to+Yersinia+pestis+in+the+flea+midgut&rft.au=Hinnebusch%2C+B+J%3BRosso%2C+M%3BSchwan%2C+T+G%3BCarniel%2C+E&rft.aulast=Hinnebusch&rft.aufirst=B&rft.date=2002-10-01&rft.volume=46&rft.issue=2&rft.spage=349&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1046%2Fj.1365-2958.2002.03159.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1046/j.1365-2958.2002.03159.x ER - TY - JOUR T1 - Risk factors for development of systemic lupus erythematosus: Allergies, infections, and family history AN - 18620684; 5528711 AB - We examined risk factors for systemic lupus erythematosus (SLE) in 265 recently diagnosed patients in North Carolina and South Carolina and 355 control subjects identified through driver's license records and frequency matched to patients by age, sex, and state. Analyses were limited to exposures before diagnosis (cases) or reference year (control subjects). SLE patients were more likely than control subjects to report a history of allergy to medications (odds ratio [OR] 3.1, 95% confidence interval [CI], 2.1-4.5), particularly to antibiotics. SLE risk increased with history of shingles (OR 2.5, 95% CI 1.1-5.9) and with frequent (more than once per year) cold sores in the 3 years before diagnosis (OR 2.8, 95% CI 1.4-5.4). There was little association with history of mononucleosis, a marker of late infection with Epstein-Barr virus, implanted medical devices, or hepatitis B vaccination. History of lupus in parents or siblings was associated with an increased risk (OR 3.3, 95% CI 1.2-8.6). Further research is needed to clarify whether medication allergies and specific infectious agents are involved in the etiology of SLE. JF - Journal of Clinical Epidemiology AU - Cooper, G S AU - Dooley, MA AU - Treadwell, EL AU - St Clair, EW AU - Gilkeson, G S AD - Epidemiology Branch A3-05, NIEHS, PO Box 12233, Durham, NC 27709, USA, cooper1@niehs.nih.gov Y1 - 2002/10// PY - 2002 DA - Oct 2002 SP - 982 EP - 989 VL - 55 IS - 10 SN - 0895-4356, 0895-4356 KW - Epstein-Barr virus KW - hepatitis B KW - implants KW - infection KW - systemic lupus erythematosus KW - vaccination KW - Risk Abstracts KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18620684?accountid=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+Clinical+Epidemiology&rft.atitle=Risk+factors+for+development+of+systemic+lupus+erythematosus%3A+Allergies%2C+infections%2C+and+family+history&rft.au=Cooper%2C+G+S%3BDooley%2C+MA%3BTreadwell%2C+EL%3BSt+Clair%2C+EW%3BGilkeson%2C+G+S&rft.aulast=Cooper&rft.aufirst=G&rft.date=2002-10-01&rft.volume=55&rft.issue=10&rft.spage=982&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 ER - TY - JOUR T1 - Confidentiality issues for medical data miners AN - 18602801; 5510747 AB - The first task in any medical data mining effort is ensuring patient confidentiality. In the past, most data mining efforts ensured confidentiality by the dubious policy of witholding their raw data from colleagues and the public. A cursory review of medical informatics literature in the past decade reveals that much of what we have "learned" consists of assertions derived from confidential datasets unavailable for anyone's review. Without access to the original data, it is impossible to validate or improve upon a researcher's conclusions. Without access to research data, we are asked to accept findings as an act of faith, rather than as a scientific conclusion. This special issue of Artificial Intelligence in Medicine is devoted to medical data mining. The medical data miner has an obligation to conduct valid research in a way that protects human subjects. Today, data miners have the technical tools to merge large data collections and to distribute queries over disparate databases. In order to include patient-related data in shared databases, data miners will need methods to anonymize and deidentify data. This article reviews the human subject risks associated with medical data mining. This article also describes some of the innovative computational remedies that will permit researchers to conduct research AND share their data without risk to patient or institution. JF - Artificial Intelligence in Medicine AU - Berman, J J AD - Pathology Informatics Cancer Diagnosis Program, DCTD, NCI, NIH, EPN-Room 6028, 6130 Executive Building, Rockville, MD 20892, USA, bermanj@mail.nih.gov Y1 - 2002/10// PY - 2002 DA - Oct 2002 SP - 25 EP - 36 VL - 26 IS - 1-2 SN - 0933-3657, 0933-3657 KW - confidentiality KW - medical records KW - privacy KW - records management KW - security KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Risk Abstracts KW - R2 23020:Technological risks KW - W4 140:Bioinformatics & Computers in Health & Medicine KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18602801?accountid=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=Artificial+Intelligence+in+Medicine&rft.atitle=Confidentiality+issues+for+medical+data+miners&rft.au=Berman%2C+J+J&rft.aulast=Berman&rft.aufirst=J&rft.date=2002-10-01&rft.volume=26&rft.issue=1-2&rft.spage=25&rft.isbn=&rft.btitle=&rft.title=Artificial+Intelligence+in+Medicine&rft.issn=09333657&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 - Quantitative Detection of 125IdU-Induced DNA Double-Strand Breaks with gamma -H2AX Antibody AN - 18593815; 5460059 AB - When mammalian cells are exposed to ionizing radiation and other agents that introduce DSBs into DNA, histone H2AX molecules in megabase chromatin regions adjacent to the breaks become phosphorylated within minutes on a specific serine residue. An antibody to this phosphoserine motif of human H2AX ( g-H2AX) demonstrates that g-H2AX molecules appear in discrete nuclear foci. To establish the quantitative relationship between the number of these foci and the number of DSBs, we took advantage of the ability of 125I, when incorporated into DNA, to generate one DNA DSB per radioactive disintegration. SF-268 and HT-1080 cell cultures were grown in the presence of 125IdU and processed immunocytochemically to determine the number of g-H2AX foci. The numbers of 125IdU disintegrations per cell were measured by exposing the same immunocytochemically processed samples to a radiation-sensitive screen with known standards. Under appropriate conditions, the data yielded a direct correlation between the number of 125I decays and the number of foci per cell, consistent with the assumptions that each 125I decay yields a DNA DSB and each DNA DSB yields a visible g-H2AX focus. Based on these findings, we conclude that g-H2AX antibody may form the basis of a sensitive quantitative method for the detection of DNA DSBs in eukaryotic cells. JF - Radiation Research AU - Sedelnikova, O A AU - Rogakou, E P AU - Panyutin, I G AU - Bonner, WM AD - Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, olgas@helix.nih.gov Y1 - 2002/10// PY - 2002 DA - Oct 2002 SP - 486 EP - 492 PB - The Radiation Research Society VL - 158 IS - 4 SN - 0033-7587, 0033-7587 KW - breaks KW - detection KW - Toxicology Abstracts KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18593815?accountid=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=Radiation+Research&rft.atitle=Quantitative+Detection+of+125IdU-Induced+DNA+Double-Strand+Breaks+with+gamma+-H2AX+Antibody&rft.au=Sedelnikova%2C+O+A%3BRogakou%2C+E+P%3BPanyutin%2C+I+G%3BBonner%2C+WM&rft.aulast=Sedelnikova&rft.aufirst=O&rft.date=2002-10-01&rft.volume=158&rft.issue=4&rft.spage=486&rft.isbn=&rft.btitle=&rft.title=Radiation+Research&rft.issn=00337587&rft_id=info:doi/10.1043%2F0033-7587%282002%29158%280486%3AQDOIID%292.0.CO%3B2 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1043/0033-7587(2002)158(0486:QDOIID)2.0.CO;2 ER - TY - JOUR T1 - Renal Dysfunction in HIV-1-infected Patients. AN - 1859376708; 12228033 AB - Improved therapy directed against opportunistic infection and HIV-1 itself has resulted in greatly enhanced patient survival in the past decade among patients infected with HIV-1. Since patients are living longer, HIV-1 infection is associated with a rising burden of kidney disease. Approximately 14% of black patients and 6% of white patients dying with HIV-1 infection in 1999 in the United States had renal disease. Overall, 10% of patients dying with HIV-1 infection had renal failure. The most common glomerular diseases are focal segmental glomerulosclerosis and immune complex glomerulonephritis. Appropriate therapy for focal segmental glomerulosclerosis includes effective antiretroviral therapy and angiotensin antagonist medication. Drug toxicity is also common, often manifesting as electrolyte abnormalities, acute renal failure, interstitial nephritis, or nephrolithiasis. In particular, indinavir is associated with crystalluria, nephrolithiasis, interstitial nephritis, and lower urinary tract inflammation. Appropriate screening for renal disease and appropriate intervention will likely reduce the morbidity and mortality associated with progressive renal disease. JF - Current infectious disease reports AU - Kopp, Jeffrey B. AD - Kidney Disease Section, Building 10, Room 3N114, National Institutes of Health, Bethesda, MD 20892-1268, USA. jbkopp@nih.gov Y1 - 2002/10// PY - 2002 DA - October 2002 SP - 449 EP - 460 VL - 4 IS - 5 SN - 1523-3847, 1523-3847 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859376708?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+infectious+disease+reports&rft.atitle=Renal+Dysfunction+in+HIV-1-infected+Patients.&rft.au=Kopp%2C+Jeffrey+B.&rft.aulast=Kopp&rft.aufirst=Jeffrey&rft.date=2002-10-01&rft.volume=4&rft.issue=5&rft.spage=449&rft.isbn=&rft.btitle=&rft.title=Current+infectious+disease+reports&rft.issn=15233847&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2002-09-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bioavailability: A Key Factor in the Efficacy of Bioactive Food Components AN - 18556578; 5515382 AB - Bioavailability of a bioactive food component is the fraction available to exert a physiologic effect and is measured with in vitro techniques, animal models, or human studies. Among the factors that may influence a bioactive food component's bioavailability are its physical and chemical properties, food matrix, processing and preparation procedures it has undergone, and individual differences in physiologic state or status and genetic characteristics. JF - Nutrition Today AU - Picciano, M F AD - Office of Dietary Supplements, National Institutes of Health, 31 Center Dr, 1B29, Bethesda, MD 20892-2086, USA, mfp4@psu.edu Y1 - 2002/10// PY - 2002 DA - Oct 2002 SP - 206 EP - 208 VL - 37 IS - 5 SN - 0029-666X, 0029-666X KW - Physical Education Index KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18556578?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nutrition+Today&rft.atitle=Bioavailability%3A+A+Key+Factor+in+the+Efficacy+of+Bioactive+Food+Components&rft.au=Picciano%2C+M+F&rft.aulast=Picciano&rft.aufirst=M&rft.date=2002-10-01&rft.volume=37&rft.issue=5&rft.spage=206&rft.isbn=&rft.btitle=&rft.title=Nutrition+Today&rft.issn=0029666X&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - CDART: Protein Homology by Domain Architecture AN - 18504235; 5474727 AB - The Conserved Domain Architecture Retrieval Tool (CDART) performs similarity searches of the NCBI Entrez Protein Database based on domain architecture, defined as the sequential order of conserved domains in proteins. The algorithm finds protein similarities across significant evolutionary distances using sensitive protein domain profiles rather than by direct sequence similarity. Proteins similar to a query protein are grouped and scored by architecture. Relying on domain profiles allows CDART to be fast, and, because it relies on annotated functional domains, informative. Domain profiles are derived from several collections of domain definitions that include functional annotation. Searches can be further refined by taxonomy and by selecting domains of interest. CDART is available at http://www.ncbi.nlm.gov/Structure/lexington/lexington.cgi. JF - Genome Research AU - Geer, L Y AU - Domrachev, M AU - Lipman, D J AU - Bryant, SH AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA, lewisg@mail.nih.gov Y1 - 2002/10// PY - 2002 DA - Oct 2002 SP - 1619 EP - 1623 VL - 12 IS - 10 SN - 1054-9803, 1054-9803 KW - CDART KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Genetics Abstracts KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics KW - G 07300:Theoretical genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18504235?accountid=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=Genome+Research&rft.atitle=CDART%3A+Protein+Homology+by+Domain+Architecture&rft.au=Geer%2C+L+Y%3BDomrachev%2C+M%3BLipman%2C+D+J%3BBryant%2C+SH&rft.aulast=Geer&rft.aufirst=L&rft.date=2002-10-01&rft.volume=12&rft.issue=10&rft.spage=1619&rft.isbn=&rft.btitle=&rft.title=Genome+Research&rft.issn=10549803&rft_id=info:doi/10.1101%2Fgr.278202 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1101/gr.278202 ER - TY - JOUR T1 - Sequence-specific interaction of nascent antiterminator RNA with the zinc-finger motif of Escherichia coli RNA polymerase AN - 18502537; 5464593 AB - The N-terminal Zn-finger motif of the beta ' subunit of RNA polymerase contains two pairs of invariant cysteines flanking a moderately well-conserved segment of 13 amino acids that is rich in basic residues. Previous work showed that replacement of certain Zn-finger residues prevented transcription antitermination in response to phage HK022 put sites. Nascent put RNA binds to and modifies transcribing polymerase, so that it becomes resistant to termination. To characterize the Zn finger further, we replaced each of the basic residues with alanine and determined the effects of the substitutions on termination, antitermination and cell viability. All the mutants were defective in put-mediated antitermination. The severity of the defect depended on the mutant and on the sequence of the upstream stem-loop of put RNA. Some, but not all, mutants distinguished between put variants that differed in this region. This suggests that the Zn-finger motif interacts directly and specifically with put RNA. All the mutants in the basic residues complemented a temperature-sensitive beta ' mutant for cell growth at a non-permissive temperature, and those mutant enzymes that were tested transcribed and terminated normally in vitro on a template that lacked a put site. JF - Molecular Microbiology AU - Sen, R AU - King, R A AU - Mzhavia, N AU - Madsen, P L AU - Weisberg, R A AD - Section on Microbial Genetics, Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, 6B/3B308, NIH, Bethesda, MD 20892-2785, USA., rweisberg@nih.gov Y1 - 2002/10// PY - 2002 DA - Oct 2002 SP - 215 EP - 222 PB - Blackwell Science Ltd VL - 46 IS - 1 SN - 0950-382X, 0950-382X KW - antitermination KW - zinc finger KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - N 14721:RNA polymerases KW - J 02726:RNA and ribosomes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18502537?accountid=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=Sequence-specific+interaction+of+nascent+antiterminator+RNA+with+the+zinc-finger+motif+of+Escherichia+coli+RNA+polymerase&rft.au=Sen%2C+R%3BKing%2C+R+A%3BMzhavia%2C+N%3BMadsen%2C+P+L%3BWeisberg%2C+R+A&rft.aulast=Sen&rft.aufirst=R&rft.date=2002-10-01&rft.volume=46&rft.issue=1&rft.spage=215&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1046%2Fj.1365-2958.2002.03154.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1046/j.1365-2958.2002.03154.x ER - TY - JOUR T1 - The P1 plasmid is segregated to daughter cells by a 'capture and ejection' mechanism coordinated with Escherichia coli cell division AN - 18502104; 5464605 AB - The fate of the P1 plasmid of Escherichia coli was followed by time-lapse photomicroscopy. A GFP-ParB fusion marked the plasmid during partition (segregation) to daughter cells at slow growth rate. The process differs from that previously inferred from statistical analysis of fixed cells. A focus of plasmid copies is captured at the cell centre. Immediately before cell division, the copies eject bidirectionally along the long axis of the cell. Cell division traps one or more plasmid copies in each daughter. They are not directed to a prescribed position but are free to move, associate and disassociate. Later, they are captured to the new cell centre to restart the cycle. A null P1 par mutant associates to form a focus, but it is neither captured nor ejected. A dominant negative ParB protein forms a plasmid focus that attaches to the cell centre but never ejects. It remains captive at the centre and blocks host cell division. The cells elongate. Eventually the intact focus is pushed to one side and the cells divide simultaneously in several places at the same time. This suggests that the wild-type plasmid imposes a regulatory node on the host cell cycle, preventing cell division until its own segregation is completed. JF - Molecular Microbiology AU - Li, Y AU - Austin, S AD - Gene Regulation and Chromosome Biology Laboratory, Division of Basic Sciences, NCI-Frederick, Frederick, MD 21702-1201, USA ., austin@ncifcrf.gov Y1 - 2002/10// PY - 2002 DA - Oct 2002 SP - 63 EP - 74 PB - Blackwell Science Ltd VL - 46 IS - 1 SN - 0950-382X, 0950-382X KW - ParB protein KW - plasmid P1 KW - Microbiology Abstracts B: Bacteriology KW - J 02760:Plasmids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18502104?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Microbiology&rft.atitle=The+P1+plasmid+is+segregated+to+daughter+cells+by+a+%27capture+and+ejection%27+mechanism+coordinated+with+Escherichia+coli+cell+division&rft.au=Li%2C+Y%3BAustin%2C+S&rft.aulast=Li&rft.aufirst=Y&rft.date=2002-10-01&rft.volume=46&rft.issue=1&rft.spage=63&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1046%2Fj.1365-2958.2002.03156.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1046/j.1365-2958.2002.03156.x ER - TY - JOUR T1 - Faecal genetic analysis to determine the presence and distribution of elusive carnivores: design and feasibility for the Iberian lynx AN - 18499139; 5464648 AB - Noninvasive methods using genetic markers have been suggested as ways to overcome difficulties associated with documenting the presence of elusive species. We present and assess a novel, reliable and effective molecular genetic technique for the unequivocal genetic identification of faeces from the endangered Iberian lynx (Lynx pardinus). From mitochondrial DNA (mtDNA) cytochrome b and D-loop region sequences, we designed four species-specific primers (for products 130-161 bp long) that were considered to be likely to amplify degraded DNA. We compared two DNA extraction methods, various DNA amplification conditions and the robustness and specificity of the primer pairs with 87 lynx samples from 5 potentially different lynx populations and with 328 samples of other carnivore species. The utility of the identification technique was tested with faeces of different ages, with faeces from controlled field experiments, and with faeces collected from locales with possible lynx populations from throughout the state of Andalusia, Spain (8052 km super(2)). Faecal mtDNA extraction was more efficient using PBS wash of the faeces instead of a faeces homogenate. Our assay increased from 92.6 to 99% efficiency with a second amplification and a reduction in template concentration to overcome polymerase chain reaction (PCR) inhibition. Our assay never produced false positives, and correctly identified all lynx faeces. Of 252 faeces samples of unknown species collected throughout Andalusia, 26.6% (from three different areas) were classified as Iberian lynx, 1.4% showed evidence of PCR inhibition and 1.2% were of uncertain origin. This method has proven to be a reliable technique that can be incorporated into large-scale surveys of Iberian lynx populations and exemplifies an approach that can easily be extended to other species. JF - Molecular Ecology AU - Palomares, F AU - Godoy, JA AU - Piriz, A AU - O'Brien, S J AD - Department of Applied Biology, Estacion Biologica de Donana, CSIC, Avda. Maria Luisa s/n, 41013, Sevilla, Spain, Laboratory of Genomic Diversity, National Cancer Institute-FCRDC, Frederick, USA, ffpaloma@ebd.csic.es Y1 - 2002/10// PY - 2002 DA - Oct 2002 SP - 2171 EP - 2182 PB - Blackwell Science Ltd VL - 11 IS - 10 SN - 0962-1083, 0962-1083 KW - Carnivores KW - Iberian Lynx KW - cytochrome b KW - Ecology Abstracts; Genetics Abstracts KW - G 07270:Ecological genetics KW - D 04672:Mammals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18499139?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Ecology&rft.atitle=Faecal+genetic+analysis+to+determine+the+presence+and+distribution+of+elusive+carnivores%3A+design+and+feasibility+for+the+Iberian+lynx&rft.au=Palomares%2C+F%3BGodoy%2C+JA%3BPiriz%2C+A%3BO%27Brien%2C+S+J&rft.aulast=Palomares&rft.aufirst=F&rft.date=2002-10-01&rft.volume=11&rft.issue=10&rft.spage=2171&rft.isbn=&rft.btitle=&rft.title=Molecular+Ecology&rft.issn=09621083&rft_id=info:doi/10.1046%2Fj.1365-294X.2002.01608.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1046/j.1365-294X.2002.01608.x ER - TY - JOUR T1 - Mycobacterium avium Complex Promotes Recruitment of Monocyte Hosts for HIV-1 and Bacteria AN - 18494992; 5457170 AB - In lymphoid tissues coinfected with Mycobacterium avium complex (MAC) and HIV-1, increased viral replication has been observed. This study investigates the role of MAC in perpetuating both infections through the recruitment of monocytes as potential new hosts for bacteria and HIV-1. Increased numbers of macrophages were present in the lymph nodes of patients with dual infection as compared with lymph nodes from HIV super(+) patients with no known opportunistic pathogens. In a coculture system, monocyte-derived macrophages were treated with HIV-1 or M. avium and its constituents to further define the mechanism whereby MAC infection of macrophages initiates monocyte migration. Monocyte-derived macrophages treated with bacteria or bacterial products, but not HIV-1, induced a rapid 2- to 3-fold increase in recruitment of monocytes. Pretreatment of the monocytes with pertussis toxin inhibited the migration of these cells, indicating a G protein-linked pathway is necessary for induction of chemotaxis and thus suggesting the involvement of chemokines. Analysis of chemokine mRNA and protein levels from M. avium-treated cultures revealed MAC-induced increases in the expression of IL-8, macrophage-inflammatory protein (MIP)-1[alpha], and MIP-1[beta] with donor-dependent changes in monocyte chemotactic protein-1. Pyrrolidine dithiocarbamate, an antioxidant, inhibited the activation of NF-[kappa]B and significantly diminished the MAC-induced chemotaxis, concurrently lowering the levels of monocyte chemotactic protein-1 and MIP-1[beta]. These data demonstrate that MAC induces macrophage production of multiple chemotactic factors via NF-[kappa]B to promote monocyte migration to sites of MAC infection. In vivo, opportunistic infection may act as a recruitment mechanism in which newly arrived monocytes serve as naive hosts for both MAC and HIV-1, thus perpetuating both infections. JF - Journal of Immunology AU - Hale-Donze, H AU - Greenwell-Wild, T AU - Mizel, D AU - Doherty, T M AU - Chatterjee, D AU - Orenstein, J M AU - Wahl, S M AD - Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, and Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 Y1 - 2002/10/01/ PY - 2002 DA - 2002 Oct 01 SP - 3854 EP - 3862 VL - 169 IS - 7 SN - 0022-1767, 0022-1767 KW - HIV-1 KW - macrophage inflammatory protein 1 alpha KW - macrophage inflammatory protein 1 beta KW - Virology & AIDS Abstracts; Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - J 02833:Immune response and immune mechanisms KW - V 22003:AIDS: Immunological aspects KW - F 06800:Viruses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18494992?accountid=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=Mycobacterium+avium+Complex+Promotes+Recruitment+of+Monocyte+Hosts+for+HIV-1+and+Bacteria&rft.au=Hale-Donze%2C+H%3BGreenwell-Wild%2C+T%3BMizel%2C+D%3BDoherty%2C+T+M%3BChatterjee%2C+D%3BOrenstein%2C+J+M%3BWahl%2C+S+M&rft.aulast=Hale-Donze&rft.aufirst=H&rft.date=2002-10-01&rft.volume=169&rft.issue=7&rft.spage=3854&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunology&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Isolation of Chlamydia pneumoniae Clonal Variants by a Focus-Forming Assay AN - 18490626; 5457424 AB - Chlamydia pneumoniae is an obligate intracellular prokaryotic human pathogen that causes community-acquired respiratory infection and has been associated with atherosclerosis and cardiovascular disease. Unexpected results from genomic sequencing indicate that significant intrastrain polymorphism exists for some C. pneumoniae isolates. These polymorphisms could reflect genotypes with differing disease-causing characteristics. A definitive means to test this hypothesis is to obtain genetically homogeneous clonal populations of the pathogen and test them in models of infection and disease. To date, methods for cloning C. pneumoniae have not been reported. In this study, we describe the isolation of clonal variants with genetic differences in the tyrP locus from a polymorphic respiratory isolate, using a novel focus-forming assay. These results now allow investigations on the biology and pathogenesis of C. pneumoniae clonal genovars that could lead to new insights into the pathogenesis of this important human pathogen. JF - Infection and Immunity AU - Gieffers, J AU - Belland, R J AU - Whitmire, W AU - Ouellette, S AU - Crane, D AU - Maass, M AU - Byrne, GI AU - Caldwell, H D AD - Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, NIAID, NIH, 903 South 4th St., Hamilton, MT 59840, hcaldwell@niaid.nih.gov Y1 - 2002/10// PY - 2002 DA - Oct 2002 SP - 5827 EP - 5834 VL - 70 IS - 10 SN - 0019-9567, 0019-9567 KW - tyrP gene KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18490626?accountid=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=Isolation+of+Chlamydia+pneumoniae+Clonal+Variants+by+a+Focus-Forming+Assay&rft.au=Gieffers%2C+J%3BBelland%2C+R+J%3BWhitmire%2C+W%3BOuellette%2C+S%3BCrane%2C+D%3BMaass%2C+M%3BByrne%2C+GI%3BCaldwell%2C+H+D&rft.aulast=Gieffers&rft.aufirst=J&rft.date=2002-10-01&rft.volume=70&rft.issue=10&rft.spage=5827&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.70.10.5827-5834.2002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/IAI.70.10.5827-5834.2002 ER - TY - JOUR T1 - Topical colchicine selection of keratinocytes transduced with the multidrug resistance gene (MDR1) can sustain and enhance transgene expression in vivo AN - 18486120; 5457783 AB - For skin gene therapy, achieving prolonged high-level gene expression in a significant percentage of keratinocytes (KC) is difficult because we cannot selectively target KC stem cells. We now demonstrate that topical colchicine treatment can be used to select, in vivo, KC progenitor cells transduced with the multidrug resistance gene (MDR1). When human skin equivalents containing MDR1-transduced KC were grafted onto immunocompromised mice, topical colchicine treatments significantly increased (7-fold) the percentage of KC expressing MDR1, compared to vehicle-treated controls, for up to 24 wk. Topical colchicine treatment also significantly enhanced the amount of MDR1 protein expressed in individual KC. Furthermore, quantitative real-time PCR analysis of MDR1 transgene copy number demonstrates that topical colchicine treatment selects and enriches for KC progenitor cells in the skin that contain and express MDR1. For clinical skin gene therapy applications, this in vivo selection approach promises to enhance both the duration and expression level of a desired therapeutic gene in KC, by linking its expression to the MDR1 selectable marker gene. JF - Proceedings of the National Academy of Sciences, USA AU - Pfuetzner, W AU - Terunuma, A AU - Tock, CL AU - Snead, E K AU - Kolodka, T M AU - Gottesman, M M AU - Taichman, L AU - Vogel, J C AD - Dermatology Branch, Building 10/Room 12N260, National Cancer Institute, National Institutes of Health, 10 Center Drive, MSC 1908, Bethesda, MD 20892-1908, jonvogel@mail.nih.gov Y1 - 2002/10/01/ PY - 2002 DA - 2002 Oct 01 SP - 13096 EP - 13101 VL - 99 IS - 20 SN - 0027-8424, 0027-8424 KW - MDR1 gene KW - copy number KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Genetics Abstracts KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews KW - W4 120:Genetic Engineering in Medicine KW - W3 33055:Genetic engineering (general) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18486120?accountid=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=Topical+colchicine+selection+of+keratinocytes+transduced+with+the+multidrug+resistance+gene+%28MDR1%29+can+sustain+and+enhance+transgene+expression+in+vivo&rft.au=Pfuetzner%2C+W%3BTerunuma%2C+A%3BTock%2C+CL%3BSnead%2C+E+K%3BKolodka%2C+T+M%3BGottesman%2C+M+M%3BTaichman%2C+L%3BVogel%2C+J+C&rft.aulast=Pfuetzner&rft.aufirst=W&rft.date=2002-10-01&rft.volume=99&rft.issue=20&rft.spage=13096&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.192247899 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1073/pnas.192247899 ER - TY - JOUR T1 - Effect of CYP1A2 deficiency on heterocyclic amine DNA adduct levels in mice AN - 18471104; 5443509 AB - The contribution of CYP1A2 to the formation of DNA adducts of the cooked meat-derived heterocyclic amines (HCAs) 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was examined in CYP1A2-null (knock-out, KO) and wild-type (WT) mice. IQ (25 mg and 75 mg/kg) and PhIP (150 mg/kg) were administered by gavage to mice and DNA adduct levels in liver, kidney, mammary gland and colon were examined by the super(32)P-postlabeling assay. Three hours after either dose of IQ, adducts levels in liver and kidney of KO mice were 20-30% of the levels in WT mice, a difference that was statistically significant (Student's t-test, P < 0.05). In the colon, adduct levels in KO mice were significantly lower than in the WT mice only at the lowest dose of IQ (1.6 plus or minus 0.6 vs 4.6 plus or minus 0.7, respectively, relative adduct labeling (RAL)x10 super(8), mean- plus or minus S.E.M., n=3-5 mice). In the mammary gland, however, there was no difference in IQ-DNA adduct levels in KO and WT mice at either dose of IQ. Three hours after dosing with PhIP, PhIP-DNA adduct levels were statistically significantly lower in KO mice than in WT mice in all tissues examined. PhIP-DNA adducts in liver and kidney of WT mice were 9.9 plus or minus 1.1 and 22.5 plus or minus 6.9, respectively, whereas no PhIP-DNA adducts were detected in either organ of KO mice (limit of detection, 1.4-2.8x10 super(9)). PhIP-DNA adduct levels in mammary gland and colon of WT mice were 47.1 plus or minus 9.5 and 58.0 plus or minus 21.7, respectively, but accordingly only 3.8 plus or minus 0.7 and 5.4 plus or minus 0.9 in KO mice. The findings indicate that CYP1A2, responsible for IQ and PhIP N-hydroxylation, the first step in the metabolic action, significantly effects DNA adduct formation in vivo. However, the data raise the possibility that other cytochromes P450 as well as other pathways of activation potentially contribute to DNA adduct formation in specific organs, depending on the HCA substrate. JF - Food and Chemical Toxicology AU - Snyderwine, E G AU - Yu, M AU - Schut, HAJ AU - Knight-Jones, L AU - Kimura, S AD - Chemical Carcinogenesis Section, Laboratory of Experimental Carcinogenesis, Building 37, Room 3C28, 37 Convent Dr. MSC-4258, National Cancer Institute Center for Cancer Research, Bethesda, MD 20892, USA, elizabeth_snyderwine@nih.gov Y1 - 2002/10// PY - 2002 DA - Oct 2002 SP - 1529 EP - 1533 VL - 40 IS - 10 SN - 0278-6915, 0278-6915 KW - CYP1A2 protein KW - rats KW - Toxicology Abstracts KW - X 24155:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18471104?accountid=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=Effect+of+CYP1A2+deficiency+on+heterocyclic+amine+DNA+adduct+levels+in+mice&rft.au=Snyderwine%2C+E+G%3BYu%2C+M%3BSchut%2C+HAJ%3BKnight-Jones%2C+L%3BKimura%2C+S&rft.aulast=Snyderwine&rft.aufirst=E&rft.date=2002-10-01&rft.volume=40&rft.issue=10&rft.spage=1529&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 ER - TY - JOUR T1 - Utility of reverse phase protein arrays: Applications to signalling pathways and human body arrays AN - 1434026235; 18513426 AB - Protein microarrays offer a new means by which to conduct quantitative profiling of disease-associated proteins. The knowledge gained may provide novel strategies for early detection, diagnosis and therapeutic intervention. A variety of sophisticated approaches, including gene arrays, sequencing consortiums and large-scale two-dimensional gel electrophoresis, continue to generate lists of proteins potentially linked to disease aetiology and progression. The challenge is to evaluate quantitatively promising lead protein candidates using matched normal and diseased cell populations. In contrast to the antibody array, the reverse phase protein microarrays (RPPA) do not require labelling of cellular protein lysates, and constitute a sensitive high throughput platform for marker screening, pathophysiology investigation and therapeutic monitoring. In this paper, examples will be provided using RPPAs in the study of the apoptotic signalling cascade and in the evaluation of the expression of organ-specific protein makers using microdissected human organ cell lysates configured as 'human body arrays'. JF - Briefings in Functional Genomics and Proteomics AU - Charboneau, Lu AU - Scott, Heather AU - Chen, Tina AU - Winters, Mary AU - Petricoin, Emanuel F AU - Liotta, Lance A AU - Paweletz, Cloud P AD - Manager of the Laser Capture Microdissection Core Facility at NIH and working with the National Cancer Institute (NCI) in the Laboratory of Pathology., paweletz@cber.fda.gov Y1 - 2002/10// PY - 2002 DA - Oct 2002 SP - 305 EP - 315 PB - Oxford University Press VL - 1 IS - 3 SN - 1473-9550, 1473-9550 KW - Genetics Abstracts; Biotechnology and Bioengineering Abstracts KW - Antibodies KW - Apoptosis KW - Protein arrays KW - Therapeutic applications KW - proteomics KW - Gel electrophoresis KW - Signal transduction KW - G 07730:Development & Cell Cycle KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1434026235?accountid=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=Briefings+in+Functional+Genomics+and+Proteomics&rft.atitle=Utility+of+reverse+phase+protein+arrays%3A+Applications+to+signalling+pathways+and+human+body+arrays&rft.au=Charboneau%2C+Lu%3BScott%2C+Heather%3BChen%2C+Tina%3BWinters%2C+Mary%3BPetricoin%2C+Emanuel+F%3BLiotta%2C+Lance+A%3BPaweletz%2C+Cloud+P&rft.aulast=Charboneau&rft.aufirst=Lu&rft.date=2002-10-01&rft.volume=1&rft.issue=3&rft.spage=305&rft.isbn=&rft.btitle=&rft.title=Briefings+in+Functional+Genomics+and+Proteomics&rft.issn=14739550&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2013-09-01 N1 - Last updated - 2013-09-20 N1 - SubjectsTermNotLitGenreText - Antibodies; Apoptosis; Protein arrays; Therapeutic applications; proteomics; Gel electrophoresis; Signal transduction ER - TY - CONF T1 - Highlights of the eighth international conference on carcinogenic/mutagenic N-substituted aryl compounds. AN - 72135609; 12351139 AB - Research in the 20th century initially identified arylamines as causative factors in occupational carcinogenesis, especially bladder cancer, and subsequently identified arylamines as a major class of mutagens/carcinogens in the environment and diet that are potential risk factors in a variety of human cancers. Current research focuses on understanding of mechanisms of arylamine carcinogenesis, such as the role of metabolic processing, DNA adduct formation, and mutagenesis, and learning more about the molecular alterations in carcinomas induced by these compounds. Furthermore, research to identify human exposures, including developing more sensitive methods for analyzing environmental samples and identifying suitable biomarkers are important aspects of contemporary investigations. In addition, better evaluation of the risk of these compounds in human cancer especially with regard to the impact of genetic polymorphisms is a major focus of research in this field. Although current population studies have sometimes been described as equivocal, improved tools for epidemiology, refined human biomonitoring methods and collaborative endeavors to study multiple population groups now provide a better means to ultimately define the role of arylamines in human carcinogenesis. The purpose of the Eighth International Conference on Carcinogenic/Mutagenic N-Substituted Aryl Compounds, held in Washington, DC, 12-14 November 2001, was to explore the current scope of studies on arylamine carcinogenesis among scientists in basic research and epidemiology and to discuss future research priorities. With the intent of providing a view to the current field of research on aromatic amines, this review presents a synopsis of the Proceedings of the Eighth International Conference and highlights the manuscripts contained in this special issue of Mutation Research. JF - Mutation research AU - Snyderwine, Elizabeth G AU - Sinha, Rashmi AU - Felton, James S AU - Ferguson, Lynnette R Y1 - 2002/09/30/ PY - 2002 DA - 2002 Sep 30 SP - 1 EP - 8 VL - 506-507 KW - Aminobiphenyl Compounds KW - 0 KW - Carcinogens KW - Carcinogens, Environmental KW - DNA Adducts KW - DNA, Neoplasm KW - Mutagens KW - Index Medicus KW - Environmental Monitoring KW - DNA Adducts -- analysis KW - DNA Damage KW - Risk Factors KW - Humans KW - DNA, Neoplasm -- genetics KW - Diet KW - Aminobiphenyl Compounds -- adverse effects KW - Carcinogens, Environmental -- adverse effects KW - Mutagens -- adverse effects KW - Neoplasms -- chemically induced KW - Neoplasms -- genetics KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72135609?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Mutation+research&rft.atitle=Highlights+of+the+eighth+international+conference+on+carcinogenic%2Fmutagenic+N-substituted+aryl+compounds.&rft.au=Snyderwine%2C+Elizabeth+G%3BSinha%2C+Rashmi%3BFelton%2C+James+S%3BFerguson%2C+Lynnette+R&rft.aulast=Snyderwine&rft.aufirst=Elizabeth&rft.date=2002-09-30&rft.volume=506-507&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-27 N1 - Date created - 2002-09-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mammary gland carcinogenesis by food-derived heterocyclic amines and studies on the mechanisms of carcinogenesis of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) AN - 19812632; 5455628 AB - The heterocyclic amines (HCAs) comprise a family of mutagenic /carcinogenic compounds found in cooked meat. Several HCAs including 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (8-MeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are mammary gland carcinogens in rats. One mammary gland carcinogen, PhIP, is the most prevalent in the human diet. This article reviews the mechanisms of mammary gland carcinogenesis of PhIP including metabolic processing, DNA adduct formation, effects on mammary gland development, cell signaling, and the genomic alterations found in PhIP-induced rat mammary gland carcinomas. JF - Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis AU - Snyderwine, E G AU - Venugopal, M AU - Yu, M AD - Chemical Carcinogenesis Section, Laboratory of Experimental Carcinogenesis, NCI Center for Cancer Research, Building 37, Room 3C28, 37 Convent Drive MSC 4258, Bethesda, MD 20892, USA, elizabeth_snyderwine@nih.gov Y1 - 2002/09/30/ PY - 2002 DA - 2002 Sep 30 SP - 145 EP - 152 PB - Elsevier Science VL - 506-507 SN - 0027-5107, 0027-5107 KW - Toxicology Abstracts KW - Diets KW - DNA adducts KW - Molecular modelling KW - Heterocyclic amines KW - Mammary gland KW - Food KW - Carcinogens KW - Carcinoma KW - Mutagenesis KW - Meat KW - Intelligence KW - Carcinogenesis KW - genomics KW - Signal transduction KW - X 24320:Food Additives & Contaminants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19812632?accountid=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-Fundamental+and+Molecular+Mechanisms+of+Mutagenesis&rft.atitle=Mammary+gland+carcinogenesis+by+food-derived+heterocyclic+amines+and+studies+on+the+mechanisms+of+carcinogenesis+of+2-amino-1-methyl-6-phenylimidazo%5B4%2C5-b%5Dpyridine+%28PhIP%29&rft.au=Snyderwine%2C+E+G%3BVenugopal%2C+M%3BYu%2C+M&rft.aulast=Snyderwine&rft.aufirst=E&rft.date=2002-09-30&rft.volume=506-507&rft.issue=&rft.spage=145&rft.isbn=&rft.btitle=&rft.title=Mutation+Research-Fundamental+and+Molecular+Mechanisms+of+Mutagenesis&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-05-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Diets; Heterocyclic amines; Molecular modelling; DNA adducts; Mammary gland; Food; Carcinogens; Mutagenesis; Carcinoma; Meat; Intelligence; Carcinogenesis; genomics; Signal transduction ER - TY - JOUR T1 - Depleted uranium-uranyl chloride induces apoptosis in mouse J774 macrophages AN - 18621405; 5495886 AB - Depleted uranium entering the body as a result of inhalation or embedded fragments becomes associated to a great extent with macrophages. As part of our continuing studies on the health effects of internalized depleted uranium, we investigated the effect of soluble depleted uranium-uranyl chloride on the mouse macrophage cell line, J774. Using a cytochemical staining protocol specific for uranium, we found that uranium uptake by the macrophages increased in a time-dependent manner. Treatment with 1, 10, or 100 mu M depleted uranium-uranyl chloride resulted in decreased viability of the J774 cells within 24 h. Flow cytometric analysis of the treated cells with annexin V showed the translocation of phosphatidylserine from the inner face of the plasma membrane to the outer surface indicating the loss of phospholipid symmetry and the beginning of the apoptotic process. Significant differences in annexin V labeling between control cells and cells treated with 100 mu M depleted uranium-uranyl chloride were apparent within 2 h. Other events associated with apoptosis, including morphological changes and DNA fragmentation, were also apparent after depleted uranium-uranyl chloride treatment. These results suggest that the uptake and concentration of soluble depleted uranium by macrophages initiates events that results in the apoptotic death of these cells. JF - Toxicology AU - Kalinich, J F AU - Ramakrishnan, N AU - Villa, V AU - McClain, DE AD - Center for Scientific Review, Grant Referral Section, National Institutes of Health, Bethesda, MD 20892, USA, kalinich@afrri.usuhs.mil Y1 - 2002/09/30/ PY - 2002 DA - 2002 Sep 30 SP - 105 EP - 114 VL - 179 IS - 1-2 SN - 0300-483X, 0300-483X KW - cell lines KW - mice KW - uranium KW - uranyl chloride KW - Toxicology Abstracts KW - X 24210:Radiation & radioactive materials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18621405?accountid=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=Depleted+uranium-uranyl+chloride+induces+apoptosis+in+mouse+J774+macrophages&rft.au=Kalinich%2C+J+F%3BRamakrishnan%2C+N%3BVilla%2C+V%3BMcClain%2C+DE&rft.aulast=Kalinich&rft.aufirst=J&rft.date=2002-09-30&rft.volume=179&rft.issue=1-2&rft.spage=105&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - An epidemiologic approach to studying heterocyclic amines AN - 18492757; 5455634 AB - Diets containing substantial amounts of red meat may increase the risk of colorectal, pancreatic, breast, prostate, and renal cancer. The association with red meat intake may be due to a combination of factors, such as content of fat, protein, and iron, and/or meat preparation (e.g. cooking or preserving methods). Laboratory results have shown that meats cooked at high temperatures contain heterocyclic amines (HCAs) known to be mutagenic and carcinogenic in animals. Many older epidemiologic studies of colon cancer using surrogates for HCA exposure from meat (for example, doneness level, surface browning, frying, intake of gravy) have produced suggestive but inconsistent results. These discrepancies may have resulted in part from having used dietary questionnaires that combined meat-cooking practices in ways that made the intake of HCAs difficult to estimate. Thus, over the last decade we have taken a multidisciplinary approach to investigating whether the association with red meat intake can be explained by meat-cooking practices that produce mutagens/carcinogens. To estimate intake, a database for HCAs have been developed and used in conjunction with a validated meat-cooking food frequency questionnaire (FFQ). To develop biological markers of internal exposure, a metabolic study was conducted where subjects consumed controlled amounts of meat cooked at low and high temperatures. The role of meat type, cooking methods, doneness levels, and meat-cooking mutagens were examined in case-control studies of colorectal adenomas, lung, and breast cancers using both questionnaire information and biomarkers. In a case-control study of colorectal adenomas, an increased risk was associated with a high intake of red meat. Most of this risk was due to intake of red meat cooked until well/very well done and/or by high-temperature cooking techniques such as grilling. Linking the FFQ information to HCA database, the impact several HCAs on risk was evaluated. An increased risk was associated with higher intake of MeIQx, possibly PhIP. Red meat, especially fried and/or well-done red meat, was associated with increased risk of lung cancer in a population-based case-control study. In addition, an increase in risk was demonstrated among non-smokers and moderate smokers for MeIQx intake. In a case-control study of breast cancer well-done red meat and PhIP was associated with increased risk of breast cancer. In this manuscript I will provide one approach to studying the relation of meat cooking-mutagens and cancer risk and will suggest the types of studies that may be required in the future to clarify these associations. JF - Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis AU - Sinha, R AD - Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, Rm. 7028, National Cancer Institute, 6120 Executive Boulevard, EPS 3024, Rockville, MD 20892, USA Y1 - 2002/09/30/ PY - 2002 DA - 2002 Sep 30 SP - 197 EP - 204 PB - Elsevier Science B.V. VL - 506-507 SN - 0027-5107, 0027-5107 KW - 2-Amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - heterocyclic amines KW - Toxicology Abstracts KW - X 24120:Food, additives & contaminants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18492757?accountid=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-Fundamental+and+Molecular+Mechanisms+of+Mutagenesis&rft.atitle=An+epidemiologic+approach+to+studying+heterocyclic+amines&rft.au=Sinha%2C+R&rft.aulast=Sinha&rft.aufirst=R&rft.date=2002-09-30&rft.volume=506-507&rft.issue=&rft.spage=197&rft.isbn=&rft.btitle=&rft.title=Mutation+Research-Fundamental+and+Molecular+Mechanisms+of+Mutagenesis&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Mutational analysis of human hydroxysteroid sulfotransferase SULT2B1 isoforms reveals that exon 1B of the SULT2B1 gene produces cholesterol sulfotransferase, whereas exon 1A yields pregnenolone sulfotransferase. AN - 72110280; 12145317 AB - As a result of an alternative exon 1, the gene for human hydroxysteroid sulfotransferase (SULTB1) encodes for two peptides differing only at their amino termini. The SULT2B1b isoform preferentially sulfonates cholesterol. Conversely, the SULT2B1a isoform avidly sulfonates pregnenolone but not cholesterol. The outstanding structural feature that distinguishes the SULT2B1 isoforms from the prototypical SULT2A1 isozyme is the presence of extended amino- and carboxyl-terminal ends in the former. Investigating the functional significance of this unique characteristic reveals that removal of 53 amino acids from the relatively long carboxyl-terminal end that is common to both SULT2B1 isoforms has no effect on the catalytic activity of either isoform. On the other hand, removal of 23 amino acids from the amino-terminal end that is unique to SULT2B1b results in loss of cholesterol sulfotransferase activity, whereas removal of 8 amino acids from the amino-terminal end that is unique to SULT2B1a has no effect on pregnenolone sulfotransferase activity. Deletion analysis along with site-directed mutagenesis of SULT2B1b reveal that the amino acid segment 19-23 residues from the amino terminus and particularly isoleucines at positions 21 and 23 are crucial for cholesterol catalysis. In the gene for SULT2B1, exon 1B encodes for only the unique amino-terminal region of SULT2B1b; however, exon 1A encodes for the unique amino-terminal end of SULT2B1a plus an additional 48 amino acids. Thus, if the gene for SULT2B1 employs exon 1B, cholesterol sulfotransferase is synthesized, whereas if exon 1A is used, pregnenolone sulfotransferase is produced. JF - The Journal of biological chemistry AU - Fuda, Hirotoshi AU - Lee, Young C AU - Shimizu, Chikara AU - Javitt, Norman B AU - Strott, Charles A AD - Section on Steroid Regulation, Endocrinology and Reproduction Research Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892-4510, USA. Y1 - 2002/09/27/ PY - 2002 DA - 2002 Sep 27 SP - 36161 EP - 36166 VL - 277 IS - 39 SN - 0021-9258, 0021-9258 KW - Oligonucleotides KW - 0 KW - Protein Isoforms KW - Cholesterol KW - 97C5T2UQ7J KW - Sulfotransferases KW - EC 2.8.2.- KW - cholesterol sulfotransferase KW - pregnenolone sulfotransferase KW - SULT2B1 protein, human KW - EC 2.8.2.2 KW - alcohol sulfotransferase KW - Index Medicus KW - Dose-Response Relationship, Drug KW - Exons KW - DNA Mutational Analysis KW - Humans KW - Amino Acid Sequence KW - Gene Deletion KW - Mutagenesis, Site-Directed KW - Oligonucleotides -- chemistry KW - Cholesterol -- metabolism KW - Genetic Vectors KW - Kinetics KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Protein Structure, Tertiary KW - Catalysis KW - Sulfotransferases -- genetics KW - Sulfotransferases -- metabolism KW - Sulfotransferases -- chemistry KW - Sulfotransferases -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72110280?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+human+hydroxysteroid+sulfotransferase+SULT2B1+isoforms+reveals+that+exon+1B+of+the+SULT2B1+gene+produces+cholesterol+sulfotransferase%2C+whereas+exon+1A+yields+pregnenolone+sulfotransferase.&rft.au=Fuda%2C+Hirotoshi%3BLee%2C+Young+C%3BShimizu%2C+Chikara%3BJavitt%2C+Norman+B%3BStrott%2C+Charles+A&rft.aulast=Fuda&rft.aufirst=Hirotoshi&rft.date=2002-09-27&rft.volume=277&rft.issue=39&rft.spage=36161&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 - 2002-11-13 N1 - Date created - 2002-09-23 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U92315; GENBANK; U92314 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structural determinants of A(3) adenosine receptor activation: nucleoside ligands at the agonist/antagonist boundary. AN - 72103300; 12238926 AB - Mutagenesis of the human A(3) adenosine receptor (AR) suggested that certain amino acid residues contributed differently to ligand binding and activation processes. Here we demonstrated that various adenosine modifications, including adenine substitution and ribose ring constraints, also contributed differentially to these processes. The ligand effects on cyclic AMP production in intact CHO cells expressing the A(3)AR and in receptor binding were compared. Notably, the simple 2-fluoro group alone or 2-chloro in combination with N(6)-substitution dramatically diminished the efficacy of adenosine derivatives, even converting agonist into antagonist. Other affinity-increasing substitutions, including N(6)-(3-iodobenzyl) 4 and the (Northern)-methanocarba 15, also reduced efficacy, except in combination with a flexible 5'-uronamide. 2-Cl-N(6)-(3-iodobenzyl) derivatives, both in the (N)-methanocarba (i.e., of the Northern conformation) and riboside series 18 and 5, respectively, were potent antagonists with little residual agonism. Ring-constrained 2',3'-epoxide derivatives in both riboside and (N)-methanocarba series 13 and 21, respectively, and a cyclized (spiral) 4',5'-uronamide derivative 14 were synthesized and found to be human A(3)AR antagonists. 14 bound potently at both human (26 nM) and rat (49 nM) A(3)ARs. A rhodopsin-based A(3)AR model, containing all domains except the C-terminal region, indicated separate structural requirements for receptor binding and activation for these adenosine analogues. Ligand docking, taking into account binding of selected derivatives at mutant A(3)ARs, featured interactions of TM3 (His95) with the adenine moiety and TMs 6 and 7 with the ribose 5'-region. The 5'-OH group of antagonist N(6)-(3-iodobenzyl)-2-chloroadenosine 5 formed a H-bond with N274 but not with S271. The 5'-substituent of nucleoside antagonists moved toward TM7 and away from TM6. The conserved Trp243 (6.48) side chain, involved in recognition of the classical (nonnucleoside) A(3)AR antagonists but not adenosine-derived ligands, displayed a characteristic movement exclusively upon docking of agonists. Thus, A(3)AR activation appeared to require flexibility at the 5'- and 3'-positions, which was diminished in (N)-methanocarba, spiro, and epoxide analogues, and was characteristic of ribose interactions at TM6 and TM7. JF - Journal of medicinal chemistry AU - Gao, Zhan-Guo AU - Kim, Soo-Kyung AU - Biadatti, Thibaud AU - Chen, Wangzhong AU - Lee, Kyeong AU - Barak, Dov AU - Kim, Seong Gon AU - Johnson, Carl R AU - Jacobson, Kenneth A AD - Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/09/26/ PY - 2002 DA - 2002 Sep 26 SP - 4471 EP - 4484 VL - 45 IS - 20 SN - 0022-2623, 0022-2623 KW - Epoxy Compounds KW - 0 KW - Ligands KW - Purinergic P1 Receptor Agonists KW - Purinergic P1 Receptor Antagonists KW - Receptor, Adenosine A3 KW - Receptors, Purinergic P1 KW - Spiro Compounds KW - Guanosine 5'-O-(3-Thiotriphosphate) KW - 37589-80-3 KW - Ribose KW - 681HV46001 KW - Adenosine KW - K72T3FS567 KW - Index Medicus KW - Animals KW - Stereoisomerism KW - Epoxy Compounds -- chemical synthesis KW - Spiro Compounds -- chemistry KW - Models, Molecular KW - Humans KW - Radioligand Assay KW - Guanosine 5'-O-(3-Thiotriphosphate) -- pharmacology KW - Structure-Activity Relationship KW - Rats KW - Spiro Compounds -- pharmacology KW - Receptors, Purinergic P1 -- genetics KW - Epoxy Compounds -- pharmacology KW - Binding, Competitive KW - Spiro Compounds -- chemical synthesis KW - Epoxy Compounds -- chemistry KW - CHO Cells KW - Mutation KW - Cricetinae KW - Adenosine -- pharmacology KW - Ribose -- chemistry KW - Adenosine -- chemistry KW - Adenosine -- analogs & derivatives KW - Adenosine -- chemical synthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72103300?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Structural+determinants+of+A%283%29+adenosine+receptor+activation%3A+nucleoside+ligands+at+the+agonist%2Fantagonist+boundary.&rft.au=Gao%2C+Zhan-Guo%3BKim%2C+Soo-Kyung%3BBiadatti%2C+Thibaud%3BChen%2C+Wangzhong%3BLee%2C+Kyeong%3BBarak%2C+Dov%3BKim%2C+Seong+Gon%3BJohnson%2C+Carl+R%3BJacobson%2C+Kenneth+A&rft.aulast=Gao&rft.aufirst=Zhan-Guo&rft.date=2002-09-26&rft.volume=45&rft.issue=20&rft.spage=4471&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 - 2002-10-21 N1 - Date created - 2002-09-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protein kinase C(alpha) is required for vanilloid receptor 1 activation. Evidence for multiple signaling pathways. AN - 72097360; 12095983 AB - Activation of vanilloid receptor (VR1) by protein kinase C (PKC) was investigated in cells ectopically expressing VR1 and primary cultures of dorsal root ganglion neurons. Submicromolar phorbol 12,13-dibutyrate (PDBu), which stimulates PKC, acutely activated Ca(2+) uptake in VR1-expressing cells at pH 5.5, but not at mildly acidic or neutral pH. PDBu was antagonized by bisindolylmaleimide, a PKC inhibitor, and ruthenium red, a VR1 ionophore blocker, but not capsazepine, a vanilloid antagonist indicating that catalytic activity of PKC is required for PDBu activation of VR1 ion conductance, and is independent of the vanilloid site. Chronic PDBu dramatically down-regulated PKC(alpha) in dorsal root ganglion neurons or the VR1 cell lines, whereas only partially influencing PKCbeta, -delta, -epsilon, and -zeta. Loss of PKC(alpha) correlated with loss of response to acute re-challenge with PDBu. Anandamide, a VR1 agonist in acidic conditions, acts additively with PDBu and remains effective after chronic PKC down-regulation. Thus, two independent VR1 activation pathways can be discriminated: (i) direct ligand binding (anandamide, vanilloids) or (ii) extracellular ligands coupled to PKC by intracellular signaling. Experiments in cell lines co-expressing VR1 with different sets of PKC isozymes showed that acute PDBu-induced activation requires PKC(alpha), but not PKC(epsilon). These studies suggest that PKC(alpha) in sensory neurons may elicit or enhance pain during inflammation or ischemia. JF - The Journal of biological chemistry AU - Olah, Zoltan AU - Karai, Laszlo AU - Iadarola, Michael J AD - Neuronal Gene Expression Unit, Pain and Neurosensory Mechanisms Branch, NIDCR, National Institutes of Health, Bethesda, Maryland 20892, USA. zoltan.olah@nih.gov Y1 - 2002/09/20/ PY - 2002 DA - 2002 Sep 20 SP - 35752 EP - 35759 VL - 277 IS - 38 SN - 0021-9258, 0021-9258 KW - DNA Primers KW - 0 KW - Indoles KW - Isoenzymes KW - Maleimides KW - Receptors, Drug KW - Ruthenium Red KW - 11103-72-3 KW - Prkca protein, mouse KW - EC 2.7.11.13 KW - Protein Kinase C KW - Protein Kinase C-alpha KW - bisindolylmaleimide KW - MBK3OO5K8T KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Hydrogen-Ion Concentration KW - Amino Acid Sequence KW - Mice KW - Base Sequence KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Indoles -- pharmacology KW - Ruthenium Red -- pharmacology KW - Maleimides -- pharmacology KW - Protein Kinase C -- metabolism KW - Isoenzymes -- antagonists & inhibitors KW - Receptors, Drug -- metabolism KW - Protein Kinase C -- antagonists & inhibitors KW - Signal Transduction KW - Receptors, Drug -- antagonists & inhibitors KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72097360?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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%28alpha%29+is+required+for+vanilloid+receptor+1+activation.+Evidence+for+multiple+signaling+pathways.&rft.au=Olah%2C+Zoltan%3BKarai%2C+Laszlo%3BIadarola%2C+Michael+J&rft.aulast=Olah&rft.aufirst=Zoltan&rft.date=2002-09-20&rft.volume=277&rft.issue=38&rft.spage=35752&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 - 2002-10-24 N1 - Date created - 2002-09-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of the mammary carcinoma angiogenic switch in C3(1)/SV40 transgenic mice by a mutated form of human endostatin. AN - 72055232; 12209972 AB - Cancer therapies based on the inhibition of angiogenesis by endostatin have recently been developed. We demonstrate that a mutated form of human endostatin (P125A) can inhibit the angiogenic switch in the C3(1)/Tag mammary cancer model. P125A has a stronger growth-inhibitory effect on endothelial cell proliferation than wild-type endostatin. We characterize the angiogenic switch, which occurs during the transition from preinvasive lesions to invasive carcinoma in this model, and which is accompanied by a significant increase in total protein levels of vascular endothelial growth factor (VEGF) and an invasion of blood vessels. Expression of the VEGF(188) mRNA isoform, however, is suppressed in invasive carcinomas. The VEGF receptors fetal liver kinase-1 (Flk-1) and Fms-like tyrosine kinase-1 (Flt-1) become highly expressed in epithelial tumor and endothelial cells in the mammary carcinomas, suggesting a potential autocrine effect for VEGF on tumor cell growth. Angiopoietin-2 mRNA levels are also increased during tumor progression. CD-31 (platelet-endothelial cell adhesion molecule [PECAM]) staining revealed that blood vessels developed in tumors larger than 1 mm The administration of P125A human endostatin in C3(1)/Tag females resulted in a significant delay in tumor onset, decreased tumor multiplicity and tumor burden and prolonged survival of the animals. Endostatin treatment did not reduce the number of preinvasive lesions, proliferation rates or apoptotic index, compared with controls. However, mRNA levels of a variety of proangiogenic factors (VEGF, VEGF receptors Flk-1 and Flt-1, angiopoietin-2, Tie-1, cadherin-5 and PECAM) were significantly decreased in the endostatin-treated group compared with controls. These results demonstrate that P125A endostatin inhibits the angiogenic switch during mammary gland adenocarcinoma tumor progression in the C3(1)/Tag transgenic model. Copyright 2002 Wiley-Liss, Inc. JF - International journal of cancer AU - Calvo, Alfonso AU - Yokoyama, Yumi AU - Smith, Lois E AU - Ali, Iqbal AU - Shih, Shu-Ching AU - Feldman, Andrew L AU - Libutti, Steven K AU - Sundaram, Ramakrishnan AU - Green, Jeffrey E AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 2002/09/20/ PY - 2002 DA - 2002 Sep 20 SP - 224 EP - 234 VL - 101 IS - 3 SN - 0020-7136, 0020-7136 KW - DNA Primers KW - 0 KW - Endostatins KW - Endothelial Growth Factors KW - Lymphokines KW - Peptide Fragments KW - Receptors, Growth Factor KW - Vascular Endothelial Growth Factor A KW - Vascular Endothelial Growth Factors KW - RNA KW - 63231-63-0 KW - Collagen KW - 9007-34-5 KW - Receptor Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Receptors, Vascular Endothelial Growth Factor KW - Index Medicus KW - Animals KW - Lymphokines -- metabolism KW - Humans KW - Endothelial Growth Factors -- genetics KW - Mice, Transgenic KW - Body Weight KW - Mutagenesis, Site-Directed KW - In Situ Hybridization KW - RNA -- metabolism KW - Lymphokines -- genetics KW - Enzyme-Linked Immunosorbent Assay KW - Endothelium, Vascular -- metabolism KW - Mice KW - Cloning, Molecular KW - In Situ Nick-End Labeling KW - Polymerase Chain Reaction KW - Survival Rate KW - Endothelial Growth Factors -- metabolism KW - Mutation KW - Immunoenzyme Techniques KW - Female KW - DNA Primers -- chemistry KW - Collagen -- genetics KW - Peptide Fragments -- therapeutic use KW - Neovascularization, Pathologic -- drug therapy KW - Peptide Fragments -- genetics KW - Receptors, Growth Factor -- metabolism KW - Mammary Neoplasms, Experimental -- blood supply KW - Adenocarcinoma -- blood supply KW - Adenocarcinoma -- therapy KW - Receptor Protein-Tyrosine Kinases -- metabolism KW - Neovascularization, Pathologic -- pathology KW - Collagen -- therapeutic use KW - Mammary Neoplasms, Experimental -- therapy KW - Mammary Neoplasms, Experimental -- pathology KW - Adenocarcinoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72055232?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Inhibition+of+the+mammary+carcinoma+angiogenic+switch+in+C3%281%29%2FSV40+transgenic+mice+by+a+mutated+form+of+human+endostatin.&rft.au=Calvo%2C+Alfonso%3BYokoyama%2C+Yumi%3BSmith%2C+Lois+E%3BAli%2C+Iqbal%3BShih%2C+Shu-Ching%3BFeldman%2C+Andrew+L%3BLibutti%2C+Steven+K%3BSundaram%2C+Ramakrishnan%3BGreen%2C+Jeffrey+E&rft.aulast=Calvo&rft.aufirst=Alfonso&rft.date=2002-09-20&rft.volume=101&rft.issue=3&rft.spage=224&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 - 2002-09-26 N1 - Date created - 2002-09-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular archeology of L1 insertions in the human genome. AN - 72167795; 12372140 AB - As the rough draft of the human genome sequence nears a finished product and other genome-sequencing projects accumulate sequence data exponentially, bioinformatics is emerging as an important tool for studies of transposon biology. In particular, L1 elements exhibit a variety of sequence structures after insertion into the human genome that are amenable to computational analysis. We carried out a detailed analysis of the anatomy and distribution of L1 elements in the human genome using a new computer program, TSDfinder, designed to identify transposon boundaries precisely. Structural variants of L1 elements shared similar trends in the length and quality of their target site duplications (TSDs) and poly(A) tails. Furthermore, we found no correlation between the composition and genomic location of the pre-insertion locus and the resulting anatomy of the L1 insertion. We verified that L1 insertions with TSDs have the 5'-TTAAAA-3' cleavage site associated with L1 endonuclease activity. In addition, the second target DNA cut required for L1 insertion weakly matches the consensus pattern TTAAAA. On the other hand, the L1-internal breakpoints of deleted and inverted L1 elements do not resemble L1 endonuclease cleavage sites. Finally, the genome sequence data indicate that whereas singly inverted elements are common, doubly inverted elements are almost never found. The sequence data give no indication that the creation of L1 structural variants depends on characteristics of the insertion locus. In addition, the formation of 5' truncated and 5' inverted L1s are probably not due to the action of the L1 endonuclease. JF - Genome biology AU - Szak, Suzanne T AU - Pickeral, Oxana K AU - Makalowski, Wojciech AU - Boguski, Mark S AU - Landsman, David AU - Boeke, Jef D AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA. Y1 - 2002/09/19/ PY - 2002 DA - 2002 Sep 19 SP - 1 VL - 3 IS - 10 KW - Retroelements KW - 0 KW - Poly A KW - 24937-83-5 KW - Index Medicus KW - Base Sequence KW - Humans KW - Recombination, Genetic KW - Computational Biology -- methods KW - Poly A -- genetics KW - Algorithms KW - Binding Sites -- genetics KW - Retroelements -- genetics KW - Genome, Human KW - Mutagenesis, Insertional -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72167795?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genome+biology&rft.atitle=Molecular+archeology+of+L1+insertions+in+the+human+genome.&rft.au=Szak%2C+Suzanne+T%3BPickeral%2C+Oxana+K%3BMakalowski%2C+Wojciech%3BBoguski%2C+Mark+S%3BLandsman%2C+David%3BBoeke%2C+Jef+D&rft.aulast=Szak&rft.aufirst=Suzanne&rft.date=2002-09-19&rft.volume=3&rft.issue=10&rft.spage=research0052&rft.isbn=&rft.btitle=&rft.title=Genome+biology&rft.issn=1474-760X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-12-20 N1 - Date created - 2002-10-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 2001 Feb 15;409(6822):860-921 [11237011] Science. 2001 Feb 16;291(5507):1304-51 [11181995] Mol Biol Evol. 2001 Dec;18(12):2186-94 [11719568] Genome Res. 2001 Dec;11(12):2050-8 [11731495] Genome Res. 2001 Dec;11(12):2059-65 [11731496] Cell. 2002 Aug 9;110(3):327-38 [12176320] Cell. 1984 Aug;38(1):153-63 [6088060] Nucleic Acids Res. 1985 Nov 11;13(21):7813-27 [2999705] Biochim Biophys Acta. 1987 Dec 8;910(3):203-12 [2445384] Genomics. 1987 Oct;1(2):113-25 [3692483] Cell. 1988 Aug 26;54(5):685-91 [2842063] J Mol Evol. 1989 Dec;29(6):496-503 [2515296] Nucleic Acids Res. 1990 Oct 25;18(20):6019-23 [2172925] Nucleic Acids Res. 1990 Oct 25;18(20):6097-100 [2172928] Mol Cell Biol. 1990 Dec;10(12):6718-29 [1701022] Science. 1991 Dec 20;254(5039):1805-8 [1662412] Science. 1991 Dec 20;254(5039):1808-10 [1722352] Nucleic Acids Res. 1992 Jun 25;20(12):3139-45 [1320255] Cell. 1993 Feb 26;72(4):595-605 [7679954] J Clin Invest. 1993 May;91(5):1862-7 [8387534] Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6513-7 [8393568] Gene. 1993 Dec 15;135(1-2):183-8 [8276257] Mol Cell Biol. 1994 Jul;14(7):4485-92 [7516468] Nat Genet. 1994 Jun;7(2):143-8 [7920631] J Mol Biol. 1995 Feb 24;246(3):401-417 [7877164] Genomics. 1995 Sep 1;29(1):136-44 [8530063] Cell. 1996 Nov 29;87(5):905-16 [8945517] Cell. 1996 Nov 29;87(5):917-27 [8945518] Curr Opin Genet Dev. 1996 Dec;6(6):743-8 [8994846] Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1872-7 [9050872] Nat Genet. 1997 May;16(1):6-7 [9140383] Nat Genet. 1997 May;16(1):37-43 [9140393] Nucleic Acids Res. 1997 Sep 1;25(17):3389-402 [9254694] EMBO J. 1997 Nov 3;16(21):6590-602 [9351839] Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2083-8 [9482842] Nat Genet. 1998 May;19(1):19-24 [9590283] Nucleic Acids Res. 1998 Aug 1;26(15):3528-35 [9671814] Nat Genet. 1998 Nov;20(3):288-90 [9806550] Biochemistry. 1998 Dec 22;37(51):18081-93 [9922177] Science. 1999 Mar 5;283(5407):1465;1467 [10206876] FEMS Microbiol Lett. 1999 May 15;174(2):247-50 [10339815] Hum Mol Genet. 1999 Aug;8(8):1557-60 [10401005] Science. 1999 Oct 29;286(5441):964-7 [10542153] Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14440-4 [10588724] Curr Opin Genet Dev. 1999 Dec;9(6):657-63 [10607616] Hum Mol Genet. 2000 Mar 1;9(4):653-7 [10699189] Nat Genet. 2000 Apr;24(4):363-7 [10742098] Genome Res. 2000 Apr;10(4):411-5 [10779482] Mol Biol Evol. 2000 Jun;17(6):915-28 [10833198] Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6634-9 [10841562] Nucleic Acids Res. 2000 Jul 1;28(13):2467-72 [10871395] Nucleic Acids Res. 2001 Jan 15;29(2):573-7 [11139628] Mol Biol Evol. 2001 Jun;18(6):926-35 [11371580] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Odorant receptors instruct functional circuitry in the mouse olfactory bulb AN - 18494381; 5455177 AB - The mammalian olfactory system detects and discriminates thousands of odorants using many different receptors expressed by sensory neurons in the nasal epithelium. Axonal projections from these neurons to the main olfactory bulbs form reproducible patterns of glomeruli in two widely separated regions of each bulb, creating two mirror-symmetric maps of odorant receptor projections. To investigate whether odorant receptors organize neural circuitry in the olfactory bulb, we have examined a genetically modified mouse line, rI7 arrow right M71, in which a functionally characterized receptor, rI7, has been substituted into the M71 receptor locus. Here we show that despite their ectopic location the resulting glomeruli are responsive to known ligands of the rI7 receptor, attract postsynaptic innervation by mitral/tufted cell dendrites, and endow these cells with responses that are characteristic of the rI7 receptor. External tufted cells receiving input from rI7 arrow right M71 glomeruli form precise intrabulbar projections that link medial and lateral rI7 arrow right M71 glomeruli anatomically, thus providing a substrate for coordinating isofunctional glomeruli. We conclude that odorant receptor identity in epithelial neurons determines not only glomerular convergence and function, but also functional circuitry in the olfactory bulb. JF - Nature AU - Belluscio, L AU - Lodovichi, C AU - Feinstein, P AU - Mombaerts, P AU - Katz, L C AD - Howard Hughes Medical Institute, Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA, belluscl@ninds.nih.gov Y1 - 2002/09/19/ PY - 2002 DA - 2002 Sep 19 SP - 296 EP - 300 PB - Macmillan Publishers Ltd. VL - 419 IS - 6904 SN - 0028-0836, 0028-0836 KW - mice KW - odorant receptors KW - rI7 protein KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Genetics Abstracts; Chemoreception Abstracts; CSA Neurosciences Abstracts KW - R 18032:Vertebrates KW - G 07397:Rodentia (mice) KW - W4 340:Neurocomputing & Neural Networks KW - N3 11017:Taste, smell and chemical senses KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18494381?accountid=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=Odorant+receptors+instruct+functional+circuitry+in+the+mouse+olfactory+bulb&rft.au=Belluscio%2C+L%3BLodovichi%2C+C%3BFeinstein%2C+P%3BMombaerts%2C+P%3BKatz%2C+L+C&rft.aulast=Belluscio&rft.aufirst=L&rft.date=2002-09-19&rft.volume=419&rft.issue=6904&rft.spage=296&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 - 2011-12-13 ER - TY - JOUR T1 - STAT4 serine phosphorylation is critical for IL-12-induced IFN-gamma production but not for cell proliferation. AN - 72101869; 12213961 AB - T helper 1 (T(H)1) differentiation and IFN-gamma production are crucial in cell-mediated immune responses. IL-12 is an important regulator of this process and mediates its effects through signal transducer and activator of transcription 4 (STAT4). IFN-gamma production is also regulated by the p38 mitogen-activated kinase pathway, although the mechanisms are ill-defined. We show here that GADD45-beta and GADD45-gamma can induce STAT4 S721 phosphorylation via the MKK6/p38 pathway. Thus, STAT4 could be a target that accounts for the defects in cell-mediated immunity associated with perturbations in the p38 pathway. To investigate the biological significance of STAT4 S721 phosphorylation, we reconstituted primary spleen cells from STAT4-deficient mice with wild-type and mutated STAT4, by using a retroviral gene transduction. We demonstrated that expression of wild-type STAT4, but not the S721A mutant, restored normal T(H)1 differentiation and IFN-gamma synthesis. The inability of STAT4 S721 to restore IFN-gamma production was not caused by decreased IL-12R expression because the STAT4 S721 mutant also failed to restore IFN-gamma production in STAT4-deficient IL-12Rbeta2 transgenic cells. Importantly, STAT4 S721A-transduced cells showed normal proliferative response to IL-12, illustrating that serine phosphorylation is not required for IL-12-induced proliferation. Additionally, the results imply the existence of STAT4 serine phosphorylation-dependent and -independent target genes. We conclude that phosphorylation of STAT4 on both tyrosine and serine residues is important in promoting normal T(H)1 differentiation and IFN-gamma secretion. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Morinobu, Akio AU - Gadina, Massimo AU - Strober, Warren AU - Visconti, Roberta AU - Fornace, Albert AU - Montagna, Cristina AU - Feldman, Gerald M AU - Nishikomori, Ryuta AU - O'Shea, John J AD - Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal, and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA. morinoba@mail.nih.gov Y1 - 2002/09/17/ PY - 2002 DA - 2002 Sep 17 SP - 12281 EP - 12286 VL - 99 IS - 19 SN - 0027-8424, 0027-8424 KW - DNA-Binding Proteins KW - 0 KW - GADD45 protein KW - Intracellular Signaling Peptides and Proteins KW - Proteins KW - Receptors, Interleukin KW - Receptors, Interleukin-12 KW - Recombinant Proteins KW - STAT4 Transcription Factor KW - Stat4 protein, mouse KW - Trans-Activators KW - Interleukin-12 KW - 187348-17-0 KW - Tyrosine KW - 42HK56048U KW - Serine KW - 452VLY9402 KW - Interferon-gamma KW - 82115-62-6 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - p38 Mitogen-Activated Protein Kinases KW - MAP Kinase Kinase 6 KW - EC 2.7.12.2 KW - Map2k6 protein, mouse KW - Index Medicus KW - Animals KW - Receptors, Interleukin -- genetics KW - Cell Division -- physiology KW - Th1 Cells -- metabolism KW - Mice, Transgenic KW - Mice, Inbred BALB C KW - Mice, Knockout KW - Mutagenesis, Site-Directed KW - Phosphorylation KW - Recombinant Proteins -- metabolism KW - Recombinant Proteins -- chemistry KW - Signal Transduction KW - Th1 Cells -- immunology KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Receptors, Interleukin -- metabolism KW - Mitogen-Activated Protein Kinases -- metabolism KW - Mice KW - Recombinant Proteins -- genetics KW - Proteins -- metabolism KW - Serine -- chemistry KW - Tyrosine -- chemistry KW - Receptors, Interleukin -- deficiency KW - Cells, Cultured KW - Th1 Cells -- drug effects KW - Mice, Inbred C57BL KW - Trans-Activators -- metabolism KW - Trans-Activators -- deficiency KW - Interleukin-12 -- metabolism KW - DNA-Binding Proteins -- deficiency KW - DNA-Binding Proteins -- chemistry KW - Trans-Activators -- genetics KW - Trans-Activators -- chemistry KW - DNA-Binding Proteins -- genetics KW - Interferon-gamma -- biosynthesis KW - Interleukin-12 -- pharmacology KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72101869?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=STAT4+serine+phosphorylation+is+critical+for+IL-12-induced+IFN-gamma+production+but+not+for+cell+proliferation.&rft.au=Morinobu%2C+Akio%3BGadina%2C+Massimo%3BStrober%2C+Warren%3BVisconti%2C+Roberta%3BFornace%2C+Albert%3BMontagna%2C+Cristina%3BFeldman%2C+Gerald+M%3BNishikomori%2C+Ryuta%3BO%27Shea%2C+John+J&rft.aulast=Morinobu&rft.aufirst=Akio&rft.date=2002-09-17&rft.volume=99&rft.issue=19&rft.spage=12281&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 - 2002-10-28 N1 - Date created - 2002-09-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1996 Aug 9;273(5276):794-7 [8670419] Immunopharmacology. 2000 May;47(2-3):185-201 [10878289] Nature. 1996 Oct 31;383(6603):787-93 [8893001] J Immunol. 1996 Dec 1;157(11):4781-9 [8943379] Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1074-9 [9037008] Nature. 1997 Mar 20;386(6622):296-9 [9069290] Mol Cell Biol. 1997 May;17(5):2360-71 [9111305] Annu Rev Immunol. 1997;15:563-91 [9143700] J Immunol. 1997 Aug 15;159(4):1658-65 [9257825] J Immunol. 1998 Apr 15;160(8):3642-7 [9558063] EMBO J. 1998 May 15;17(10):2817-29 [9582275] Annu Rev Immunol. 1998;16:495-521 [9597139] Science. 1998 May 29;280(5368):1432-5 [9603732] Science. 1998 May 29;280(5368):1435-8 [9603733] J Exp Med. 1998 Sep 21;188(6):1191-6 [9743537] J Immunol. 1998 Oct 1;161(7):3400-7 [9759857] Cell. 1998 Nov 13;95(4):521-30 [9827804] EMBO J. 1998 Dec 1;17(23):6963-71 [9843502] J Clin Invest. 1998 Dec 15;102(12):2035-40 [9854038] EMBO J. 1999 Apr 1;18(7):1845-57 [10202148] Mol Cell Biol. 1999 Oct;19(10):7138-46 [10490649] Immunol Rev. 1999 Aug;170:65-72 [10566142] Genes Dev. 2000 Jul 15;14(14):1693-711 [10898785] J Immunol. 2000 Aug 1;165(3):1374-80 [10903740] Blood. 2000 Sep 1;96(5):1844-52 [10961885] J Immunol. 2000 Dec 1;165(11):6221-8 [11086056] J Immunol. 2000 Dec 15;165(12):6803-8 [11120802] Curr Opin Hematol. 2001 Jan;8(1):47-51 [11138626] EMBO J. 2001 Jan 15;20(1-2):91-100 [11226159] Nat Immunol. 2001 Feb;2(2):157-64 [11175814] Immunity. 2001 May;14(5):583-90 [11371360] Science. 2001 Jun 8;292(5523):1907-10 [11397944] Oncogene. 2001 Apr 30;20(19):2490-7 [11402343] J Biol Chem. 2001 Oct 19;276(42):39330-9 [11498536] Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15137-42 [11752460] Science. 2002 Jan 11;295(5553):338-42 [11786644] Nat Immunol. 2002 Jun;3(6):506-8 [12032561] Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11964-8 [1334553] Annu Rev Immunol. 1994;12:635-73 [7912089] J Exp Med. 1995 Jan 1;181(1):399-404 [7528775] J Biol Chem. 1995 Mar 31;270(13):7420-6 [7535770] J Exp Med. 1995 May 1;181(5):1755-62 [7722452] Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7307-11 [7638186] Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9097-101 [7568080] Immunity. 1996 May;4(5):471-81 [8630732] Nature. 1996 Jul 11;382(6587):171-4 [8700208] Nature. 1996 Jul 11;382(6587):174-7 [8700209] Oncogene. 1999 Nov 11;18(47):6573-82 [10597261] J Exp Med. 2000 Mar 6;191(5):847-58 [10704465] Annu Rev Immunol. 2000;18:451-94 [10837066] Oncogene. 2000 May 15;19(21):2628-37 [10851062] Science. 2000 Jun 23;288(5474):2219-22 [10864872] Nature. 1996 Sep 26;383(6598):344-7 [8848048] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Raloxifene, a mixed estrogen agonist/antagonist, induces apoptosis in androgen-independent human prostate cancer cell lines. AN - 72102138; 12235008 AB - Raloxifene, a selective estrogen receptor (ER) modulator, is a mixed estrogen agonist/antagonist that has been shown to prevent osteoporosis and breast cancer in women. Because the prostate contains high levels of ER-beta, the present study investigated the effect of raloxifene in three well-characterized, androgen-independent human prostate cancer cell lines: (a) PC3; (b) PC3M; and (c) DU145. Reverse transcriptase-PCR and Western blot analysis for ER-alpha and ER-beta demonstrated that all three cell lines express ER-beta, whereas only PC3 and PC3M cells were positive for ER-alpha. After the treatment with raloxifene, a dramatic increase in cell death was observed in a dose-dependent manner in the three prostate cancer cell lines (10(-9) to 10(-6) M range). Because the three prostate cancer cell lines demonstrated similar morphological changes after the raloxifene treatment, PC3 (ER-alpha/ER-beta+) and DU145 (ER-beta+ only) cells were selected to further characterize the raloxifene-induced cell death. Using the nucleus-specific stain 4',6-diamidino-2-phenylindole, nuclear fragmentation was observed in a time-dependent manner in both cell lines after exposure to 10(-6) M raloxifene. Using the terminal deoxynucleotidyl transferase-mediated nick end labeling apoptotic assay, it was demonstrated that the nuclear fragmentation was caused by apoptosis. To investigate the possibility that caspase activation is involved in raloxifene-induced apoptosis, cells were treated with the pan-caspase inhibitor ZVAD. The results demonstrated that the dramatic change in cellular morphology after treatment with raloxifene was no longer observed when cells were pretreated with ZVAD. Immunoblot demonstrated activation of caspases 8 and 9 in PC3 and DU145 cells, respectively. Taken together, these results demonstrate that the mixed estrogen agonist/antagonist, raloxifene, induces apoptosis in androgen-independent human prostate cancer cell lines. JF - Cancer research AU - Kim, Isaac Yi AU - Kim, Byung-Chul AU - Seong, Do Hwan AU - Lee, Dug Keun AU - Seo, Jeong-Meen AU - Hong, Young Jin AU - Kim, Heung-Tae AU - Morton, Ronald A AU - Kim, Seong-Jin AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute/NIH, Building 41, Room C629, 9000 Rockville Pike, Bethesda, MD 20892, USA. Y1 - 2002/09/15/ PY - 2002 DA - 2002 Sep 15 SP - 5365 EP - 5369 VL - 62 IS - 18 SN - 0008-5472, 0008-5472 KW - Selective Estrogen Receptor Modulators KW - 0 KW - Raloxifene Hydrochloride KW - 4F86W47BR6 KW - Index Medicus KW - Tumor Cells, Cultured KW - Humans KW - Neoplasms, Hormone-Dependent -- drug therapy KW - Neoplasms, Hormone-Dependent -- pathology KW - Male KW - Prostatic Neoplasms -- pathology KW - Raloxifene Hydrochloride -- pharmacology KW - Apoptosis -- drug effects KW - Selective Estrogen Receptor Modulators -- pharmacology KW - Prostatic Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72102138?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Raloxifene%2C+a+mixed+estrogen+agonist%2Fantagonist%2C+induces+apoptosis+in+androgen-independent+human+prostate+cancer+cell+lines.&rft.au=Kim%2C+Isaac+Yi%3BKim%2C+Byung-Chul%3BSeong%2C+Do+Hwan%3BLee%2C+Dug+Keun%3BSeo%2C+Jeong-Meen%3BHong%2C+Young+Jin%3BKim%2C+Heung-Tae%3BMorton%2C+Ronald+A%3BKim%2C+Seong-Jin&rft.aulast=Kim&rft.aufirst=Isaac&rft.date=2002-09-15&rft.volume=62&rft.issue=18&rft.spage=5365&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 - 2002-10-08 N1 - Date created - 2002-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer prevention clinical trials. AN - 72098966; 12235220 AB - Prevention of cancer through interventions based on sound scientific research remains an important strategy of oncology research at the National Cancer Institute (NCI). Reducing the burden of cancer in the United States is focused on clinical investigations in medical settings and public health intervention research on cancer risk factors regarding lifestyle and diet. Chemoprevention research at the NCI has progressed systematically to identify potential agents that reduce cancer risk and to develop public health strategies that take advantage of basic research results. In addition, advances in our understanding of molecular targets and pathways and our use of new and emerging technologies have become important tools for oncology research. Priority areas for chemoprevention research, identified from experimental and clinical research, are investigated in clinical trials to determine their ability to reduce cancer risk in selected populations or in the general population. Priority areas discussed in this review are the relationship of the arachidonic acid pathway to carcinogenesis, lung cancer prevention in former smokers, breast cancer prevention, and prostate cancer prevention. In addition, two lifestyle factors that have potential to influence cancer risk-obesity and functionally enhanced foods-are discussed in the context of their link between clinical and public health-related research. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Greenwald, Peter AD - Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-7309, USA. pg37g@nih.gov Y1 - 2002/09/15/ PY - 2002 DA - 2002 Sep 15 SP - 14S EP - 22S VL - 20 IS - 18 Suppl SN - 0732-183X, 0732-183X KW - Anticarcinogenic Agents KW - 0 KW - Index Medicus KW - Humans KW - Exercise KW - Diet KW - Research Design KW - Male KW - Female KW - Lung Neoplasms -- prevention & control KW - Breast Neoplasms -- prevention & control KW - Prostatic Neoplasms -- prevention & control KW - Clinical Trials as Topic -- trends UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72098966?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Cancer+prevention+clinical+trials.&rft.au=Greenwald%2C+Peter&rft.aulast=Greenwald&rft.aufirst=Peter&rft.date=2002-09-15&rft.volume=20&rft.issue=18+Suppl&rft.spage=14S&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 - 2002-10-03 N1 - Date created - 2002-09-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Clin Oncol. 2004 Jan 15;22(2):383-5 [14722055] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alterations in gene expression profiles during prostate cancer progression: functional correlations to tumorigenicity and down-regulation of selenoprotein-P in mouse and human tumors. AN - 72096545; 12235003 AB - To identify molecular changes that occur during prostate tumor progression, we have characterized a series of prostate cancer cell lines isolated at different stages of tumorigenesis from C3(1)/Tag transgenic mice. Cell lines derived from low- and high-grade prostatic intraepithelial neoplasia, invasive carcinoma, and a lung metastasis exhibited significant differences in cell growth, tumorigenicity, invasiveness, and angiogenesis. cDNA microarray analysis of 8700 features revealed correlations between the tumorigenicity of the C3(1)/Tag-Pr cells and changes in the expression levels of genes regulating cell growth, angiogenesis, and invasion. Many changes observed in transcriptional regulation in this in vitro system are similar to those reported for human prostate cancer, as well as other types of human tumors. This analysis of expression patterns has also identified novel genes that may be involved in mechanisms of prostate oncogenesis or serve as potential biomarkers or therapeutic targets for prostate cancer. Examples include the L1-cell adhesion molecule, metastasis-associated gene (MTA-2), Rab-25, tumor-associated signal transducer-2 (Trop-2), and Selenoprotein-P, a gene that binds selenium and prevents oxidative stress. Many genes identified in the Pr-cell line model have been shown to be altered in human prostate cancer. The comprehensive microarray data provides a rational basis for using this model system for studies where alterations of specific genes or pathways are of particular interest. Quantitative real-time reverse transcription-PCR for Selenoprotein-P demonstrated a similar down-regulation of the transcript of this gene in a subset of human prostate tumors, mouse tumors, and prostate carcinoma cell lines. This work demonstrates that expression profiling in animal models may lead to the identification of novel genes involved in human prostate cancer biology. JF - Cancer research AU - Calvo, Alfonso AU - Xiao, Nianqing AU - Kang, Jason AU - Best, Carolyn J M AU - Leiva, Isabel AU - Emmert-Buck, Michael R AU - Jorcyk, Cheryl AU - Green, Jeffrey E AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute/NIH, Building 41, Room C629, 41 Library Drive, Bethesda, MD 20892, USA. Y1 - 2002/09/15/ PY - 2002 DA - 2002 Sep 15 SP - 5325 EP - 5335 VL - 62 IS - 18 SN - 0008-5472, 0008-5472 KW - Cell Adhesion Molecules KW - 0 KW - Proteins KW - Selenoprotein P KW - Selenoproteins KW - Index Medicus KW - Neoplasm Invasiveness KW - Animals KW - Cell Adhesion Molecules -- genetics KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - Neovascularization, Pathologic -- metabolism KW - Cell Division -- physiology KW - Disease Progression KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - Neovascularization, Pathologic -- pathology KW - Gene Expression Profiling KW - Tumor Cells, Cultured KW - Down-Regulation KW - Neovascularization, Pathologic -- genetics KW - Cell Adhesion Molecules -- biosynthesis KW - Cluster Analysis KW - Cell Division -- genetics KW - Male KW - Prostatic Neoplasms -- metabolism KW - Prostatic Neoplasms -- pathology KW - Prostatic Neoplasms -- blood supply KW - Prostatic Neoplasms -- genetics KW - Proteins -- metabolism KW - Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72096545?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Alterations+in+gene+expression+profiles+during+prostate+cancer+progression%3A+functional+correlations+to+tumorigenicity+and+down-regulation+of+selenoprotein-P+in+mouse+and+human+tumors.&rft.au=Calvo%2C+Alfonso%3BXiao%2C+Nianqing%3BKang%2C+Jason%3BBest%2C+Carolyn+J+M%3BLeiva%2C+Isabel%3BEmmert-Buck%2C+Michael+R%3BJorcyk%2C+Cheryl%3BGreen%2C+Jeffrey+E&rft.aulast=Calvo&rft.aufirst=Alfonso&rft.date=2002-09-15&rft.volume=62&rft.issue=18&rft.spage=5325&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 - 2002-10-08 N1 - Date created - 2002-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Impaired effector function of hepatitis C virus-specific CD8+ T cells in chronic hepatitis C virus infection. AN - 72068887; 12218168 AB - The cellular immune response contributes to clearance of hepatitis C virus (HCV) and persists for decades after recovery from infection. The immunological basis for the inefficiency of the cellular immune response in chronically infected persons is not known. Here, we used four HLA-A2 tetramers, specific for two HCV core and two HCV NS3 epitopes, to investigate at the single-cell level effector function and phenotype of HCV-specific CD8+ T cells in 20 chronically infected and 12 long-term recovered patients. Overall, HCV-specific, tetramer+ T cells were more frequently found in PBMCs of chronically infected patients than in those of recovered patients. However, when compared with HCV-tetramer+ T cells of recovered patients, they displayed an impaired proliferative capacity. As a result of the impaired proliferative capacity, HCV-specific T cell lines derived from chronically infected patients displayed less peptide-specific cytotoxicity than those from recovered patients. In addition, proliferation and ex vivo IFN-gamma production of HCV-tetramer+ cells, but not influenza-virus-specific T cells, were defective in chronically infected patients and could not be restored by in vitro stimulation with peptide and IL-2. At least three distinct phenotypes of HCV-specific CD8+ T cells were identified and associated with certain functional characteristics. In addition, impairment of proliferative, cytokine, and cytotoxic effector functions of tetramer+ T cells in viremic patients was associated with weak ex vivo HCV-specific CD4+ T cell responses. Thus, the defective functions of HCV-specific CD8+ T cells might contribute to viral persistence in chronically infected patients, and knowledge on their reversibility may facilitate the development of immunotherapeutic vaccines. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Wedemeyer, Heiner AU - He, Xiao-Song AU - Nascimbeni, Michelina AU - Davis, Anthony R AU - Greenberg, Harry B AU - Hoofnagle, Jay H AU - Liang, T Jake AU - Alter, Harvey AU - Rehermann, Barbara AD - Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2002/09/15/ PY - 2002 DA - 2002 Sep 15 SP - 3447 EP - 3458 VL - 169 IS - 6 SN - 0022-1767, 0022-1767 KW - Epitopes, T-Lymphocyte KW - 0 KW - NS3 protein, hepatitis C virus KW - Viral Core Proteins KW - Viral Nonstructural Proteins KW - Interferon-gamma KW - 82115-62-6 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - CD4-Positive T-Lymphocytes -- immunology KW - Interferon-gamma -- biosynthesis KW - T-Lymphocyte Subsets -- metabolism KW - Lymphocyte Activation KW - Lymphocyte Count KW - CD4-Positive T-Lymphocytes -- metabolism KW - Viral Core Proteins -- immunology KW - CD4-Positive T-Lymphocytes -- virology KW - T-Lymphocyte Subsets -- immunology KW - Adult KW - T-Lymphocyte Subsets -- virology KW - Cytotoxicity Tests, Immunologic KW - Middle Aged KW - Viral Nonstructural Proteins -- immunology KW - Immunophenotyping KW - Male KW - Cell Line KW - Female KW - Epitopes, T-Lymphocyte -- blood KW - Hepatitis C, Chronic -- immunology KW - Hepacivirus -- immunology KW - CD8-Positive T-Lymphocytes -- metabolism KW - CD8-Positive T-Lymphocytes -- immunology KW - Hepatitis C, Chronic -- virology KW - CD8-Positive T-Lymphocytes -- virology KW - Epitopes, T-Lymphocyte -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72068887?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Impaired+effector+function+of+hepatitis+C+virus-specific+CD8%2B+T+cells+in+chronic+hepatitis+C+virus+infection.&rft.au=Wedemeyer%2C+Heiner%3BHe%2C+Xiao-Song%3BNascimbeni%2C+Michelina%3BDavis%2C+Anthony+R%3BGreenberg%2C+Harry+B%3BHoofnagle%2C+Jay+H%3BLiang%2C+T+Jake%3BAlter%2C+Harvey%3BRehermann%2C+Barbara&rft.aulast=Wedemeyer&rft.aufirst=Heiner&rft.date=2002-09-15&rft.volume=169&rft.issue=6&rft.spage=3447&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 - 2002-10-23 N1 - Date created - 2002-09-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - MHC allele-specific molecular features determine peptide/HLA-A2 conformations that are recognized by HLA-A2-restricted T cell receptors. AN - 72068143; 12218132 AB - The structures of alphabeta TCRs bound to complexes of class I MHC molecules and peptide show that the TCRs make multiple contacts with the alpha1 and alpha2 helixes of the MHC. Previously we have shown that the A6 TCR in complex with the HLA-A2/Tax peptide has 15 contact sites on HLA-A2. Single amino acid mutagenesis of these contact sites demonstrated that mutation of only three amino acids clustered on the alpha1 helix (R65, K66, A69) disrupted recognition by the A6 TCR. In the present study we have asked whether TCRs that recognize four other peptides presented by HLA-A2 interact with the MHC in identical, similar, or different patterns as the A6 TCR. Mutants K66A and Q155A had the highest frequency of negative effects on lysis. A subset of peptide-specific CTL also selectively recognized mutants K66A or Q155A in the absence of exogenous cognate peptides, indicating that these mutations affected the presentation of endogenous peptide/HLA-A2 complexes. These findings suggest that most HLA-A2-restricted TCRs recognize surfaces on the HLA-A2/peptide complex that are dependent upon the side chains of K66 and Q155 in the central portion of the peptide binding groove. Crystallographic structures of several peptide/HLA-A2 structures have shown that the side chains of these critical amino acids that make contact with the A6 TCR also contact the bound peptide. Collectively, our results indicate that the generalized effects of changes at these critical amino acids are probably due to the fact that they can be directly contacted by TCRs as well as influence the binding and presentation of the bound peptides. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Wang, Zichun AU - Turner, Richard AU - Baker, Brian M AU - Biddison, William E AD - Molecular Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2002/09/15/ PY - 2002 DA - 2002 Sep 15 SP - 3146 EP - 3154 VL - 169 IS - 6 SN - 0022-1767, 0022-1767 KW - Epitopes KW - 0 KW - Gene Products, tax KW - HLA-A2 Antigen KW - MART-1-Melan-A(27-35) epitope KW - Membrane Glycoproteins KW - Neoplasm Proteins KW - PMEL protein, human KW - Peptide Fragments KW - Phosphoproteins KW - Receptors, Antigen, T-Cell KW - Viral Matrix Proteins KW - cytomegalovirus matrix protein 65kDa KW - gp100 Melanoma Antigen KW - influenza matrix peptide (58-66) KW - Abridged Index Medicus KW - Index Medicus KW - Amino Acid Substitution -- immunology KW - Gene Products, tax -- metabolism KW - Phosphoproteins -- immunology KW - Neoplasm Proteins -- immunology KW - Humans KW - Cytomegalovirus -- immunology KW - Gene Products, tax -- immunology KW - Melanoma -- immunology KW - Protein Binding -- immunology KW - Mutagenesis, Site-Directed KW - Tumor Cells, Cultured KW - Amino Acid Substitution -- genetics KW - Cytotoxicity Tests, Immunologic KW - Protein Binding -- genetics KW - Epitopes -- immunology KW - Neoplasm Proteins -- metabolism KW - Membrane Glycoproteins -- immunology KW - Viral Matrix Proteins -- immunology KW - Cell Line KW - Epitopes -- metabolism KW - Viral Matrix Proteins -- metabolism KW - Protein Conformation KW - Phosphoproteins -- metabolism KW - Membrane Glycoproteins -- metabolism KW - Peptide Fragments -- metabolism KW - Alleles KW - Peptide Fragments -- chemistry KW - Peptide Fragments -- genetics KW - Receptors, Antigen, T-Cell -- metabolism KW - HLA-A2 Antigen -- genetics KW - Receptors, Antigen, T-Cell -- immunology KW - Peptide Fragments -- immunology KW - HLA-A2 Antigen -- metabolism KW - HLA-A2 Antigen -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72068143?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=MHC+allele-specific+molecular+features+determine+peptide%2FHLA-A2+conformations+that+are+recognized+by+HLA-A2-restricted+T+cell+receptors.&rft.au=Wang%2C+Zichun%3BTurner%2C+Richard%3BBaker%2C+Brian+M%3BBiddison%2C+William+E&rft.aulast=Wang&rft.aufirst=Zichun&rft.date=2002-09-15&rft.volume=169&rft.issue=6&rft.spage=3146&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 - 2002-10-23 N1 - Date created - 2002-09-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rituximab treatment of refractory fludarabine-associated immune thrombocytopenia in chronic lymphocytic leukemia. AN - 72040628; 12200396 AB - Fludarabine can exacerbate idiopathic thrombocytopenia (ITP) in chronic lymphocytic leukemia (CLL). We report 3 CLL patients with refractory fludarabine-associated ITP who responded to rituximab. The patients had Rai stages III, III, and IV disease. Before fludarabine treatment, the platelet counts were 141 000/microL, 118 000/microL, and 70 000/microL. ITP developed within week 1 of cycle 3 in 2 patients and within week 2 of cycle 1 in 1 patient. Platelet count nadirs were 4000/microL, 1000/microL, and 2000/microL, respectively, and did not respond to treatment with steroids or intravenous immunoglobulin. Rituximab therapy (375 mg/m(2) per week for 4 weeks) was begun on days 18, 23, and 20 of ITP. Patient 1 achieved a platelet count of more than 50 000/microL at day 21 and more than 133 000/microL at day 28, patient 2 achieved a platelet count of more than 50 000/microL at day 4 and more than 150 000/microL at day 10, and patient 3 achieved a platelet count of more than 50 000/microL at day 5 and 72 000/microL at day 28 of rituximab therapy, with platelet response durations of 17+, 6+, and 6 months. These results suggest rituximab can rapidly reverse refractory fludarabine-associated ITP. JF - Blood AU - Hegde, Upendra P AU - Wilson, Wyndham H AU - White, Therese AU - Cheson, Bruce D AD - Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 2002/09/15/ PY - 2002 DA - 2002 Sep 15 SP - 2260 EP - 2262 VL - 100 IS - 6 SN - 0006-4971, 0006-4971 KW - Antibodies, Monoclonal KW - 0 KW - Antibodies, Monoclonal, Murine-Derived KW - Antineoplastic Agents KW - Rituximab KW - 4F4X42SYQ6 KW - Vidarabine KW - FA2DM6879K KW - fludarabine KW - P2K93U8740 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Salvage Therapy KW - Treatment Outcome KW - Middle Aged KW - Male KW - Female KW - Platelet Count KW - Purpura, Thrombocytopenic, Idiopathic -- drug therapy KW - Vidarabine -- analogs & derivatives KW - Leukemia, Lymphocytic, Chronic, B-Cell -- drug therapy KW - Antineoplastic Agents -- administration & dosage KW - Purpura, Thrombocytopenic, Idiopathic -- chemically induced KW - Leukemia, Lymphocytic, Chronic, B-Cell -- complications KW - Vidarabine -- adverse effects KW - Antibodies, Monoclonal -- administration & dosage KW - Vidarabine -- immunology KW - Purpura, Thrombocytopenic, Idiopathic -- immunology KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72040628?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Rituximab+treatment+of+refractory+fludarabine-associated+immune+thrombocytopenia+in+chronic+lymphocytic+leukemia.&rft.au=Hegde%2C+Upendra+P%3BWilson%2C+Wyndham+H%3BWhite%2C+Therese%3BCheson%2C+Bruce+D&rft.aulast=Hegde&rft.aufirst=Upendra&rft.date=2002-09-15&rft.volume=100&rft.issue=6&rft.spage=2260&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-10-24 N1 - Date created - 2002-08-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Stanford V regimen and concomitant HAART in 59 patients with Hodgkin disease and HIV infection. AN - 72038234; 12200356 AB - A phase 2 prospective study was performed to evaluate the feasibility and activity of a short, dose-intensive chemotherapy regimen and radiotherapy (the Stanford V regimen) plus highly active antiretroviral therapy (HAART) and granulocyte colony-stimulating factor (G-CSF) support in patients with Hodgkin disease and HIV infection. Fifty-nine patients were enrolled. Stanford V was well tolerated and 69% of the patients completed treatment with no dose reduction or delayed chemotherapy administration. The most important dose-limiting side effects were bone marrow toxicity and neurotoxicity. Complete remission was achieved by 81% of the patients, and after a median follow-up of 17 months 33 patients (56%) were alive and disease-free. The estimated 3-year overall survival (OS), disease-free survival (DFS), and freedom from progression (FFP) were 51%, 68%, and 60%, respectively. Probability of FFP was significantly (P =.02) higher among patients with an International Prognostic Score (IPS) of 2 or lower than in those with an IPS higher than 2, and the percentages of FFP at 2 years in these groups were 83% and 41%, respectively. Similarly, the probability of OS was significantly (P =.0004) different in the 2 groups, and the percentages of OS at 3 years were 76% and 33%, respectively. Our data confirm that the Stanford V regimen with concomitant HAART is feasible and active in an HIV setting. However, a more intensive approach should be considered in patients with high IPSs. JF - Blood AU - Spina, Michele AU - Gabarre, Jean AU - Rossi, Giuseppe AU - Fasan, Marco AU - Schiantarelli, Clara AU - Nigra, Ezio AU - Mena, Maurizio AU - Antinori, Andrea AU - Ammassari, Adriana AU - Talamini, Renato AU - Vaccher, Emanuela AU - di Gennaro, Giampiero AU - Tirelli, Umberto AD - Division of Medical Oncology A, National Cancer Institute, Via Pedemontana Occidentale 12, 33081 Aviano (PN), Italy. Y1 - 2002/09/15/ PY - 2002 DA - 2002 Sep 15 SP - 1984 EP - 1988 VL - 100 IS - 6 SN - 0006-4971, 0006-4971 KW - Bleomycin KW - 11056-06-7 KW - Mechlorethamine KW - 50D9XSG0VR KW - Vincristine KW - 5J49Q6B70F KW - Vinblastine KW - 5V9KLZ54CY KW - Etoposide KW - 6PLQ3CP4P3 KW - Doxorubicin KW - 80168379AG KW - Prednisone KW - VB0R961HZT KW - Abridged Index Medicus KW - Index Medicus KW - Disease-Free Survival KW - Mechlorethamine -- administration & dosage KW - Bleomycin -- administration & dosage KW - Humans KW - Vincristine -- administration & dosage KW - Prognosis KW - Aged KW - Doxorubicin -- administration & dosage KW - HIV-1 KW - Prospective Studies KW - Survival Rate KW - Etoposide -- administration & dosage KW - Adult KW - Vinblastine -- administration & dosage KW - Remission Induction -- methods KW - Middle Aged KW - Male KW - Prednisone -- administration & dosage KW - Survival Analysis KW - Lymphoma, AIDS-Related -- mortality KW - HIV Infections -- complications KW - Hodgkin Disease -- drug therapy KW - HIV Infections -- drug therapy KW - Lymphoma, AIDS-Related -- drug therapy KW - HIV Infections -- mortality KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Hodgkin Disease -- virology KW - Antiretroviral Therapy, Highly Active -- methods KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Antineoplastic Combined Chemotherapy Protocols -- toxicity KW - Hodgkin Disease -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72038234?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Stanford+V+regimen+and+concomitant+HAART+in+59+patients+with+Hodgkin+disease+and+HIV+infection.&rft.au=Spina%2C+Michele%3BGabarre%2C+Jean%3BRossi%2C+Giuseppe%3BFasan%2C+Marco%3BSchiantarelli%2C+Clara%3BNigra%2C+Ezio%3BMena%2C+Maurizio%3BAntinori%2C+Andrea%3BAmmassari%2C+Adriana%3BTalamini%2C+Renato%3BVaccher%2C+Emanuela%3Bdi+Gennaro%2C+Giampiero%3BTirelli%2C+Umberto&rft.aulast=Spina&rft.aufirst=Michele&rft.date=2002-09-15&rft.volume=100&rft.issue=6&rft.spage=1984&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-10-24 N1 - Date created - 2002-08-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ingress and reactive chemistry of nitroxyl-derived species within human cells AN - 18506583; 5466781 AB - The mechanisms that control the biological signaling and toxicological properties of the nitrogen oxide species nitroxyl (HNO) are largely unknown. The ingress and intracellular reactivity of nitroxyl-derived species were examined using Angeli's salt (AS), which decomposes initially to HNO and nitrite at physiologic pH. Exposure of 4,5-diaminofluorescein (DAF) to AS resulted in fluorescent product formation only in the presence of molecular oxygen. Kinetic analysis and the lack of signal from a nitric oxide (NO)-sensitive electrode suggested that these processes did not involve conversion of HNO to NO. On an equimolar basis, bolus peroxynitrite (ONOO super(-)) exposure generated only 15% of fluorescent product formation observed from AS decomposition. Moreover, infusion of synthetic ONOO super(-) at a rate comparable to AS decomposition resulted in only 4% of the signal. Quenching of AS-mediated product formation within intact human MCF-7 breast carcinoma cells containing DAF by addition of urate to buffer suggested involvement of an oxidized intermediate formed from reaction between HNO and oxygen. Conversely, intact cells competitively sequestered the HNO-derived species from reaction with DAF in solution. These data show this intermediate to be a long-lived diffusible species. Relative product yield from intracellular DAF was decreased 5- to 8-fold when cells were lysed immediately prior to AS addition, consistent with the partitioning of HNO and/or derived species into the cellular membrane, thereby shielding these reactive intermediates from either hydrolysis or cytoplasmic scavenger pools. These findings establish that oxygen-derived species of nitroxyl can readily penetrate and engage the intracellular milieu of cells and suggest this process to be independent of NO and ONOO super(-) intermediacy. The substantial facilitation of oxygen-dependent nitroxyl chemistry by intact lipid bilayers supports a focusing role for the membrane in modulation of cellular constituents proteins by this unique species. JF - Free Radical Biology & Medicine AU - Espey, M G AU - Miranda, K M AU - Thomas, D D AU - Wink, DA AD - Radiation Biology Branch, National Cancer Institute, NIH, Building 10, Room B3-B69, Bethesda, MD 20892, USA, SP@nih.gov Y1 - 2002/09/15/ PY - 2002 DA - 2002 Sep 15 SP - 827 EP - 834 VL - 33 IS - 6 SN - 0891-5849, 0891-5849 KW - MCF-7 cells KW - intracellular reactivity KW - man KW - nitroxyl KW - Toxicology Abstracts KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18506583?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+Radical+Biology+%26+Medicine&rft.atitle=Ingress+and+reactive+chemistry+of+nitroxyl-derived+species+within+human+cells&rft.au=Espey%2C+M+G%3BMiranda%2C+K+M%3BThomas%2C+D+D%3BWink%2C+DA&rft.aulast=Espey&rft.aufirst=M&rft.date=2002-09-15&rft.volume=33&rft.issue=6&rft.spage=827&rft.isbn=&rft.btitle=&rft.title=Free+Radical+Biology+%26+Medicine&rft.issn=08915849&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Macrophage foam cell formation with native low density lipoprotein. AN - 72073191; 12118008 AB - This investigation has elucidated a mechanism for development of macrophage foam cells when macrophages are incubated with native low density lipoprotein (LDL). LDL is believed to be the main source of cholesterol that accumulates in monocyte-derived macrophages within atherosclerotic plaques, but native LDL has not previously been shown to cause substantial cholesterol accumulation when incubated with macrophages. We have found that activation of human monocyte-derived macrophages with phorbol 12-myristate 13-acetate (PMA) stimulates LDL uptake and degradation and acyl-CoA:cholesterol acyltransferase-mediated esterification of LDL-derived cholesterol, resulting in massive macrophage cholesterol accumulation that could exceed 400 nmol/mg of cell protein. Cholesterol accumulation showed a biphasic linear LDL concentration dependence with LDL levels as high as 4 mg/ml, similar to LDL levels in artery intima. Protein kinase C mediated the PMA-stimulated macrophage uptake of LDL because the protein kinase C inhibitors, Gö6983 and GF109203X, inhibited cholesterol accumulation. LDL receptors did not mediate macrophage cholesterol accumulation because accumulation occurred with reductively methylated LDL and in the presence of an anti-LDL receptor-blocking monoclonal antibody. LDL-induced cholesterol accumulation was not inhibited by antioxidants, was not accompanied by increased LDL binding to macrophages, did not depend on the apoB component of LDL, and was not down-regulated by prior cholesterol enrichment of macrophages. We have shown that the mechanism of LDL uptake by macrophages was PMA-stimulated endocytosis of LDL taken up as part of the bulk phase fluid (i.e. fluid phase endocytosis). The amount of LDL taken up with the bulk phase fluid was measured with [(3)H]sucrose and accounted for a minimum of 83% of the LDL cholesterol delivery and accumulation in PMA-activated macrophages. This novel mechanism of macrophage cholesterol accumulation shows that modification of LDL is not necessary for foam cell formation to occur. In addition, the findings direct attention to macrophage fluid phase endocytosis as a relevant pathway to target for modulating macrophage cholesterol accumulation in atherosclerosis. JF - The Journal of biological chemistry AU - Kruth, Howard S AU - Huang, Wei AU - Ishii, Itsuko AU - Zhang, Wei-Yang AD - Section of Experimental Atherosclerosis, NHLBI/National Institutes of Health, Bldg. 10 Rm. 5N-113, 10 Center Drive, MSC 1422, Bethesda, MD 20892, USA. kruthh@nhlbi.nih.gov Y1 - 2002/09/13/ PY - 2002 DA - 2002 Sep 13 SP - 34573 EP - 34580 VL - 277 IS - 37 SN - 0021-9258, 0021-9258 KW - Apolipoproteins B KW - 0 KW - Lipoproteins, LDL KW - Cholesterol KW - 97C5T2UQ7J KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Endocytosis KW - Cholesterol -- metabolism KW - Cells, Cultured KW - Humans KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Apolipoproteins B -- physiology KW - Macrophages -- drug effects KW - Macrophages -- metabolism KW - Foam Cells -- physiology KW - Lipoproteins, LDL -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72073191?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Macrophage+foam+cell+formation+with+native+low+density+lipoprotein.&rft.au=Kruth%2C+Howard+S%3BHuang%2C+Wei%3BIshii%2C+Itsuko%3BZhang%2C+Wei-Yang&rft.aulast=Kruth&rft.aufirst=Howard&rft.date=2002-09-13&rft.volume=277&rft.issue=37&rft.spage=34573&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 - 2002-12-03 N1 - Date created - 2002-09-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Beta-glucoside kinase (BglK) from Klebsiella pneumoniae. Purification, properties, and preparative synthesis of 6-phospho-beta-D-glucosides. AN - 72069024; 12110692 AB - ATP-dependent beta-glucoside kinase (BglK) has been purified from cellobiose-grown cells of Klebsiella pneumoniae. In solution, the enzyme (EC ) exists as a homotetramer composed of non-covalently linked subunits of M(r) approximately 33,000. Determination of the first 28 residues from the N terminus of the protein allowed the identification and cloning of bglK from genomic DNA of K. pneumoniae. The open reading frame (ORF) of bglK encodes a 297-residue polypeptide of calculated M(r) 32,697. A motif of 7 amino acids (AFD(7)IG(9)GT) near the N terminus may comprise the ATP-binding site, and residue changes D7G and G9A yielded catalytically inactive proteins. BglK was progressively inactivated (t(12) approximately 19 min) by N-ethylmaleimide, but ATP afforded considerable protection against the inhibitor. By the presence of a centrally located signature sequence, BglK can be assigned to the ROK (Repressor, ORF, Kinase) family of proteins. Preparation of (His6)BglK by nickel-nitrilotriacetic acid-agarose chromatography provided high purity enzyme in quantity sufficient for the preparative synthesis (200-500 mg) of ten 6-phospho-beta-d-glucosides, including cellobiose-6'-P, gentiobiose-6'-P, cellobiitol-6-P, salicin-6-P, and arbutin-6-P. These (and other) derivatives are substrates for phospho-beta-glucosidase(s) belonging to Families 1 and 4 of the glycosylhydrolase superfamily. The structures, physicochemical properties, and phosphorylation site(s) of the 6-phospho-beta-d-glucosides have been determined by fast atom bombardment-negative ion spectrometry, thin-layer chromatography, and (1)H and (13)C NMR spectroscopy. The recently sequenced genomes of two Listeria species, L. monocytogenes EGD-e and L. innocua CLIP 11262, contain homologous genes (lmo2764 and lin2907, respectively) that encode a 294-residue polypeptide (M(r) approximately 32,200) that exhibits approximately 58% amino acid identity with BglK. The protein encoded by the two genes exhibits beta-glucoside kinase activity and cross-reacts with polyclonal antibody to (His6)BglK from K. pneumoniae. The location of lmo2764 and lin2907 within a beta-glucoside (cellobiose):phosphotransferase system operon, may presage both enzymatic (kinase) and regulatory functions for the BglK homolog in Listeria species. JF - The Journal of biological chemistry AU - Thompson, John AU - Lichtenthaler, Frieder W AU - Peters, Siegfried AU - Pikis, Andreas AD - Microbial Biochemistry and Genetics Unit, Oral Infection and Immunity Branch, NIDCR/National Institutes of Health, 30 Convent Drive, MSC-4350, Bethesda, MD 20892, USA. jthompson@dir.nidcr.nih.gov Y1 - 2002/09/13/ PY - 2002 DA - 2002 Sep 13 SP - 34310 EP - 34321 VL - 277 IS - 37 SN - 0021-9258, 0021-9258 KW - Glucosides KW - 0 KW - Phosphotransferases (Alcohol Group Acceptor) KW - EC 2.7.1.- KW - beta-glucoside kinase KW - EC 2.7.1.85 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Kinetics KW - Hydrogen-Ion Concentration KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Substrate Specificity KW - Glucosides -- metabolism KW - Phosphotransferases (Alcohol Group Acceptor) -- chemistry KW - Phosphotransferases (Alcohol Group Acceptor) -- isolation & purification KW - Klebsiella pneumoniae -- enzymology KW - Phosphotransferases (Alcohol Group Acceptor) -- metabolism KW - Klebsiella pneumoniae -- growth & development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72069024?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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-glucoside+kinase+%28BglK%29+from+Klebsiella+pneumoniae.+Purification%2C+properties%2C+and+preparative+synthesis+of+6-phospho-beta-D-glucosides.&rft.au=Thompson%2C+John%3BLichtenthaler%2C+Frieder+W%3BPeters%2C+Siegfried%3BPikis%2C+Andreas&rft.aulast=Thompson&rft.aufirst=John&rft.date=2002-09-13&rft.volume=277&rft.issue=37&rft.spage=34310&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 - 2002-12-03 N1 - Date created - 2002-09-09 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AY035305; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human T-cell lymphotropic virus type 1 tax inhibits transforming growth factor-beta signaling by blocking the association of Smad proteins with Smad-binding element. AN - 72068556; 12097320 AB - The human T-cell lymphotropic virus type 1 (HTLV-1) oncoprotein Tax is implicated in various clinical manifestations associated with infection by HTLV-1, including an aggressive and fatal T-cell malignancy. Because many human HTLV-1-infected T-cell lines are resistant to the growth inhibitory activity of transforming growth factor beta (TGF-beta), we examined the possibility that the HTVL-1-Tax oncoprotein regulates TGF-beta signaling. We show that Tax significantly decreases transcriptional activity and growth inhibition in response to TGF-beta. Tax inhibits TGF-beta-induced plasminogen activator inhibitor-1 expression and Smad2 phosphorylation. Competitive interaction studies show that Tax inhibits TGF-beta signaling, in part, by disrupting the interaction of the Smads with the transcriptional co-activator p300. Tax directly interacts with Smad2, Smad3, and Smad4; the Smad MH2 domain binds to Tax. Furthermore, Tax inhibits Smad3.Smad4 complex formation and its DNA binding. These results suggest that suppression of Smad-mediated signaling by Tax may contribute to HTLV-1-associated leukemogenesis. JF - The Journal of biological chemistry AU - Lee, Dug Keun AU - Kim, Byung-Chul AU - Brady, John N AU - Jeang, Kuan-Teh AU - Kim, Seong-Jin AD - Laboratory of Cell Regulation and Carcinogenesis, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/09/13/ PY - 2002 DA - 2002 Sep 13 SP - 33766 EP - 33775 VL - 277 IS - 37 SN - 0021-9258, 0021-9258 KW - DNA-Binding Proteins KW - 0 KW - Gene Products, tax KW - Nuclear Proteins KW - Repressor Proteins KW - SMAD2 protein, human KW - SMAD3 protein, human KW - SMAD4 protein, human KW - Smad2 Protein KW - Smad3 Protein KW - Smad4 Protein KW - Trans-Activators KW - Transforming Growth Factor beta KW - Index Medicus KW - Leukemia-Lymphoma, Adult T-Cell -- etiology KW - Repressor Proteins -- physiology KW - Humans KW - Binding, Competitive KW - Nuclear Proteins -- metabolism KW - Signal Transduction KW - Trans-Activators -- metabolism KW - Transforming Growth Factor beta -- physiology KW - DNA-Binding Proteins -- chemistry KW - Trans-Activators -- chemistry KW - DNA-Binding Proteins -- antagonists & inhibitors KW - Trans-Activators -- antagonists & inhibitors KW - Gene Products, tax -- physiology KW - Transforming Growth Factor beta -- antagonists & inhibitors KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72068556?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Human+T-cell+lymphotropic+virus+type+1+tax+inhibits+transforming+growth+factor-beta+signaling+by+blocking+the+association+of+Smad+proteins+with+Smad-binding+element.&rft.au=Lee%2C+Dug+Keun%3BKim%2C+Byung-Chul%3BBrady%2C+John+N%3BJeang%2C+Kuan-Teh%3BKim%2C+Seong-Jin&rft.aulast=Lee&rft.aufirst=Dug&rft.date=2002-09-13&rft.volume=277&rft.issue=37&rft.spage=33766&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 - 2002-12-03 N1 - Date created - 2002-09-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increased affinity and stability of an anti-HIV-1 envelope immunotoxin by structure-based mutagenesis. AN - 72065338; 12119300 AB - HIV-infected cells are selectively killed by an immunotoxin in which a truncated form of Pseudomonas exotoxin A is joined to the variable region of a broadly neutralizing antibody (3B3) that recognizes the viral envelope glycoprotein (Env). To improve the efficacy of this molecule, we used three-dimensional structural information and phage selection data to design 23 single and multiple point mutations in the antibody variable region sequences that contact Env. Substituting an aromatic residue for an aspartate in the third complementarity-determining region of V(H) increased the potency of the immunotoxin by approximately 10-fold in a cell-killing assay. Detailed analysis of one such mutant, N31H/Q100eY, revealed both a higher affinity for monomeric and cell surface Env and an increased stability against aggregation compared with the starting immunotoxin. Conversion to a disulfide-linked two-chain format further stabilized the protein. N31H/Q100eY retained the ability to bind to Env from multiple viral isolates, to inhibit Env-mediated cell fusion, and to limit spreading viral infection in peripheral blood mononuclear cells. Such site-directed mutants may increase the utility of immunotoxins for reducing or eradicating persistent HIV-1 infection in humans. JF - The Journal of biological chemistry AU - McHugh, Louise AU - Hu, Stella AU - Lee, B K AU - Santora, Kenneth AU - Kennedy, Paul E AU - Berger, Edward A AU - Pastan, Ira AU - Hamer, Dean H AD - Laboratory of Biochemistry, National Cancer Institute/National Institutes of Health, 37 Convent Drive, Bethesda, MD 20892, USA. Y1 - 2002/09/13/ PY - 2002 DA - 2002 Sep 13 SP - 34383 EP - 34390 VL - 277 IS - 37 SN - 0021-9258, 0021-9258 KW - Anti-HIV Agents KW - 0 KW - Bacterial Toxins KW - Exotoxins KW - HIV Envelope Protein gp120 KW - Immunotoxins KW - Viral Envelope 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 - Membrane Fusion KW - Humans KW - HIV Envelope Protein gp120 -- metabolism KW - Structure-Activity Relationship KW - Mutagenesis KW - Anti-HIV Agents -- chemistry KW - Virulence Factors -- chemistry KW - Exotoxins -- chemistry KW - Immunotoxins -- metabolism KW - Immunotoxins -- chemistry KW - ADP Ribose Transferases -- chemistry KW - Bacterial Toxins -- metabolism KW - Viral Envelope Proteins -- chemistry KW - Virulence Factors -- metabolism KW - ADP Ribose Transferases -- metabolism KW - Exotoxins -- metabolism KW - Bacterial Toxins -- chemistry KW - Viral Envelope Proteins -- metabolism KW - HIV-1 -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72065338?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Increased+affinity+and+stability+of+an+anti-HIV-1+envelope+immunotoxin+by+structure-based+mutagenesis.&rft.au=McHugh%2C+Louise%3BHu%2C+Stella%3BLee%2C+B+K%3BSantora%2C+Kenneth%3BKennedy%2C+Paul+E%3BBerger%2C+Edward+A%3BPastan%2C+Ira%3BHamer%2C+Dean+H&rft.aulast=McHugh&rft.aufirst=Louise&rft.date=2002-09-13&rft.volume=277&rft.issue=37&rft.spage=34383&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 - 2002-12-03 N1 - Date created - 2002-09-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of mercury vapor exposure on metallothionein and glutathione s-transferase gene expression in the kidney of nonpregnant, pregnant, and neonatal rats. AN - 71985288; 12167210 AB - Elemental mercury (Hg(0)) is a ubiquitous toxic pollutant. Exposure to Hg(0) vapor typically is by inhalation, and the kidney is the primary target organ. Glutathione (GSH) and metallothionein (MT) appear to mitigate mercury toxicity. However, little is known about GSH or MT regulation after Hg(0) vapor exposure, particularly during pregnancy, a time of high sensitivity to most metals. Thus, this study sought to determine renal mercury accumulation and MT- and GSH-related gene expression following Hg(0) vapor exposure in nonpregnant, pregnant, and neonatal rats exposed in utero. Groups (n = 5) of pregnant rats (Long-Evans) were exposed to Hg(0) vapor (4 mg/m(3)) or air (control) for 2 h/d from gestational day (GD) 6 to 15, and kidneys from dams and pups were removed at various times during and after the onset of exposure. For comparative purposes, nonpregnant female rats were exposed to Hg(0) for 10 d under the same conditions. Renal mercury, MT protein, and GST activity were assayed by standard analytical techniques. Western blot analysis was also performed using antibodies against MT and GST-pi. GSH-related gene expression was studied by cDNA microarray. Hg(0) vapor exposure produced renal accumulation of mercury in nonpregnant, pregnant, and neonatal rats. However, the transplacentally exposed neonates accumulated approximately 1000-fold less mercury than adults. Hg(0) vapor exposure produced a time-dependent increase in renal MT protein in nonpregnant and pregnant rats, but not in neonatal rats. Maximum MT increases were observed on d 10 (fivefold) in nonpregnant and GD 15 (threefold) in pregnant rats. Activation of the MT gene by Hg(0) was confirmed at the translational level by Western blot analysis and at the transcriptional level by Northern blot analysis. Microarray analysis revealed a significant upregulation in the renal expression of the GST-pi, GST-Ya, and microsomal GST and GST5-5 genes in nonpregnant and pregnant rats. Western blot and enzyme assay confirmed the upregulation of GST genes after Hg(0) exposure. Thus, in response to Hg(0) vapor exposure, the expression of the MT gene and various GST genes is activated in nonpregnant and pregnant rats. Activation of these genes could be part of a defensive response directed at decreasing renal mercury toxicity, and may help divert the metal away from the fetus. JF - Journal of toxicology and environmental health. Part A AU - Brambila, Eduardo AU - Liu, Jie AU - Morgan, Daniel L AU - Beliles, Robert P AU - Waalkes, Michael P AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2002/09/13/ PY - 2002 DA - 2002 Sep 13 SP - 1273 EP - 1288 VL - 65 IS - 17 SN - 1528-7394, 1528-7394 KW - Metallothionein KW - 9038-94-2 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Mercury KW - FXS1BY2PGL KW - Index Medicus KW - Rats KW - Animals KW - Blotting, Western KW - Rats, Long-Evans KW - Blotting, Northern KW - Oligonucleotide Array Sequence Analysis KW - Administration, Inhalation KW - Female KW - Pregnancy KW - Kidney -- metabolism KW - Metallothionein -- biosynthesis KW - Mercury -- metabolism KW - Gene Expression Regulation, Enzymologic -- genetics KW - Glutathione Transferase -- biosynthesis KW - Kidney -- enzymology KW - Metallothionein -- genetics KW - Glutathione Transferase -- genetics KW - Mercury -- toxicity KW - Animals, Newborn -- physiology KW - Pregnancy, Animal -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71985288?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+toxicology+and+environmental+health.+Part+A&rft.atitle=Effect+of+mercury+vapor+exposure+on+metallothionein+and+glutathione+s-transferase+gene+expression+in+the+kidney+of+nonpregnant%2C+pregnant%2C+and+neonatal+rats.&rft.au=Brambila%2C+Eduardo%3BLiu%2C+Jie%3BMorgan%2C+Daniel+L%3BBeliles%2C+Robert+P%3BWaalkes%2C+Michael+P&rft.aulast=Brambila&rft.aufirst=Eduardo&rft.date=2002-09-13&rft.volume=65&rft.issue=17&rft.spage=1273&rft.isbn=&rft.btitle=&rft.title=Journal+of+toxicology+and+environmental+health.+Part+A&rft.issn=15287394&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-09-19 N1 - Date created - 2002-08-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structures of the Complexes of a Potent Anti-HIV Protein Cyanovirin-N and High Mannose Oligosaccharides AN - 18484809; 5450448 AB - The development of anti-human immunodeficiency virus (HIV) microbicides for either topical or ex vivo use is of considerable interest, mainly due to the difficulties in creating a vaccine that would be active against multiple clades of HIV. Cyanovirin-N (CV-N), an 11-kDa protein from the cyanobacterium (blue-green algae) Nostoc ellipsosporum with potent virucidal activity, was identified in the search for such antiviral agents. The binding of CV-N to the heavily glycosylated HIV envelope protein gp120 is carbohydrate-dependent. Since previous CV-N-dimannose structures could not fully explain CV-N-oligomannose binding, we determined the crystal structures of recombinant CV-N complexed to Man-9 and a synthetic hexamannoside, at 2.5- and 2.4-Aa resolution, respectively. CV-N is a three-dimensional domain-swapped dimer in the crystal structures with two primary sites near the hinge region and two secondary sites on the opposite ends of the dimer. The binding interface is constituted of three stacked [alpha]1[right-arrow]2-linked mannose rings for Man-9 and two stacked mannose rings for hexamannoside with the rest of the saccharide molecules pointing to the solution. These structures show unequivocally the binding geometry of high mannose sugars to CV-N, permitting a better understanding of carbohydrate binding to this potential new lead for the design of drugs against AIDS. JF - Journal of Biological Chemistry AU - Botos, I AU - O'Keefe, B R AU - Shenoy AU - Cartner, L K AU - Ratner, D M AU - Seeberger, PH AU - Boyd, M R AU - Wlodawer, A AD - Macromolecular Crystallography Laboratory, NCI, National Institutes of Health, Frederick, Maryland 21702-1201, wlodawer@ncifcrf.gov. Y1 - 2002/09/13/ PY - 2002 DA - 2002 Sep 13 SP - 34336 EP - 34342 VL - 277 IS - 37 SN - 0021-9258, 0021-9258 KW - HIV KW - cyanovirin-N KW - oligosaccharides KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; ASFA Marine Biotechnology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology KW - A 01068:Antiviral & viricidal KW - Q4 27380:Pharmaceuticals KW - V 22100:Antiviral agents KW - W3 33372:Antiviral agents KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18484809?accountid=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=Structures+of+the+Complexes+of+a+Potent+Anti-HIV+Protein+Cyanovirin-N+and+High+Mannose+Oligosaccharides&rft.au=Botos%2C+I%3BO%27Keefe%2C+B+R%3BShenoy%3BCartner%2C+L+K%3BRatner%2C+D+M%3BSeeberger%2C+PH%3BBoyd%2C+M+R%3BWlodawer%2C+A&rft.aulast=Botos&rft.aufirst=I&rft.date=2002-09-13&rft.volume=277&rft.issue=37&rft.spage=34336&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 - A Photoactivatable GFP for Selective Photolabeling of Proteins and Cells AN - 18478073; 5448845 AB - We report a photoactivatable variant of the Aequorea victoria green fluorescent protein (GFP) that, after intense irradiation with 413-nanometer light, increases fluorescence 100 times when excited by 488-nanometer light and remains stable for days under aerobic conditions. These characteristics offer a new tool for exploring intracellular protein dynamics by tracking photoactivated molecules that are the only visible GFPs in the cell. Here, we use the photoactivatable GFP both as a free protein to measure protein diffusion across the nuclear envelope and as a chimera with a lysosomal membrane protein to demonstrate rapid interlysosomal membrane exchange. JF - Science (Washington) AU - Patterson, G H AU - Lippincott-Schwartz, J AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA, jlippin@helix.nih.gov Y1 - 2002/09/13/ PY - 2002 DA - 2002 Sep 13 SP - 1873 EP - 1877 PB - American Association for the Advancement of Science VL - 297 IS - 5588 SN - 0036-8075, 0036-8075 KW - photolabeling KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33340:Other proteins, peptides, amino acids KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18478073?accountid=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=A+Photoactivatable+GFP+for+Selective+Photolabeling+of+Proteins+and+Cells&rft.au=Patterson%2C+G+H%3BLippincott-Schwartz%2C+J&rft.aulast=Patterson&rft.aufirst=G&rft.date=2002-09-13&rft.volume=297&rft.issue=5588&rft.spage=1873&rft.isbn=&rft.btitle=&rft.title=Science+%28Washington%29&rft.issn=00368075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Restoring the addicted brain. AN - 72087953; 12226158 JF - The New England journal of medicine AU - Goldman, David AU - Barr, Christina S AD - National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20852, USA. Y1 - 2002/09/12/ PY - 2002 DA - 2002 Sep 12 SP - 843 EP - 845 VL - 347 IS - 11 KW - Corticotropin-Releasing Hormone KW - 9015-71-8 KW - Abridged Index Medicus KW - Index Medicus KW - Substance-Related Disorders -- physiopathology KW - Models, Animal KW - Animals KW - Humans KW - Mice KW - Substance-Related Disorders -- rehabilitation KW - Substance-Related Disorders -- genetics KW - Corticotropin-Releasing Hormone -- metabolism KW - Stress, Physiological -- physiopathology KW - Brain -- physiopathology KW - Alcohol-Related Disorders -- physiopathology KW - Alcohol-Related Disorders -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72087953?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Restoring+the+addicted+brain.&rft.au=Goldman%2C+David%3BBarr%2C+Christina+S&rft.aulast=Goldman&rft.aufirst=David&rft.date=2002-09-12&rft.volume=347&rft.issue=11&rft.spage=843&rft.isbn=&rft.btitle=&rft.title=The+New+England+journal+of+medicine&rft.issn=1533-4406&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-09-19 N1 - Date created - 2002-09-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Purification and some properties of phospho- beta -galactosidase from the Gram-negative oral bacterium Leptotrichia buccalis ATCC 14201 AN - 18490735; 5455547 AB - Phospho- beta -galactosidase (P- beta -gal; EC 3.2.1.85) is induced during growth of Leptotrichia buccalis ATCC 14201 on lactose and lactulose. The enzyme has been purified to electrophoretic homogeneity (Mr 53 kDa, pI 4.8), and kinetic parameters have been determined using the chromogenic analog o-nitrophenyl- beta -D-galactopyranoside-6-phosphate as substrate. Both ATP and galactose-6-phosphate are inhibitors of P- beta -gal activity. Microsequence analysis has identified the first 32 residues from the N-terminus of the protein, and by comparative sequence alignment the enzyme can be assigned to Family 1 of the glycosylhydrolase superfamily. Polyclonal antibody against the enzyme permits the highly specific immuno-detection of P- beta -gal in cell-free extracts of L. buccalis. Although described previously in several Gram-positive species, this is the first reported purification of P- beta -gal from a Gram-negative organism. JF - FEMS Microbiology Letters AU - Thompson, J AD - Microbial Biochemistry and Genetics Unit, Oral Infection and Immunity Branch, NIDCR, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 2002/09/10/ PY - 2002 DA - 2002 Sep 10 SP - 183 EP - 188 PB - Federation of European Microbiological Societies VL - 214 IS - 2 SN - 0378-1097, 0378-1097 KW - Microbiology Abstracts B: Bacteriology KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18490735?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FEMS+Microbiology+Letters&rft.atitle=Purification+and+some+properties+of+phospho-+beta+-galactosidase+from+the+Gram-negative+oral+bacterium+Leptotrichia+buccalis+ATCC+14201&rft.au=Thompson%2C+J&rft.aulast=Thompson&rft.aufirst=J&rft.date=2002-09-10&rft.volume=214&rft.issue=2&rft.spage=183&rft.isbn=&rft.btitle=&rft.title=FEMS+Microbiology+Letters&rft.issn=03781097&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Genetic analysis of GalR tetramerization in DNA looping during repressosome assembly. AN - 72052969; 12065579 AB - The Gal repressosome is a nucleoprotein complex consisting of 2 GalR dimers, 1 HU, and 1 DNA loop, which represses the transcription of the gal operon. We have adopted a structure-based genetic approach to complement ongoing physical studies of the complex. Homology-based and subsequent alanine-scanning mutageneses suggest that five residues in the DNA-distal subdomain of GalR dimer are important for repressosome formation. A further analysis of these and intragenic suppressors of looping-defective GalR mutants as well as gain-of-function mutants that permit repressosome assembly in the absence of HU show that GalR dimers contact each other in the repressosome in a partially stacked configuration. JF - The Journal of biological chemistry AU - Geanacopoulos, Mark AU - Adhya, Sankar AD - Laboratory of Molecular Biology, NCI, National Institutes of Health, Bethesda, Maryland 20892-4264, USA. Y1 - 2002/09/06/ PY - 2002 DA - 2002 Sep 06 SP - 33148 EP - 33152 VL - 277 IS - 36 SN - 0021-9258, 0021-9258 KW - Escherichia coli Proteins KW - 0 KW - Galactose repressor proteins KW - Repressor Proteins KW - DNA KW - 9007-49-2 KW - Alanine KW - OF5P57N2ZX KW - Index Medicus KW - Plasmids -- metabolism KW - Escherichia coli -- metabolism KW - Models, Molecular KW - Dimerization KW - Transcription, Genetic KW - Alanine -- chemistry KW - Nucleic Acid Conformation KW - Mutagenesis KW - Mutagenesis, Site-Directed KW - Promoter Regions, Genetic KW - Alleles KW - Models, Genetic KW - DNA -- chemistry KW - Mutation KW - Protein Conformation KW - Repressor Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72052969?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Genetic+analysis+of+GalR+tetramerization+in+DNA+looping+during+repressosome+assembly.&rft.au=Geanacopoulos%2C+Mark%3BAdhya%2C+Sankar&rft.aulast=Geanacopoulos&rft.aufirst=Mark&rft.date=2002-09-06&rft.volume=277&rft.issue=36&rft.spage=33148&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 - 2002-10-29 N1 - Date created - 2002-09-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An adjacent pair of human NUDT genes on chromosome X are preferentially expressed in testis and encode two new isoforms of diphosphoinositol polyphosphate phosphohydrolase. AN - 72041815; 12105228 AB - Combinatorial expression of the various isoforms of diphosphoinositol synthases and phosphohydrolases determines the rates of phosphorylation/dephosphorylation cycles that have been functionally linked to vesicle trafficking, stress responses, DNA repair, and apoptosis. We now describe two new 19-kDa diphosphoinositol polyphosphate phosphohydrolases (DIPPs), named types 3alpha and 3beta, which possess the canonical Nudix-type catalytic motif flanked on either side by short Gly-rich sequences. The two enzymes differ only in that Pro-89 in the alpha form is replaced by Arg-89 in the beta form, making the latter approximately 2-fold more active in vitro. Another Nudix substrate, diadenosine hexaphosphate, was hydrolyzed less efficiently (k(cat)/K(m) = 0.2 x 10(5) m(-1) s(-1)) compared with diphosphoinositol polyphosphates (k(cat)/K(m) = 2-40 x 10(5) m(-1) s(-1)). Catalytic activity in vivo was established by individual overexpression of the human (h) DIPP3 isoforms in HEK293 cells, which reduced cellular levels of diphosphoinositol polyphosphates by 40-50%. The hDIPP3 mRNA is preferentially expressed in testis, accompanied by relatively weak expression in the brain, contrasting with hDIPP1 and hDIPP2 which are widely expressed. The hDIPP3 genes (NUDT10 encodes hDIPP3alpha; NUDT11 encodes hDIPP3beta) are only 152 kbp apart at p11.22 on chromosome X and probably arose by duplication. Transcription of both genes is inactivated on one of the X chromosomes of human females to maintain appropriate gene dosage. The hDIPP3 pair add tissue-specific diversity to the molecular mechanisms regulating diphosphoinositol polyphosphate turnover. JF - The Journal of biological chemistry AU - Hidaka, Kiyoshi AU - Caffrey, James J AU - Hua, Len AU - Zhang, Tong AU - Falck, J R AU - Nickel, Gabrielle C AU - Carrel, Laura AU - Barnes, Larry D AU - Shears, Stephen B AD - Inositide Signaling Section, Laboratory of Signal Transduction, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2002/09/06/ PY - 2002 DA - 2002 Sep 06 SP - 32730 EP - 32738 VL - 277 IS - 36 SN - 0021-9258, 0021-9258 KW - DNA, Complementary KW - 0 KW - Protein Isoforms KW - RNA, Messenger KW - Recombinant Proteins KW - Acid Anhydride Hydrolases KW - EC 3.6.- KW - diphosphoinositol polyphosphate phosphohydrolase KW - EC 3.6.1.- KW - Index Medicus KW - Immunoblotting KW - Blotting, Northern KW - Protein Isoforms -- metabolism KW - Humans KW - Amino Acid Sequence KW - Tissue Distribution KW - Sequence Analysis, DNA KW - Mutagenesis, Site-Directed KW - Blotting, Western KW - RNA, Messenger -- metabolism KW - Recombinant Proteins -- metabolism KW - DNA, Complementary -- metabolism KW - Kinetics KW - Models, Genetic KW - Molecular Sequence Data KW - Substrate Specificity KW - Sequence Homology, Amino Acid KW - Protein Isoforms -- genetics KW - Cell Line KW - Male KW - Catalysis KW - X Chromosome KW - Acid Anhydride Hydrolases -- chemistry KW - Testis -- enzymology KW - Acid Anhydride Hydrolases -- genetics KW - Acid Anhydride Hydrolases -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72041815?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=An+adjacent+pair+of+human+NUDT+genes+on+chromosome+X+are+preferentially+expressed+in+testis+and+encode+two+new+isoforms+of+diphosphoinositol+polyphosphate+phosphohydrolase.&rft.au=Hidaka%2C+Kiyoshi%3BCaffrey%2C+James+J%3BHua%2C+Len%3BZhang%2C+Tong%3BFalck%2C+J+R%3BNickel%2C+Gabrielle+C%3BCarrel%2C+Laura%3BBarnes%2C+Larry+D%3BShears%2C+Stephen+B&rft.aulast=Hidaka&rft.aufirst=Kiyoshi&rft.date=2002-09-06&rft.volume=277&rft.issue=36&rft.spage=32730&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 - 2002-10-29 N1 - Date created - 2002-09-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Raloxifene, a mixed estrogen agonist/antagonist, induces apoptosis through cleavage of BAD in TSU-PR1 human cancer cells. AN - 72041602; 12084714 AB - Selective estrogen receptor modulator is a proven agent for chemoprevention and chemotherapy of cancer. Raloxifene, a mixed estrogen agonist/antagonist, was developed to prevent osteoporosis and potentially reduce the risk of breast cancer. In this study, we examined the effect of raloxifene on the TSU-PR1 cell line. This cell line was originally reported to be a prostate cancer cell line, but recently it has been shown to be a human bladder transitional cell carcinoma cell line. The TSU-PR1 cell line contains high levels of estrogen receptor beta. Following treatment with raloxifene, evidence of apoptosis, including change in nuclear morphology, DNA fragmentation, and cytochrome c release, was observed in a dose-dependent manner in the TSU-PR1 cells (10(-9) to 10(-6) m range). We observed no detectable change in the steady-state levels of Bax, Bcl-2, and Bcl-X(L) following raloxifene treatment. However, raloxifene induced caspase-dependent cleavage of BAD to generate a 15-kDa truncated protein. Overexpression of a double mutant BAD resistant to caspase 3 cleavage blocked raloxifene-induced apoptosis. These results demonstrate that raloxifene induces apoptosis through the cleavage of BAD in TSU-PR1 cells. This molecular mechanism of apoptosis suggests that raloxifene may be a therapeutic agent for human bladder cancer. JF - The Journal of biological chemistry AU - Kim, Heung Tae AU - Kim, Byung Chul AU - Kim, Isaac Yi AU - Mamura, Mizuko AU - Seong, Do Hwan AU - Jang, Ja-June AU - Kim, Seong-Jin AD - Laboratory of Cell Regulation and Carcinogenesis, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/09/06/ PY - 2002 DA - 2002 Sep 06 SP - 32510 EP - 32515 VL - 277 IS - 36 SN - 0021-9258, 0021-9258 KW - Amino Acid Chloromethyl Ketones KW - 0 KW - Antineoplastic Agents KW - BAD protein, human KW - BCL2L1 protein, human KW - Carrier Proteins KW - Cytochrome c Group KW - Estrogen Receptor Modulators KW - Protein Synthesis Inhibitors KW - Proto-Oncogene Proteins c-bcl-2 KW - bcl-Associated Death Protein KW - bcl-X Protein KW - benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone KW - Raloxifene Hydrochloride KW - 4F86W47BR6 KW - Cycloheximide KW - 98600C0908 KW - CASP3 protein, human KW - EC 3.4.22.- KW - Caspase 3 KW - Caspases KW - Index Medicus KW - Retroviridae -- metabolism KW - Cell Nucleus -- pathology KW - Dose-Response Relationship, Drug KW - Humans KW - Protein Binding KW - Caspases -- metabolism KW - In Situ Nick-End Labeling KW - Tumor Cells, Cultured KW - Protein Synthesis Inhibitors -- pharmacology KW - Phosphorylation KW - Cycloheximide -- pharmacology KW - Proto-Oncogene Proteins c-bcl-2 -- metabolism KW - Mitochondria -- metabolism KW - Membrane Potentials KW - Cell Membrane -- metabolism KW - Amino Acid Chloromethyl Ketones -- pharmacology KW - Cytochrome c Group -- metabolism KW - Time Factors KW - DNA Fragmentation KW - Cell Division KW - Urinary Bladder Neoplasms -- pathology KW - Carrier Proteins -- metabolism KW - Apoptosis KW - Raloxifene Hydrochloride -- pharmacology KW - Urinary Bladder Neoplasms -- metabolism KW - Antineoplastic Agents -- pharmacology KW - Estrogen Receptor Modulators -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72041602?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Raloxifene%2C+a+mixed+estrogen+agonist%2Fantagonist%2C+induces+apoptosis+through+cleavage+of+BAD+in+TSU-PR1+human+cancer+cells.&rft.au=Kim%2C+Heung+Tae%3BKim%2C+Byung+Chul%3BKim%2C+Isaac+Yi%3BMamura%2C+Mizuko%3BSeong%2C+Do+Hwan%3BJang%2C+Ja-June%3BKim%2C+Seong-Jin&rft.aulast=Kim&rft.aufirst=Heung&rft.date=2002-09-06&rft.volume=277&rft.issue=36&rft.spage=32510&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 - 2002-10-29 N1 - Date created - 2002-09-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dietary sugar, glycemic load, and pancreatic cancer risk in a prospective study. AN - 72058722; 12208894 AB - Evidence from both animal and human studies suggests that abnormal glucose metabolism plays an important role in pancreatic carcinogenesis. We investigated whether diets high in foods that increase postprandial glucose levels are associated with an increased risk of pancreatic cancer. In a cohort of U.S. women (n = 88 802) participating in the Nurses' Health Study, 180 case subjects with pancreatic cancer were diagnosed during 18 years of follow-up. We used frequency of intake of individual foods as reported on a food-frequency questionnaire in 1980 to calculate sucrose, fructose, and carbohydrate intakes; glycemic index (postprandial blood glucose response as compared with a reference food); and glycemic load (glycemic index multiplied by carbohydrate content). Analyses of relative risk (RR) were performed by using multivariable Cox proportional hazards models to adjust for potential confounders. All statistical tests were two-sided. Carbohydrate and sucrose intake were not associated with overall pancreatic cancer risk in this cohort. A statistically nonsignificant 53% increase in risk of pancreatic cancer (RR = 1.53, 95% confidence interval [CI] = 0.96 to 2.45) was observed among women with a high glycemic load intake, and a similar association was observed for fructose intake (RR = 1.57, 95% CI = 0.95 to 2.57). The associations of glycemic load and fructose intakes with pancreatic cancer risk were most apparent among women with elevated body mass index (>or=25 kg/m(2)) or with low physical activity. Among women who were both overweight and sedentary, a high glycemic load was associated with an RR of 2.67 (95% CI = 1.02 to 6.99; highest versus lowest quartile of intake; P for trend =.03), and high fructose was associated with an RR of 3.17 (95% CI = 1.13 to 8.91; P for trend =.04). Our data support other findings that impaired glucose metabolism may play a role in pancreatic cancer etiology. A diet high in glycemic load may increase the risk of pancreatic cancer in women who already have an underlying degree of insulin resistance. JF - Journal of the National Cancer Institute AU - Michaud, Dominique S AU - Liu, Simin AU - Giovannucci, Edward AU - Willett, Walter C AU - Colditz, Graham A AU - Fuchs, Charles S AD - Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20852, USA. michaudd@mail.nih.gov Y1 - 2002/09/04/ PY - 2002 DA - 2002 Sep 04 SP - 1293 EP - 1300 VL - 94 IS - 17 SN - 0027-8874, 0027-8874 KW - Blood Glucose KW - 0 KW - Dietary Sucrose KW - Index Medicus KW - Prospective Studies KW - Nutrition Assessment KW - Risk Factors KW - Humans KW - Cohort Studies KW - Adult KW - Surveys and Questionnaires KW - Middle Aged KW - Follow-Up Studies KW - Body Mass Index KW - Feeding Behavior KW - United States -- epidemiology KW - Female KW - Dietary Sucrose -- administration & dosage KW - Pancreatic Neoplasms -- blood KW - Blood Glucose -- metabolism KW - Pancreatic Neoplasms -- epidemiology KW - Pancreatic Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72058722?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Dietary+sugar%2C+glycemic+load%2C+and+pancreatic+cancer+risk+in+a+prospective+study.&rft.au=Michaud%2C+Dominique+S%3BLiu%2C+Simin%3BGiovannucci%2C+Edward%3BWillett%2C+Walter+C%3BColditz%2C+Graham+A%3BFuchs%2C+Charles+S&rft.aulast=Michaud&rft.aufirst=Dominique&rft.date=2002-09-04&rft.volume=94&rft.issue=17&rft.spage=1293&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 - 2002-09-30 N1 - Date created - 2002-09-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Guidelines for using antiretroviral agents among HIV-infected adults and adolescents. AN - 72853217; 12617573 AB - The availability of an increasing number of antiretroviral agents and the rapid evolution of new information have introduced substantial complexity into treatment regimens for persons infected with human immunodeficiency virus (HIV). In 1996, the Department of Health and Human Services and the Henry J. Kaiser Family Foundation convened the Panel on Clinical Practices for the Treatment of HIV to develop guidelines for clinical management of HIV-infected adults and adolescents (CDC. Report of the NIH Panel To Define Principles of Therapy of HIV Infection and Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. MMWR. 1998;47[RR-5]:1-41). This report, which updates the 1998 guidelines, addresses 1) using testing for plasma HIV ribonucleic acid levels (i.e., viral load) and CD4+ T cell count; 2) using testing for antiretroviral drug resistance; 3) considerations for when to initiate therapy; 4) adherence to antiretroviral therapy; 5) considerations for therapy among patients with advanced disease; 6) therapy-related adverse events; 7) interruption of therapy; 8) considerations for changing therapy and available therapeutic options; 9) treatment for acute HIV infection; 10) considerations for antiretroviral therapy among adolescents; 11) considerations for antiretroviral therapy among pregnant women; and 12) concerns related to transmission of HIV to others. Antiretroviral regimens are complex, have serious side effects, pose difficulty with adherence, and carry serious potential consequences from the development of viral resistance because of nonadherence to the drug regimen or suboptimal levels of antiretroviral agents. Patient education and involvement in therapeutic decisions are critical. Treatment should usually be offered to all patients with symptoms ascribed to HIV infection. Recommendations for offering antiretroviral therapy among asymptomatic patients require analysis of real and potential risks and benefits. In general, treatment should be offered to persons who have 55,000 copies/mL (by b-deoxyribonucleic acid [bDNA] or reverse transcriptase-polymerase chain reaction [RT-PCR] assays). The recommendation to treat asymptomatic patients should be based on the willingness and readiness of the person to begin therapy; the degree of existing immunodeficiency as determined by the CD4+ T cell count; the risk for disease progression as determined by the CD4+ T cell count and level of plasma HIV RNA; the potential benefits and risks of initiating therapy in an asymptomatic person; and the likelihood, after counseling and education, of adherence to the prescribed treatment regimen. Treatment goals should be maximal and durable suppression of viral load, restoration and preservation of immunologic function, improvement of quality of life, and reduction of HIV-related morbidity and mortality. Results of therapy are evaluated through plasma HIV RNA levels, which are expected to indicate a 1.0 log10 decrease at 2-8 weeks and no detectable virus (<50 copies/mL) at 4-6 months after treatment initiation. Failure of therapy at 4-6 months might be ascribed to nonadherence, inadequate potency of drugs or suboptimal levels of antiretroviral agents, viral resistance, and other factors that are poorly understood. Patients whose therapy fails in spite of a high level of adherence to the regimen should have their regimen changed; this change should be guided by a thorough drug treatment history and the results of drug-resistance testing. Because of limitations in the available alternative antiretroviral regimens that have documented efficacy, optimal changes in therapy might be difficult to achieve for patients in whom the preferred regimen has failed. These decisions are further confounded by problems with adherence, toxicity, and resistance. For certain patients, participating in a clinical trial with or without access to new drugs or using a regimen that might not achieve complete suppression of viral replicatioing a regimen that might not achieve complete suppression of viral replication might be preferable. Because concepts regarding HIV management are evolving rapidly, readers should check regularly for additional information and updates at the HIV/AIDS Treatment Information Service website ( http://www.hivatis.org ). JF - Annals of internal medicine AU - Dybul, Mark AU - Fauci, Anthony S AU - Bartlett, John G AU - Kaplan, Jonathan E AU - Pau, Alice K AU - Panel on Clinical Practices for Treatment of HIV AD - National Institutes of Health, Bethesda, Maryland, USA. ; Panel on Clinical Practices for Treatment of HIV Y1 - 2002/09/03/ PY - 2002 DA - 2002 Sep 03 SP - 381 EP - 433 VL - 137 IS - 5 Pt 2 KW - Anti-HIV Agents KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Viral Load KW - Drug Resistance, Viral KW - Patient Compliance KW - Humans KW - Adult KW - Counseling KW - CD4 Lymphocyte Count KW - Adolescent KW - Pregnancy Complications, Infectious -- drug therapy KW - Male KW - Female KW - Pregnancy KW - Antiretroviral Therapy, Highly Active -- adverse effects KW - Antiretroviral Therapy, Highly Active -- standards KW - Anti-HIV Agents -- therapeutic use KW - HIV Infections -- immunology KW - HIV Infections -- drug therapy KW - Anti-HIV Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72853217?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Guidelines+for+using+antiretroviral+agents+among+HIV-infected+adults+and+adolescents.&rft.au=Dybul%2C+Mark%3BFauci%2C+Anthony+S%3BBartlett%2C+John+G%3BKaplan%2C+Jonathan+E%3BPau%2C+Alice+K%3BPanel+on+Clinical+Practices+for+Treatment+of+HIV&rft.aulast=Dybul&rft.aufirst=Mark&rft.date=2002-09-03&rft.volume=137&rft.issue=5+Pt+2&rft.spage=381&rft.isbn=&rft.btitle=&rft.title=Annals+of+internal+medicine&rft.issn=1539-3704&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-05 N1 - Date created - 2003-03-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Guidelines for preventing opportunistic infections among HIV-infected persons--2002. Recommendations of the U.S. Public Health Service and the Infectious Diseases Society of America. AN - 72851529; 12617574 AB - In 1995, the U.S. Public Health Service (USPHS) and the Infectious Diseases Society of America (IDSA) developed guidelines for preventing opportunistic infections (OIs) among persons infected with human immunodeficiency virus (HIV); these guidelines were updated in 1997 and 1999. This fourth edition of the guidelines, made available on the Internet in 2001, is intended for clinicians and other health-care providers who care for HIV-infected persons. The goal of these guidelines is to provide evidence-based guidelines for preventing OIs among HIV-infected adults and adolescents, including pregnant women, and HIV-exposed or infected children. Nineteen OIs, or groups of OIs, are addressed, and recommendations are included for preventing exposure to opportunistic pathogens, preventing first episodes of disease by chemoprophylaxis or vaccination (primary prophylaxis), and preventing disease recurrence (secondary prophylaxis). Major changes since the last edition of the guidelines include 1) updated recommendations for discontinuing primary and secondary OI prophylaxis among persons whose CD4+ T lymphocyte counts have increased in response to antiretroviral therapy; 2) emphasis on screening all HIV-infected persons for infection with hepatitis C virus; 3) new information regarding transmission of human herpesvirus 8 infection; 4) new information regarding drug interactions, chiefly related to rifamycins and antiretroviral drugs; and 5) revised recommendations for immunizing HIV-infected adults and adolescents and HIV-exposed or infected children. JF - Annals of internal medicine AU - Masur, Henry AU - Kaplan, Jonathan E AU - Holmes, King K AU - U.S. Public Health Service AU - Infectious Diseases Society of America AD - National Institutes of Health, Bethesda, Maryland, USA. ; U.S. Public Health Service ; Infectious Diseases Society of America Y1 - 2002/09/03/ PY - 2002 DA - 2002 Sep 03 SP - 435 EP - 478 VL - 137 IS - 5 Pt 2 KW - Abridged Index Medicus KW - Index Medicus KW - Travel KW - Hepatitis C -- prevention & control KW - Animals KW - Food KW - Humans KW - Chickenpox -- prevention & control KW - Child KW - Cryptococcosis -- prevention & control KW - Occupational Exposure -- prevention & control KW - Sarcoma, Kaposi -- prevention & control KW - Adult KW - Bartonella Infections -- prevention & control KW - Cytomegalovirus Infections -- prevention & control KW - Sexually Transmitted Diseases -- prevention & control KW - Respiratory Tract Infections -- prevention & control KW - Animals, Domestic KW - Herpes Simplex -- prevention & control KW - Toxoplasmosis, Cerebral -- prevention & control KW - Gastrointestinal Diseases -- prevention & control KW - Papillomavirus Infections -- prevention & control KW - Cryptosporidiosis -- prevention & control KW - Tuberculosis -- prevention & control KW - Pneumonia, Pneumocystis -- prevention & control KW - Bacterial Infections -- prevention & control KW - Mycobacterium avium-intracellulare Infection -- prevention & control KW - Candidiasis -- prevention & control KW - Herpes Zoster -- prevention & control KW - Environmental Exposure -- prevention & control KW - Substance Abuse, Intravenous KW - AIDS-Related Opportunistic Infections -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72851529?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Guidelines+for+preventing+opportunistic+infections+among+HIV-infected+persons--2002.+Recommendations+of+the+U.S.+Public+Health+Service+and+the+Infectious+Diseases+Society+of+America.&rft.au=Masur%2C+Henry%3BKaplan%2C+Jonathan+E%3BHolmes%2C+King+K%3BU.S.+Public+Health+Service%3BInfectious+Diseases+Society+of+America&rft.aulast=Masur&rft.aufirst=Henry&rft.date=2002-09-03&rft.volume=137&rft.issue=5+Pt+2&rft.spage=435&rft.isbn=&rft.btitle=&rft.title=Annals+of+internal+medicine&rft.issn=1539-3704&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-05 N1 - Date created - 2003-03-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Salvinorin A: A potent naturally occurring nonnitrogenous mu opioid selective agonist AN - 18486096; 5453600 AB - Salvia divinorum, whose main active ingredient is the neoclerodane diterpene Salvinorin A, is a hallucinogenic plant in the mint family that has been used in traditional spiritual practices for its psychoactive properties by the Mazatecs of Oaxaca, Mexico. More recently, S. divinorum extracts and Salvinorin A have become more widely used in the U.S. as legal hallucinogens. We discovered that Salvinorin A potently and selectively inhibited super(3)H-bremazocine binding to cloned mu opioid receptors. Salvinorin A had no significant activity against a battery of 50 receptors, transporters, and ion channels and showed a distinctive profile compared with the prototypic hallucinogen lysergic acid diethylamide. Functional studies demonstrated that Salvinorin A is a potent mu opioid agonist at cloned mu opioid receptors expressed in human embryonic kidney-293 cells and at native mu opioid receptors expressed in guinea pig brain. Importantly, Salvinorin A had no actions at the 5-HT sub(2A) serotonin receptor, the principal molecular target responsible for the actions of classical hallucinogens. Salvinorin A thus represents, to our knowledge, the first naturally occurring nonnitrogenous opioid-receptor subtype-selective agonist. Because Salvinorin A is a psychotomimetic selective for mu opioid receptors, mu opioid-selective antagonists may represent novel psychotherapeutic compounds for diseases manifested by perceptual distortions (e.g., schizophrenia, dementia, and bipolar disorders). Additionally, these results suggest that [kappa] opioid receptors play a prominent role in the modulation of human perception. JF - Proceedings of the National Academy of Sciences, USA AU - Roth, B L AU - Baner, K AU - Westkaemper, R AU - Siebert, D AU - Rice, K C AU - Steinberg, S AU - Ernsberger, P AU - Rothman, R B AD - NIMH Psychoactive Drug Screening Program, and Departments of Biochemistry, Psychiatry, Neurosciences, and Pharmacology and Nutrition, Case Western Reserve University Medical School, Cleveland, OH 44106, roth@biocserver.cwru.edu Y1 - 2002/09/03/ PY - 2002 DA - 2002 Sep 03 SP - 11934 EP - 11939 VL - 99 IS - 18 SN - 0027-8424, 0027-8424 KW - salvinorin A KW - CSA Neurosciences Abstracts; Toxicology Abstracts KW - N3 11138:Pharmacological correlates KW - X 24172:Plants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18486096?accountid=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=Salvinorin+A%3A+A+potent+naturally+occurring+nonnitrogenous+mu+opioid+selective+agonist&rft.au=Roth%2C+B+L%3BBaner%2C+K%3BWestkaemper%2C+R%3BSiebert%2C+D%3BRice%2C+K+C%3BSteinberg%2C+S%3BErnsberger%2C+P%3BRothman%2C+R+B&rft.aulast=Roth&rft.aufirst=B&rft.date=2002-09-03&rft.volume=99&rft.issue=18&rft.spage=11934&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.182234399 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1073/pnas.182234399 ER - TY - JOUR T1 - Bromotyrosine-derived natural and synthetic products as inhibitors of mycothiol-S-conjugate amidase. AN - 71978509; 12161164 AB - A series of bromotyrosine-derived compounds, including marine natural products and members of a psammaplin A-inspired combinatorial synthetic library, were screened for their ability to inhibit the Mycobacterium tuberculosis detoxification enzyme mycothiol-S-conjugate amidase (MCA). Correlations between the structures and their respective IC(50) values (which range from 3 microM to 2.7 mM) should prove valuable when optimizing more potent inhibitors of MCA. JF - Bioorganic & medicinal chemistry letters AU - Nicholas, Gillian M AU - Eckman, Lisa L AU - Ray, Satyajit AU - Hughes, Robert O AU - Pfefferkorn, Jeffrey A AU - Barluenga, Sofia AU - Nicolaou, K C AU - Bewley, Carole A AD - Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0820, USA. Y1 - 2002/09/02/ PY - 2002 DA - 2002 Sep 02 SP - 2487 EP - 2490 VL - 12 IS - 17 SN - 0960-894X, 0960-894X KW - Anti-Bacterial Agents KW - 0 KW - Enzyme Inhibitors KW - bromotyrosine KW - Tyrosine KW - 42HK56048U KW - Amidohydrolases KW - EC 3.5.- KW - mycothiol S-conjugate amidase KW - EC 3.5.1.- KW - Index Medicus KW - Tyrosine -- chemistry KW - Mycobacterium tuberculosis -- enzymology KW - Anti-Bacterial Agents -- pharmacology KW - Tyrosine -- pharmacology KW - Anti-Bacterial Agents -- chemical synthesis KW - Tyrosine -- analogs & derivatives KW - Inhibitory Concentration 50 KW - Structure-Activity Relationship KW - Enzyme Inhibitors -- pharmacology KW - Enzyme Inhibitors -- chemical synthesis KW - Amidohydrolases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71978509?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioorganic+%26+medicinal+chemistry+letters&rft.atitle=Bromotyrosine-derived+natural+and+synthetic+products+as+inhibitors+of+mycothiol-S-conjugate+amidase.&rft.au=Nicholas%2C+Gillian+M%3BEckman%2C+Lisa+L%3BRay%2C+Satyajit%3BHughes%2C+Robert+O%3BPfefferkorn%2C+Jeffrey+A%3BBarluenga%2C+Sofia%3BNicolaou%2C+K+C%3BBewley%2C+Carole+A&rft.aulast=Nicholas&rft.aufirst=Gillian&rft.date=2002-09-02&rft.volume=12&rft.issue=17&rft.spage=2487&rft.isbn=&rft.btitle=&rft.title=Bioorganic+%26+medicinal+chemistry+letters&rft.issn=0960894X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-31 N1 - Date created - 2002-08-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Early pitch-shift response is active in both steady and dynamic voice pitch control. AN - 85360369; pmid-12243154 AB - When air conducted auditory feedback pitch is experimentally shifted upward or downward during steady phonation, voice pitch changes in response. The first pitch change is an automatic deflection opposite in direction to the feedback shift. It appears to help stabilize voice pitch by counteracting unintended changes. But what happens during an intended pitch change? If the purpose of the first pitch-shift response is to stabilize voice pitch around a fixed target, it should be suppressed during voluntary pitch changes. Alternatively, if the pitch-shift response is a general process of voice control it should be modified during intended pitch changes to bring production in line with the desired output. Auditory feedback pitch was shifted during steady pitch and upward glissando vocalizations by thirty trained singers. Contrary to the "steady-specific" hypothesis, pitch-shift responses occurred during dynamic pitch vocalizations. Responses were comparable in direction, peak time, and slope, but had significantly longer latency and smaller magnitude than responses elicited during steady note phonation. Results indicate that the early pitch-shift response is a general component of voice control that serves to automatically bring phonation pitch into agreement with an intended target, whether that target is constant or changing in time. JF - The Journal of the Acoustical Society of America AU - Burnett, Theresa A AU - Larson, Charles R AD - Department of Communication Disorders, Northwestern University, Evanston, Illinois 60208, USA. burnettt@ninds.nih.gov Y1 - 2002/09// PY - 2002 DA - Sep 2002 SP - 1058 EP - 1063 VL - 112 IS - 3 Pt 1 SN - 0001-4966, 0001-4966 KW - Index Medicus KW - National Library of Medicine KW - Adolescent KW - Adult KW - *Feedback KW - Female KW - Humans KW - Male KW - Music KW - Phonation KW - *Pitch Perception KW - Psychoacoustics KW - *Sound Spectrography KW - Voice Quality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85360369?accountid=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=Early+pitch-shift+response+is+active+in+both+steady+and+dynamic+voice+pitch+control.&rft.au=Burnett%2C+Theresa+A%3BLarson%2C+Charles+R&rft.aulast=Burnett&rft.aufirst=Theresa&rft.date=2002-09-01&rft.volume=112&rft.issue=3+Pt+1&rft.spage=1058&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+the+Acoustical+Society+of+America&rft.issn=00014966&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Developing an anatomical model of the human laryngeal cartilages from magnetic resonance imaging. AN - 85357486; pmid-12243156 AB - The purpose of this work was to construct a three-dimensional anatomical framework of the cartilages of the human larynx. The framework included representative surface models of the four laryngeal cartilages and estimated attachment points for the intrinsic laryngeal muscles. High-resolution magnetic resonance imaging (MRI) was used to scan one female and four male human cadaveric larynges. The cartilages were segmented manually from the MRI volume for analysis. Two of these larynges were subsequently dissected and the landmark distances on the cartilages measured for comparison with the MRI measures and previous studies. The MRI measures were 8% smaller than the anatomical measures and 12% smaller than data reported in the literature. A laryngeal coordinate system was defined using the plane of symmetry of the cricoid cartilage. Measures of cricoid cartilage symmetry had less than 3% difference between the two sides for a series of measures. An algorithm for registering larynges that minimized the root-mean-square distance between the surface of a reference cricoid cartilage and the surfaces of nonisotropically scaled candidate cricoid cartilages was evaluated. This study provided an anatomical framework for registering different larynges to the same coordinate space. JF - The Journal of the Acoustical Society of America AU - Selbie, W Scott AU - Gewalt, Sally L AU - Ludlow, Christy L AD - Laryngeal and Speech Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892-1416, USA. Y1 - 2002/09// PY - 2002 DA - Sep 2002 SP - 1077 EP - 1090 VL - 112 IS - 3 Pt 1 SN - 0001-4966, 0001-4966 KW - Index Medicus KW - National Library of Medicine KW - Aged KW - Algorithms KW - Arytenoid Cartilage: anatomy & histology KW - Cricoid Cartilage: anatomy & histology KW - Female KW - Humans KW - *Image Processing, Computer-Assisted KW - *Imaging, Three-Dimensional KW - *Laryngeal Cartilages: anatomy & histology KW - Laryngeal Muscles: anatomy & histology KW - *Magnetic Resonance Imaging KW - Male KW - *Models, Anatomic KW - Thyroid Cartilage: anatomy & histology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85357486?accountid=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=Developing+an+anatomical+model+of+the+human+laryngeal+cartilages+from+magnetic+resonance+imaging.&rft.au=Selbie%2C+W+Scott%3BGewalt%2C+Sally+L%3BLudlow%2C+Christy+L&rft.aulast=Selbie&rft.aufirst=W&rft.date=2002-09-01&rft.volume=112&rft.issue=3+Pt+1&rft.spage=1077&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+the+Acoustical+Society+of+America&rft.issn=00014966&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Mutations in a novel gene, TMIE, are associated with hearing loss linked to the DFNB6 locus. AN - 85238552; pmid-12145746 AB - We have identified five different homozygous recessive mutations in a novel gene, TMIE (transmembrane inner ear expressed gene), in affected members of consanguineous families segregating severe-to-profound prelingual deafness, consistent with linkage to DFNB6. The mutations include an insertion, a deletion, and three missense mutations, and they indicate that loss of function of TMIE causes hearing loss in humans. TMIE encodes a protein with 156 amino acids and exhibits no significant nucleotide or deduced amino acid sequence similarity to any other gene. JF - American Journal of Human Genetics AU - Naz Sadaf AU - Giguere, Chantal M AU - Kohrman, David C AU - Mitchem, Kristina L AU - Riazuddin Saima AU - Morell, Robert J AU - Arabandi, Ramesh AU - Srisailpathy Srikumari AU - Deshmukh Dilip AU - Sheikh, Riazuddin AU - Griffith, Andrew James AU - Friedman, Thomas B AU - Smith Richard J H AU - Wilcox, Edward R AD - Section on Human Genetics, Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD, 20850, USA.; National Institute on Deafness and Other Communication Disorders PY - 2002 SP - 632 EP - 636 VL - 71 IS - 3 SN - 0002-9297, 0002-9297 KW - Pedigree KW - Linkage (Genetics) KW - Support, U.S. Gov't, P.H.S. KW - Homozygote KW - Human KW - Amino Acid Sequence KW - Membrane Proteins KW - Base Sequence KW - Chromosomes, Human, Pair 3 KW - Consanguinity KW - Deafness KW - Haplotypes KW - Molecular Sequence Data KW - Mutation KW - Male KW - Genes, Recessive KW - Female UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85238552?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Human+Genetics&rft.atitle=Mutations+in+a+novel+gene%2C+TMIE%2C+are+associated+with+hearing+loss+linked+to+the+DFNB6+locus.&rft.au=Naz+Sadaf%3BGiguere%2C+Chantal+M%3BKohrman%2C+David+C%3BMitchem%2C+Kristina+L%3BRiazuddin+Saima%3BMorell%2C+Robert+J%3BArabandi%2C+Ramesh%3BSrisailpathy+Srikumari%3BDeshmukh+Dilip%3BSheikh%2C+Riazuddin%3BGriffith%2C+Andrew+James%3BFriedman%2C+Thomas+B%3BSmith+Richard+J+H%3BWilcox%2C+Edward+R&rft.aulast=Naz+Sadaf&rft.aufirst=&rft.date=2002-09-01&rft.volume=71&rft.issue=3&rft.spage=632&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Human+Genetics&rft.issn=00029297&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Economical multi-site intradermal regimen with purified chick embryo cell vaccine (Rabipur) prevents rabies in people bitten by confirmed rabid animals. AN - 72878803; 12718837 AB - To determine the efficacy of a cost-effective multi-site intradermal regimen with purified chick embryo cell vaccine (PCECV, Rabipur) in preventing rabies in people bitten by confirmed rabid dogs. Thirty-two people of different age groups who were severely bitten by confirmed rabid dogs were immunized with PCECV using the WHO recommended multi-site intradermal regimen of 0.1 mL of vaccine at eight sites on day 0, at four sites on day 7, and at one site each on days 28 and 90. In addition, passive immunization with human or equine rabies immunoglobulin was administered to 22 of these people before administering vaccine. They were followed for up to 3 years with periodic estimation of neutralizing antibody levels in their serum by mouse neutralization test (MNT). There was an excellent immune response with more than protective titers (>0.5 IU/mL) on all days tested up to the end of the 3-year observation period. More significantly, protective titers were seen in all subjects by day 7. Only minimal side effects were observed. All the patients were doing well at the end of the 3-year observation period, which is generally considered to be the maximum incubation period for rabies in humans. It can be concluded that this multi-site regimen with or without passive immunization has prevented the development of rabies encephalitis in these people bitten by confirmed rabid dogs. This should encourage more such studies, so that this cost-effective economical regimen with safe and potent cell culture vaccines can replace highly reactogenic neural tissue-derived Semple vaccine in developing countries such as India. JF - International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases AU - Madhusudana, S N AU - Anand, N Prem AU - Shamsundar, Ranjini AD - National Institute of Mental Health and Neuroscience, Bangalore, India. mshampur@hotmail.com Y1 - 2002/09// PY - 2002 DA - September 2002 SP - 210 EP - 214 VL - 6 IS - 3 SN - 1201-9712, 1201-9712 KW - Antibodies, Viral KW - 0 KW - Rabies Vaccines KW - Index Medicus KW - Animals KW - Dog Diseases -- virology KW - Humans KW - Chick Embryo KW - Bites and Stings -- complications KW - Mice KW - Child KW - Immunization Schedule KW - India KW - Injections, Intradermal KW - Antibodies, Viral -- blood KW - Cost-Benefit Analysis KW - Adult KW - Neutralization Tests KW - Dogs KW - Adolescent KW - Male KW - Female KW - Dog Diseases -- diagnosis KW - Rabies -- veterinary KW - Rabies Vaccines -- economics KW - Rabies -- prevention & control KW - Rabies -- virology KW - Rabies Vaccines -- immunology KW - Rabies Vaccines -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72878803?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+infectious+diseases+%3A+IJID+%3A+official+publication+of+the+International+Society+for+Infectious+Diseases&rft.atitle=Economical+multi-site+intradermal+regimen+with+purified+chick+embryo+cell+vaccine+%28Rabipur%29+prevents+rabies+in+people+bitten+by+confirmed+rabid+animals.&rft.au=Madhusudana%2C+S+N%3BAnand%2C+N+Prem%3BShamsundar%2C+Ranjini&rft.aulast=Madhusudana&rft.aufirst=S&rft.date=2002-09-01&rft.volume=6&rft.issue=3&rft.spage=210&rft.isbn=&rft.btitle=&rft.title=International+journal+of+infectious+diseases+%3A+IJID+%3A+official+publication+of+the+International+Society+for+Infectious+Diseases&rft.issn=12019712&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-11 N1 - Date created - 2003-04-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role and prognostic significance of CD44s expression in colorectal cancer. AN - 72827809; 12529980 AB - The purpose of this study was to clarify the role and the predictive strength of the adhesion molecule CD44s (standard isoform) in colorectal carcinogenesis. CD44s immunohistochemical expression was evaluated in 100 patients with colon adenoma and 100 patients with colon adenocarcinoma and adjacent non-neoplastic mucosa (ANNM). The patients were followed-up for five years. CD44s immunoreactivity was expressed in low-moderate-high-grade dysplasia adenomas and associated with adenocarcinoma (p = 0.01), ANNM (p = 0.05) and pTNM stage (p = 0.00001). Univariate analysis revealed that CD44s expression was associated with overall survival (OS) in carcinomas (p = 0.01) and ANNM (p = 0.05). Bivariate analysis revealed that CD44s was associated with OS in stages I and II patients (p = 0.03). Multivariate analysis revealed that stage (p = 0.0001) and CD44s expression (p = 0.05) were independent predictors of OS. CD44s is involved in colon carcinogenesis and is associated with aggressive carcinomas. The immunohistochemical expression of CD44s may reveal cells that have lost their adhesion ability and therefore detect carcinomas with high metastatic power. JF - Anticancer research AU - Visca, Paolo AU - Del Nonno, Franca AU - Botti, Claudio AU - Marandino, Ferdinando AU - Sebastiani, Valeria AU - Di Tondo, Ugo AU - Donnorso, Raffaele Perrone AU - Trombetta, Giorgio AU - Filippi, Stefania AU - Alo, Piero Luigi AD - Department of Pathology, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy. PY - 2002 SP - 2671 EP - 2675 VL - 22 IS - 5 SN - 0250-7005, 0250-7005 KW - Antigens, CD44 KW - 0 KW - Protein Isoforms KW - Index Medicus KW - Epithelial Cells -- metabolism KW - Neoplasm Staging KW - Humans KW - Prognosis KW - Epithelial Cells -- immunology KW - Middle Aged KW - Immunohistochemistry KW - Male KW - Female KW - Survival Analysis KW - Multivariate Analysis KW - Antigens, CD44 -- biosynthesis KW - Adenocarcinoma -- metabolism KW - Adenoma -- metabolism KW - Colorectal Neoplasms -- pathology KW - Colorectal Neoplasms -- metabolism KW - Antigens, CD44 -- immunology KW - Colorectal Neoplasms -- immunology KW - Adenoma -- immunology KW - Adenocarcinoma -- immunology KW - Adenoma -- pathology KW - Adenocarcinoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72827809?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anticancer+research&rft.atitle=Role+and+prognostic+significance+of+CD44s+expression+in+colorectal+cancer.&rft.au=Visca%2C+Paolo%3BDel+Nonno%2C+Franca%3BBotti%2C+Claudio%3BMarandino%2C+Ferdinando%3BSebastiani%2C+Valeria%3BDi+Tondo%2C+Ugo%3BDonnorso%2C+Raffaele+Perrone%3BTrombetta%2C+Giorgio%3BFilippi%2C+Stefania%3BAlo%2C+Piero+Luigi&rft.aulast=Visca&rft.aufirst=Paolo&rft.date=2002-09-01&rft.volume=22&rft.issue=5&rft.spage=2671&rft.isbn=&rft.btitle=&rft.title=Anticancer+research&rft.issn=02507005&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-20 N1 - Date created - 2003-01-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tolerability of Raltitrexed ('Tomudex') in elderly patients with colorectal cancer. AN - 72827550; 12530045 AB - Colorectal cancer (CRC) is one of the major health problems of the Western world and the proportion of elderly patients with CRC is growing. Raltitrexed ('Tomudex'), a specific thymidylate synthase inhibitor, has shown efficacy and manageable toxicity in elderly CRC patients. In this retrospective study, the tolerability of raltitrexed in patients with CRC was examined in relation to age. Toxicity parameters, graded according to World Health Organization criteria, were assessed in two patient groups: or = 70 years old. In total, 56% (50 out of 90) of patients treated with raltitrexed (3 mg/m2 as a 15-minute intravenous infusion every 3 weeks) were aged > 70 years (M:F 28:22; Eastern Cooperative Oncology Group performance status 0-1:2 38:12). Overall, 437 cycles of chemotherapy were administered and grade 3-4 toxicity was reported in or = 70 and or = 70 years compared with those patients < 70 years of age. The raltitrexed toxicity profile does not appear to be significantly influenced by age; however caution is recommended in the management of elderly patients, particularly in the presence of impaired renal function. JF - Anticancer research AU - Romiti, Adriana AU - Tonini, Giuseppe AU - Santini, Daniele AU - Di Seri, Marisa AU - Masciangelo, Raffaele AU - Mezi, Silvia AU - Verì, Attilio AU - Santuari, Lucia AU - Vincenzi, Bruno AU - Brescia, Antonio AU - Marchei, Paolo AU - Frati, Luigi AU - Tomao, Silverio AD - National Cancer Institute of Genoa, Section of Rome, Department of Experimental Medicine and Pathology, La Sapienza University of Rome, Rome, Italy. adriana.romi@tin.it PY - 2002 SP - 3071 EP - 3076 VL - 22 IS - 5 SN - 0250-7005, 0250-7005 KW - Antimetabolites, Antineoplastic KW - 0 KW - Quinazolines KW - Thiophenes KW - Creatinine KW - AYI8EX34EU KW - raltitrexed KW - FCB9EGG971 KW - Index Medicus KW - Kidney -- metabolism KW - Age Factors KW - Creatinine -- urine KW - Sex Factors KW - Aged, 80 and over KW - Humans KW - Adult KW - Retrospective Studies KW - Aged KW - Middle Aged KW - Creatinine -- blood KW - Male KW - Female KW - Chemotherapy, Adjuvant KW - Quinazolines -- pharmacokinetics KW - Thiophenes -- adverse effects KW - Adenocarcinoma -- metabolism KW - Thiophenes -- therapeutic use KW - Colorectal Neoplasms -- metabolism KW - Antimetabolites, Antineoplastic -- adverse effects KW - Thiophenes -- pharmacokinetics KW - Quinazolines -- therapeutic use KW - Antimetabolites, Antineoplastic -- pharmacokinetics KW - Quinazolines -- adverse effects KW - Adenocarcinoma -- drug therapy KW - Colorectal Neoplasms -- drug therapy KW - Antimetabolites, Antineoplastic -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72827550?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anticancer+research&rft.atitle=Tolerability+of+Raltitrexed+%28%27Tomudex%27%29+in+elderly+patients+with+colorectal+cancer.&rft.au=Romiti%2C+Adriana%3BTonini%2C+Giuseppe%3BSantini%2C+Daniele%3BDi+Seri%2C+Marisa%3BMasciangelo%2C+Raffaele%3BMezi%2C+Silvia%3BVer%C3%AC%2C+Attilio%3BSantuari%2C+Lucia%3BVincenzi%2C+Bruno%3BBrescia%2C+Antonio%3BMarchei%2C+Paolo%3BFrati%2C+Luigi%3BTomao%2C+Silverio&rft.aulast=Romiti&rft.aufirst=Adriana&rft.date=2002-09-01&rft.volume=22&rft.issue=5&rft.spage=3071&rft.isbn=&rft.btitle=&rft.title=Anticancer+research&rft.issn=02507005&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-20 N1 - Date created - 2003-01-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mismatch repair gene mutations in renal cell carcinoma. AN - 72792165; 12496483 AB - We investigated the spectrum and genetic basis for mismatch repair (MMR) deficiency in renal cell carcinoma (RCC) by examining expression of four MMR genes important for hereditary and sporadic carcinogenesis. MMR deficiency was assessed using microsatellite instability (MSI) and genetic analyses of 25 cell lines derived from renal tumors. MMR gene alterations were detected using reverse transcription of RNA coupled with polymerase chain reaction (RT-PCR) and DNA sequencing. Three RCC lines with undetectable MLH1 were identified and investigated for MSI and inactivating mutations in the hMLH1 MMR gene. Genetic instability and hMLH1 mutations were identified in two RCC lines and their corresponding tumors. Genetic alterations affecting expression were limited to MLH1 since other MMR proteins (MSH2, MSH6 and PMS2) were detectable in our RCC lines. Complete inactivation of MMR is apparently uncommon in RCC and occurs predominantly through inactivating mutations in the hMLH1 gene. JF - Cancer biology & therapy AU - Leach, Fredrick S AU - Koh, Moon AU - Sharma, Kirti AU - McWilliams, Glenn AU - Talifero-Smith, LaTonia AU - Codd, Amanda AU - Olea, Raul AU - Elbahloul, Ossama AD - Urologic Oncology Branch/NCI, National Institutes of Health, 10 Center Drive, Bldg.10/Room 2B47, Bethesda, MD 20892-1501, USA. leachf@mail.nih.gov PY - 2002 SP - 530 EP - 536 VL - 1 IS - 5 SN - 1538-4047, 1538-4047 KW - Neoplasm Proteins KW - 0 KW - Index Medicus KW - DNA Repair -- genetics KW - Microsatellite Repeats KW - Chromosomes, Human, Pair 3 KW - Base Sequence KW - Tumor Cells, Cultured KW - Exons KW - Humans KW - Base Pair Mismatch KW - Neoplasm Proteins -- genetics KW - Molecular Sequence Data KW - Neoplasm Proteins -- metabolism KW - Sequence Deletion KW - Kidney Neoplasms -- genetics KW - Carcinoma, Renal Cell -- pathology KW - Kidney Neoplasms -- pathology KW - Mutation KW - Carcinoma, Renal Cell -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72792165?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+biology+%26+therapy&rft.atitle=Mismatch+repair+gene+mutations+in+renal+cell+carcinoma.&rft.au=Leach%2C+Fredrick+S%3BKoh%2C+Moon%3BSharma%2C+Kirti%3BMcWilliams%2C+Glenn%3BTalifero-Smith%2C+LaTonia%3BCodd%2C+Amanda%3BOlea%2C+Raul%3BElbahloul%2C+Ossama&rft.aulast=Leach&rft.aufirst=Fredrick&rft.date=2002-09-01&rft.volume=1&rft.issue=5&rft.spage=530&rft.isbn=&rft.btitle=&rft.title=Cancer+biology+%26+therapy&rft.issn=15384047&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-15 N1 - Date created - 2002-12-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Cancer Biol Ther. 2002 Sep-Oct;1(5):537-8 [12496484] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Arachidonic acid cytotoxicity in leukocytes: implications of oxidative stress and eicosanoid synthesis. AN - 72777603; 12489694 AB - Arachidonic acid (AA)-induced cytotoxicity was evaluated in leukocytes: the human leukemia cell lines HL-60, Jurkat and Raji and in rat lymphocytes. Such cytotoxicity was dose- and time-dependent. At concentrations below 5 microM, AA was not toxic; at 10-400 microM, AA induced apoptosis and at concentrations beyond 400 microM, necrosis. The minimum exposure time to trigger cell death was of around 1 h, but the effect was increased by longer exposure times until 6-24 h. Apoptosis was morphologically characterized by a decrease in cell and nuclear volume, chromatin condensation and DNA fragmentation and the presence of lipid bodies, without changes in organelle integrity. Biochemically, AA-induced apoptosis was associated with internucleosomal fragmentation and caspase activation, evaluated by PARP cleavage and the use of a caspase inhibitor. Necrosis was characterized by increased cell volume, presence of loose chromatin, appearance of vacuoles, loss of membrane integrity and of the definition of organelles. The apoptotic effect of AA was studied as to oxidative-reductive imbalance and the participation of eicosanoids. Apoptotic AA treatment was accompanied by an increase in the quantity of thiobarbituric acid reactive substances (TBARS), low-level chemiluminescence and in the glutathione disulfide/reduced glutathione ratio, indicating oxidative stress. The addition of tocopherol, ascorbate, prostaglandin E2 and lipoxygenase inhibitors delayed cell death, whereas the inhibition of cyclooxygenase promoted AA-induced cell death. Cell treatment with AA was accompanied by increased cellular production of LTB4. AA, therefore, is cytotoxic at physiological and supraphysiological concentrations, causing apoptosis and necrosis. Cell treatment with apoptotic concentrations of AA involves oxidative stress and changes in eicosanoid biosynthesis. JF - Biology of the cell AU - Pompeia, Celine AU - Freitas, Jofre J S AU - Kim, Jung S AU - Zyngier, Szulim B AU - Curi, Rui AD - National Institute of Deafness and other Communication Disorders, National Institutes of Health, Room 4249, Building 50, 50 South Drive, Bethesda, MD 20892, USA. cpompeia@nidcd.nih.gov Y1 - 2002/09// PY - 2002 DA - September 2002 SP - 251 EP - 265 VL - 94 IS - 4-5 SN - 0248-4900, 0248-4900 KW - Antioxidants KW - 0 KW - Cyclooxygenase Inhibitors KW - Cytotoxins KW - Eicosanoids KW - Proteins KW - Thiobarbituric Acid Reactive Substances KW - Leukotriene B4 KW - 1HGW4DR56D KW - Arachidonic Acid KW - 27YG812J1I KW - Parp1 protein, rat KW - EC 2.4.2.30 KW - Poly (ADP-Ribose) Polymerase-1 KW - Poly(ADP-ribose) Polymerases KW - Caspases KW - EC 3.4.22.- KW - Glutathione Disulfide KW - ULW86O013H KW - Index Medicus KW - Animals KW - Cell Nucleus -- metabolism KW - Glutathione Disulfide -- metabolism KW - Humans KW - Jurkat Cells KW - Cell Nucleus -- drug effects KW - DNA Fragmentation -- physiology KW - Caspases -- metabolism KW - Rats KW - Necrosis KW - Antioxidants -- pharmacology KW - DNA Fragmentation -- drug effects KW - Caspases -- drug effects KW - Drug Administration Schedule KW - Cell Nucleus -- pathology KW - Leukotriene B4 -- metabolism KW - Dose-Response Relationship, Drug KW - HL-60 Cells KW - Proteins -- metabolism KW - Cyclooxygenase Inhibitors -- pharmacology KW - Thiobarbituric Acid Reactive Substances -- metabolism KW - Proteins -- drug effects KW - Glutathione Disulfide -- drug effects KW - Leukocytes -- metabolism KW - Oxidative Stress -- physiology KW - Cytotoxins -- metabolism KW - Arachidonic Acid -- toxicity KW - Cytotoxins -- toxicity KW - Apoptosis -- physiology KW - Apoptosis -- drug effects KW - Oxidative Stress -- drug effects KW - Eicosanoids -- biosynthesis KW - Arachidonic Acid -- metabolism KW - Leukocytes -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72777603?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biology+of+the+cell&rft.atitle=Arachidonic+acid+cytotoxicity+in+leukocytes%3A+implications+of+oxidative+stress+and+eicosanoid+synthesis.&rft.au=Pompeia%2C+Celine%3BFreitas%2C+Jofre+J+S%3BKim%2C+Jung+S%3BZyngier%2C+Szulim+B%3BCuri%2C+Rui&rft.aulast=Pompeia&rft.aufirst=Celine&rft.date=2002-09-01&rft.volume=94&rft.issue=4-5&rft.spage=251&rft.isbn=&rft.btitle=&rft.title=Biology+of+the+cell&rft.issn=02484900&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-30 N1 - Date created - 2002-12-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - NTP center for the evaluation of risks to human reproduction phthalates expert panel reports. AN - 72633903; 12406491 JF - Reproductive toxicology (Elmsford, N.Y.) AU - Shelby, Michael D AD - CERHR, NIEHS EC-32, P.O. Box 12233, Research Triangle Park, NC 27709, USA. shelby@niehs.nih.gov PY - 2002 SP - 451 VL - 16 IS - 5 SN - 0890-6238, 0890-6238 KW - Phthalic Acids KW - 0 KW - Plasticizers KW - phthalic acid KW - 6O7F7IX66E KW - Index Medicus KW - United States KW - Animals KW - Environmental Health KW - Humans KW - Government Programs KW - Child KW - Plasticizers -- toxicity KW - Male KW - Female KW - Reproduction -- drug effects KW - Government Agencies KW - Phthalic Acids -- toxicity KW - Risk Assessment UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72633903?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Reproductive+toxicology+%28Elmsford%2C+N.Y.%29&rft.atitle=NTP+center+for+the+evaluation+of+risks+to+human+reproduction+phthalates+expert+panel+reports.&rft.au=Shelby%2C+Michael+D&rft.aulast=Shelby&rft.aufirst=Michael&rft.date=2002-09-01&rft.volume=16&rft.issue=5&rft.spage=451&rft.isbn=&rft.btitle=&rft.title=Reproductive+toxicology+%28Elmsford%2C+N.Y.%29&rft.issn=08906238&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-15 N1 - Date created - 2002-10-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Uncertainty, low-dose extrapolation and the threshold hypothesis. AN - 72620586; 12400961 AB - Risk-based radiation protection policy is influenced by estimated risk and by the uncertainty of that estimate. Thus, if the upper limit, at (say) 95% probability, of risk associated with a given radiation dose is at an 'acceptable' level, it is unlikely (or not credible) that the true level of risk associated with the dose is at an unacceptable level. Central estimates presented alone, in the absence of probability limits, lack this safety factor. Estimating cancer risks from low doses of ionising radiation involves extrapolation of risk estimates based on high-dose data to the much lower dose levels that characterize the vast majority of exposures of regulatory concern. Proof of a universal low-dose threshold, below which there is no radiation-related risk, would revolutionise radiation protection. Available data fail to provide such proof and, in fact, leave considerable room for the possibility that DNA damage from a single photon can contribute to the carcinogenic process. Allowing for the possibility of a threshold would, however, remove very little of the regulatory burden associated with the so-called linear, no-threshold hypothesis, unless that possibility were a virtual certainty. JF - Journal of radiological protection : official journal of the Society for Radiological Protection AU - Land, Charles E AD - Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. Y1 - 2002/09// PY - 2002 DA - September 2002 SP - A129 EP - A135 VL - 22 IS - 3A SN - 0952-4746, 0952-4746 KW - Index Medicus KW - Risk KW - Radiation Dosage KW - Humans KW - Neoplasms, Radiation-Induced -- etiology KW - Neoplasms, Radiation-Induced -- prevention & control KW - Radiation Protection -- standards UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72620586?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+radiological+protection+%3A+official+journal+of+the+Society+for+Radiological+Protection&rft.atitle=Uncertainty%2C+low-dose+extrapolation+and+the+threshold+hypothesis.&rft.au=Land%2C+Charles+E&rft.aulast=Land&rft.aufirst=Charles&rft.date=2002-09-01&rft.volume=22&rft.issue=3A&rft.spage=A129&rft.isbn=&rft.btitle=&rft.title=Journal+of+radiological+protection+%3A+official+journal+of+the+Society+for+Radiological+Protection&rft.issn=09524746&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-12 N1 - Date created - 2002-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ritonavir protects hippocampal neurons against oxidative stress-induced apoptosis. AN - 72187606; 12387358 AB - Oxidative stress plays an important role in many neurodegenerative conditions including Alzheimer's disease and Parkinson's disease. 4-Hydroxynonenal (HNE), a lipid-soluble aldehydic product of membrane peroxidation, has been known to decrease neuronal survival by impairing Na+, K+, and -ATPase activity. HNE also increases neuronal vulnerability to excitotoxic injury and disrupts homeostasis by activating proteases which mediate the destruction of cellular protein and structure. The present study demonstrated that the hydrophobic HIV protease inhibitor, ritonavir inhibited HNE-mediated apoptosis in hippocampal primary neurons. In neurons exposed to oxidative stress induced by HNE (1 microM), ritonavir at 100 pM increased cell survival and completely abolished the apoptotic effects of HNE (P < 0.01). Ritonavir and its analogues might have useful cytoprotective effects for use in limiting the natural course of tissue injury after conditions where oxidative stress plays a role. JF - Neurotoxicology AU - Wan, Wenshuai AU - DePetrillo, Paolo B AD - Unit of Clinical and Biochemical Pharmacology, Laboratory of Clinical Studies, Division of Intramural Clinical and Biochemical Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892-1256, USA. Y1 - 2002/09// PY - 2002 DA - September 2002 SP - 301 EP - 306 VL - 23 IS - 3 SN - 0161-813X, 0161-813X KW - Aldehydes KW - 0 KW - Anti-HIV Agents KW - 4-hydroxy-2-nonenal KW - K1CVM13F96 KW - Ritonavir KW - O3J8G9O825 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Cell Survival -- drug effects KW - Dose-Response Relationship, Drug KW - Aldehydes -- pharmacology KW - Ritonavir -- pharmacology KW - Neurons -- drug effects KW - Anti-HIV Agents -- pharmacology KW - Hippocampus -- cytology KW - Apoptosis -- drug effects KW - Oxidative Stress -- drug effects KW - Hippocampus -- chemistry KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72187606?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurotoxicology&rft.atitle=Ritonavir+protects+hippocampal+neurons+against+oxidative+stress-induced+apoptosis.&rft.au=Wan%2C+Wenshuai%3BDePetrillo%2C+Paolo+B&rft.aulast=Wan&rft.aufirst=Wenshuai&rft.date=2002-09-01&rft.volume=23&rft.issue=3&rft.spage=301&rft.isbn=&rft.btitle=&rft.title=Neurotoxicology&rft.issn=0161813X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-21 N1 - Date created - 2002-10-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The relationship between two intermediate phenotypes for alcoholism: low voltage alpha EEG and low P300 ERP amplitude. AN - 72177954; 12380845 AB - There is considerable evidence that the amplitude of the heritable P300 event-related potential (ERP) is reduced in alcoholics and their alcohol-naive children. Low voltage alpha (LVA), a heritable resting electroencephalogram (EEG) trait present in 7-14% of the population, has been shown to be associated with alcoholism and anxiety disorders. A few studies have demonstrated a modest correlation between pre-stimulus alpha power and P300 amplitude. We aimed to test this finding in community volunteers, hypothesizing that LVA would be associated with low P300 amplitude. Digitized resting EEG was recorded at the central parietal site (Pz) from 85 male and 113 female community volunteers (120 unrelated). ERPs were elicited at Pz by auditory and visual oddball paradigms. All participants were interviewed with the Schedule for Affective Disorders, Lifetime Version (SADS-L) and assigned blind-rated psychiatric diagnoses according to the American Psychiatric Association DSM-III-R criteria. LVA participants (including alcoholics and nonalcoholics) had significantly lower auditory and visual P300 amplitudes. Absolute alpha power was modestly correlated with auditory and visual P300 amplitude and was associated with 9.4% and 4.6% of the variance, respectively. The association between LVA and low P300 amplitude, two distinct electrophysiological traits, suggests that, at least in individuals with the LVA trait, some aspects of resting, unstimulated brain activity and activated brain function in the form of attentional response may be fundamentally related. JF - Journal of studies on alcohol AU - Enoch, Mary-Anne AU - White, Kenneth V AU - Harris, Claudia R AU - Rohrbaugh, John W AU - Goldman, David AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892-8110, USA. maenoch@niaaa.nih.gov Y1 - 2002/09// PY - 2002 DA - September 2002 SP - 509 EP - 517 VL - 63 IS - 5 SN - 0096-882X, 0096-882X KW - Index Medicus KW - Anxiety Disorders -- genetics KW - Analysis of Variance KW - Humans KW - Aged KW - Electroencephalography -- methods KW - Anxiety Disorders -- physiopathology KW - Evoked Potentials, Visual -- genetics KW - Aged, 80 and over KW - Evoked Potentials, Auditory -- genetics KW - Adult KW - Middle Aged KW - Adolescent KW - Male KW - Female KW - Phenotype KW - Alpha Rhythm -- methods KW - Event-Related Potentials, P300 -- genetics KW - Alcoholism -- physiopathology KW - Alcoholism -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72177954?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=The+relationship+between+two+intermediate+phenotypes+for+alcoholism%3A+low+voltage+alpha+EEG+and+low+P300+ERP+amplitude.&rft.au=Enoch%2C+Mary-Anne%3BWhite%2C+Kenneth+V%3BHarris%2C+Claudia+R%3BRohrbaugh%2C+John+W%3BGoldman%2C+David&rft.aulast=Enoch&rft.aufirst=Mary-Anne&rft.date=2002-09-01&rft.volume=63&rft.issue=5&rft.spage=509&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 - 2003-03-03 N1 - Date created - 2002-10-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of uterine leiomyomas in CD-1 mice following developmental exposure to diethylstilbestrol (DES). AN - 72164101; 12371671 AB - Experimental animal and clinical studies have well established the association of prenatal exposure to diethylstilbestrol (DES) and the subsequent development of reproductive tract abnormalities, including poor reproductive outcome and neoplasia. Overwhelmingly, the focus has been on DES-induced epithelial lesions, particularly vaginal adenosis and adenocarcinoma; however, uterine smooth muscle cells are also recognized as cellular targets of DES. This descriptive report characterizes uterine leiomyomas that occur in outbred CD-1 mice following exposure to DES prenatally on days 9 to 16 of gestation or on neonatal days 1 to 5. These DES-induced uterine leiomyomas have typical histomorphologic, and some immunohistochemical characteristics of spontaneously occurring uterine smooth muscle tumors of B6C3F1 mice previously described in our laboratory, and they are also similar to uterine leiomyomas (fibroids) commonly observed in premenopausal women. JF - Toxicologic pathology AU - Newbold, Retha R AU - Moore, Alicia B AU - Dixon, Darlene AD - Developmental Endocrinology Section, Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. PY - 2002 SP - 611 EP - 616 VL - 30 IS - 5 SN - 0192-6233, 0192-6233 KW - Carcinogens KW - 0 KW - Proliferating Cell Nuclear Antigen KW - Transforming Growth Factor alpha KW - Diethylstilbestrol KW - 731DCA35BT KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Index Medicus KW - Mice, Inbred Strains KW - Animals KW - Dose-Response Relationship, Drug KW - Injections, Subcutaneous KW - Transforming Growth Factor alpha -- analysis KW - Proliferating Cell Nuclear Antigen -- analysis KW - Mice KW - Receptor, Epidermal Growth Factor -- analysis KW - Immunohistochemistry KW - Female KW - Pregnancy KW - Uterine Neoplasms -- chemistry KW - Carcinogens -- administration & dosage KW - Leiomyoma -- pathology KW - Uterine Neoplasms -- chemically induced KW - Diethylstilbestrol -- toxicity KW - Carcinogens -- toxicity KW - Leiomyoma -- chemically induced KW - Leiomyoma -- chemistry KW - Diethylstilbestrol -- administration & dosage KW - Maternal Exposure KW - Uterine Neoplasms -- pathology KW - Prenatal Exposure Delayed Effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72164101?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Characterization+of+uterine+leiomyomas+in+CD-1+mice+following+developmental+exposure+to+diethylstilbestrol+%28DES%29.&rft.au=Newbold%2C+Retha+R%3BMoore%2C+Alicia+B%3BDixon%2C+Darlene&rft.aulast=Newbold&rft.aufirst=Retha&rft.date=2002-09-01&rft.volume=30&rft.issue=5&rft.spage=611&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 - 2003-03-18 N1 - Date created - 2002-10-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - N-nitroso compounds and mutagens in Chinese fermented (sour) corn pancakes. AN - 72154791; 12374403 AB - Stomach cancer rates in rural Linqu County, Shandong Province, China, are exceptionally high. A previous case-control study revealed that the risk of stomach cancer was 30% higher among those who consumed sour (fermented) corn pancakes at least daily. A previous study of the sour pancakes reported volatile nitrosamines in most specimens, and almost half reportedly showed mutagenic activity. Few households currently consume sour pancakes, and the duration of fermentation has been shortened. We tested specimens of pancake batter and sour pancakes from Linqu County for mutagenic activity using the Ames test; for N-nitroso compounds (NOC) we used the Nitrolite-thermal energy analysis (TEA) method. Results of the Ames test were inconclusive: only 1 out of 15 cooked pancakes showed a positive mutagenic response, and all 15 batter specimens were negative; however, several batter specimens showed a weakly positive trend of mutagenicity with extract concentration. Our assay for total nitroso compounds was weakly positive in only 1 out of 15 specimens of sour pancake batter. That specimen was also tested by gas chromatography-TEA for nitrosaminoacids and volatile nitrosamines, but none were detected. It seems unlikely that the Chinese sour pancakes are significantly contaminated by NOC or other mutagens. JF - Journal of AOAC International AU - Groves, Frank D AU - Issaq, Haleem AU - Fox, Stephen AU - Jeffrey, Alan M AU - Whysner, John AU - Zhang, Lian AU - You, Wei-Cheng AU - Fraumeni, Joseph F AD - National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, MD 20892-7242, USA. grovesf@musc.edu PY - 2002 SP - 1052 EP - 1056 VL - 85 IS - 5 SN - 1060-3271, 1060-3271 KW - Mutagens KW - 0 KW - Nitrosamines KW - Nitroso Compounds KW - Index Medicus KW - Rats KW - Salmonella -- drug effects KW - Animals KW - Salmonella -- genetics KW - Mutagenicity Tests KW - Fermentation KW - In Vitro Techniques KW - Nitrosamines -- analysis KW - Mutagens -- analysis KW - Zea mays -- chemistry KW - Food Analysis KW - Nitroso Compounds -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72154791?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=N-nitroso+compounds+and+mutagens+in+Chinese+fermented+%28sour%29+corn+pancakes.&rft.au=Groves%2C+Frank+D%3BIssaq%2C+Haleem%3BFox%2C+Stephen%3BJeffrey%2C+Alan+M%3BWhysner%2C+John%3BZhang%2C+Lian%3BYou%2C+Wei-Cheng%3BFraumeni%2C+Joseph+F&rft.aulast=Groves&rft.aufirst=Frank&rft.date=2002-09-01&rft.volume=85&rft.issue=5&rft.spage=1052&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 - 2003-04-01 N1 - Date created - 2002-10-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increased K-ras protein and activity in mouse and human lung epithelial cells at confluence. AN - 72137461; 12354753 AB - Although K-ras is frequently mutated in lung adenocarcinomas, the normal function of K-ras p21 in lung is not known. In two mouse (E10 and C10) and one human (HPL1D) immortalized lung cell lines from peripheral epithelium, we have measured total K-ras p21 and active K-ras p21-GTP during cell proliferation and at growth arrest caused by confluence. In all three cell types, total K-ras p21 increased 2- to 4-fold at confluence, and active K-ras p21-GTP increased 10- to 200-fold. It was estimated that 0.03% of total K-ras p21 was in the active GTP-bound state at 50% confluence, compared with 1.4% at postconfluence. By contrast, stimulation of proliferation by serum-containing medium did not involve K-ras p21 activation, even though a rapid, marked activation of both Erk1/2 and Akt occurred. At confluence, large increases, up to 14-fold, were seen in Grb2/Sos1 complexes, which may activate K-ras p21. In sum, increased protein expression and activity of K-ras p21 are associated with growth arrest, not with proliferation, in mouse and human lung cell lines. JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Kammouni, Wafa AU - Ramakrishna, Gayatri AU - Sithanandam, Gunamani AU - Smith, George T AU - Fornwald, Laura W AU - Masuda, Akira AU - Takahashi, Takashi AU - Anderson, Lucy M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA. Y1 - 2002/09// PY - 2002 DA - September 2002 SP - 441 EP - 448 VL - 13 IS - 9 SN - 1044-9523, 1044-9523 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - GRB2 Adaptor Protein KW - GRB2 protein, human KW - Grb2 protein, mouse KW - Proteins KW - Proto-Oncogene Proteins KW - Guanosine Triphosphate KW - 86-01-1 KW - AKT1 protein, human KW - EC 2.7.11.1 KW - Protein-Serine-Threonine Kinases KW - Proto-Oncogene Proteins c-akt KW - Mitogen-Activated Protein Kinase 1 KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinase 3 KW - Mitogen-Activated Protein Kinases KW - HRAS protein, human KW - EC 3.6.5.2 KW - Proto-Oncogene Proteins p21(ras) KW - Index Medicus KW - Animals KW - Immunoblotting KW - Mitogen-Activated Protein Kinases -- metabolism KW - Enzyme Activation KW - Humans KW - Proto-Oncogene Proteins -- metabolism KW - Mice KW - Precipitin Tests KW - Mice, Inbred BALB C KW - Proteins -- metabolism KW - Guanosine Triphosphate -- metabolism KW - Tumor Cells, Cultured KW - Mitogen-Activated Protein Kinase 1 -- metabolism KW - Time Factors KW - Cell Line KW - Cell Division KW - Epithelial Cells -- metabolism KW - Proto-Oncogene Proteins p21(ras) -- biosynthesis KW - Lung -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72137461?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Increased+K-ras+protein+and+activity+in+mouse+and+human+lung+epithelial+cells+at+confluence.&rft.au=Kammouni%2C+Wafa%3BRamakrishna%2C+Gayatri%3BSithanandam%2C+Gunamani%3BSmith%2C+George+T%3BFornwald%2C+Laura+W%3BMasuda%2C+Akira%3BTakahashi%2C+Takashi%3BAnderson%2C+Lucy+M&rft.aulast=Kammouni&rft.aufirst=Wafa&rft.date=2002-09-01&rft.volume=13&rft.issue=9&rft.spage=441&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 - 2003-02-24 N1 - Date created - 2002-09-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - NAALADase (GCP II) inhibition prevents cocaine-kindled seizures. AN - 72114567; 12243764 AB - The prediction that inhibition of NAALADase, an enzyme catalyzing the cleavage of glutamate from N-acetyl-aspartyl-glutamate, would produce antiepileptogenic effects against cocaine was tested. Cocaine kindled seizures were developed in male, Swiss-Webster mice by daily administration of 60 mg/kg cocaine for 5 days. The NAALADase inhibitor 2-(phosphonomethyl)pentanedioic acid (2-PMPA) produced dose-dependent protection (10-100 mg/kg) against both the development of seizure kindling and the occurrence of seizures during the kindling process without observable behavioral side-effects. It is not likely that 2-PMPA produced protection against cocaine kindling by altering the potency of the convulsant stimulus as daily administration of 2-PMPA did not alter the convulsant thresholds for cocaine. Lower daily doses of cocaine (40 mg/kg) did not increase the incidence of seizures but produced kindling, as evidenced by the increase in seizure susceptibility when mice were probed with a higher dose of cocaine. 2-PMPA was also effective in preventing the development of sensitization to this covert kindling process. In contrast to its efficacy against cocaine kindled seizures, 2-PMPA failed to attenuate the convulsions engendered by acute challenges with pentylenetetrazole, bicuculline, N-methyl-D-aspartate, maximal electroshock or cocaine. Similarly, acutely-administered 2-PMPA did not block cocaine seizures in fully-kindled mice. NAALADase inhibition thus provides a novel means of attenuating the development of cocaine seizure kindling. JF - Neuropharmacology AU - Witkin, Jeffrey M AU - Gasior, Maciej AU - Schad, Christina AU - Zapata, Agustin AU - Shippenberg, Toni AU - Hartman, Theresa AU - Slusher, Barbara S AD - Drug Development Group, Addiction Research Center, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA. jwitkin@lilly.com Y1 - 2002/09// PY - 2002 DA - September 2002 SP - 348 EP - 356 VL - 43 IS - 3 SN - 0028-3908, 0028-3908 KW - 2-(phosphonomethyl)pentanedioic acid KW - 0 KW - Anticonvulsants KW - Convulsants KW - Dopamine Uptake Inhibitors KW - Organophosphorus Compounds KW - Carboxypeptidases KW - EC 3.4.- KW - Glutamate Carboxypeptidase II KW - EC 3.4.17.21 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Behavior, Animal -- drug effects KW - Animals KW - Epilepsy, Tonic-Clonic -- psychology KW - Epilepsy, Tonic-Clonic -- chemically induced KW - Dose-Response Relationship, Drug KW - Mice KW - Male KW - Seizures -- chemically induced KW - Anticonvulsants -- pharmacology KW - Kindling, Neurologic -- drug effects KW - Carboxypeptidases -- antagonists & inhibitors KW - Dopamine Uptake Inhibitors -- administration & dosage KW - Convulsants -- pharmacology KW - Organophosphorus Compounds -- pharmacology KW - Convulsants -- administration & dosage KW - Seizures -- prevention & control KW - Cocaine -- pharmacology KW - Cocaine -- administration & dosage KW - Dopamine Uptake Inhibitors -- pharmacology KW - Cocaine -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72114567?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=NAALADase+%28GCP+II%29+inhibition+prevents+cocaine-kindled+seizures.&rft.au=Witkin%2C+Jeffrey+M%3BGasior%2C+Maciej%3BSchad%2C+Christina%3BZapata%2C+Agustin%3BShippenberg%2C+Toni%3BHartman%2C+Theresa%3BSlusher%2C+Barbara+S&rft.aulast=Witkin&rft.aufirst=Jeffrey&rft.date=2002-09-01&rft.volume=43&rft.issue=3&rft.spage=348&rft.isbn=&rft.btitle=&rft.title=Neuropharmacology&rft.issn=00283908&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-12-17 N1 - Date created - 2002-09-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A latent autoregressive model for longitudinal binary data subject to informative missingness. AN - 72092332; 12229998 AB - Longitudinal clinical trials often collect long sequences of binary data. Our application is a recent clinical trial in opiate addicts that examined the effect of a new treatment on repeated binary urine tests to assess opiate use over an extended follow-up. The dataset had two sources of missingness: dropout and intermittent missing observations. The primary endpoint of the study was comparing the marginal probability of a positive urine test over follow-up across treatment arms. We present a latent autoregressive model for longitudinal binary data subject to informative missingness. In this model, a Gaussian autoregressive process is shared between the binary response and missing-data processes, thereby inducing informative missingness. Our approach extends the work of others who have developed models that link the various processes through a shared random effect but do not allow for autocorrelation. We discuss parameter estimation using Monte Carlo EM and demonstrate through simulations that incorporating within-subject autocorrelation through a latent autoregressive process can be very important when longitudinal binary data is subject to informative missingness. We illustrate our new methodology using the opiate clinical trial data. JF - Biometrics AU - Albert, Paul S AU - Follmann, Dean A AU - Wang, Shaohua A AU - Suh, Edward B AD - Biometric Research Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. albertp@ctep.nci.nih.gov Y1 - 2002/09// PY - 2002 DA - September 2002 SP - 631 EP - 642 VL - 58 IS - 3 SN - 0006-341X, 0006-341X KW - Narcotics KW - 0 KW - Buprenorphine KW - 40D3SCR4GZ KW - Methadone KW - UC6VBE7V1Z KW - Index Medicus KW - Regression Analysis KW - Biometry KW - Methadone -- therapeutic use KW - Buprenorphine -- therapeutic use KW - Humans KW - Narcotics -- urine KW - Algorithms KW - Opioid-Related Disorders -- rehabilitation KW - Opioid-Related Disorders -- urine KW - Monte Carlo Method KW - Longitudinal Studies KW - Models, Statistical KW - Clinical Trials as Topic -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72092332?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+latent+autoregressive+model+for+longitudinal+binary+data+subject+to+informative+missingness.&rft.au=Albert%2C+Paul+S%3BFollmann%2C+Dean+A%3BWang%2C+Shaohua+A%3BSuh%2C+Edward+B&rft.aulast=Albert&rft.aufirst=Paul&rft.date=2002-09-01&rft.volume=58&rft.issue=3&rft.spage=631&rft.isbn=&rft.btitle=&rft.title=Biometrics&rft.issn=0006341X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-07 N1 - Date created - 2002-09-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA repair gene XRCC3 codon 241 polymorphism, its interaction with smoking and XRCC1 polymorphisms, and bladder cancer risk. AN - 72081918; 12223443 AB - DNA repair efficiency varies among individuals, with reduced repair capacity as a risk factor for various cancers. This variability could be partly explained by allelic variants for different DNA repair genes. We examined the role of a common polymorphism in the XRCC3 gene (codon 241: threonine to methionine change) and bladder cancer risk. This gene plays a role in the homologous recombination pathway, which repairs double-strand breaks. The functional consequences of the XRCC3 codon 241 polymorphism are still unknown. We hypothesized that this polymorphism could affect repair of smoking-associated DNA damage and could thereby affect bladder cancer risk. We genotyped 233 bladder cancer cases and 209 controls who had been frequency matched to cases on age, sex, and ethnicity. We observed little evidence of a positive association between subjects who carried at least one copy of the codon 241 Met allele and bladder cancer (odds ratio: 1.3; 95% confidence interval: 0.9-1.9). Among heavy smokers, individuals with the Met allele had about twice the risk of those without it; however, a test of interaction was not statistically significant (P = 0.26). Previously, we observed in these subjects an association between bladder cancer risk and allelic variants of the XRCC1 gene, which is involved in the repair of base damage and single-strand breaks. In this study, we found some evidence for a gene-gene interaction between the XRCC1 codon 194 and XRCC3 codon 241 polymorphisms (P = 0.09) and some support for a possible gene-gene-smoking three-way interaction (P = 0.08). JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Stern, Mariana C AU - Umbach, David M AU - Lunn, Ruth M AU - Taylor, Jack A AD - Molecular and Genetic Epidemiology Section, Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709, USA. Y1 - 2002/09// PY - 2002 DA - September 2002 SP - 939 EP - 943 VL - 11 IS - 9 SN - 1055-9965, 1055-9965 KW - Codon KW - 0 KW - DNA-Binding Proteins KW - X-ray repair cross complementing protein 1 KW - X-ray repair cross complementing protein 3 KW - Index Medicus KW - Genotype KW - Polymorphism, Genetic KW - Humans KW - Female KW - DNA Repair -- genetics KW - Urinary Bladder Neoplasms -- prevention & control KW - DNA-Binding Proteins -- genetics KW - Smoking -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72081918?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=DNA+repair+gene+XRCC3+codon+241+polymorphism%2C+its+interaction+with+smoking+and+XRCC1+polymorphisms%2C+and+bladder+cancer+risk.&rft.au=Stern%2C+Mariana+C%3BUmbach%2C+David+M%3BLunn%2C+Ruth+M%3BTaylor%2C+Jack+A&rft.aulast=Stern&rft.aufirst=Mariana&rft.date=2002-09-01&rft.volume=11&rft.issue=9&rft.spage=939&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 - 2003-02-25 N1 - Date created - 2002-09-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Putting drug abuse research to use in real-life settings. AN - 72080154; 12220602 JF - Journal of substance abuse treatment AU - Hanson, Glen R AU - Leshner, Alan I AU - Tai, Betty AD - National Institute on Drug Abuse, 6001 Executive Boulevard, Room 4123, Bethesda, MD 20892, USA. Y1 - 2002/09// PY - 2002 DA - September 2002 SP - 69 EP - 70 VL - 23 IS - 2 SN - 0740-5472, 0740-5472 KW - Index Medicus KW - United States KW - Brain -- physiopathology KW - Substance Abuse Treatment Centers KW - Humans KW - Communication KW - Clinical Trials as Topic KW - Research KW - Substance-Related Disorders -- physiopathology KW - Substance-Related Disorders -- rehabilitation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72080154?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+substance+abuse+treatment&rft.atitle=Putting+drug+abuse+research+to+use+in+real-life+settings.&rft.au=Hanson%2C+Glen+R%3BLeshner%2C+Alan+I%3BTai%2C+Betty&rft.aulast=Hanson&rft.aufirst=Glen&rft.date=2002-09-01&rft.volume=23&rft.issue=2&rft.spage=69&rft.isbn=&rft.btitle=&rft.title=Journal+of+substance+abuse+treatment&rft.issn=07405472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-21 N1 - Date created - 2002-09-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanistic insight into exclusive nitric oxide recovery from a carbon-bound diazeniumdiolate. AN - 72079716; 12223179 AB - We report that NaON=N(O)-X-N(O)=NONa (1), where X is para-disubstituted benzene, hydrolyzes to 2 mol of nitric oxide (NO) with concurrent production of 1 mol of p-benzoquinone dioxime at physiological pH. The reaction is acid catalyzed, with a rate that slows as the substrate concentration is increased. The results demonstrate that a carbon-bound diazeniumdiolate can be quantitatively hydrolyzed to produce NO as the only gaseous nitrogen-containing product. The data also suggest that N-N bond cleavage is the rate-determining step in NO release, since C-N cleavage followed by dissociation of O=N-N=O to two NO molecules cannot be operative in this case. The finding that this oxime can absorb NO in organic media and regenerate it quantitatively at physiological pHs extends the potential pharmacological implications of the carbon-bound diazeniumdiolates. JF - Nitric oxide : biology and chemistry AU - Arnold, Ernst V AU - Citro, Michael L AU - Saavedra, Evelyn A AU - Davies, Keith M AU - Keefer, Larry K AU - Hrabie, Joseph A AD - Chemistry Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, MD 21702, USA. Y1 - 2002/09// PY - 2002 DA - September 2002 SP - 103 EP - 108 VL - 7 IS - 2 SN - 1089-8603, 1089-8603 KW - Azo Compounds KW - 0 KW - Gases KW - diazeniumdiolate KW - Nitric Oxide KW - 31C4KY9ESH KW - Carbon KW - 7440-44-0 KW - Index Medicus KW - Molecular Structure KW - Gases -- chemistry KW - Half-Life KW - Luminescent Measurements KW - Kinetics KW - Hydrogen-Ion Concentration KW - Hydrolysis KW - Catalysis KW - Azo Compounds -- chemistry KW - Nitric Oxide -- chemistry KW - Carbon -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72079716?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nitric+oxide+%3A+biology+and+chemistry&rft.atitle=Mechanistic+insight+into+exclusive+nitric+oxide+recovery+from+a+carbon-bound+diazeniumdiolate.&rft.au=Arnold%2C+Ernst+V%3BCitro%2C+Michael+L%3BSaavedra%2C+Evelyn+A%3BDavies%2C+Keith+M%3BKeefer%2C+Larry+K%3BHrabie%2C+Joseph+A&rft.aulast=Arnold&rft.aufirst=Ernst&rft.date=2002-09-01&rft.volume=7&rft.issue=2&rft.spage=103&rft.isbn=&rft.btitle=&rft.title=Nitric+oxide+%3A+biology+and+chemistry&rft.issn=10898603&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-17 N1 - Date created - 2002-09-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Serine/threonine protein kinases synergistically regulate phospholipase D1 and 2 and secretion in RBL-2H3 mast cells. AN - 72079608; 12217394 AB - The role of phospholipase (PL) D in secretion was examined in RBL-2H3 mast cells which contain both PLD1 and 2. The effects of pharmacologic stimulants and inhibitors of Ca(2+)/calmodulin-dependent kinase II, protein kinase C, and protein kinase A suggested that all three kinases synergistically stimulate PLD and, when associated with a calcium signal, secretion as well to indicate a possible linkage between these two events. Overexpression of either PLD1 or 2 markedly enhanced the activation of PLD by pharmacologic stimulants as well as antigen and both isoforms thus appear co-ordinately regulated. As the expressed PLD1 was associated with secretory granules and PLD2 with the plasma membrane, the two isoforms may serve distinct but complementary functions in secretion. JF - Molecular immunology AU - Chahdi, Ahmed AU - Choi, Wahn Soo AU - Kim, Young Mi AU - Fraundorfer, Paul F AU - Beaven, Michael A AD - Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institute of Health, Bethesda, MD 20892-1760, USA. Y1 - 2002/09// PY - 2002 DA - September 2002 SP - 1269 EP - 1276 VL - 38 IS - 16-18 SN - 0161-5890, 0161-5890 KW - Antigens KW - 0 KW - Enzyme Inhibitors KW - Thapsigargin KW - 67526-95-8 KW - Carbachol KW - 8Y164V895Y KW - Cholera Toxin KW - 9012-63-9 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - phospholipase D2 KW - EC 3.1.4.- KW - Phospholipase D KW - EC 3.1.4.4 KW - phospholipase D1 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Thapsigargin -- pharmacology KW - Rats KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Animals KW - Tumor Cells, Cultured KW - Cholera Toxin -- pharmacology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Carbachol -- pharmacology KW - Antigens -- immunology KW - Mast Cells -- secretion KW - Phospholipase D -- metabolism KW - Mast Cells -- immunology KW - Protein-Serine-Threonine Kinases -- metabolism KW - Phospholipase D -- antagonists & inhibitors KW - Mast Cells -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72079608?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+immunology&rft.atitle=Serine%2Fthreonine+protein+kinases+synergistically+regulate+phospholipase+D1+and+2+and+secretion+in+RBL-2H3+mast+cells.&rft.au=Chahdi%2C+Ahmed%3BChoi%2C+Wahn+Soo%3BKim%2C+Young+Mi%3BFraundorfer%2C+Paul+F%3BBeaven%2C+Michael+A&rft.aulast=Chahdi&rft.aufirst=Ahmed&rft.date=2002-09-01&rft.volume=38&rft.issue=16-18&rft.spage=1269&rft.isbn=&rft.btitle=&rft.title=Molecular+immunology&rft.issn=01615890&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-22 N1 - Date created - 2002-09-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - ACC/AHA/NHLBI Clinical Advisory on the Use and Safety of Statins. AN - 72067784; 12215610 JF - Stroke AU - Pasternak, Richard C AU - Smith, Sidney C AU - Bairey-Merz, C Noel AU - Grundy, Scott M AU - Cleeman, James I AU - Lenfant, Claude AU - American College of Cardiology AU - American Heart Association AU - National Heart, Lung and Blood Institute AD - American College of Cardiology ; American Heart Association ; National Heart, Lung and Blood Institute Y1 - 2002/09// PY - 2002 DA - September 2002 SP - 2337 EP - 2341 VL - 33 IS - 9 KW - Anticholesteremic Agents KW - 0 KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors KW - Pyridines KW - cerivastatin KW - AM91H2KS67 KW - Creatine Kinase KW - EC 2.7.3.2 KW - Index Medicus KW - Drug Interactions KW - Humans KW - Aged KW - Pyridines -- therapeutic use KW - Monitoring, Physiologic KW - Muscular Diseases -- prevention & control KW - Coronary Disease -- drug therapy KW - Creatine Kinase -- blood KW - Muscular Diseases -- chemically induced KW - Aged, 80 and over KW - Risk Factors KW - Middle Aged KW - Pyridines -- adverse effects KW - Female KW - Male KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors -- contraindications KW - Anticholesteremic Agents -- contraindications KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors -- therapeutic use KW - Anticholesteremic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72067784?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Stroke&rft.atitle=ACC%2FAHA%2FNHLBI+Clinical+Advisory+on+the+Use+and+Safety+of+Statins.&rft.au=Pasternak%2C+Richard+C%3BSmith%2C+Sidney+C%3BBairey-Merz%2C+C+Noel%3BGrundy%2C+Scott+M%3BCleeman%2C+James+I%3BLenfant%2C+Claude%3BAmerican+College+of+Cardiology%3BAmerican+Heart+Association%3BNational+Heart%2C+Lung+and+Blood+Institute&rft.aulast=Pasternak&rft.aufirst=Richard&rft.date=2002-09-01&rft.volume=33&rft.issue=9&rft.spage=2337&rft.isbn=&rft.btitle=&rft.title=Stroke&rft.issn=1524-4628&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-09-23 N1 - Date created - 2002-09-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Curr Atheroscler Rep. 2003 Jan;5(1):10 [12562534] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Probes for the dopamine transporter: new leads toward a cocaine-abuse therapeutic--A focus on analogues of benztropine and rimcazole. AN - 72057206; 12210554 AB - In an attempt to discover a cocaine-abuse pharmacotherapeutic, extensive investigation has been directed toward elucidating the molecular mechanisms underlying the reinforcing effects of this psychostimulant drug. The results of these studies have been consistent with the inhibition of dopamine uptake, at the dopamine transporter (DAT), which results in a rapid and excessive accumulation of extracellular dopamine in the synapse as being the mechanism primarily responsible for the locomotor stimulant actions of cocaine. Nevertheless, investigation of the serotonin (SERT) and norepinephrine (NET) transporters, as well as other receptor systems, with which cocaine either directly or indirectly interacts, has suggested that the DAT is not solely responsible for the reinforcing effects of cocaine. In an attempt to further elucidate the roles of these systems in the reinforcing effects of cocaine, selective molecular probes, in the form of drug molecules, have been designed, synthesized, and characterized. Many of these compounds bind potently and selectively to the DAT, block dopamine reuptake, and are behaviorally cocaine-like in animal models of psychostimulant abuse. However, there have been exceptions noted in several classes of dopamine uptake inhibitors that demonstrate behavioral profiles that are distinctive from cocaine. Structure-activity relationships between chemically diverse dopamine uptake inhibitors have suggested that different binding interactions, at the molecular level on the DAT, as well as divergent actions at the other monoamine transporters may be related to the differing pharmacological actions of these compounds, in vivo. These studies suggest that novel dopamine uptake inhibitors, which are structurally and pharmacologically distinct from cocaine, may be developed as potential cocaine-abuse therapeutics. Copyright 2002 Wiley Periodicals, Inc. Med Res Rev, 22, No. 5, 429-464, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/med.10014 JF - Medicinal research reviews AU - Newman, Amy Hauck AU - Kulkarni, Santosh AD - Medicinal Chemistry Section, National Institute on Drug Abuse--Intramural Research Program, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, Maryland 21224, USA. anewman@intra.nida.nih.gov Y1 - 2002/09// PY - 2002 DA - September 2002 SP - 429 EP - 464 VL - 22 IS - 5 SN - 0198-6325, 0198-6325 KW - Dopamine Plasma Membrane Transport Proteins KW - 0 KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Molecular Probes KW - Nerve Tissue Proteins KW - SLC6A3 protein, human KW - Benztropine KW - 1NHL2J4X8K KW - Index Medicus KW - Humans KW - Drug Design KW - Cocaine-Related Disorders -- drug therapy KW - Benztropine -- analogs & derivatives KW - Membrane Transport Proteins -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72057206?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Medicinal+research+reviews&rft.atitle=Probes+for+the+dopamine+transporter%3A+new+leads+toward+a+cocaine-abuse+therapeutic--A+focus+on+analogues+of+benztropine+and+rimcazole.&rft.au=Newman%2C+Amy+Hauck%3BKulkarni%2C+Santosh&rft.aulast=Newman&rft.aufirst=Amy&rft.date=2002-09-01&rft.volume=22&rft.issue=5&rft.spage=429&rft.isbn=&rft.btitle=&rft.title=Medicinal+research+reviews&rft.issn=01986325&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-10-24 N1 - Date created - 2002-09-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Occupational exposures and the risk of ovarian cancer in Sweden. AN - 72054855; 12210689 AB - Studies of occupational exposures and ovarian cancer, often limited by few subjects or proportionate mortality data, have yielded inconsistent results. Swedish women employed in 1960, 1970, or during both years were followed from 1971 to 1989 using census data linked to nationwide cancer and death registries. A total of 9,591 ovarian cancer cases were identified among 1,670,517 women. Poisson regression was used to estimate the relative risk of ovarian cancer in specific occupational groups and in women exposed to particular occupational exposures defined by job exposure matrices. We lacked data on reproductive factors. Jobs associated with elevated ovarian cancer rates in this and previous studies include dry cleaning, telegraph and telephone work, paper packaging, and graphic and printing work. In contrast to results of some previous studies, we found that hairdressers and beauticians were not at increased risk of ovarian cancer. Organic dusts, aromatic amines, aliphatic and aromatic hydrocarbons are suggested as specific etiologic agents. In this large study, we have confirmed some results from smaller studies and identified some new relationships that need to be confirmed elsewhere. Published 2002 Wiley-Liss, Inc. JF - American journal of industrial medicine AU - Shields, Tammy AU - Gridley, Gloria AU - Moradi, Tahere AU - Adami, Johanna AU - Plato, Nils AU - Dosemeci, Mustafa AD - National Cancer Institute, Environmental Epidemiology Branch, Bethesda, Maryland 20892-7234, USA. shieldst@mail.nih.gov Y1 - 2002/09// PY - 2002 DA - September 2002 SP - 200 EP - 213 VL - 42 IS - 3 SN - 0271-3586, 0271-3586 KW - Index Medicus KW - Humans KW - Poisson Distribution KW - Age Distribution KW - Population Surveillance KW - Risk Assessment KW - Registries KW - Risk Factors KW - Adult KW - Sweden -- epidemiology KW - Confidence Intervals KW - Incidence KW - Middle Aged KW - Female KW - Survival Analysis KW - Ovarian Neoplasms -- etiology KW - Occupational Exposure -- adverse effects KW - Occupations KW - Ovarian Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72054855?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Occupational+exposures+and+the+risk+of+ovarian+cancer+in+Sweden.&rft.au=Shields%2C+Tammy%3BGridley%2C+Gloria%3BMoradi%2C+Tahere%3BAdami%2C+Johanna%3BPlato%2C+Nils%3BDosemeci%2C+Mustafa&rft.aulast=Shields&rft.aufirst=Tammy&rft.date=2002-09-01&rft.volume=42&rft.issue=3&rft.spage=200&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 - 2002-10-10 N1 - Date created - 2002-09-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Allopregnanolone activates GABA(A) receptor/Cl(-) channels in a multiphasic manner in embryonic rat hippocampal neurons. AN - 72053849; 12205136 AB - Although 3alpha-substituted metabolites of progesterone are well established to interact with GABA(A) receptor/Cl(-) channels, the nature of the interaction(s) remains uncertain. We used patch-clamp recording to study the interaction with GABA(A) receptor/Cl(-) channels expressed by embryonic hippocampal neurons differentiating in culture and nonneuronal cells transfected with GABA(A) receptor subunits. Allopregnanolone primarily induced multiphasic current responses in neurons, which were eliminated by bicuculline, an antagonist of GABA at GABA(A) receptor/Cl(-) channels. Similar multiphasic responses blocked by bicuculline were induced by allopregnanollone in nonneuronal cells transfected with alpha(1) and gamma(2) subunits, indicating that the steroid activation of GABA(A) receptor/Cl(-) channels occurred independently of GABA. Fluctuation analyses of current responses to allopregnanolone and GABA revealed underlying channel activities with similar estimated unitary properties. However, although both agonists activated Cl(-) channels with similar estimated short and long burst-length durations, most of those stimulated by the steroid were short, while most of those opened by GABA were long. Allopregnanolone potentiated GABA-evoked Cl(-) currents in nonneuronal cells transfected with alpha(1) and beta(2) or beta(3) subunits, which did not exhibit multiphasic responses to the steroid, indicating another, independent action of the steroid at activated receptors. Pertussis toxin treatment eliminated the low-amplitude current and attenuated the high-amplitude current induced by allopregnanolone in a reversible manner. Mastoparan, which activates G proteins directly, triggered a high-amplitude current after a delay, which was blocked by bicuculline. The results indicate that allopregnanolone interacts with GABA(A) receptor/Cl(-) channels expressed by embryonic hippocampal neurons in multiple ways, some of which are mediated by G proteins. JF - Journal of neurophysiology AU - Liu, Qi-Ying AU - Chang, Yoong H AU - Schaffner, Anne E AU - Smith, Susan V AU - Barker, Jeffery L AD - Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/09// PY - 2002 DA - September 2002 SP - 1147 EP - 1158 VL - 88 IS - 3 SN - 0022-3077, 0022-3077 KW - Chloride Channels KW - 0 KW - Chlorides KW - Receptors, GABA-A KW - Steroids KW - Virulence Factors, Bordetella KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - Pregnanolone KW - BXO86P3XXW KW - Pertussis Toxin KW - EC 2.4.2.31 KW - Index Medicus KW - Animals KW - Electric Conductivity KW - Dose-Response Relationship, Drug KW - gamma-Aminobutyric Acid -- pharmacology KW - Steroids -- pharmacology KW - Cell Differentiation KW - Chlorides -- physiology KW - Rats KW - Virulence Factors, Bordetella -- pharmacology KW - Animals, Newborn KW - Cells, Cultured KW - Steroids -- chemistry KW - Drug Synergism KW - Embryo, Mammalian KW - Reaction Time KW - Receptors, GABA-A -- physiology KW - Neurons -- metabolism KW - Pregnanolone -- administration & dosage KW - Neurons -- drug effects KW - Neurons -- cytology KW - Hippocampus -- metabolism KW - Chloride Channels -- physiology KW - Chloride Channels -- drug effects KW - Receptors, GABA-A -- drug effects KW - Pregnanolone -- pharmacology KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72053849?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurophysiology&rft.atitle=Allopregnanolone+activates+GABA%28A%29+receptor%2FCl%28-%29+channels+in+a+multiphasic+manner+in+embryonic+rat+hippocampal+neurons.&rft.au=Liu%2C+Qi-Ying%3BChang%2C+Yoong+H%3BSchaffner%2C+Anne+E%3BSmith%2C+Susan+V%3BBarker%2C+Jeffery+L&rft.aulast=Liu&rft.aufirst=Qi-Ying&rft.date=2002-09-01&rft.volume=88&rft.issue=3&rft.spage=1147&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurophysiology&rft.issn=00223077&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-10-23 N1 - Date created - 2002-09-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - cDNA array analysis of gene expression profiles in the striata of wild-type and Cu/Zn superoxide dismutase transgenic mice treated with neurotoxic doses of amphetamine. AN - 72051073; 12205029 AB - Amphetamine (AMPH) is a drug of abuse that causes the degeneration of striatal dopamine terminals in mammals. Superoxide radicals seem to participate in AMPH-induced damage because its toxicity is attenuated in Cu/Zn superoxide dismutase transgenic (SOD-tg) mice. To provide a detailed analysis of molecular changes associated with AMPH toxicity, we used cDNA arrays consisting of 1176 genes to detect differential changes in gene expression in the striata of wild-type and SOD-tg mice treated with neurotoxic doses of the drug. We found 42 genes that showed >1.8-fold changes in at least two consecutive time points during the course of the study and were differentially affected by AMPH in the two genotypes. Specifically, more transcription factors and genes involved in responses to injury/inflammation were affected in wild-type mice after AMPH administration. Some of these stimulant-induced superoxide-dependent alterations in gene expression might affect neuronal functions and promote neuronal damage. Other changes might help to provide some degree of protection against AMPH toxicity. These results support the view that the use of global array analysis of gene expression will help to identify novel molecular mediators of AMPH-induced neurodegeneration. JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Krasnova, Irina N AU - McCoy, Michael T AU - Ladenheim, Bruce AU - Cadet, Jean Lud AD - Molecular Neuropsychiatry Section, National Institute on Drug Abuse-Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 2002/09// PY - 2002 DA - September 2002 SP - 1379 EP - 1388 VL - 16 IS - 11 KW - Psychotropic Drugs KW - 0 KW - RNA, Messenger KW - Amphetamine KW - CK833KGX7E KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Index Medicus KW - Gene Expression Profiling KW - Animals KW - Oligonucleotide Array Sequence Analysis KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - Mice, Transgenic KW - RNA, Messenger -- biosynthesis KW - Male KW - Psychotropic Drugs -- pharmacology KW - Corpus Striatum -- metabolism KW - Amphetamine -- administration & dosage KW - Superoxide Dismutase -- genetics KW - Corpus Striatum -- drug effects KW - Psychotropic Drugs -- administration & dosage KW - Amphetamine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72051073?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.atitle=cDNA+array+analysis+of+gene+expression+profiles+in+the+striata+of+wild-type+and+Cu%2FZn+superoxide+dismutase+transgenic+mice+treated+with+neurotoxic+doses+of+amphetamine.&rft.au=Krasnova%2C+Irina+N%3BMcCoy%2C+Michael+T%3BLadenheim%2C+Bruce%3BCadet%2C+Jean+Lud&rft.aulast=Krasnova&rft.aufirst=Irina&rft.date=2002-09-01&rft.volume=16&rft.issue=11&rft.spage=1379&rft.isbn=&rft.btitle=&rft.title=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.issn=1530-6860&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-09-11 N1 - Date created - 2002-09-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tramtrack co-operates to prevent inappropriate neural development in Drosophila. AN - 72049002; 12204250 AB - Each sensory organ of the Drosophila peripheral nervous system is derived from a single sensory organ precursor cell (SOP). These originate in territories defined by expression of the proneural genes of the Achaete-Scute complex (AS-C). Formation of ectopic sensilla outside these regions is prevented by transcriptional repression of proneural genes. We demonstrate that the BTB/POZ-domain transcriptional repressor Tramtrack (Ttk) co-operates in this repression. Ttk is expressed ubiquitously, except in proneural clusters and SOPs. Ttk over-expression represses proneural genes and sensilla formation. Loss of Ttk enhances bristle-promoting mutants. Using neural repression as an assay, we dissected functional domains of Ttk, confirming the importance of the bric-à-brac-tramtrack-broad complex (BTB) motif. We show that the Ttk BTB domain is a protein-protein interaction motif mediating tetramer formation. Copyright 2002 Elsevier Science Ireland Ltd. JF - Mechanisms of development AU - Badenhorst, Paul AU - Finch, John T AU - Travers, Andrew A AD - MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, England, UK. badenhop@pop.nci.nih.gov Y1 - 2002/09// PY - 2002 DA - September 2002 SP - 87 EP - 101 VL - 117 IS - 1-2 SN - 0925-4773, 0925-4773 KW - Drosophila Proteins KW - 0 KW - Recombinant Fusion Proteins KW - Repressor Proteins KW - ttk protein, Drosophila KW - Index Medicus KW - Recombinant Fusion Proteins -- metabolism KW - Animals KW - Recombinant Fusion Proteins -- genetics KW - Sense Organs -- metabolism KW - Sense Organs -- growth & development KW - Protein Structure, Tertiary KW - Genes, Insect KW - Male KW - Gene Expression Regulation, Developmental KW - Female KW - Recombinant Fusion Proteins -- chemistry KW - Mutagenesis KW - Binding Sites KW - Peripheral Nerves -- growth & development KW - Repressor Proteins -- metabolism KW - Drosophila -- metabolism KW - Peripheral Nerves -- metabolism KW - Drosophila -- genetics KW - Repressor Proteins -- genetics KW - Repressor Proteins -- chemistry KW - Drosophila -- growth & development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72049002?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mechanisms+of+development&rft.atitle=Tramtrack+co-operates+to+prevent+inappropriate+neural+development+in+Drosophila.&rft.au=Badenhorst%2C+Paul%3BFinch%2C+John+T%3BTravers%2C+Andrew+A&rft.aulast=Badenhorst&rft.aufirst=Paul&rft.date=2002-09-01&rft.volume=117&rft.issue=1-2&rft.spage=87&rft.isbn=&rft.btitle=&rft.title=Mechanisms+of+development&rft.issn=09254773&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-09 N1 - Date created - 2002-09-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - AP-1, NF-kappa-B, and ERK activation thresholds for promotion of neoplastic transformation in the mouse epidermal JB6 model. AN - 72048511; 12204819 AB - The promotion-sensitive mouse epidermal JB6 cells (clone 41) have been used to identify the tumor-promoting activity of various compounds. Because treatment by tumor promoters [12-O-tetradecanoylphorbol-13-acetate (TPA), epidermal growth factor (EGF), or tumor necrosis factor alpha (TNF-alpha)] transforms clone 41 cells to anchorage-independent and tumorigenic phenotypes, they are considered to be undergoing late-stage tumor promotion. Here we address the question of how much activation of transformation-relevant transcription factors [activator protein-1 (AP-1), ternary complex factors (TCFs), or nuclear factor kappa-B (NF-kappa-B)] is required for transformation response and how much tumor promoter produces significant risk of transformation. Stable transfectants harboring a reporter construct with an AP-1 response element, serum-response element (SRE), or NF-kappa-B response element were established. We examined the relationship between concentration of tumor promoters, key signaling events, and activation of the transcription factors. A concentration of > 0.2 nM TPA or 0.12 ng/mL (0.02 nM) EGF produced a significant increase in transformation response as well as in extracellular signal-regulated protein kinase (ERK), SRE, or AP-1 activation. Treatment with > 0.4 U/mL (2.35 pM) TNF-alpha increased NF-kappa-B activity and transformation response in a dose-dependent manner. However, transformation response decreased at > 33 U/mL TNF-alpha due to a cytotoxic response. These findings suggest that the signaling pathway leading to the activation of ERK, TCF, and AP-1 proteins constitutes a major factor determining the risk of tumor promotion by TPA or EGF. Cell toxicity in addition to NF-kappa-B activation should be considered in predicting TNF-alpha-induced transformation response. JF - Environmental health perspectives AU - Suzukawa, Kazumi AU - Weber, Thomas J AU - Colburn, Nancy H AD - Gene Regulation Section, Basic Research Laboratory, National Cancer Institute, Frederick, Maryland 21702, USA. Y1 - 2002/09// PY - 2002 DA - September 2002 SP - 865 EP - 870 VL - 110 IS - 9 SN - 0091-6765, 0091-6765 KW - Mutagens KW - 0 KW - NF-kappa B KW - Transcription Factor AP-1 KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Cell Culture Techniques KW - Skin -- cytology KW - Mice KW - Signal Transduction KW - Risk Assessment KW - Mutagens -- adverse effects KW - NF-kappa B -- pharmacology KW - Mitogen-Activated Protein Kinases -- pharmacology KW - Transcription Factor AP-1 -- pharmacology KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72048511?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=AP-1%2C+NF-kappa-B%2C+and+ERK+activation+thresholds+for+promotion+of+neoplastic+transformation+in+the+mouse+epidermal+JB6+model.&rft.au=Suzukawa%2C+Kazumi%3BWeber%2C+Thomas+J%3BColburn%2C+Nancy+H&rft.aulast=Suzukawa&rft.aufirst=Kazumi&rft.date=2002-09-01&rft.volume=110&rft.issue=9&rft.spage=865&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 - 2002-10-29 N1 - Date created - 2002-09-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Oncogene. 1998 Dec 31;17(26):3493-8 [10030673] Oncogene. 1998 May 28;16(21):2711-21 [9652737] J Biol Chem. 1999 May 21;274(21):14595-601 [10329651] Oncogene. 1999 May 6;18(18):2828-35 [10362253] Nat Med. 1999 Jul;5(7):828-31 [10395330] Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9827-32 [10449779] Cancer Res. 1999 Sep 15;59(18):4516-8 [10493498] Cancer Res. 2000 Feb 1;60(3):553-9 [10676636] Free Radic Biol Med. 2000 May 1;28(9):1338-48 [10924853] Mol Carcinog. 2000 Nov;29(3):159-69 [11108661] J Dermatol Sci. 2001 Feb;25(2):139-49 [11164710] Cancer Res. 2001 Feb 1;61(3):850-3 [11221868] Proc Natl Acad Sci U S A. 2001 May 8;98(10):5786-91 [11331771] Cancer Res. 2001 May 15;61(10):4160-8 [11358840] Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7510-5 [11416221] Nature. 1979 Oct 18;281(5732):589-91 [492322] Cancer Res. 1986 Nov;46(11):5923-32 [3093072] Science. 1989 May 5;244(4904):566-9 [2541502] Annu Rev Cell Biol. 1990;6:539-57 [2125830] Biochim Biophys Acta. 1991 Dec 10;1072(2-3):129-57 [1751545] Mol Carcinog. 1992;5(1):62-74 [1543542] Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):609-13 [8290571] Environ Health Perspect. 1994 Jan;102 Suppl 1:255-64 [8187717] Carcinogenesis. 1994 Oct;15(10):2363-70 [7955078] Semin Cancer Biol. 1994 Aug;5(4):261-8 [7803762] Science. 1995 Jul 21;269(5222):403-7 [7618106] Curr Biol. 1995 Oct 1;5(10):1191-200 [8548291] Cancer Res. 1996 Feb 1;56(3):483-9 [8564958] Regul Toxicol Pharmacol. 1996 Feb;23(1 Pt 1):44-8 [8628919] Oncol Res. 1995;7(7-8):353-62 [8747598] EMBO J. 1996 Dec 2;15(23):6552-63 [8978682] J Biol Chem. 1997 Apr 11;272(15):9962-70 [9092536] EMBO J. 1997 Apr 1;16(7):1620-7 [9130707] Carcinogenesis. 1997 Jul;18(7):1365-70 [9230281] Cancer Res. 1997 Aug 15;57(16):3569-76 [9270030] Semin Cancer Biol. 1997 Apr;8(2):63-73 [9299584] Cancer Res. 1997 Oct 1;57(19):4414-9 [9331105] Proc Natl Acad Sci U S A. 1998 Jan 6;95(1):156-61 [9419345] Environ Health Perspect. 1999 Mar;107(3):195-8 [10064548] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - New genes involved in cancer identified by retroviral tagging. AN - 72046600; 12185365 AB - Retroviral insertional mutagenesis in BXH2 and AKXD mice induces a high incidence of myeloid leukemia and B- and T-cell lymphoma, respectively. The retroviral integration sites (RISs) in these tumors thus provide powerful genetic tags for the discovery of genes involved in cancer. Here we report the first large-scale use of retroviral tagging for cancer gene discovery in the post-genome era. Using high throughput inverse PCR, we cloned and analyzed the sequences of 884 RISs from a tumor panel composed primarily of B-cell lymphomas. We then compared these sequences, and another 415 RIS sequences previously cloned from BXH2 myeloid leukemias and from a few AKXD lymphomas, against the recently assembled mouse genome sequence. These studies identified 152 loci that are targets of retroviral integration in more than one tumor (common retroviral integration sites, CISs) and therefore likely to encode a cancer gene. Thirty-six CISs encode genes that are known or predicted to be genes involved in human cancer or their homologs, whereas others encode candidate genes that have not yet been examined for a role in human cancer. Our studies demonstrate the power of retroviral tagging for cancer gene discovery in the post-genome era and indicate a largely unrecognized complexity in mouse and presumably human cancer. JF - Nature genetics AU - Suzuki, Takeshi AU - Shen, Haifa AU - Akagi, Keiko AU - Morse, Herbert C AU - Malley, James D AU - Naiman, Daniel Q AU - Jenkins, Nancy A AU - Copeland, Neal G AD - Mouse Cancer Genetics Program, National Cancer Institute, Frederick, Maryland 21702, USA. Y1 - 2002/09// PY - 2002 DA - September 2002 SP - 166 EP - 174 VL - 32 IS - 1 SN - 1061-4036, 1061-4036 KW - Index Medicus KW - Polymerase Chain Reaction KW - Mice, Inbred Strains KW - Animals KW - Oncogenes KW - Genes, Tumor Suppressor KW - Humans KW - Proviruses -- genetics KW - Mice KW - Leukemia, Myeloid -- genetics KW - Lymphoma, B-Cell -- genetics KW - Retroviridae -- genetics KW - Virus Integration -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72046600?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=New+genes+involved+in+cancer+identified+by+retroviral+tagging.&rft.au=Suzuki%2C+Takeshi%3BShen%2C+Haifa%3BAkagi%2C+Keiko%3BMorse%2C+Herbert+C%3BMalley%2C+James+D%3BNaiman%2C+Daniel+Q%3BJenkins%2C+Nancy+A%3BCopeland%2C+Neal+G&rft.aulast=Suzuki&rft.aufirst=Takeshi&rft.date=2002-09-01&rft.volume=32&rft.issue=1&rft.spage=166&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 - 2002-09-27 N1 - Date created - 2002-09-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Nat Genet 2002 Oct;32(2):331 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selective pericyte degeneration in the retinal capillaries of galactose-fed dogs results from apoptosis linked to aldose reductase-catalyzed galactitol accumulation. AN - 72038641; 12200082 AB - Galactose-fed dogs develop retinal capillary changes similar to diabetic retinopathy with pericyte degeneration as the initial lesion. This is followed by the formation of microaneurysms, hemorrhages, and some areas of acellularity. To investigate the mechanisms for selective pericyte degeneration, retinal capillary pericytes and endothelial cells isolated from beagle dog retina were cultured for 2 weeks in Dulbecco's modified Eagle's medium (DMEM) containing 50 mM D-galactose. Apoptosis was detected in pericytes but not endothelial cells by in situ terminal deoxynucleotidyl transferase (TdT)-mediated biotin-dUTP nick end labelling (TUNEL) staining and the DNA fragmentation assay on agarose gel electrophoresis. This apoptosis was prevented by the addition of the aldose reductase inhibitor AL 1576 to the culture medium containing galactose. Apoptosis was not observed when pericytes were similarly cultured in control DMEM medium. These data support the premise that the selective degeneration of retinal capillary pericytes observed in galactose-fed dogs is linked to increased aldose reductase activity in these cells. JF - Journal of diabetes and its complications AU - Murata, M AU - Ohta, N AU - Fujisawa, S AU - Tsai, J-Y AU - Sato, S AU - Akagi, Y AU - Takahashi, Y AU - Neuenschwander, H AU - Kador, P F AD - Laboratory of Ocular Therapeutics, National Eye Institute, National Institutes of Health, Building 10, Room 10B11, 10 Center Drive, MSC 1850, Bethesda, MD 20892-1850, USA. PY - 2002 SP - 363 EP - 370 VL - 16 IS - 5 SN - 1056-8727, 1056-8727 KW - Galactitol KW - 113ZQ1Y7DD KW - Aldehyde Reductase KW - EC 1.1.1.21 KW - Galactose KW - X2RN3Q8DNE KW - Index Medicus KW - Animals KW - Gene Expression Regulation, Enzymologic -- drug effects KW - Cells, Cultured KW - Dogs KW - Male KW - Pericytes -- pathology KW - Capillaries -- pathology KW - Capillaries -- drug effects KW - Pericytes -- metabolism KW - Apoptosis -- drug effects KW - Retinal Vessels -- drug effects KW - Galactose -- toxicity KW - Pericytes -- drug effects KW - Galactitol -- metabolism KW - Aldehyde Reductase -- genetics KW - Retinal Vessels -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72038641?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+diabetes+and+its+complications&rft.atitle=Selective+pericyte+degeneration+in+the+retinal+capillaries+of+galactose-fed+dogs+results+from+apoptosis+linked+to+aldose+reductase-catalyzed+galactitol+accumulation.&rft.au=Murata%2C+M%3BOhta%2C+N%3BFujisawa%2C+S%3BTsai%2C+J-Y%3BSato%2C+S%3BAkagi%2C+Y%3BTakahashi%2C+Y%3BNeuenschwander%2C+H%3BKador%2C+P+F&rft.aulast=Murata&rft.aufirst=M&rft.date=2002-09-01&rft.volume=16&rft.issue=5&rft.spage=363&rft.isbn=&rft.btitle=&rft.title=Journal+of+diabetes+and+its+complications&rft.issn=10568727&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-13 N1 - Date created - 2002-08-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sampling private wells at past homes to estimate arsenic exposure: a methodologic study in New England. AN - 72036131; 12198581 AB - We are conducting a collaborative, population-based case-control study in Maine, New Hampshire, and Vermont to investigate the reasons for the elevated bladder cancer mortality in northern New England. Arsenic in drinking water is one of the primary exposures under investigation. To estimate subjects' lifetime exposure to waterborne arsenic, it will be necessary to obtain water samples from private wells that subjects used in the past. We conducted a methodologic study to assess the feasibility of locating and sampling from private wells at subjects' past residences. Ninety-eight New Hampshire residents (mean age 67 years) completed a questionnaire requesting the complete address, dates of occupancy, and drinking water sources for each home lived in since birth. An interviewer then asked subjects for more detailed information about each home to assist in a field search of past homes in the three-state study area of Maine, New Hampshire, and Vermont. Fifty-eight of the 98 subjects indicated that they had used a total of 103 private wells in 95 previous homes located in these three states. We conducted a field search to locate these 95 homes, visited town offices to find the properties on tax maps and obtain the current owners' names and addresses, attempted to obtain permission from the current owners to sample the wells, and collected water samples. In all, 48 (47%) of the 103 past wells in the study area were sampled successfully. The remaining wells were not sampled because the homes were not located (22%) or had been demolished (2%), permission to sample the wells was not obtained (17%), the wells had been destroyed (7%) or could not be found on the grounds of the residence (3%), or for other reasons (2%). Various approaches for improving the success rates for sampling water from private wells are discussed, as is the use of predictive modeling to impute exposures when sampling is not feasible. JF - Journal of exposure analysis and environmental epidemiology AU - Colt, Joanne S AU - Baris, Dalsu AU - Clark, Stewart F AU - Ayotte, Joseph D AU - Ward, Mary AU - Nuckols, John R AU - Cantor, Kenneth P AU - Silverman, Debra T AU - Karagas, Margaret AD - Occupational Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892-7240, USA. coltj@mail.nih.gov Y1 - 2002/09// PY - 2002 DA - September 2002 SP - 329 EP - 334 VL - 12 IS - 5 SN - 1053-4245, 1053-4245 KW - Arsenic KW - N712M78A8G KW - Index Medicus KW - Urinary Bladder Neoplasms -- etiology KW - Housing KW - Humans KW - Aged KW - Risk Assessment KW - Feasibility Studies KW - Adult KW - Case-Control Studies KW - Urinary Bladder Neoplasms -- mortality KW - Epidemiological Monitoring KW - Middle Aged KW - New England -- epidemiology KW - Female KW - Male KW - Arsenic -- analysis KW - Water Supply KW - Environmental Exposure KW - Environmental Monitoring -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72036131?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Sampling+private+wells+at+past+homes+to+estimate+arsenic+exposure%3A+a+methodologic+study+in+New+England.&rft.au=Colt%2C+Joanne+S%3BBaris%2C+Dalsu%3BClark%2C+Stewart+F%3BAyotte%2C+Joseph+D%3BWard%2C+Mary%3BNuckols%2C+John+R%3BCantor%2C+Kenneth+P%3BSilverman%2C+Debra+T%3BKaragas%2C+Margaret&rft.aulast=Colt&rft.aufirst=Joanne&rft.date=2002-09-01&rft.volume=12&rft.issue=5&rft.spage=329&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 - 2002-11-19 N1 - Date created - 2002-08-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Accuracy of self-reported pesticide use duration information from licensed pesticide applicators in the Agricultural Health Study. AN - 72033794; 12198579 AB - Epidemiologists frequently rely on self-reported information regarding a variety of exposures including smoking history, medication use, and occupational exposure because other sources of information are either unavailable or difficult to obtain. One way to evaluate the accuracy of self-reported information is through logic checks using other sources. To assess the quality of the self-reported pesticide product use history of 57,311 licensed pesticide applicators in the Agricultural Health Study (AHS), we compared the self-reported decade of first use and total years of use to the year the pesticide active ingredient was first registered for use. We obtained pesticide active ingredient registration information from the United States Environmental Protection Agency (USEPA) and other publicly available sources for the 52 pesticides on the AHS initial questionnaires administered from 1994 to 1997. Based on the registration year, we assessed 19 pesticides for potential inaccuracies regarding duration of use or decade of first use. When calculating potential total years of use, we did not consider the impact of chemicals being removed from the market, since the possibility for continued use existed. The majority of respondents provided plausible responses for both decade of first use and total duration of use. On average, 1% of the subjects overestimated total possible duration of use, ranging from less than 1% for carbofuran and chlorpyrifos to 5% for imazethapyr. Decade of first use was also reasonably reported, although more subjects did not report decade of first use than duration of use, with an average of 6% of subjects missing decade information for an individual chemical. For subjects who reported a decade of first use, 98% gave plausible responses on average, with overestimates highest for cyanazine, introduced in 1971 (6% reported earlier use), and chlorimuron ethyl, introduced in 1985 (7% reported earlier use). This analysis provided the opportunity to consider only one source of potential overreporting of exposure, and while underreporting may have also occurred, we cannot evaluate its role nor the balance between these potential inaccuracies. While we are unable to validate directly the accuracy of a respondent's use of pesticides, this analysis suggests that participants provide plausible information regarding their pesticide use. JF - Journal of exposure analysis and environmental epidemiology AU - Hoppin, Jane A AU - Yucel, Fikri AU - Dosemeci, Mustafa AU - Sandler, Dale P AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709-2233, USA. hoppin1@niehs.nih.gov Y1 - 2002/09// PY - 2002 DA - September 2002 SP - 313 EP - 318 VL - 12 IS - 5 SN - 1053-4245, 1053-4245 KW - Pesticides KW - 0 KW - Index Medicus KW - Reproducibility of Results KW - Epidemiologic Studies KW - Humans KW - Retrospective Studies KW - Mental Recall KW - Time Factors KW - Quality Control KW - Pesticides -- chemistry KW - Occupational Exposure KW - Pesticides -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72033794?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Accuracy+of+self-reported+pesticide+use+duration+information+from+licensed+pesticide+applicators+in+the+Agricultural+Health+Study.&rft.au=Hoppin%2C+Jane+A%3BYucel%2C+Fikri%3BDosemeci%2C+Mustafa%3BSandler%2C+Dale+P&rft.aulast=Hoppin&rft.aufirst=Jane&rft.date=2002-09-01&rft.volume=12&rft.issue=5&rft.spage=313&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 - 2002-11-19 N1 - Date created - 2002-08-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer incidence after nasopharyngeal radium irradiation. AN - 72027779; 12192225 AB - From 1940 until 1970, nasopharyngeal radium irradiation was used to treat children and military personnel suffering from Eustachian tube failure attributable to local lymphoid hyperplasia. We studied cancer incidence in a cohort of 4339 Dutch patients treated with nasopharyngeal radium irradiation, mostly in childhood, and 4104 frequency-matched nonexposed subjects. Average doses to the nasopharynx, pituitary gland, brain, and thyroid gland were 275, 10.9, 1.8, and 1.5 cGy, respectively. We assessed cancer incidence from cancer registry linkage (1989-1996), self-report including medical verification (1945-1988), and death certificates (1945-1996). During 18-50 years of follow-up, four thyroid malignancies (standardized incidence ratio [SIR] = 2.8; 95% confidence interval [CI] = 0.8-7.2) and five malignant brain tumors (SIR = 1.3; CI = 0.4-3.1) were observed. Increased risks were observed for malignancies of lymphoproliferative and hematopoietic origin (SIR = 1.9; CI = 1.2-2.8) and breast cancer (SIR = 1.5; CI = 1.1-2.1). Strong dose-response trends could not be demonstrated for any cancer outcome, although relative risk estimates were elevated in the highest-dose category for head and neck cancer and breast cancer. These data provide little evidence for a high excess risk of cancer associated with nasopharyngeal radium irradiation treatment as applied in the Netherlands. Inconsistent findings across studies and public concern warrant the continuing follow-up of available cohorts. JF - Epidemiology (Cambridge, Mass.) AU - Ronckers, Cécile M AU - Van Leeuwen, Flora E AU - Hayes, Richard B AU - Verduijn, Pieter G AU - Stovall, Marilyn AU - Land, Charles E AD - Department of Ear-Nose and Throat Medicine, Reinaert Kliniek, Maastricht, the Netherlands. ronckerc@mail.nih.gov Y1 - 2002/09// PY - 2002 DA - September 2002 SP - 552 EP - 560 VL - 13 IS - 5 SN - 1044-3983, 1044-3983 KW - Radium KW - W90AYD6R3Q KW - Index Medicus KW - Netherlands -- epidemiology KW - Brain Neoplasms -- epidemiology KW - Humans KW - Child KW - Head and Neck Neoplasms -- epidemiology KW - Child, Preschool KW - Lymphoid Tissue -- radiation effects KW - Lymphoma, Non-Hodgkin -- epidemiology KW - Head and Neck Neoplasms -- etiology KW - Radiotherapy Dosage KW - Adult KW - Lymphoma, Non-Hodgkin -- etiology KW - Incidence KW - Middle Aged KW - Follow-Up Studies KW - Adolescent KW - Male KW - Female KW - Brain Neoplasms -- etiology KW - Neoplasms, Radiation-Induced -- etiology KW - Neoplasms, Radiation-Induced -- epidemiology KW - Radium -- therapeutic use KW - Otorhinolaryngologic Diseases -- radiotherapy KW - Nasopharynx -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72027779?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cancer+incidence+after+nasopharyngeal+radium+irradiation.&rft.au=Ronckers%2C+C%C3%A9cile+M%3BVan+Leeuwen%2C+Flora+E%3BHayes%2C+Richard+B%3BVerduijn%2C+Pieter+G%3BStovall%2C+Marilyn%3BLand%2C+Charles+E&rft.aulast=Ronckers&rft.aufirst=C%C3%A9cile&rft.date=2002-09-01&rft.volume=13&rft.issue=5&rft.spage=552&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 - 2002-10-01 N1 - Date created - 2002-08-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Anti-tumor activities of the angiogenesis inhibitors interferon-inducible protein-10 and the calreticulin fragment vasostatin. AN - 72024384; 12192535 AB - Tumor growth depends upon an adequate supply of oxygen and nutrients achieved through angiogenesis and maintenance of an intact tumor vasculature. Therapy with individual agents that target new vessel formation or existing vessels has suppressed experimental tumor growth, but rarely resulted in the eradication of tumors. We therefore tested the combined anti-tumor activity of vasostatin and interferon-inducible protein-10 (IP-10), agents that differently target the tumor vasculature. Vasostatin, a selective and direct inhibitor of endothelial cell proliferation, significantly reduced Burkitt tumor growth and tumor vessel density. IP-10, an "angiotoxic" chemokine, caused vascular damage and focal necrosis in Burkitt tumors. When combined, vasostatin plus IP-10 reduced tumor growth more effectively than each agent alone, but complete tumor regression was not observed. Microscopically, these tumors displayed focal necrosis and reduction in vessel density. Combination therapy with the inhibitors of angiogenesis vasostatin and IP-10 is effective in reducing the rate of tumor growth but fails to induce tumor regression, suggesting that curative treatment may require supplemental drugs targeting directly the tumor cells. JF - Cancer immunology, immunotherapy : CII AU - Yao, Lei AU - Pike, Sandra E AU - Pittaluga, Stefania AU - Cherney, Barry AU - Gupta, Ghanshyam AU - Jaffe, Elaine S AU - Tosato, Giovanna AD - Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Building 10, Room 12N226 MSC 1907, 10 Center Drive, Bethesda, MD, USA. yaol@mail.nih.gov Y1 - 2002/09// PY - 2002 DA - September 2002 SP - 358 EP - 366 VL - 51 IS - 7 SN - 0340-7004, 0340-7004 KW - Actins KW - 0 KW - Angiogenesis Inhibitors KW - Antigens, CD31 KW - Antineoplastic Agents KW - Calcium-Binding Proteins KW - Calreticulin KW - Chemokine CXCL10 KW - Peptide Fragments KW - Recombinant Fusion Proteins KW - Ribonucleoproteins KW - vasostatin KW - Index Medicus KW - Animals KW - Muscle, Smooth, Vascular -- drug effects KW - Cell Division -- drug effects KW - Mice KW - Mice, Nude KW - Mice, Inbred BALB C KW - Endothelium, Vascular -- drug effects KW - Apoptosis -- drug effects KW - Xenograft Model Antitumor Assays KW - Drug Synergism KW - Recombinant Fusion Proteins -- therapeutic use KW - Actins -- analysis KW - Antigens, CD31 -- analysis KW - Drug Evaluation, Preclinical KW - Angiogenesis Inhibitors -- therapeutic use KW - Peptide Fragments -- therapeutic use KW - Neovascularization, Pathologic -- drug therapy KW - Burkitt Lymphoma -- prevention & control KW - Ribonucleoproteins -- therapeutic use KW - Calcium-Binding Proteins -- therapeutic use KW - Chemokine CXCL10 -- therapeutic use KW - Antineoplastic Agents -- therapeutic use KW - Burkitt Lymphoma -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72024384?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Anti-tumor+activities+of+the+angiogenesis+inhibitors+interferon-inducible+protein-10+and+the+calreticulin+fragment+vasostatin.&rft.au=Yao%2C+Lei%3BPike%2C+Sandra+E%3BPittaluga%2C+Stefania%3BCherney%2C+Barry%3BGupta%2C+Ghanshyam%3BJaffe%2C+Elaine+S%3BTosato%2C+Giovanna&rft.aulast=Yao&rft.aufirst=Lei&rft.date=2002-09-01&rft.volume=51&rft.issue=7&rft.spage=358&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 - 2002-09-27 N1 - Date created - 2002-08-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of insulin-like growth factor II on protecting myoblast cells against cisplatin-induced apoptosis through p70 S6 kinase pathway. AN - 72021401; 12192598 AB - Insulin-like growth factor (IGF-II) is overexpressed in a variety of human tumors and has both mitogenic and antiapoptotic activity. Although the mechanisms of IGF-II-induced proliferation have been well studied, the mechanisms underlying its survival signaling have been less well characterized. In this report, we investigated the role of IGF-II on cisplatin-induced apoptosis. We found that IGF-II overexpression was associated with an increase in p70 ribosomal protein S6 kinase (p70 S6K). Cisplatin treatment of C2C12 mouse myoblasts led to cell death associated with an inhibition of p70 S6K activity. Endogenous or exogenous IGF-II addition to C2C12 cells caused protection to cisplatin-induced apoptosis. This protection was associated in both cases with an increase in p70 S6K basal activity as well as resistance to cisplatin-induced decreased activity. Blockade of p70 S6K activation by rapamycin abrogated the IGF-II-mediated protection of cells to cisplatin-induced apoptosis. Furthermore, treatment of IGF-II-overexpressing Rh30 and CTR rhabdomyosarcoma cells with rapamycin restored sensitivity to cisplatin-induced apoptosis. These data together suggest that IGF-II-associated protection to cisplatin-induced apoptosis is mediated through an activation of the p70 S6K pathway. Thus, inhibition of the p70 S6 pathway may enhance chemotherapy-induced apoptosis in the treatment of IGF-II-overexpressing tumors. JF - Neoplasia (New York, N.Y.) AU - Wan, Xiaolin AU - Helman, Lee J AD - Molecular Oncology Section, Pediatric Oncology Branch, NCI, National Institutes of Health, Bethesda, MD 20892-1928, USA. PY - 2002 SP - 400 EP - 408 VL - 4 IS - 5 SN - 1522-8002, 1522-8002 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - Antibiotics, Antineoplastic KW - Antineoplastic Agents KW - Carrier Proteins KW - EIF4EBP1 protein, human KW - Eif4ebp1 protein, mouse KW - Phosphoproteins KW - Insulin-Like Growth Factor II KW - 67763-97-7 KW - Ribosomal Protein S6 Kinases, 70-kDa KW - EC 2.7.11.1 KW - Cisplatin KW - Q20Q21Q62J KW - Sirolimus KW - W36ZG6FT64 KW - Index Medicus KW - Animals KW - Carrier Proteins -- antagonists & inhibitors KW - Humans KW - Cytoprotection KW - Drug Resistance, Neoplasm KW - Mice KW - Blotting, Western KW - Phosphorylation KW - Transfection KW - Antibiotics, Antineoplastic -- pharmacology KW - Sirolimus -- pharmacology KW - Flow Cytometry KW - Up-Regulation KW - Rhabdomyosarcoma -- drug therapy KW - Phosphoproteins -- antagonists & inhibitors KW - Cell Line KW - Cell Division KW - Ribosomal Protein S6 Kinases, 70-kDa -- antagonists & inhibitors KW - Myoblasts -- enzymology KW - Myoblasts -- pathology KW - Myoblasts -- drug effects KW - Cisplatin -- toxicity KW - Apoptosis -- drug effects KW - Antineoplastic Agents -- toxicity KW - Ribosomal Protein S6 Kinases, 70-kDa -- metabolism KW - Signal Transduction KW - Insulin-Like Growth Factor II -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72021401?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neoplasia+%28New+York%2C+N.Y.%29&rft.atitle=Effect+of+insulin-like+growth+factor+II+on+protecting+myoblast+cells+against+cisplatin-induced+apoptosis+through+p70+S6+kinase+pathway.&rft.au=Wan%2C+Xiaolin%3BHelman%2C+Lee+J&rft.aulast=Wan&rft.aufirst=Xiaolin&rft.date=2002-09-01&rft.volume=4&rft.issue=5&rft.spage=400&rft.isbn=&rft.btitle=&rft.title=Neoplasia+%28New+York%2C+N.Y.%29&rft.issn=15228002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-20 N1 - Date created - 2002-08-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: FEBS Lett. 1997 Jun 23;410(1):78-82 [9247127] EMBO J. 1997 Jun 16;16(12):3693-704 [9218810] Mutat Res. 1997 Nov 19;381(1):67-75 [9403032] Curr Opin Cell Biol. 1997 Dec;9(6):782-7 [9425342] Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1432-7 [9465032] Oncogene. 1998 Jan 29;16(4):533-40 [9484843] Biochem Cell Biol. 1997;75(4):315-25 [9493954] Curr Biol. 1998 Mar 26;8(7):R248-50 [9545190] Curr Opin Cell Biol. 1998 Apr;10(2):268-75 [9561852] Cell. 1999 Jan 22;96(2):235-44 [9988218] Cancer Res. 1999 Feb 15;59(4):886-94 [10029080] J Biol Chem. 1999 May 7;274(19):13118-26 [10224065] Oncogene. 2000 Jun 15;19(26):3021-31 [10871854] J Biol Chem. 2000 Aug 11;275(32):24776-80 [10811643] Ann Intern Med. 1984 May;100(5):704-13 [6370067] Nature. 1985 May 9-15;315(6015):115-22 [2986015] Nature. 1985 Sep 19-25;317(6034):258-60 [2995817] EMBO J. 1986 Oct;5(10):2503-12 [2877871] Cell Growth Differ. 1990 Jul;1(7):325-31 [2177632] J Clin Invest. 1991 Feb;87(2):648-57 [1991849] Cancer Res. 1992 Apr 15;52(8):2243-7 [1559227] Curr Probl Cancer. 1992 Mar-Apr;16(2):61-126 [1617996] Annu Rev Biochem. 1992;61:441-70 [1497317] Prog Growth Factor Res. 1992;4(3):257-90 [1307492] Nature. 1994 Jun 2;369(6479):414-8 [7910953] Endocr Rev. 1995 Feb;16(1):3-34 [7758431] Cell Growth Differ. 1995 Mar;6(3):263-9 [7794794] Nature. 1995 Sep 28;377(6547):358-62 [7566093] Trends Biochem Sci. 1995 Oct;20(10):435-9 [8533159] EMBO J. 1995 Nov 1;14(21):5279-87 [7489717] EMBO J. 1996 Feb 1;15(3):658-64 [8599949] Curr Opin Cell Biol. 1995 Dec;7(6):806-14 [8608011] Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4076-80 [8633019] J Endocrinol. 1996 Jun;149(3):367-72 [8691094] Trends Biochem Sci. 1996 May;21(5):181-5 [8871403] Physiol Rev. 1996 Oct;76(4):1005-26 [8874492] Endocrinol Metab Clin North Am. 1996 Sep;25(3):591-614 [8879988] Oncogene. 1996 Dec 5;13(11):2415-20 [8957083] Oncogene. 1997 May 8;14(18):2127-36 [9174048] Eur J Cancer. 1997 Apr;33(4):638-44 [9274448] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Abeta 17-42 in Alzheimer's disease activates JNK and caspase-8 leading to neuronal apoptosis. AN - 72014508; 12183349 AB - The p3 peptide [amyloid beta-peptide (Abeta) 17-40/42], derived by alpha- and gamma-secretase cleavage of the amyloid precursor protein (APP), is a major constituent of diffuse plaques in Alzheimer's disease and cerebellar pre-amyloid in Down's syndrome. However, the importance of p3 peptide accumulation in Alzheimer's disease and its toxic properties is not clear. Here, we demonstrate that treatment of cells with Abeta 17-42 leads to apoptosis in two human neuroblastoma cell lines, SH-SY5Y and IMR-32. Abeta 17-42 activated caspase-8 and caspase-3, induced poly(ADP-ribose) polymerase cleavage, but did not activate caspase-9. Selective caspase-8 and caspase-3 inhibitors completely blocked Abeta 17-42-induced neuronal death. Abeta 17-42 moderately activated c-Jun N-terminal kinase (JNK); however, overexpression of a dominant-negative mutant of SEK1, the upstream kinase of JNK, protected against Abeta 17-42 induced neuronal death. These results demonstrate that Abeta 17-42 induced neuronal apoptosis via a Fas-like/caspase-8 activation pathway. Our findings reveal the previously unrecognized toxic effect of Abeta 17-42. We propose that Abeta 17-42 constitutes an additional toxic peptide derived from APP proteolysis and may thus contribute to the neuronal cell loss characteristic of Alzheimer's disease. JF - Brain : a journal of neurology AU - Wei, Wanli AU - Norton, Darrell D AU - Wang, Xiantao AU - Kusiak, John W AD - Molecular Neurobiology Unit, Laboratory of Cellular and Molecular Biology, Intramural Research Program, National Institute on Aging/NIH, 5600 Nathan Shock Drive, Baltimore, MD 21224-6825, USA. wanliwei@hotmail.com Y1 - 2002/09// PY - 2002 DA - September 2002 SP - 2036 EP - 2043 VL - 125 SN - 0006-8950, 0006-8950 KW - Amyloid beta-Peptides KW - 0 KW - Peptide Fragments KW - amyloid beta-protein (17-42) KW - 155178-13-5 KW - JNK Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinases KW - CASP8 protein, human KW - EC 3.4.22.- KW - CASP9 protein, human KW - Caspase 8 KW - Caspase 9 KW - Caspases KW - Abridged Index Medicus KW - Index Medicus KW - Tumor Cells, Cultured KW - Humans KW - Enzyme Activation -- physiology KW - Peptide Fragments -- chemistry KW - Mitogen-Activated Protein Kinases -- metabolism KW - Neurons -- drug effects KW - Apoptosis -- physiology KW - Peptide Fragments -- pharmacology KW - Amyloid beta-Peptides -- pharmacology KW - Amyloid beta-Peptides -- chemistry KW - Neurons -- physiology KW - Amyloid beta-Peptides -- physiology KW - Peptide Fragments -- physiology KW - Caspases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72014508?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+%3A+a+journal+of+neurology&rft.atitle=Abeta+17-42+in+Alzheimer%27s+disease+activates+JNK+and+caspase-8+leading+to+neuronal+apoptosis.&rft.au=Wei%2C+Wanli%3BNorton%2C+Darrell+D%3BWang%2C+Xiantao%3BKusiak%2C+John+W&rft.aulast=Wei&rft.aufirst=Wanli&rft.date=2002-09-01&rft.volume=125&rft.issue=&rft.spage=2036&rft.isbn=&rft.btitle=&rft.title=Brain+%3A+a+journal+of+neurology&rft.issn=00068950&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-09-17 N1 - Date created - 2002-08-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dose escalation using twice-daily radiotherapy for nasopharyngeal carcinoma: does heavier dosing result in a happier ending? AN - 72010473; 12182970 AB - To present our experience using a twice-daily radiotherapy (RT) technique, including hyperfractionated and accelerated-hyperfractionated RT, on nasopharyngeal carcinoma (NPC) patients. The dose to the primary tumor was increased in the hope that local control could be increased without the cost of increased late complications. We analyzed acute and late complications and local control and compared the results with the results of NPC patients treated during the same period using conventional once-daily RT. Between October 1991 and July 1998, 222 histologically confirmed, Stage M0, previously unirradiated NPC patients completed RT at our hospital. Most patients had American Joint Committee on Cancer (AJCC) 1992 Stage III and IV disease. Among them, 88 received altered fractionated, twice-daily RT; 76 patients received hyperfractionated RT and 12 accelerated-hyperfractionated RT. The remaining 134 patients received a conventional once-daily regimen. Hyperfractionated RT was delivered using 120 cGy b.i.d. separated by 6-h intervals throughout the course. For the accelerated-hyperfractionated patients, 160 cGy b.i.d. was given, also at 6-h intervals. The median dose in the twice-daily group was 7810 cGy (range 6840-8200). In the once-daily regimen, RT was delivered using 180-200 cGy q.d. The median tumor dose to the primary tumor was 7000 cGy (range 6560-8100) given during about 8 weeks. The median follow-up time was 70.5 and 72 months for the twice-daily and once-daily groups, respectively. The incidence of acute toxicities was higher in the twice-daily group with more severe mucositis and moist desquamation than in the once-daily group. Both groups had a similar incidence of late complications, except for 3 cases of temporal lobe necrosis in the twice-daily group, all in patients treated with 160 cGy. No difference was noted in recurrence-free local control between the two groups when the individual T stage was compared using AJCC 1992 or 1997 criteria (p = 0.51 and 0.59, respectively). The 5-year local control rate for T1-3 (AJCC 1997) was 93.2% for the twice-daily group and 86.4% for the once-daily group (p = 0.45). In Stage T4 (AJCC 1997) patients, the local control rate dropped drastically to 43.5% and 36.9% for the twice-daily and once-daily groups, respectively. The overall neck control rate at 5 years was 87.3% and 80.3% for the twice-daily and once-daily patients, respectively (p = 0.16). The overall locoregional control rate was 82.7% for the twice-daily group and 66.6% for the once-daily group. The difference was again not statistically significant, but showed a tendency in favor of the twice-daily regimen (p = 0.055). Locoregional failure occurred mainly in Stage T4 patients with central nervous invasion for whom local control was particularly poor, with a failure rate of about 60%. The present data suggest that NPC patients can be safely treated using a 120-cGy twice-daily program with a 6-h interval up to 8000 cGy. The accelerated-hyperfractionated technique is not recommended. A large discrepancy in local control between patients with T1-3 and T4 disease was noted. For T1-3 disease, an excellent local control rate >90% was achieved using the twice-daily regimen. In contrast, failure in the T4 patients was as high as 55% in the twice-daily group and reached 65% in the once-daily group. More rigorous treatment is needed using either additional dose escalation or other strategies for T4 NPC patients. With a dose escalation of 1000 cGy using 120-cGy twice-daily RT, a trend toward better locoregional control and disease-specific survival was noted in the twice-daily group. Whether this difference was truly the result of an increased dose needs additional confirmation in studies with larger patient numbers. JF - International journal of radiation oncology, biology, physics AU - Jen, Yee-Min AU - Lin, Yaoh-Shiang AU - Su, Wan-Fu AU - Hsu, Wen-Lin AU - Hwang, Jing-Min AU - Chao, Hsing-Lung AU - Liu, Dai-Wei AU - Chen, Chang-Ming AU - Lin, Hon-Yi AU - Wu, Ching-Jung AU - Chang, Li-Ping AU - Shueng, Pei-Wei AD - Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, 325 Section 2 Cheng-Kong Road, Nei-Hu, Taipei, Taiwan, ROC. ymjen@seed.net.tw Y1 - 2002/09/01/ PY - 2002 DA - 2002 Sep 01 SP - 14 EP - 22 VL - 54 IS - 1 SN - 0360-3016, 0360-3016 KW - Index Medicus KW - Treatment Failure KW - Dose Fractionation KW - Radiotherapy Dosage KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Adolescent KW - Male KW - Female KW - Radiotherapy -- adverse effects KW - Nasopharyngeal Neoplasms -- radiotherapy KW - Nasopharyngeal Neoplasms -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72010473?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dose+escalation+using+twice-daily+radiotherapy+for+nasopharyngeal+carcinoma%3A+does+heavier+dosing+result+in+a+happier+ending%3F&rft.au=Jen%2C+Yee-Min%3BLin%2C+Yaoh-Shiang%3BSu%2C+Wan-Fu%3BHsu%2C+Wen-Lin%3BHwang%2C+Jing-Min%3BChao%2C+Hsing-Lung%3BLiu%2C+Dai-Wei%3BChen%2C+Chang-Ming%3BLin%2C+Hon-Yi%3BWu%2C+Ching-Jung%3BChang%2C+Li-Ping%3BShueng%2C+Pei-Wei&rft.aulast=Jen&rft.aufirst=Yee-Min&rft.date=2002-09-01&rft.volume=54&rft.issue=1&rft.spage=14&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 - 2002-09-26 N1 - Date created - 2002-08-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition by naloxone stereoisomers of beta-amyloid peptide (1-42)-induced superoxide production in microglia and degeneration of cortical and mesencephalic neurons. AN - 72008006; 12183682 AB - Previously we reported that naloxone stereoisomers, in an opioid receptor-independent manner, attenuated the inflammation-mediated degeneration of dopaminergic neurons by inhibition of the activation of microglia, the resident immune cells in the brain. Recently we discovered that beta-amyloid peptide Abeta (1-42) exhibited enhanced neurotoxicity toward both cortical and mesencephalic neurons through the activation of microglia and production of superoxide. The purpose of this study was to determine whether naloxone isomers had any effect on Abeta (1-42)-induced neurodegeneration. Pretreatment of either cortical or mesencephalic neuron-glia cultures with 1 to 10 microM (-)-naloxone, prior to treatment for up to 11 days with 0.1 to 3 microM Abeta (1-42), afforded significant neuroprotection as judged by neurotransmitter uptake, immunocytochemical analysis, and cell counting. More importantly, (+)-naloxone, the ineffective enantiomer of (-)-naloxone in binding opioid receptors, was equally effective in affording neuroprotection. Mechanistically, inhibition of Abeta (1-42)-induced production of superoxide in microglia underlay the neuroprotective effect of naloxone stereoisomers. Moreover, neuroprotection and inhibition of Abeta (1-42)-induced superoxide production was also achieved with naloxone methiodide, a charged analog with quaternary amine, suggesting that the site of action for naloxone isomers is at the cell surface of microglia. These results demonstrated that naloxone isomers, through mechanisms unrelated to the opioid receptors, were capable of inhibiting Abeta (1-42)-induced microglial activation and degeneration of both cortical and mesencephalic neurons. Combined with our previous observations with inflammagen-induced neurodegeneration, naloxone analogs, especially (+)-naloxone, may have potential therapeutic efficacy for the treatment of Alzheimer's and Parkinson's disease. JF - The Journal of pharmacology and experimental therapeutics AU - Liu, Yuxin AU - Qin, Liya AU - Wilson, Belinda C AU - An, Lijia AU - Hong, Jau-Shyong AU - Liu, Bin AD - Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences/NIH, Research Triangle Park, NC 27709, USA. liu3@niehs.nih.gov Y1 - 2002/09// PY - 2002 DA - September 2002 SP - 1212 EP - 1219 VL - 302 IS - 3 SN - 0022-3565, 0022-3565 KW - Amyloid beta-Peptides KW - 0 KW - Narcotic Antagonists KW - Peptide Fragments KW - amyloid beta-protein (1-42) KW - Superoxides KW - 11062-77-4 KW - Naloxone KW - 36B82AMQ7N KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Animals KW - Tyrosine 3-Monooxygenase -- metabolism KW - Stereoisomerism KW - Rats, Inbred F344 KW - Cells, Cultured KW - Dopamine -- metabolism KW - gamma-Aminobutyric Acid -- metabolism KW - Immunohistochemistry KW - Male KW - Naloxone -- pharmacology KW - Mesencephalon -- pathology KW - Neurons -- drug effects KW - Naloxone -- analogs & derivatives KW - Nerve Degeneration -- chemically induced KW - Peptide Fragments -- antagonists & inhibitors KW - Neurons -- pathology KW - Superoxides -- metabolism KW - Cerebral Cortex -- pathology KW - Peptide Fragments -- pharmacology KW - Amyloid beta-Peptides -- pharmacology KW - Nerve Degeneration -- pathology KW - Microglia -- drug effects KW - Narcotic Antagonists -- pharmacology KW - Amyloid beta-Peptides -- antagonists & inhibitors KW - Microglia -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72008006?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Inhibition+by+naloxone+stereoisomers+of+beta-amyloid+peptide+%281-42%29-induced+superoxide+production+in+microglia+and+degeneration+of+cortical+and+mesencephalic+neurons.&rft.au=Liu%2C+Yuxin%3BQin%2C+Liya%3BWilson%2C+Belinda+C%3BAn%2C+Lijia%3BHong%2C+Jau-Shyong%3BLiu%2C+Bin&rft.aulast=Liu&rft.aufirst=Yuxin&rft.date=2002-09-01&rft.volume=302&rft.issue=3&rft.spage=1212&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 - 2002-09-18 N1 - Date created - 2002-08-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase III study of ibuprofen versus placebo for radiation-induced genitourinary side effects. AN - 72006350; 12182991 AB - On the basis of our anecdotal clinical observations that nonsteroidal anti-inflammatory agents relieved dysuria during radiotherapy for patients with prostate cancer, we conducted a Phase III randomized trial of ibuprofen vs. placebo for patients who had an increase in acute urinary symptoms. Our in vitro and in vivo laboratory data with a higher concentration of ibuprofen than achievable in this study demonstrated radiosensitization. This study examined whether the inflammatory response within the prostate during radiotherapy would respond to the standard dose of ibuprofen as assessed by a symptom score. Patients were registered to the study and were followed weekly with a formal symptom assessment. A double-blind randomization to ibuprofen, 400 mg q.i.d., vs. placebo for 7 days was done at a time when the severity score increased. The symptom response was evaluated at the end of the week. Between 1995 and 1998, 100 patients were entered, 28 did not have a sufficient change in symptom score to be randomized, and 19 were either unable to take ibuprofen or withdrew before randomization. Of the 53 patients randomized, 27 received placebo and 26 ibuprofen. No statistically significant differences were found between the placebo and ibuprofen groups between baseline and randomization or between randomization and the 1-week posttreatment assessment. Neither group had a change in symptom severity between randomization and the 1-week posttreatment evaluation. The standard anti-inflammatory dose of ibuprofen did not relieve the acute urinary or rectal symptoms during radiotherapy for prostate cancer. The nonsteroidal anti-inflammatory drugs are potential radiation sensitizers with the mechanism of action as yet unknown. Clinical trials of the cyclooxygenase inhibitors as radiation sensitizers should explore a range of doses and evaluate potential mechanisms of action, including cyclooxygenase inhibition and other non-cyclooxygenase mechanisms. JF - International journal of radiation oncology, biology, physics AU - Coleman, C Norman AU - Kelly, Laura AU - Riese Daly, Nancy AU - Beard, Clair AU - Kaplan, Irving AU - Lamb, Carolyn AU - Propert, Kathleen AU - Manola, Judith AD - Joint Center for Radiation Therapy, Harvard Medical School, Boston, MA, USA. ccoleman@mail.nih.gov Y1 - 2002/09/01/ PY - 2002 DA - 2002 Sep 01 SP - 191 EP - 194 VL - 54 IS - 1 SN - 0360-3016, 0360-3016 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Cyclooxygenase Inhibitors KW - Ibuprofen KW - WK2XYI10QM KW - Index Medicus KW - Double-Blind Method KW - Aged, 80 and over KW - Humans KW - Aged KW - Middle Aged KW - Male KW - Urologic Diseases -- etiology KW - Cyclooxygenase Inhibitors -- therapeutic use KW - Anti-Inflammatory Agents, Non-Steroidal -- therapeutic use KW - Prostate -- radiation effects KW - Ibuprofen -- therapeutic use KW - Urologic Diseases -- drug therapy KW - Prostatic Neoplasms -- radiotherapy KW - Radiotherapy -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72006350?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Phase+III+study+of+ibuprofen+versus+placebo+for+radiation-induced+genitourinary+side+effects.&rft.au=Coleman%2C+C+Norman%3BKelly%2C+Laura%3BRiese+Daly%2C+Nancy%3BBeard%2C+Clair%3BKaplan%2C+Irving%3BLamb%2C+Carolyn%3BPropert%2C+Kathleen%3BManola%2C+Judith&rft.aulast=Coleman&rft.aufirst=C&rft.date=2002-09-01&rft.volume=54&rft.issue=1&rft.spage=191&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 - 2002-09-26 N1 - Date created - 2002-08-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protection and reversal of excitotoxic neuronal damage by glucagon-like peptide-1 and exendin-4. AN - 72005526; 12183643 AB - Glucagon-like peptide-1 (7-36)-amide (GLP-1) is an endogenous insulinotropic peptide that is secreted from the L cells of the gastrointestinal tract in response to food. It has potent effects on glucose-dependent insulin secretion, insulin gene expression, and pancreatic islet cell formation. In type 2 diabetes, GLP-1, by continuous infusion, can normalize blood glucose and is presently being tested in clinical trials as a therapy for this disease. More recently, GLP-1 has been found to have central nervous system (CNS) effects and to stimulate neurite outgrowth in cultured cells. We now report that GLP-1, and its longer-acting analog exendin-4, can completely protect cultured rat hippocampal neurons against glutamate-induced apoptosis. Extrapolating these effects to a well defined rodent model of neurodegeneration, GLP-1 and exendin-4 greatly reduced ibotenic acid-induced depletion of choline acetyltransferase immunoreactivity in basal forebrain cholinergic neurons. These findings identify a novel neuroprotective/neurotrophic function of GLP-1 and suggest that such peptides may have potential for halting or reversing neurodegenerative processes in CNS disorders, such as Alzheimer's disease, and in neuropathies associated with type 2 diabetes mellitus. JF - The Journal of pharmacology and experimental therapeutics AU - Perry, TracyAnn AU - Haughey, Norman J AU - Mattson, Mark P AU - Egan, Josephine M AU - Greig, Nigel H AD - Section of Drug Design and Development, Laboratory of Neuroscience, Gerontology Research Center, National Institute on Aging/NIH, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. perryt@grc.nia.nih.gov Y1 - 2002/09// PY - 2002 DA - September 2002 SP - 881 EP - 888 VL - 302 IS - 3 SN - 0022-3565, 0022-3565 KW - Excitatory Amino Acid Agonists KW - 0 KW - Excitatory Amino Acid Antagonists KW - Glial Fibrillary Acidic Protein KW - Glp1r protein, rat KW - Glucagon-Like Peptide-1 Receptor KW - Peptide Fragments KW - Peptides KW - Protein Precursors KW - Receptors, Glucagon KW - Venoms KW - Ibotenic Acid KW - 2552-55-8 KW - Glutamic Acid KW - 3KX376GY7L KW - Glucagon-Like Peptide 1 KW - 89750-14-1 KW - Glucagon KW - 9007-92-5 KW - exenatide KW - 9P1872D4OL KW - Cyclic AMP KW - E0399OZS9N KW - Choline O-Acetyltransferase KW - EC 2.3.1.6 KW - Index Medicus KW - Animals KW - Receptors, Glucagon -- drug effects KW - Glial Fibrillary Acidic Protein -- metabolism KW - Ibotenic Acid -- antagonists & inhibitors KW - Cell Death -- drug effects KW - Choline O-Acetyltransferase -- metabolism KW - Excitatory Amino Acid Agonists -- toxicity KW - Receptors, Glucagon -- metabolism KW - Hippocampus -- drug effects KW - Basal Ganglia -- pathology KW - Rats KW - Rats, Sprague-Dawley KW - Rats, Inbred F344 KW - Cell Survival -- drug effects KW - Cells, Cultured KW - Parasympathetic Nervous System -- drug effects KW - Hippocampus -- cytology KW - Cyclic AMP -- metabolism KW - Ibotenic Acid -- toxicity KW - Immunohistochemistry KW - Peptide Fragments -- metabolism KW - Protein Precursors -- metabolism KW - Neurons -- drug effects KW - Glucagon -- pharmacology KW - Nerve Degeneration -- chemically induced KW - Nerve Degeneration -- prevention & control KW - Peptides -- pharmacology KW - Neurons -- pathology KW - Protein Precursors -- pharmacology KW - Excitatory Amino Acid Antagonists -- toxicity KW - Glucagon -- metabolism KW - Glutamic Acid -- toxicity KW - Peptide Fragments -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72005526?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Protection+and+reversal+of+excitotoxic+neuronal+damage+by+glucagon-like+peptide-1+and+exendin-4.&rft.au=Perry%2C+TracyAnn%3BHaughey%2C+Norman+J%3BMattson%2C+Mark+P%3BEgan%2C+Josephine+M%3BGreig%2C+Nigel+H&rft.aulast=Perry&rft.aufirst=TracyAnn&rft.date=2002-09-01&rft.volume=302&rft.issue=3&rft.spage=881&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 - 2002-09-18 N1 - Date created - 2002-08-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transketolase haploinsufficiency reduces adipose tissue and female fertility in mice. AN - 71976102; 12167708 AB - Transketolase (TKT) is a ubiquitous enzyme used in multiple metabolic pathways. We show here by gene targeting that TKT-null mouse embryos are not viable and that disruption of one TKT allele can cause growth retardation ( approximately 35%) and preferential reduction of adipose tissue ( approximately 77%). Other TKT(+/-) tissues had moderate ( approximately 33%; liver, gonads) or relatively little ( approximately 7 to 18%; eye, kidney, heart, brain) reductions in mass. These mice expressed a normal level of growth hormone and reduced leptin levels. No phenotype was observed in the TKT(+/-) cornea, where TKT is especially abundant in wild-type mice. The small female TKT(+/-) mice mated infrequently and had few progeny (with a male/female ratio of 1.4:1) when pregnant. Thus, TKT in normal mice appears to be carefully balanced at a threshold level for well-being. Our data suggest that TKT deficiency may have clinical significance in humans and raise the possibility that obesity may be treated by partial inhibition of TKT in adipose tissue. JF - Molecular and cellular biology AU - Xu, Zheng-Ping AU - Wawrousek, Eric F AU - Piatigorsky, Joram AD - Laboratory of Molecular and Developmental Biology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-2730, USA. Y1 - 2002/09// PY - 2002 DA - September 2002 SP - 6142 EP - 6147 VL - 22 IS - 17 SN - 0270-7306, 0270-7306 KW - Eye Proteins KW - 0 KW - Leptin KW - Growth Hormone KW - 9002-72-6 KW - Transketolase KW - EC 2.2.1.1 KW - Index Medicus KW - Animals KW - Sexual Behavior, Animal KW - Disease Models, Animal KW - Organ Size KW - Introns -- genetics KW - Mice, Knockout KW - Body Weight KW - Phenotype KW - Alleles KW - Eye Proteins -- genetics KW - Heterozygote KW - Eye Proteins -- physiology KW - Growth Hormone -- blood KW - Energy Metabolism -- genetics KW - Leptin -- deficiency KW - Mice KW - Morula -- pathology KW - Pregnancy KW - Cornea -- enzymology KW - Embryonic and Fetal Development -- genetics KW - Mice, Inbred C57BL KW - Litter Size -- genetics KW - Gene Targeting KW - Female KW - Mutagenesis, Insertional KW - Growth Disorders -- enzymology KW - Transketolase -- deficiency KW - Growth Disorders -- genetics KW - Transketolase -- physiology KW - Infertility, Female -- enzymology KW - Growth Disorders -- pathology KW - Infertility, Female -- genetics KW - Adipose Tissue -- enzymology KW - Transketolase -- genetics KW - Adipose Tissue -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71976102?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Transketolase+haploinsufficiency+reduces+adipose+tissue+and+female+fertility+in+mice.&rft.au=Xu%2C+Zheng-Ping%3BWawrousek%2C+Eric+F%3BPiatigorsky%2C+Joram&rft.aulast=Xu&rft.aufirst=Zheng-Ping&rft.date=2002-09-01&rft.volume=22&rft.issue=17&rft.spage=6142&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 - 2002-09-09 N1 - Date created - 2002-08-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1992 May 1;89(9):4004-8 [1570326] Genet Res. 1999 Feb;73(1):37-44 [10218445] Nutr Cancer. 2000;36(2):150-4 [10890024] Proc Nutr Soc. 2000 Aug;59(3):359-71 [10997652] Theriogenology. 2001 Jan 1;55(1):3-14 [11198086] Curr Atheroscler Rep. 2000 Sep;2(5):390-6 [11122770] Br Med Bull. 2000;56(3):577-87 [11255546] Plant Cell. 2001 Mar;13(3):535-51 [11251095] Nat Genet. 2001 Apr;27(4):422-6 [11279525] Cornea. 2001 Nov;20(8):853-8 [11685065] Nature. 2001 Nov 1;414(6859):34-5 [11689931] Mol Cell Biol. 2002 Feb;22(3):849-55 [11784860] Biochem J. 1972 Aug;128(5):1089-96 [4404962] Arch Biochem Biophys. 1983 Apr 15;222(2):489-96 [6847198] Clin Chem. 1984 May;30(5):658-61 [6713626] Genet Res. 1988 Dec;52(3):195-201 [3243423] J Biol Chem. 1993 Jan 15;268(2):1397-404 [8419340] Metab Brain Dis. 1995 Mar;10(1):45-55 [7596328] Metab Brain Dis. 1996 Mar;11(1):9-17 [8815394] Genomics. 1996 Mar 15;32(3):309-16 [8838793] J Biol Chem. 1996 Dec 27;271(52):33568-74 [8969223] J Mol Evol. 1997 May;44(5):552-72 [9115179] Curr Eye Res. 1997 May;16(5):467-74 [9154385] J Cell Physiol. 1997 Jul;172(1):63-8 [9207926] Genomics. 1998 Mar 1;48(2):209-20 [9521875] Prog Retin Eye Res. 1998 Apr;17(2):145-74 [9695791] Genes Dev. 1998 Oct 15;12(20):3168-81 [9784492] Int J Biochem Cell Biol. 1998 Dec;30(12):1297-318 [9924800] J Cell Sci. 1999 Mar;112 ( Pt 5):613-22 [9973596] FASEB J. 2000 Jan;14(1):111-27 [10627286] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Exendin-4 differentiation of a human pancreatic duct cell line into endocrine cells: involvement of PDX-1 and HNF3beta transcription factors. AN - 71923520; 12124776 AB - Exendin-4 (EX-4), a long acting agonist of GLP-1, induces an endocrine phenotype in Capan-1 cells. Under culture conditions which include serum, approximately 10% of the cells contain insulin and glucagon. When exposed to EX-4 (0.1 nM, up to 5 days), the number of cells containing insulin and glucagon increased to approximately 40%. Western blot analysis detected a progressive increase in protein levels of glucokinase and GLUT2 over 3 days of EX-4 treatment. We explored the sequence of activation of certain transcription factors known to be essential for the beta cell phenotype: PDX-1, Beta2/NeuroD, and hepatocyte nuclear factor 3beta (HNF3beta). Double immunostaining showed that PDX-1 coexisted with insulin and glucagon in EX-4-treated cells. Treatment caused an increase in PDX-1 protein levels by 24 h and induced its nuclear translocation. Beta2/NeuroD protein levels also increased progressively over 24 h. HNF3beta protein level increased twofold as early as 6 h after EX-4 treatment. EMSA results indicated that EX-4 caused a 12-fold increase in HNF3beta binding to PDX-1 promoter area II. Beta2/NeuroD protein levels progressively increased after 24 h treatment. Differentiation to insulin-producing cells was also seen when Capan-1 cells were transfected with pdx-1, with 80% of these cells expressing insulin 3 days after transfection. PDX-1 antisense totally inhibited such conversion. During the differentiation of duct cells to endocrine cells, cAMP levels (EX-4 is a ligand for the GLP-1, G-protein coupled receptor) and MAP kinase activity increased. Our results indicate that EX-4 activates adenylyl cyclase and MAP kinase which, in turn, may lead to activation of transcription factors necessary for an endocrine phenotype. Published 2002 Wiley-Liss, Inc. JF - Journal of cellular physiology AU - Zhou, Jie AU - Pineyro, Marco A AU - Wang, Xiaolin AU - Doyle, Maire E AU - Egan, Josephine M AD - Diabetes Section, National Institute on Aging, NIH, Baltimore, Maryland 21224, USA. Y1 - 2002/09// PY - 2002 DA - September 2002 SP - 304 EP - 314 VL - 192 IS - 3 SN - 0021-9541, 0021-9541 KW - DNA-Binding Proteins KW - 0 KW - FOXA2 protein, human KW - GLP1R protein, human KW - Glucagon-Like Peptide-1 Receptor KW - Homeodomain Proteins KW - Insulin KW - Nuclear Proteins KW - Peptide Fragments KW - Peptides KW - Protein Precursors KW - Receptors, Glucagon KW - Trans-Activators KW - Transcription Factors KW - Venoms KW - pancreatic and duodenal homeobox 1 protein KW - Hepatocyte Nuclear Factor 3-beta KW - 135845-92-0 KW - Glucagon-Like Peptide 1 KW - 89750-14-1 KW - Glucagon KW - 9007-92-5 KW - exenatide KW - 9P1872D4OL KW - Cyclic AMP KW - E0399OZS9N KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Index Medicus KW - Protein Precursors -- agonists KW - Transcription Factors -- metabolism KW - Mitogen-Activated Protein Kinases -- metabolism KW - Humans KW - Insulin -- metabolism KW - Peptide Fragments -- agonists KW - Transcription Factors -- genetics KW - Receptors, Glucagon -- metabolism KW - Glucagon -- agonists KW - Promoter Regions, Genetic KW - Glucagon -- metabolism KW - Transfection KW - Cyclic AMP -- metabolism KW - Cell Differentiation -- drug effects KW - Cell Line KW - Trans-Activators -- metabolism KW - Nuclear Proteins -- genetics KW - Islets of Langerhans -- drug effects KW - DNA-Binding Proteins -- genetics KW - Pancreatic Ducts -- metabolism KW - Pancreatic Ducts -- cytology KW - Peptides -- pharmacology KW - Pancreatic Ducts -- drug effects KW - Trans-Activators -- genetics KW - Islets of Langerhans -- cytology KW - Nuclear Proteins -- metabolism KW - Islets of Langerhans -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71923520?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Exendin-4+differentiation+of+a+human+pancreatic+duct+cell+line+into+endocrine+cells%3A+involvement+of+PDX-1+and+HNF3beta+transcription+factors.&rft.au=Zhou%2C+Jie%3BPineyro%2C+Marco+A%3BWang%2C+Xiaolin%3BDoyle%2C+Maire+E%3BEgan%2C+Josephine+M&rft.aulast=Zhou&rft.aufirst=Jie&rft.date=2002-09-01&rft.volume=192&rft.issue=3&rft.spage=304&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 - 2002-08-23 N1 - Date created - 2002-07-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - More road to travel by: Implications for mobility and safety in late life AN - 57277136; 200905483 AB - The 'suburbanization' of the United States is now generating a cohort of older adults who live where driving is most often the sole means of transport to all of the external necessities and conveniences of daily life. As suburbs grow further out from cities so the distances to be driven by future cohorts of older drivers will increase beyond those of today. Much research on driving in late life has focused on assessing the competence of older adults as drivers. Now more work is needed on technological solutions to maintaining this cohort's driving mobility and safety. The presentation reviews recent changes in transportation technology (such as airbags), considers lessons learned from them in terms of their effects on older drivers and passengers and considers whether current knowledge of older drivers and their driving patterns offers guidance to the design of future technology. Adapted from the source document. JF - Gerontechnology AU - Barr, Robin A AD - Office of Extramural Activities, National Institute on Aging, USA BarrR@nia.nih.gov Y1 - 2002/09// PY - 2002 DA - September 2002 SP - 50 EP - 54 PB - International Society for Gerontechnology, Helsinki, Finland VL - 2 IS - 1 SN - 1569-1101, 1569-1101 KW - driving, driver assessment, mobility, safety KW - Mobility KW - Driving KW - Safety KW - Gerontology KW - Drivers KW - Technology KW - article UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/57277136?accountid=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=Gerontechnology&rft.atitle=More+road+to+travel+by%3A+Implications+for+mobility+and+safety+in+late+life&rft.au=Barr%2C+Robin+A&rft.aulast=Barr&rft.aufirst=Robin&rft.date=2002-09-01&rft.volume=2&rft.issue=1&rft.spage=50&rft.isbn=&rft.btitle=&rft.title=Gerontechnology&rft.issn=15691101&rft_id=info:doi/ LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Date revised - 2009-04-08 N1 - Last updated - 2016-09-27 N1 - SubjectsTermNotLitGenreText - Drivers; Driving; Mobility; Gerontology; Safety; Technology ER - TY - JOUR T1 - Clinical proteomics: translating benchside promise into bedside reality AN - 20641757; 7921028 AB - The ultimate goal of proteomics is to characterize the information flow through protein networks. This information can be a cause, or a consequence, of disease processes. Clinical proteomics is an exciting new subdiscipline of proteomics that involves the application of proteomic technologies at the bedside, and cancer, in particular, is a model disease for studying such applications. Here, we describe proteomic technologies that are being developed to detect cancer earlier, to discover the next generation of targets and imaging biomarkers, and finally to tailor the therapy to the patient. JF - Nature Reviews: Drug Discovery AU - Petricoin, Emanuel F AU - Zoon, Kathryn C AU - Kohn, Elise C AU - Barrett, JCarl AU - Liotta, Lance A AD - FDA-NCI Clinical Proteomics Program, Division of Therapeutic Proteins, Center for Biologic Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA., petricoin@cber.fda.gov Y1 - 2002/09// PY - 2002 DA - Sep 2002 SP - 683 EP - 695 PB - Nature Publishing Group, The Macmillan Building 4 Crinan Street London N1 9XW UK, [mailto:feedback@nature.com], [URL:http://www.nature.com/] VL - 1 IS - 9 SN - 1474-1784, 1474-1784 KW - Biotechnology and Bioengineering Abstracts KW - proteomics KW - imaging KW - biomarkers KW - Cancer KW - Models KW - W 30960:Bioinformatics & Computer Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20641757?accountid=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+Reviews%3A+Drug+Discovery&rft.atitle=Clinical+proteomics%3A+translating+benchside+promise+into+bedside+reality&rft.au=Petricoin%2C+Emanuel+F%3BZoon%2C+Kathryn+C%3BKohn%2C+Elise+C%3BBarrett%2C+JCarl%3BLiotta%2C+Lance+A&rft.aulast=Petricoin&rft.aufirst=Emanuel&rft.date=2002-09-01&rft.volume=1&rft.issue=9&rft.spage=683&rft.isbn=&rft.btitle=&rft.title=Nature+Reviews%3A+Drug+Discovery&rft.issn=14741784&rft_id=info:doi/10.1038%2Fnrd891 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-01-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - proteomics; biomarkers; imaging; Cancer; Models DO - http://dx.doi.org/10.1038/nrd891 ER - TY - JOUR T1 - Optimized clinical-scale culture conditions for ex vivo selective depletion of host-reactive donor lymphocytes: a strategy for GvHD prophylaxis in allogeneic PBSC transplantation AN - 20172729; 7347547 AB - Background: Ex vivo selective depletion (SD) is a strategy to prevent GvHD, in which host-reactive donor lymphocytes are selectively eliminated from a PBSC allograft while conserving useful donor immune function. Prior to testing this strategy in patients, our goal was to develop a clinical- scale SD process, which involves co-culture of donor lymphocytes and irradiated recipient cells, followed by the addition of an immunotoxin (IT) directed against the alpha-chain of the IL-2 receptor (CD25), expressed on activated donor T cells. Methods: Stimulator cells were generated from immunomagnetically selected and expanded recipient T lymphocytes. Donor PBMCs from G-CSF-mobilized peripheral blood were co-cultured for 72 h with irradiated stimulator cells. Alloreactive T cells were targeted for elimination by the addition of the anti-CD25 IT, RFT5-SMPT-dgA, and the IT enhancer, NH sub(4)Cl. Results: Stimulator-cell selection/expansion yielded > 2x10 sub(10) highly enriched CD3 sub(+) cells (98.9 plus or minus 2.2%). After SD, cell recovery was 68.5 plus or minus 23.3% and viability was 84.6 plus or minus 6.4%. This permitted a potential T-cell dose ge 1 x 10 sub(8) CD3 sub(+) cells kg sub(-1) to transplant recipients. Although SD donor lymphocytes retained little proliferative capacity against the original stimulator cells (2.6 plus or minus 0.6%), responses were conserved against third party cells (107.6 plus or minus 18.6%), the bacterial superantigen staphylococcus enterotoxin B (108.2 plus or minus 4.2%), and CMV Ag (72.1 plus or minus 3.8%). Discussion: We have demonstrated that ex vivo SD is feasible in clinical-scale culture conditions. The ability of this strategy to prevent GvHD is the subject of an ongoing clinical trial, in which the SD lymphocyte product is transplanted in conjunction with a T cell-depleted PBSC allograft. JF - Cytotherapy AU - Solomon, S AU - Tran, T AU - Carter, C AU - Donnelly, S AU - Hensel, N AU - Schindler, J AU - Bahceci, E AU - Ghetie, V AU - Michalek, J AU - Mavroudis, D AU - Read, E AU - Vitetta, E AU - Barrett, A AD - Stem Cell Allotransplantation Section, Hematology Branch, NHLBI, National Institutes of Health, Bethesda, MD, USA Y1 - 2002/09// PY - 2002 DA - Sep 2002 SP - 395 EP - 406 PB - Taylor & Francis Ltd., 11 New Fetter Lane London EC4P 4EE UK, [mailto:info@tandf.co.uk], [URL:http://www.tandf.co.uk] VL - 4 IS - 5 SN - 1465-3249, 1465-3249 KW - Microbiology Abstracts B: Bacteriology; Biotechnology and Bioengineering Abstracts; Immunology Abstracts KW - T-CELL DEPLETION KW - EX VIVO CELL CULTURE KW - ALLOREACTIVITY KW - EXPANSION KW - ALLOGENEIC STEM CELL TRANSPLANTATION KW - GRAFT-VERSUS-HOST DISEASE KW - Donors KW - Staphylococcus KW - Peripheral blood KW - Cell culture KW - Graft-versus-host reaction KW - Granulocyte colony-stimulating factor KW - CD25 antigen KW - Cytomegalovirus KW - Clinical trials KW - Interleukin 2 receptors KW - Immunotoxins KW - Enhancers KW - Superantigens KW - Prophylaxis KW - Lymphocytes T KW - CD3 antigen KW - Immune response KW - enterotoxin B KW - J 02350:Immunology KW - W 30920:Tissue Engineering KW - F 06920:Transplantation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20172729?accountid=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=Cytotherapy&rft.atitle=Optimized+clinical-scale+culture+conditions+for+ex+vivo+selective+depletion+of+host-reactive+donor+lymphocytes%3A+a+strategy+for+GvHD+prophylaxis+in+allogeneic+PBSC+transplantation&rft.au=Solomon%2C+S%3BTran%2C+T%3BCarter%2C+C%3BDonnelly%2C+S%3BHensel%2C+N%3BSchindler%2C+J%3BBahceci%2C+E%3BGhetie%2C+V%3BMichalek%2C+J%3BMavroudis%2C+D%3BRead%2C+E%3BVitetta%2C+E%3BBarrett%2C+A&rft.aulast=Solomon&rft.aufirst=S&rft.date=2002-09-01&rft.volume=4&rft.issue=5&rft.spage=395&rft.isbn=&rft.btitle=&rft.title=Cytotherapy&rft.issn=14653249&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-05-01 N1 - SuppNotes - 30 references N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Donors; Graft-versus-host reaction; Cell culture; Peripheral blood; Granulocyte colony-stimulating factor; CD25 antigen; Clinical trials; Immunotoxins; Interleukin 2 receptors; Enhancers; Superantigens; Lymphocytes T; Prophylaxis; Immune response; CD3 antigen; enterotoxin B; Staphylococcus; Cytomegalovirus ER - TY - JOUR T1 - Detergent-resistant erythrocyte membrane rafts are modified by a Plasmodium falciparum infection AN - 18846719; 5613591 AB - Detergent resistant membranes (DRMs) have been implicated in numerous cellular processes including signal transduction, membrane trafficking, and molecular sorting. Flotillins-1 and -2 have recently been shown to be large components of erythrocyte DRMs. In this study, we show that a Plasmodium falciparum infection disrupts the association of flotillins with erythrocyte DRMs. Flotillins are probably released from erythrocyte DRMs through the reduction of cholesterol and sphingomyelin levels during the course of a P. falciparum-infection. Although it is well known that a P. falciparum infection can modify the host erythrocyte membrane, this is the first report that P. falciparum can alter the DRM components of erythrocyte membranes. JF - Experimental Parasitology AU - Nagao, E AU - Seydel, K B AU - Dvorak, JA AD - Laboratory of Malaria and Vector Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 4, Room 126, 4 Center Drive MSC 0425, Bethesda, MD 20892-0425, USA, jdvorak@atlas.niaid.nih.gov Y1 - 2002/09// PY - 2002 DA - Sep 2002 SP - 57 EP - 59 PB - Elsevier Science (USA) VL - 102 IS - 1 SN - 0014-4894, 0014-4894 KW - Flotillins KW - flotillin 1 KW - flotillin 2 KW - lipid rafts KW - ASFA 1: Biological Sciences & Living Resources; ASFA 3: Aquatic Pollution & Environmental Quality; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - Parasites KW - Human diseases KW - Membranes KW - Protozoan diseases KW - Detergents KW - Erythrocytes KW - Malaria KW - Plasmodium falciparum KW - Cholesterol KW - Freshwater KW - Disease transmission KW - Cell membranes KW - Q1 08484:Species interactions: parasites and diseases KW - Q5 08524:Public health, medicines, dangerous organisms KW - K 03057:Protozoa UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18846719?accountid=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=Detergent-resistant+erythrocyte+membrane+rafts+are+modified+by+a+Plasmodium+falciparum+infection&rft.au=Nagao%2C+E%3BSeydel%2C+K+B%3BDvorak%2C+JA&rft.aulast=Nagao&rft.aufirst=E&rft.date=2002-09-01&rft.volume=102&rft.issue=1&rft.spage=57&rft.isbn=&rft.btitle=&rft.title=Experimental+Parasitology&rft.issn=00144894&rft_id=info:doi/10.1016%2FS0014-4894%2802%2900143-1 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2014-05-07 N1 - SubjectsTermNotLitGenreText - Parasites; Human diseases; Cell membranes; Protozoan diseases; Detergents; Erythrocytes; Malaria; Cholesterol; Disease transmission; Membranes; Plasmodium falciparum; Freshwater DO - http://dx.doi.org/10.1016/S0014-4894(02)00143-1 ER - TY - JOUR T1 - Functionalized Congeners of Tyrosine-Based P2X sub(7) Receptor Antagonists: Probing Multiple Sites for Linking and Dimerization AN - 18745333; 5621634 AB - Chemically funtionalized analogues of antagonists of the P2X sub(7) receptor, an ATP-gated cation channel, were synthesized as tools for biophysical studies of the receptor. These functionalized congeners were intended for use in chemical conjugation with retention of biological potency. The antagonists were L-tyrosine derivatives, related to [N-benzyloxycarbonyl-O-(4-arylsulfonyl)-L-tyrosyl]benzoylpiperazin e (such as MRS2409, 2). The analogues were demonstrated to be antagonists in an assay of human P2X sub(7) receptor function, consisting of inhibition of ATP-induced K super(+) efflux in HEK293 cells expressing the recombinant receptor. The analogues were of the general structure R sub(1)-Tyr (OR sub(2))-piperazinyl-R sub(3), in which three positions (R sub(1)-R sub(3)) were systematically varied in structure through introduction of chemically reactive groups. Each of the three positions was designed to incorporate a 3- or 4-nitrophenyl group. The nitro groups were reduced using NaBH sub(4)-copper(II) acetylacetonate to amines, which were either converted to the isothiocyanate groups, as potential affinity labels for the receptor, or acylated, as models for conjugation. An alternate route to N super( alpha )-3-aminobenzyloxycarbonyl functionalization was devised. The various positions of functionalization were compared for effects on biological potency, and the R sub(2) and R sub(3) positions were found to be most amenable to derivatization with retention of high potency. Four dimeric permutations of the antagonists were synthesized by coupling each of the isothiocyanate derivatives to either the precursor amine or to other amine congeners. Only dimers linked at the R sub(2)-position were potent antagonists. In concentration-response studies, two derivatives, a 3-nitrobenzyloxycarbonyl derivative 18 and a 4-nitrotoluenesulfonate 26b, displayed IC sub(50) values of roughly 100 nM as antagonists of P2X sub(7) receptor-mediated K super(+) flux. JF - Bioconjugate Chemistry AU - Chen, W AU - Ravi, R G AU - Kertesy, S B AU - Dubyak, G R AU - Jacobson, KA AD - Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0810, USA Y1 - 2002/09// PY - 2002 DA - Sep 2002 SP - 1100 EP - 1111 PB - American Chemical Society, P.O. Box 182426 Columbus OH 43218-2426 USA, [mailto:service@acs.org], [URL:http://pubs.acs.org] VL - 13 IS - 5 SN - 1043-1802, 1043-1802 KW - cation channels KW - isothiocyanate KW - man KW - potassium KW - purine P2X7 receptor antagonists KW - purine P2X7 receptors KW - tyrosine KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W4 130:General Biomedical Engineering: Tools & Techniques KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18745333?accountid=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=Bioconjugate+Chemistry&rft.atitle=Functionalized+Congeners+of+Tyrosine-Based+P2X+sub%287%29+Receptor+Antagonists%3A+Probing+Multiple+Sites+for+Linking+and+Dimerization&rft.au=Chen%2C+W%3BRavi%2C+R+G%3BKertesy%2C+S+B%3BDubyak%2C+G+R%3BJacobson%2C+KA&rft.aulast=Chen&rft.aufirst=W&rft.date=2002-09-01&rft.volume=13&rft.issue=5&rft.spage=1100&rft.isbn=&rft.btitle=&rft.title=Bioconjugate+Chemistry&rft.issn=10431802&rft_id=info:doi/10.1021%2Fbc020025i LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1021/bc020025i ER - TY - JOUR T1 - Specific Labeling of Polypeptides at Amino-Terminal Cysteine Residues Using Cy5-benzyl Thioester AN - 18744178; 5621628 AB - Even for moderately sized proteins, the multiple occurrence of cysteine and lysine residues often prevents the specific labeling of polypeptides with a single probe. To increase specificity, a method was developed to convert the commonly available succinimidyl esters of fluorescent dyes into benzyl thioesters via trimethyl aluminum-activated benzyl mercaptan. The thioester can then be reacted very specifically with polypeptides containing an N-terminal cysteine residue, forming a stable amide bond, analogous to the native chemical ligation of peptide fragments. Both reaction steps are easy to perform and proceed to high yields. The practicability of the approach was demonstrated using the popular cyanine dye Cy5 and a soluble peptide, and it is expected to be applicable to a wide range of succinimidyl esters and both chemically and recombinantly synthesized proteins. The method should dramatically facilitate the preparation of proteins for experiments requiring exact positioning of labels, for instance, Foerster resonance energy transfer studies. JF - Bioconjugate Chemistry AU - Schuler, B AU - Pannell, L K AD - Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520, USA Y1 - 2002/09// PY - 2002 DA - Sep 2002 SP - 1039 EP - 1043 PB - American Chemical Society, P.O. Box 182426 Columbus OH 43218-2426 USA, [mailto:service@acs.org], [URL:http://pubs.acs.org] VL - 13 IS - 5 SN - 1043-1802, 1043-1802 KW - benzyl mercaptan KW - benzyl thioester KW - cysteine KW - resonance energy transfer KW - succinimidyl esters KW - trimethyl aluminum KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W4 330:Biopolymers & Food Biotechnology KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18744178?accountid=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=Bioconjugate+Chemistry&rft.atitle=Specific+Labeling+of+Polypeptides+at+Amino-Terminal+Cysteine+Residues+Using+Cy5-benzyl+Thioester&rft.au=Schuler%2C+B%3BPannell%2C+L+K&rft.aulast=Schuler&rft.aufirst=B&rft.date=2002-09-01&rft.volume=13&rft.issue=5&rft.spage=1039&rft.isbn=&rft.btitle=&rft.title=Bioconjugate+Chemistry&rft.issn=10431802&rft_id=info:doi/10.1021%2Fbc025509t LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1021/bc025509t ER - TY - JOUR T1 - Ratio statistics of gene expression levels and applications to microarray data analysis AN - 18692460; 5579188 AB - Expression-based analysis for large families of genes has recently become possible owing to the development of cDNA microarrays, which allow simultaneous measurement of transcript levels for thousands of genes. For each spot on a microarray, signals in two channels must be extracted from their backgrounds. This requires algorithms to extract signals arising from tagged mRNA hybridized to arrayed cDNA locations and algorithms to determine the significance of signal ratios. JF - Bioinformatics AU - Chen, Y AU - Kamat, V AU - Dougherty, E R AU - Bittner, M L AU - Meltzer, P S AU - Trent, J M AD - Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Building 50, Room 5154, 50 South Drive, MSC 8000, Bethesda, MD 20892, USA Y1 - 2002/09// PY - 2002 DA - Sep 2002 SP - 1207 EP - 1215 VL - 18 IS - 9 SN - 1367-4803, 1367-4803 KW - DNA microarrays KW - cDNA KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18692460?accountid=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=Bioinformatics&rft.atitle=Ratio+statistics+of+gene+expression+levels+and+applications+to+microarray+data+analysis&rft.au=Chen%2C+Y%3BKamat%2C+V%3BDougherty%2C+E+R%3BBittner%2C+M+L%3BMeltzer%2C+P+S%3BTrent%2C+J+M&rft.aulast=Chen&rft.aufirst=Y&rft.date=2002-09-01&rft.volume=18&rft.issue=9&rft.spage=1207&rft.isbn=&rft.btitle=&rft.title=Bioinformatics&rft.issn=13674803&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 - Chronic Arsenic-Exposed Human Prostate Epithelial Cells Exhibit Stable Arsenic Tolerance: Mechanistic Implications of Altered Cellular Glutathione and Glutathione S -transferase AN - 18501803; 5465208 AB - Acquisition of stable arsenic tolerance in human cells following chronic arsenic exposure has not been previously reported. In the present work, we describe acquisition of stable arsenic tolerance in the human prostate epithelial cell line RWPE-1 following chronic arsenic exposure in vitro. RWPE-1 cells continuously exposed to 5 mu M sodium arsenite for greater than or equal to 18 weeks exhibited dramatic resistance to acute arsenite toxicity. The LC50 for acute arsenite exposure in these chronic arsenic-exposed prostate epithelial (CAsE-PE) cells was 43.8 mu M versus 17.6 mu M in control cells. Similar results were obtained using the antineoplastic agent arsenic trioxide. This tolerance was stable, as CAsE-PE cells grown in arsenic-free medium for 5 weeks retained their resistant phenotype. Compared to control cells, CAsE-PE cells showed a 90% reduction in arsenic accumulation over 24 h coupled with a 2.6-fold increase in the rate of arsenic efflux. CAsE-PE cells had increased basal GSH levels (4.9-fold) and increased GST activity (2.4-fold) and both GSH depletion and inhibition of GST activity abolished arsenic tolerance. Arsenic tolerance was also abolished by treatment with inhibitors of the Mdr1 and Mrp1 transporters, although no increases in mdr1 or mrp1 gene expression were observed. Our results indicate that this tolerance in human cells involves increases in GSH levels and GST activity that allow for more efficient arsenic efflux by MRP1 and MDR1. This study represents the first report of stable acquired arsenic tolerance in human cells, which could have important implications for both the toxicology and the pharmacology of arsenic. [copy ] 2002 Elsevier Science (USA). JF - Toxicology and Applied Pharmacology AU - Brambila, E M AU - Achanzar, W E AU - Qu, W AU - Webber, M M AU - Waalkes, M P AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at the National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709, waalkes@niehs.nih.gov Y1 - 2002/09/01/ PY - 2002 DA - 2002 Sep 01 SP - 99 EP - 107 PB - Academic Press VL - 183 IS - 2 SN - 0041-008X, 0041-008X KW - RWPE-1 cells KW - man KW - tolerance KW - Toxicology Abstracts KW - X 24162:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18501803?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+Applied+Pharmacology&rft.atitle=Chronic+Arsenic-Exposed+Human+Prostate+Epithelial+Cells+Exhibit+Stable+Arsenic+Tolerance%3A+Mechanistic+Implications+of+Altered+Cellular+Glutathione+and+Glutathione+S+-transferase&rft.au=Brambila%2C+E+M%3BAchanzar%2C+W+E%3BQu%2C+W%3BWebber%2C+M+M%3BWaalkes%2C+M+P&rft.aulast=Brambila&rft.aufirst=E&rft.date=2002-09-01&rft.volume=183&rft.issue=2&rft.spage=99&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+Applied+Pharmacology&rft.issn=0041008X&rft_id=info:doi/10.1006%2Ftaap.2002.9468 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1006/taap.2002.9468 ER - TY - JOUR T1 - Sustained hepatic and renal glucose-6-phosphatase expression corrects glycogen storage disease type la in mice AN - 18497144; 5463070 AB - Deficiency of glucose-6-phosphatase (G6Pase), a key enzyme in glucose homeostasis, causes glycogen storage disease type la (GSD-la), an autosomal recessive disorder characterized by growth retardation, hypoglycemia, hepatomegaly, nephromegaly, hyperlipidemia, hyperuricemia, and lactic acidemia. G6Pase is an endoplasmic reticulum-associated transmembrane protein expressed primarily in the liver and the kidney. Therefore, enzyme replacement therapy is not feasible using current strategies, but somatic gene therapy, targeting G6Pase to the liver and the kidney, is an attractive possibility. Previously, we reported the development of a mouse model of G6Pase deficiency that closely mimics human GSD-la. Using neonatal GSD-la mice, we now demonstrate that a combined adeno virus and adeno-associated virus vector-mediated gene transfer leads to sustained G6Pase expression in both the liver and the kidney and corrects the murine GSD-la disease for at least 12 months. Our results suggest that human GSD-la would be treatable by gene therapy. JF - Human Molecular Genetics AU - Sun, M-S AU - Pan, C-J AU - Shieh, J-J AU - Ghosh, A AU - Chen, L-Y AU - Mansfield, B C AU - Ward, J M AU - Byrne, B J AU - Chou, J Y AD - Building 10, Room 9S241, NIH, 9000 Rockville Pike, Bethesda, MD 20892-1830, USA, chou@helix.nih.gov Y1 - 2002/09/01/ PY - 2002 DA - 2002 Sep 01 SP - 2155 EP - 2164 VL - 11 IS - 18 SN - 0964-6906, 0964-6906 KW - glycogen storage disease 1a KW - man KW - mice KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33056:Animal models of human disease KW - G 07444:Animal models KW - W 30965:Miscellaneous, Reviews KW - W4 120:Genetic Engineering in Medicine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18497144?accountid=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+Molecular+Genetics&rft.atitle=Sustained+hepatic+and+renal+glucose-6-phosphatase+expression+corrects+glycogen+storage+disease+type+la+in+mice&rft.au=Sun%2C+M-S%3BPan%2C+C-J%3BShieh%2C+J-J%3BGhosh%2C+A%3BChen%2C+L-Y%3BMansfield%2C+B+C%3BWard%2C+J+M%3BByrne%2C+B+J%3BChou%2C+J+Y&rft.aulast=Sun&rft.aufirst=M-S&rft.date=2002-09-01&rft.volume=11&rft.issue=18&rft.spage=2155&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Immune Response to Fetal Calf Serum by Two Adenosine Deaminase-Deficient Patients After T Cell Gene Therapy AN - 18491257; 5454615 AB - The first approved clinical gene therapy trial for adenosine deaminase (ADA) deficiency employed autologous T cells grown in fetal calf serum (FCS)-supplemented medium and transduced with a retroviral vector (LASN) also produced in the presence of FCS. Ten years after their enrollment, both patients have circulating T cells containing vector DNA. However, whereas approximately 20% of the circulating T cells from patient 1 are still vector positive, less than 1% of patient 2's T cells have detectable vector. This difference appears to be not only a function of the original transduction efficiency and cell expansion capability in vitro, but also of the immune response that patient 2 developed to FCS components during the course of her treatment. In this study, serum samples from each patient were tested for antibodies to FCS by enzyme-linked immunosorbent assay and anti-FCS responses were demonstrated in both patients. Analysis of immunoglobulin classes revealed comparable levels of IgA and IgM anti-FCS titers. Patient 2, however, had significantly higher IgG responses to FCS than did patient 1. Investigation of the development of anti-FCS responses by IgG subclasses indicated that there was a different pattern in the development of IgG immunity to FCS between the two patients. In addition, significant antibody response to bovine lipoprotein was detected in patient 2, but not in patient 1 or in control samples. These findings suggest that the unique immune response mounted by patient 2 may have influenced the outcome of the gene transfer treatments in this patient. JF - Human Gene Therapy AU - Tuschong, L AU - Soenen, S L AU - Blaese, R M AU - Candotti, F AU - Muul, L M AD - Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Muscoloskeletal and Skin Diseases, National Institutes of Health, 10 Center Drive, Building 10, Room 9N252, Bethesda, MD 20892-1820, USA, muul1@mail.nih.gov Y1 - 2002/09/01/ PY - 2002 DA - 2002 Sep 01 SP - 1605 EP - 1610 VL - 13 IS - 13 SN - 1043-0342, 1043-0342 KW - man KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W 30965:Miscellaneous, Reviews KW - W4 120:Genetic Engineering in Medicine KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18491257?accountid=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=Immune+Response+to+Fetal+Calf+Serum+by+Two+Adenosine+Deaminase-Deficient+Patients+After+T+Cell+Gene+Therapy&rft.au=Tuschong%2C+L%3BSoenen%2C+S+L%3BBlaese%2C+R+M%3BCandotti%2C+F%3BMuul%2C+L+M&rft.aulast=Tuschong&rft.aufirst=L&rft.date=2002-09-01&rft.volume=13&rft.issue=13&rft.spage=1605&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Communication among Oral Bacteria AN - 18483796; 5440016 AB - Human oral bacteria interact with their environment by attaching to surfaces and establishing mixed-species communities. As each bacterial cell attaches, it forms a new surface to which other cells can adhere. Adherence and community development are spatiotemporal; such order requires communication. The discovery of soluble signals, such as autoinducer-2, that may be exchanged within multispecies communities to convey information between organisms has emerged as a new research direction. Direct-contact signals, such as adhesins and receptors, that elicit changes in gene expression after cell-cell contact and biofilm growth are also an active research area. Considering that the majority of oral bacteria are organized in dense three-dimensional biofilms on teeth, confocal microscopy and fluorescently labeled probes provide valuable approaches for investigating the architecture of these organized communities in situ. Oral biofilms are readily accessible to microbiologists and are excellent model systems for studies of microbial communication. One attractive model system is a saliva-coated flowcell with oral bacterial biofilms growing on saliva as the sole nutrient source; an intergeneric mutualism is discussed. Several oral bacterial species are amenable to genetic manipulation for molecular characterization of communication both among bacteria and between bacteria and the host. A successful search for genes critical for mixed-species community organization will be accomplished only when it is conducted with mixed-species communities. JF - Microbiology and Molecular Biology Reviews AU - Kolenbrander, P E AU - Andersen, R N AU - Blehert, D S AU - Egland, P G AU - Foster, J S AU - Palmer, Jr RJ AD - Building 30, Room 310, 30 Convent Drive MSC4350, National Institutes of Health/NIDCR, Bethesda, MD 20892-4350, pkolenbrander@dir.nidcr.nih.gov Y1 - 2002/09// PY - 2002 DA - Sep 2002 SP - 486 EP - 505 VL - 66 IS - 3 SN - 1092-2172, 1092-2172 KW - confocal microscopy KW - Microbiology Abstracts B: Bacteriology KW - J 02841:Microflora UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18483796?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Microbiology+and+Molecular+Biology+Reviews&rft.atitle=Communication+among+Oral+Bacteria&rft.au=Kolenbrander%2C+P+E%3BAndersen%2C+R+N%3BBlehert%2C+D+S%3BEgland%2C+P+G%3BFoster%2C+J+S%3BPalmer%2C+Jr+RJ&rft.aulast=Kolenbrander&rft.aufirst=P&rft.date=2002-09-01&rft.volume=66&rft.issue=3&rft.spage=486&rft.isbn=&rft.btitle=&rft.title=Microbiology+and+Molecular+Biology+Reviews&rft.issn=10922172&rft_id=info:doi/10.1128%2FMMBR.66.3.486-505.2002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/MMBR.66.3.486-505.2002 ER - TY - JOUR T1 - Effects of caffeine on development and behavior in infancy and childhood: a review of the published literature AN - 18479588; 5443714 AB - The Medline literature on the behavioral effects of caffeine in infants and children are reviewed. There has been little recent work in this area. Generally, caffeine is well tolerated in usual dietary amounts, and there is evidence that individuals differ in their susceptibility to caffeine-related adverse effects, which in turn may influence their consumption. Overall, the effects of caffeine in children seem to be modest and typically innocuous. JF - Food and Chemical Toxicology AU - Castellanos, F X AU - Rapoport, J L AD - National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20814, USA, fxc@helix.noh.gov Y1 - 2002/09// PY - 2002 DA - Sep 2002 SP - 1235 EP - 1242 VL - 40 IS - 9 SN - 0278-6915, 0278-6915 KW - man KW - Toxicology Abstracts KW - X 24120:Food, additives & contaminants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18479588?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Food+and+Chemical+Toxicology&rft.atitle=Effects+of+caffeine+on+development+and+behavior+in+infancy+and+childhood%3A+a+review+of+the+published+literature&rft.au=Castellanos%2C+F+X%3BRapoport%2C+J+L&rft.aulast=Castellanos&rft.aufirst=F&rft.date=2002-09-01&rft.volume=40&rft.issue=9&rft.spage=1235&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 - SuppNotes - Special Issue: ILSI Caffeine Monograph. N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Eighteen polymorphic microsatellite markers for the highly endangered Spanish imperial eagle (Aquila adalberti ) and related species AN - 18477425; 5443146 AB - Here we describe the development of 18 polymorphic microsatellite markers for the endangered Spanish imperial eagle (Aquila adalberti). Microsatellites were tested in five other raptor species. These markers were revealed as good molecular tools for genetic population studies, individual identification and parentage assessment in Spanish imperial eagle and closely related species. JF - Molecular Ecology Notes AU - Martinez-Cruz, B AU - David, V A AU - Godoy, JA AU - Negro, J J AU - O'Brien, S J AU - Johnson, W E AD - Estacion Biologica de Donana (CSIC), Avda. Maria Luisa s/n, 41013 Sevilla, Spain, Laboratory of Genomic Diversity, NCI-FCRDC, Frederick, MD, 21702-1201, USA, bemar@ebd.csic.es Y1 - 2002/09// PY - 2002 DA - Sep 2002 SP - 323 EP - 326 PB - Blackwell Science Ltd VL - 2 IS - 3 SN - 1471-8278, 1471-8278 KW - Aquila adalberti KW - Spanish imperial eagle KW - Ecology Abstracts; Genetics Abstracts KW - D 04671:Birds KW - G 07270:Ecological genetics KW - G 07377:Birds UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18477425?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Ecology+Notes&rft.atitle=Eighteen+polymorphic+microsatellite+markers+for+the+highly+endangered+Spanish+imperial+eagle+%28Aquila+adalberti+%29+and+related+species&rft.au=Martinez-Cruz%2C+B%3BDavid%2C+V+A%3BGodoy%2C+JA%3BNegro%2C+J+J%3BO%27Brien%2C+S+J%3BJohnson%2C+W+E&rft.aulast=Martinez-Cruz&rft.aufirst=B&rft.date=2002-09-01&rft.volume=2&rft.issue=3&rft.spage=323&rft.isbn=&rft.btitle=&rft.title=Molecular+Ecology+Notes&rft.issn=14718278&rft_id=info:doi/10.1046%2Fj.1471-8286.2002.00231.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1046/j.1471-8286.2002.00231.x ER - TY - JOUR T1 - Effects of the P1 Plasmid Centromere on Expression of P1 Partition Genes AN - 18472191; 5439675 AB - The partition operon of P1 plasmid encodes two proteins, ParA and ParB, required for the faithful segregation of plasmid copies to daughter cells. The operon is followed by a centromere analog, parS, at which ParB binds. ParA, a weak ATPase, represses the par promoter most effectively in its ADP-bound form. ParB can recruit ParA to parS, stimulate its ATPase, and significantly stimulate the repression. We report here that parS also participates in the regulation of expression of the par genes. A single chromosomal parS was shown to augment repression of several copies of the par promoter by severalfold. The repression increase was sensitive to the levels of ParA and ParB and to their ratio. The increase may be attributable to a conformational change in ParA mediated by the parS-ParB complex, possibly acting catalytically. We also observed an in cis effect of parS which enhanced expression of parB, presumably due to a selective modulation of the mRNA level. Although ParB had been earlier found to spread into and silence genes flanking parS, silencing of the par operon by ParB spreading was not significant. Based upon analogies between partitioning and septum placement, we speculate that the regulatory switch controlled by the parS-ParB complex might be essential for partitioning itself. JF - Journal of Bacteriology AU - Hao, J AU - Yarmolinsky, M AD - Laboratory of Biochemistry, National Cancer Institute, NIH, 37 Convent Dr., Bethesda, MD 20892-4255, myarmo@helix.nih.gov Y1 - 2002/09// PY - 2002 DA - Sep 2002 SP - 4857 EP - 4867 VL - 184 IS - 17 SN - 0021-9193, 0021-9193 KW - ParA protein KW - ParB protein KW - par operon KW - parS gene KW - plasmid P1 KW - Microbiology Abstracts B: Bacteriology KW - J 02760:Plasmids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18472191?accountid=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+the+P1+Plasmid+Centromere+on+Expression+of+P1+Partition+Genes&rft.au=Hao%2C+J%3BYarmolinsky%2C+M&rft.aulast=Hao&rft.aufirst=J&rft.date=2002-09-01&rft.volume=184&rft.issue=17&rft.spage=4857&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.184.17.4857-4867.2002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/JB.184.17.4857-4867.2002 ER - TY - JOUR T1 - The metD D-Methionine Transporter Locus of Escherichia coli Is an ABC Transporter Gene Cluster AN - 18472077; 5439694 AB - The metD D-methionine transporter locus of Escherichia coli was identified as the abc-yaeE-yaeC cluster (now renamed metNIQ genes). The abc open reading frame is preceded by tandem MET boxes bracketed by the -10 and -35 boxes of a promoter. The expression driven by this promoter is controlled by the MetJ repressor and the level of methionine. JF - Journal of Bacteriology AU - Gal, J AU - Szvetnik, A AU - Schnell, R AU - Kalman, M AD - Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, 6 Center Dr., Building 6B, Room 3B-316, Bethesda, MD 20892-2785, galj2@mail.nih.gov Y1 - 2002/09// PY - 2002 DA - Sep 2002 SP - 4930 EP - 4932 VL - 184 IS - 17 SN - 0021-9193, 0021-9193 KW - D-methionine transporter KW - MetJ protein KW - metD gene KW - Microbiology Abstracts B: Bacteriology KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18472077?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=The+metD+D-Methionine+Transporter+Locus+of+Escherichia+coli+Is+an+ABC+Transporter+Gene+Cluster&rft.au=Gal%2C+J%3BSzvetnik%2C+A%3BSchnell%2C+R%3BKalman%2C+M&rft.aulast=Gal&rft.aufirst=J&rft.date=2002-09-01&rft.volume=184&rft.issue=17&rft.spage=4930&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.184.17.4930-4932.2002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/JB.184.17.4930-4932.2002 ER - TY - JOUR T1 - Health websites in Italy: use, classification and international policy AN - 17884365; 6064681 AB - In this paper, we discuss international policy in relation to the use of health websites and we describe the results obtained from application of a search engine to the recognition and classification of health websites in Italy. We then compare the results with health websites in other countries. Effective use of technology has led to medical advances that have not only extended life expectancy, but also fuelled an increasingly well-informed public to expect more and more from today's healthcare providers. As a consequence of the Web's rapid, chaotic growth, the resulting network of information lacks organization and structure and the quest for a method of quickly finding relevant and reliable information is spawning the growth of Internet portal sites. The US and the European Union and now Italy, have established the importance of rules to check the quality of health sites both for the non-professional users (citizens), mainly for privacy and security (for example, of medical records); and for health operators (physicians and others), where the most important thing is to evaluate the quality of content. In June 2001, the search engine used here found 2627 Italian health sites, of which only 46 exhibited the HON Code, and they can be classified into: 1% personal medical sites, 17% health portals, 18% metasites, 27% documental sites and 37% information sites for health operators and/or for citizens. JF - Medical Informatics and the Internet in Medicine AU - Di giacomo, P AU - Maceratini, R AD - Centro Interdipartimentale di Ricerca per l'Analisis dei Modelli e dell'Informazione nei Sistemi Biomedici, Universita 'La Sapienza' di Roma, Corso Vittorio Emanuele 244-00186, Roma Y1 - 2002/09// PY - 2002 DA - Sep 2002 SP - 153 EP - 160 PB - Taylor & Francis Ltd., 11 New Fetter Lane London EC4P 4EE UK, [mailto:info@tandf.co.uk], [URL:http://www.tandf.co.uk] VL - 27 IS - 3 SN - 1463-9238, 1463-9238 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - medical records KW - Life span KW - Internet KW - W4 140:Bioinformatics & Computers in Health & Medicine KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17884365?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Medical+Informatics+and+the+Internet+in+Medicine&rft.atitle=Health+websites+in+Italy%3A+use%2C+classification+and+international+policy&rft.au=Di+giacomo%2C+P%3BMaceratini%2C+R&rft.aulast=Di+giacomo&rft.aufirst=P&rft.date=2002-09-01&rft.volume=27&rft.issue=3&rft.spage=153&rft.isbn=&rft.btitle=&rft.title=Medical+Informatics+and+the+Internet+in+Medicine&rft.issn=14639238&rft_id=info:doi/10.1080%2F1463923021000014112 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Internet; medical records; Life span DO - http://dx.doi.org/10.1080/1463923021000014112 ER - TY - JOUR T1 - Thoughts On Qualitative Research Methods at NIH AN - 1417524265; 201306091 AB - These are brief comments describing the history, process and purpose leading to the publication of 'Qualitative Methods in Health Research: Opportunities and Considerations in Application and Review' (NIH Publication No. 02-!5046, December 2001). For more extensive information regarding qualitative research methods, other research questions, funding history, and general information regarding the US National Institutes of Health (NIH) and its components, the reader is advised to consult NIH's websites, literature, program staff and previously funded researchers. [Reprinted by permission of Sage Publications Ltd., copyright holder.] JF - Qualitative Social Work AU - Heurtin-Roberts, Suzanne AD - National Cancer Institute of the National Institutes of Health, USA Sheurtin@mail.nih.gov Y1 - 2002/09// PY - 2002 DA - September 2002 SP - 376 EP - 379 PB - Sage Publications, London UK VL - 1 IS - 3 SN - 1473-3250, 1473-3250 KW - NIH, qualitative methods, research funding KW - Health Research KW - United States of America KW - Health KW - article KW - 6111: social work theory/research UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1417524265?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocialservices&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Qualitative+Social+Work&rft.atitle=Thoughts+On+Qualitative+Research+Methods+at+NIH&rft.au=Heurtin-Roberts%2C+Suzanne&rft.aulast=Heurtin-Roberts&rft.aufirst=Suzanne&rft.date=2002-09-01&rft.volume=1&rft.issue=3&rft.spage=376&rft.isbn=&rft.btitle=&rft.title=Qualitative+Social+Work&rft.issn=14733250&rft_id=info:doi/10.1177%2F147332500200100310 LA - English DB - Social Services Abstracts N1 - Date revised - 2013-08-01 N1 - Last updated - 2016-09-28 N1 - SubjectsTermNotLitGenreText - United States of America; Health Research; Health DO - http://dx.doi.org/10.1177/147332500200100310 ER - TY - JOUR T1 - Analysis of Survival Data from Case-Control Family Studies AN - 1034815260; 15992694 AB - Summary. In case-control family studies with survival endpoint, age of onset of diseases can be used to assess the familial aggregation of the disease and the relationship between the disease and genetic or environmental risk factors. Because of the retrospective nature of the case-control study, methods for analyzing prospectively collected correlated failure time data do not apply directly. In this article, we propose a semiparametric quasi-partial-likelihood approach to simultaneously estimate the effect of covariates on the age of onset and the association of ages of onset among family members that does not require specification of the baseline marginal distribution. We conducted a simulation study to evaluate the performance of the proposed approach and compare it with the existing semiparametric ones. Simulation results demonstrate that the proposed approach has better performance in terms of consistency and efficiency. We illustrate the methodology using a subset of data from the Washington Ashkenazi Study. JF - Biometrics AU - Shih, Joanna H AU - Chatterjee, Nilanjan AD - Division of Cancer Treatment and Diagnosis, National Cancer Institute, 6130 Executive Boulevard, Bethesda, Maryland 20892-7434, U.S.A. Y1 - 2002/09// PY - 2002 DA - Sep 2002 SP - 502 EP - 509 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 58 IS - 3 SN - 0006-341X, 0006-341X KW - Risk Abstracts KW - USA, Washington KW - Age KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1034815260?accountid=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=Biometrics&rft.atitle=Analysis+of+Survival+Data+from+Case-Control+Family+Studies&rft.au=Shih%2C+Joanna+H%3BChatterjee%2C+Nilanjan&rft.aulast=Shih&rft.aufirst=Joanna&rft.date=2002-09-01&rft.volume=58&rft.issue=3&rft.spage=502&rft.isbn=&rft.btitle=&rft.title=Biometrics&rft.issn=0006341X&rft_id=info:doi/10.1111%2Fj.0006-341X.2002.00502.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2012-08-01 N1 - Last updated - 2014-02-21 N1 - SubjectsTermNotLitGenreText - Age; USA, Washington DO - http://dx.doi.org/10.1111/j.0006-341X.2002.00502.x ER - TY - JOUR T1 - Nm23-H1 metastasis suppressor phosphorylation of kinase suppressor of Ras via a histidine protein kinase pathway. AN - 72039977; 12105213 AB - The metastasis-suppressive activity of Nm23-H1 was previously correlated with its in vitro histidine protein kinase activity, but physiological substrates have not been identified. We hypothesized that proteins that interact with histidine kinases throughout evolution may represent partners for Nm23-H1 and focused on the interaction of Arabidopsis "two-component" histidine kinase ERS with CTR1. A mammalian homolog of CTR1 was previously reported to be c-Raf; we now report that CTR1 also exhibits homology to the kinase suppressor of Ras (KSR), a scaffold protein for the mitogen-activated protein kinase (MAPK) cascade. Nm23-H1 co-immunoprecipitated KSR from lysates of transiently transfected 293T cells and at endogenous protein expression levels in MDA-MB-435 breast carcinoma cells. Autophosphorylated recombinant Nm23-H1 phosphorylated KSR in vitro. Phosphoamino acid analysis identified serine as the major target, and two peaks of Nm23-H1 phosphorylation were identified upon high performance liquid chromatography analysis of KSR tryptic peptides. Using site-directed mutagenesis, we found that Nm23-H1 phosphorylated KSR serine 392, a 14-3-3-binding site, as well as serine 434 when serine 392 was mutated. Phosphorylated MAPK but not total MAPK levels were reduced in an nm23-H1 transfectant of MDA-MB-435 cells. The data identify a complex in vitro histidine-to-serine protein kinase pathway, which may contribute to signal transduction and metastasis. JF - The Journal of biological chemistry AU - Hartsough, Melanie T AU - Morrison, Deborah K AU - Salerno, Massimiliano AU - Palmieri, Diane AU - Ouatas, Taoufik AU - Mair, Michael AU - Patrick, Jilma AU - Steeg, Patricia S AD - Women's Cancers Section, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/08/30/ PY - 2002 DA - 2002 Aug 30 SP - 32389 EP - 32399 VL - 277 IS - 35 SN - 0021-9258, 0021-9258 KW - Antigens, Neoplasm KW - 0 KW - DNA Primers KW - NM23 Nucleoside Diphosphate Kinases KW - Recombinant Proteins KW - Transcription Factors KW - Serine KW - 452VLY9402 KW - Protein Kinases KW - EC 2.7.- KW - Histidine Kinase KW - EC 2.7.13.1 KW - NME1 protein, human KW - EC 2.7.4.6 KW - Nucleoside-Diphosphate Kinase KW - Monomeric GTP-Binding Proteins KW - EC 3.6.5.2 KW - ras Proteins KW - Alanine KW - OF5P57N2ZX KW - Index Medicus KW - Humans KW - Breast Neoplasms KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Tumor Cells, Cultured KW - Phosphorylation KW - Transfection KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Antigens, Neoplasm -- metabolism KW - Substrate Specificity KW - Recombinant Proteins -- chemistry KW - Neoplasm Metastasis -- prevention & control KW - Amino Acid Substitution KW - Cell Line KW - Female KW - Protein Kinases -- metabolism KW - ras Proteins -- antagonists & inhibitors KW - Transcription Factors -- metabolism KW - Monomeric GTP-Binding Proteins -- metabolism KW - Transcription Factors -- chemistry KW - ras Proteins -- metabolism KW - Transcription Factors -- genetics KW - Monomeric GTP-Binding Proteins -- chemistry KW - Monomeric GTP-Binding Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72039977?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Nm23-H1+metastasis+suppressor+phosphorylation+of+kinase+suppressor+of+Ras+via+a+histidine+protein+kinase+pathway.&rft.au=Hartsough%2C+Melanie+T%3BMorrison%2C+Deborah+K%3BSalerno%2C+Massimiliano%3BPalmieri%2C+Diane%3BOuatas%2C+Taoufik%3BMair%2C+Michael%3BPatrick%2C+Jilma%3BSteeg%2C+Patricia+S&rft.aulast=Hartsough&rft.aufirst=Melanie&rft.date=2002-08-30&rft.volume=277&rft.issue=35&rft.spage=32389&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 - 2002-10-17 N1 - Date created - 2002-08-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tumor necrosis factor induces apoptosis in hepatoma cells by increasing Ca(2+) release from the endoplasmic reticulum and suppressing Bcl-2 expression. AN - 72039938; 12077131 AB - Tumor necrosis factor (TNF) plays an import role in the control of apoptosis. The most well known apoptotic pathway regulated by TNF involves the TNFR1-associated death domain protein, Fas-associated death domain protein, and caspase-8. This study examines the mechanism of TNF-induced apoptosis in FaO rat hepatoma cells. TNF treatment significantly increased the percentage of apoptotic cells. TNF did not activate caspase-8 but activated caspase-3, -10, and -12. The effect of TNF on the expression of different members of the Bcl-2 family in these cells was studied. We observed no detectable changes in the steady-state levels of Bcl-X(L), Bax, and Bid, although TNF suppresses Bcl-2 expression. Dantrolene suppressed the inhibitory effect of TNF on Bcl-2 expression. TNF induced release of Ca(2+) from the endoplasmic reticulum (ER) that was blocked by dantrolene. Importantly, the expression of Bcl-2 blocked TNF-induced apoptosis and decreased TNF-induced Ca(2+) release. These results suggest that TNF induces apoptosis by a mechanism that involves increasing Ca(2+) release from the ER and suppression of Bcl-2 expression. JF - The Journal of biological chemistry AU - Kim, Byung-Chul AU - Kim, Heung-Tae AU - Mamura, Mizuko AU - Ambudkar, Indu S AU - Choi, Kyeong-Sook AU - Kim, Seong-Jin AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/08/30/ PY - 2002 DA - 2002 Aug 30 SP - 31381 EP - 31389 VL - 277 IS - 35 SN - 0021-9258, 0021-9258 KW - Bcl2l1 protein, rat KW - 0 KW - Proto-Oncogene Proteins c-bcl-2 KW - Transforming Growth Factor beta KW - Tumor Necrosis Factor-alpha KW - bcl-X Protein KW - Dantrolene KW - F64QU97QCR KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Rats KW - Transforming Growth Factor beta -- pharmacology KW - Animals KW - Tumor Cells, Cultured KW - Dantrolene -- pharmacology KW - Kinetics KW - Genes, bcl-2 -- drug effects KW - Endoplasmic Reticulum -- metabolism KW - Calcium -- metabolism KW - Liver Neoplasms, Experimental -- pathology KW - Liver Neoplasms, Experimental -- metabolism KW - Apoptosis -- physiology KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Proto-Oncogene Proteins c-bcl-2 -- metabolism KW - Gene Expression Regulation, Neoplastic -- physiology KW - Proto-Oncogene Proteins c-bcl-2 -- genetics KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Endoplasmic Reticulum -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72039938?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Tumor+necrosis+factor+induces+apoptosis+in+hepatoma+cells+by+increasing+Ca%282%2B%29+release+from+the+endoplasmic+reticulum+and+suppressing+Bcl-2+expression.&rft.au=Kim%2C+Byung-Chul%3BKim%2C+Heung-Tae%3BMamura%2C+Mizuko%3BAmbudkar%2C+Indu+S%3BChoi%2C+Kyeong-Sook%3BKim%2C+Seong-Jin&rft.aulast=Kim&rft.aufirst=Byung-Chul&rft.date=2002-08-30&rft.volume=277&rft.issue=35&rft.spage=31381&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 - 2002-10-17 N1 - Date created - 2002-08-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The processing of Holliday junctions by BLM and WRN helicases is regulated by p53. AN - 72035475; 12080066 AB - BLM, WRN, and p53 are involved in the homologous DNA recombination pathway. The DNA structure-specific helicases, BLM and WRN, unwind Holliday junctions (HJ), an activity that could suppress inappropriate homologous recombination during DNA replication. Here, we show that purified, recombinant p53 binds to BLM and WRN helicases and attenuates their ability to unwind synthetic HJ in vitro. The p53 248W mutant reduces abilities of both to bind HJ and inhibit helicase activities, whereas the p53 273H mutant loses these abilities. Moreover, full-length p53 and a C-terminal polypeptide (residues 373-383) inhibit the BLM and WRN helicase activities, but phosphorylation at Ser(376) or Ser(378) completely abolishes this inhibition. Following blockage of DNA replication, Ser(15) phospho-p53, BLM, and RAD51 colocalize in nuclear foci at sites likely to contain DNA replication intermediates in cells. Our results are consistent with a novel mechanism for p53-mediated regulation of DNA recombinational repair that involves p53 post-translational modifications and functional protein-protein interactions with BLM and WRN DNA helicases. JF - The Journal of biological chemistry AU - Yang, Qin AU - Zhang, Ran AU - Wang, Xin Wei AU - Spillare, Elisa A AU - Linke, Steven P AU - Subramanian, Deepa AU - Griffith, Jack D AU - Li, Ji Liang AU - Hickson, Ian D AU - Shen, Jiang Cheng AU - Loeb, Lawrence A AU - Mazur, Sharlyn J AU - Appella, Ettore AU - Brosh, Robert M AU - Karmakar, Parimal AU - Bohr, Vilhelm A AU - Harris, Curtis C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/08/30/ PY - 2002 DA - 2002 Aug 30 SP - 31980 EP - 31987 VL - 277 IS - 35 SN - 0021-9258, 0021-9258 KW - Recombinant Fusion Proteins KW - 0 KW - Tumor Suppressor Protein p53 KW - Exodeoxyribonucleases KW - EC 3.1.- KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - Bloom syndrome protein KW - DNA Helicases KW - EC 3.6.4.- KW - RecQ Helicases KW - EC 3.6.4.12 KW - WRN protein, human KW - Werner Syndrome Helicase KW - Index Medicus KW - Recombinant Fusion Proteins -- metabolism KW - Fluorescent Antibody Technique, Indirect KW - Kinetics KW - Humans KW - Lymphocytes KW - Tumor Suppressor Protein p53 -- metabolism KW - Cell Line KW - Mutagenesis KW - Binding Sites KW - DNA Helicases -- metabolism KW - Adenosine Triphosphatases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72035475?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+processing+of+Holliday+junctions+by+BLM+and+WRN+helicases+is+regulated+by+p53.&rft.au=Yang%2C+Qin%3BZhang%2C+Ran%3BWang%2C+Xin+Wei%3BSpillare%2C+Elisa+A%3BLinke%2C+Steven+P%3BSubramanian%2C+Deepa%3BGriffith%2C+Jack+D%3BLi%2C+Ji+Liang%3BHickson%2C+Ian+D%3BShen%2C+Jiang+Cheng%3BLoeb%2C+Lawrence+A%3BMazur%2C+Sharlyn+J%3BAppella%2C+Ettore%3BBrosh%2C+Robert+M%3BKarmakar%2C+Parimal%3BBohr%2C+Vilhelm+A%3BHarris%2C+Curtis+C&rft.aulast=Yang&rft.aufirst=Qin&rft.date=2002-08-30&rft.volume=277&rft.issue=35&rft.spage=31980&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 - 2002-10-17 N1 - Date created - 2002-08-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Overexpression of the Atypical Protein Kinase C [zeta] Reduces Topoisomerase II Catalytic Activity, Cleavable Complexes Formation, and Drug-induced Cytotoxicity in Monocytic U937 Leukemia Cells AN - 18492865; 5450131 AB - In this study, we evaluated the influence of protein kinase C[zeta] (PKC[zeta]) on topoisomerase II inhibitor-induced cytotoxicity in monocytic U937 cells. In U937-[zeta]J and U937-[zeta]B cells, enforced PKC[zeta] expression, conferred by stable transfection of PKC[zeta] cDNA, resulted in total inhibition of VP-16- and mitoxantrone-induced apoptosis and decreased drug-induced cytotoxicity, compared with U937-neo control cells. In PKC[zeta]-overexpressing cells, drug resistance correlated with decreased VP-16-induced DNA strand breaks and DNA protein cross-links measured by alkaline elution. Kinetoplast decatenation assay revealed that PKC[zeta] overexpression resulted in reduced global topoisomerase II activity. Moreover, in PKC[zeta]-overexpressing cells, we found that PKC[zeta] interacted with both [alpha] and [beta] isoforms of topoisomerase II, and these two enzymes were constitutively phosphorylated. However, when human recombinant PKC[zeta] (rH-PKC[zeta]) was incubated with purified topoisomerase II isoforms, rH-PKC[zeta] interacted with topoisomerase II[beta] but not with topoisomerase II[alpha]. PKC[zeta]/topoisomerase II[beta] interaction resulted in phosphorylation of this enzyme and in decrease of its catalytic activity. Finally, this report shows for the first time that topoisomerase II[beta] is a substrate for PKC[zeta], and that PKC[zeta] may significantly influence topoisomerase II inhibitor-induced cytotoxicity by altering topoisomerase II[beta] activity through its kinase function. JF - Journal of Biological Chemistry AU - Plo, I AU - Hernandez, H AU - Kohlhagen, G AU - Lautier, D AU - Pommier, Y AU - Laurent, G AD - INSERM E9910, Institut Claudius Regaud, 20 rue Du Pont Saint Pierre, 31052 Toulouse cedex, France, the Laboratory of Molecular Pharmacology, NCI, National Institutes of Health, Bethesda, Maryland 20892-4255, and the Service d'Hematologie, Centre Hospitalier Universitaire Purpan, 31059 Toulouse, France, plo@icr.fnclcc.fr. Y1 - 2002/08/30/ PY - 2002 DA - 2002 Aug 30 SP - 31407 EP - 31415 VL - 277 IS - 35 SN - 0021-9258, 0021-9258 KW - U937 cells KW - mitoxantrone KW - Biochemistry Abstracts 2: Nucleic Acids; Toxicology Abstracts KW - X 24117:Biochemistry KW - N 14731:DNA-unwinding enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18492865?accountid=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=Overexpression+of+the+Atypical+Protein+Kinase+C+%5Bzeta%5D+Reduces+Topoisomerase+II+Catalytic+Activity%2C+Cleavable+Complexes+Formation%2C+and+Drug-induced+Cytotoxicity+in+Monocytic+U937+Leukemia+Cells&rft.au=Plo%2C+I%3BHernandez%2C+H%3BKohlhagen%2C+G%3BLautier%2C+D%3BPommier%2C+Y%3BLaurent%2C+G&rft.aulast=Plo&rft.aufirst=I&rft.date=2002-08-30&rft.volume=277&rft.issue=35&rft.spage=31407&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 - Deletion of the M5 muscarinic acetylcholine receptor attenuates morphine reinforcement and withdrawal but not morphine analgesia. AN - 72020613; 12154229 AB - Little is known about the physiological roles of the M5 muscarinic receptor, the last member of the muscarinic receptor family (M1-M5) to be cloned. In the brain, the M5 receptor subtype is preferentially expressed by dopaminergic neurons of the substantia nigra and the ventral tegmental area. Dopaminergic neurons located in the ventral tegmental area are known to play important roles in mediating both the rewarding effects of opiates and other drugs of abuse and the manifestations of opiate/drug withdrawal symptoms. We therefore speculated that acetylcholine-dependent activation of M5 receptors might modulate the manifestations of opiate reward and withdrawal. This hypothesis was tested in a series of behavioral, biochemical, and neurochemical studies using M5 receptor-deficient mice (M5-/- mice) as novel experimental tools. We found that the rewarding effects of morphine, as measured in the conditioned place preference paradigm, were substantially reduced in M5-/- mice. Furthermore, both the somatic and affective components of naloxone-induced morphine withdrawal symptoms were significantly attenuated in M5-/- mice. In contrast, the analgesic efficacy of morphine and the development of tolerance to the analgesic effects of morphine remained unaltered by the lack of M5 receptors. The finding that M5 receptor activity modulates both morphine reward and withdrawal processes suggests that M5 receptors may represent a novel target for the treatment of opiate addiction. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Basile, Anthony S AU - Fedorova, Irina AU - Zapata, Agustin AU - Liu, Xiaoguang AU - Shippenberg, Toni AU - Duttaroy, Alokesh AU - Yamada, Masahisa AU - Wess, Jurgen AD - Neuroscience Group, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD 20892, USA. anthony.basile@alkermes.com Y1 - 2002/08/20/ PY - 2002 DA - 2002 Aug 20 SP - 11452 EP - 11457 VL - 99 IS - 17 SN - 0027-8424, 0027-8424 KW - Receptor, Muscarinic M5 KW - 0 KW - Receptors, Muscarinic KW - Morphine KW - 76I7G6D29C KW - Acetylcholine KW - N9YNS0M02X KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Dopamine -- secretion KW - Animals KW - Neurons -- drug effects KW - Reinforcement (Psychology) KW - Acetylcholine -- pharmacology KW - Mice KW - Ventral Tegmental Area -- physiopathology KW - Ventral Tegmental Area -- physiology KW - Mice, Knockout KW - Mutagenesis KW - Conditioning (Psychology) KW - Neurons -- physiology KW - Ventral Tegmental Area -- drug effects KW - Receptors, Muscarinic -- genetics KW - Analgesia KW - Substance Withdrawal Syndrome -- physiopathology KW - Nucleus Accumbens -- drug effects KW - Nucleus Accumbens -- physiology KW - Substance Withdrawal Syndrome -- genetics KW - Receptors, Muscarinic -- physiology KW - Nucleus Accumbens -- physiopathology KW - Receptors, Muscarinic -- deficiency KW - Morphine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72020613?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Deletion+of+the+M5+muscarinic+acetylcholine+receptor+attenuates+morphine+reinforcement+and+withdrawal+but+not+morphine+analgesia.&rft.au=Basile%2C+Anthony+S%3BFedorova%2C+Irina%3BZapata%2C+Agustin%3BLiu%2C+Xiaoguang%3BShippenberg%2C+Toni%3BDuttaroy%2C+Alokesh%3BYamada%2C+Masahisa%3BWess%2C+Jurgen&rft.aulast=Basile&rft.aufirst=Anthony&rft.date=2002-08-20&rft.volume=99&rft.issue=17&rft.spage=11452&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 - 2002-09-27 N1 - Date created - 2002-08-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Neuropharmacology. 1999 Dec;38(12):1903-12 [10608285] Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10483-8 [10468635] Br J Pharmacol. 2000 May;130(1):13-21 [10780992] Nature. 2000 May 11;405(6783):180-3 [10821273] Synapse. 2000 Aug;37(2):118-24 [10881033] Eur J Neurosci. 2000 Oct;12(10):3596-604 [11029630] J Neurosci. 2000 Dec 1;20(23):8861-7 [11102495] Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):14096-101 [11707605] J Neurosci. 2002 Jan 1;22(1):RC190 [11756520] J Biol Chem. 1989 May 5;264(13):7328-37 [2540186] Neuron. 1988 Jul;1(5):403-10 [3272174] J Pharmacol Exp Ther. 1990 Apr;253(1):395-400 [2329522] Neurosci Lett. 1990 Jul 3;114(2):154-9 [2395528] Proc Natl Acad Sci U S A. 1990 Sep;87(18):7050-4 [2402490] Trends Pharmacol Sci. 1992 May;13(5):177-84 [1604710] Mol Pharmacol. 1993 Feb;43(2):149-57 [8429821] J Neurosci Methods. 1993 Jul;48(3):263-76 [8105154] J Neurochem. 1995 Sep;65(3):1124-30 [7643090] J Neurosci. 1995 Sep;15(9):5859-69 [7666171] J Neurosci. 1996 Jan 15;16(2):714-22 [8551354] Mol Pharmacol. 1996 Apr;49(4):636-45 [8609891] Trends Neurosci. 1996 May;19(5):177-81 [8723200] Curr Opin Neurobiol. 1996 Apr;6(2):243-51 [8725967] Crit Rev Neurobiol. 1996;10(1):69-99 [8853955] Nature. 1996 Oct 31;383(6603):819-23 [8893006] Life Sci. 1997;60(13-14):1105-12 [9121354] Nature. 1997 Aug 7;388(6642):586-9 [9252189] Pharmacol Biochem Behav. 1997 Aug;57(4):915-21 [9259024] Pharmacol Rev. 1998 Jun;50(2):279-90 [9647869] Neuron. 1998 Sep;21(3):467-76 [9768834] Prog Neurobiol. 1998 Dec;56(6):613-72 [9871940] Crit Rev Neurobiol. 1998;12(4):267-303 [10348612] Psychopharmacology (Berl). 2000 Jan;147(4):347-55 [10672627] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - ACC/AHA/NHLBI Clinical Advisory on the Use and Safety of Statins. AN - 72017560; 12186811 JF - Circulation AU - Pasternak, Richard C AU - Smith, Sidney C AU - Bairey-Merz, C Noel AU - Grundy, Scott M AU - Cleeman, James I AU - Lenfant, Claude AU - American College of Cardiology AU - American Heart Association AU - National Heart, Lung and Blood Institute AD - American College of Cardiology ; American Heart Association ; National Heart, Lung and Blood Institute Y1 - 2002/08/20/ PY - 2002 DA - 2002 Aug 20 SP - 1024 EP - 1028 VL - 106 IS - 8 KW - Anticholesteremic Agents KW - 0 KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors KW - Pyridines KW - cerivastatin KW - AM91H2KS67 KW - Creatine Kinase KW - EC 2.7.3.2 KW - Abridged Index Medicus KW - Index Medicus KW - Drug Interactions KW - Humans KW - Aged KW - Monitoring, Physiologic KW - Muscular Diseases -- prevention & control KW - Coronary Disease -- drug therapy KW - Creatine Kinase -- blood KW - Muscular Diseases -- chemically induced KW - Aged, 80 and over KW - Risk Factors KW - Middle Aged KW - Female KW - Male KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors -- contraindications KW - Anticholesteremic Agents -- contraindications KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors -- therapeutic use KW - Pyridines -- therapeutic use KW - Anticholesteremic Agents -- therapeutic use KW - Pyridines -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72017560?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=ACC%2FAHA%2FNHLBI+Clinical+Advisory+on+the+Use+and+Safety+of+Statins.&rft.au=Pasternak%2C+Richard+C%3BSmith%2C+Sidney+C%3BBairey-Merz%2C+C+Noel%3BGrundy%2C+Scott+M%3BCleeman%2C+James+I%3BLenfant%2C+Claude%3BAmerican+College+of+Cardiology%3BAmerican+Heart+Association%3BNational+Heart%2C+Lung+and+Blood+Institute&rft.aulast=Pasternak&rft.aufirst=Richard&rft.date=2002-08-20&rft.volume=106&rft.issue=8&rft.spage=1024&rft.isbn=&rft.btitle=&rft.title=Circulation&rft.issn=1524-4539&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-09-03 N1 - Date created - 2002-08-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Are Pfiesteria species toxicogenic? Evidence against production of ichthyotoxins by Pfiesteria shumwayae AN - 18452907; 5431907 AB - The estuarine genus Pfiesteria has received considerable attention since it was first identified and proposed to be the causative agent of fish kills along the mid-Atlantic coast in 1992. The presumption has been that the mechanism of fish death is by release of one or more toxins by the dinoflagellate. In this report, we challenge the notion that Pfiesteria species produce ichthyotoxins. Specifically, we show that (i) simple centrifugation, with and without ultrasonication, is sufficient to "detoxify" water of actively fish-killing cultures of Pfiesteria shumwayae, (ii) organic extracts of lyophilized cultures are not toxic to fish, (iii) degenerate primers that amplify PKS genes from several polyketide-producing dinoflagellates failed to yield a product with P. shumwayae DNA or cDNA, and (iv) degenerate primers for NRPS genes failed to amplify any NRPS genes but (unexpectedly) yielded a band (among several) that corresponded to known or putative PKSs and fatty acid synthases. We conclude that P. shumwayae is able to kill fish by means other than releasing a toxin into bulk water. Alternative explanations of the effects attributed to Pfiesteria are suggested. JF - Proceedings of the National Academy of Sciences, USA AU - Berry, J P AU - Reece, K S AU - Rein, K S AU - Baden, D G AU - Haas, L W AU - Ribeiro, W L AU - Shields, J D AU - Snyder, R V AU - Vogelbein, W K AU - Gawley, R E AD - Department of Chemistry/National Institute of Environmental Health Sciences, Marine and Freshwater Biomedical Science Center, University of Miami, P.O. Box 249118, Coral Gables, FL 33124, rgawley@miami.edu Y1 - 2002/08/20/ PY - 2002 DA - 2002 Aug 20 SP - 10970 EP - 10975 VL - 99 IS - 17 SN - 0027-8424, 0027-8424 KW - NPRS gene KW - ichthyotoxins KW - ASFA 1: Biological Sciences & Living Resources; Oceanic Abstracts; Toxicology Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology; Genetics Abstracts KW - Q1 01206:Physiology, biochemistry, biophysics KW - X 24171:Microbial KW - O 1010:Viruses, Bacteria, Protists, Fungi and Plants KW - K 03092:Others KW - G 07340:Algal genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18452907?accountid=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=Are+Pfiesteria+species+toxicogenic%3F+Evidence+against+production+of+ichthyotoxins+by+Pfiesteria+shumwayae&rft.au=Berry%2C+J+P%3BReece%2C+K+S%3BRein%2C+K+S%3BBaden%2C+D+G%3BHaas%2C+L+W%3BRibeiro%2C+W+L%3BShields%2C+J+D%3BSnyder%2C+R+V%3BVogelbein%2C+W+K%3BGawley%2C+R+E&rft.aulast=Berry&rft.aufirst=J&rft.date=2002-08-20&rft.volume=99&rft.issue=17&rft.spage=10970&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.172221699 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1073/pnas.172221699 ER - TY - JOUR T1 - Surface cathepsin B protects cytotoxic lymphocytes from self-destruction after degranulation. AN - 72006931; 12186841 AB - The granule exocytosis cytotoxicity pathway is the major molecular mechanism for cytotoxic T lymphocyte (CTL) and natural killer (NK) cytotoxicity, but the question of how these cytotoxic lymphocytes avoid self-destruction after secreting perforin has remained unresolved. We show that CTL and NK cells die within a few hours if they are triggered to degranulate in the presence of nontoxic thiol cathepsin protease inhibitors. The potent activity of the impermeant, highly cathepsin B-specific membrane inhibitors CA074 and NS-196 strongly implicates extracellular cathepsin B. CTL suicide in the presence of cathepsin inhibitors requires the granule exocytosis cytotoxicity pathway, as it is normal with CTLs from gld mice, but does not occur in CTLs from perforin knockout mice. Flow cytometry shows that CTLs express low to undetectable levels of cathepsin B on their surface before degranulation, with a substantial rapid increase after T cell receptor triggering. Surface cathepsin B eluted from live CTL after degranulation by calcium chelation is the single chain processed form of active cathepsin B. Degranulated CTLs are surface biotinylated by the cathepsin B-specific affinity reagent NS-196, which exclusively labels immunoreactive cathepsin B. These experiments support a model in which granule-derived surface cathepsin B provides self-protection for degranulating cytotoxic lymphocytes. JF - The Journal of experimental medicine AU - Balaji, Kithiganahalli N AU - Schaschke, Norbert AU - Machleidt, Werner AU - Catalfamo, Marta AU - Henkart, Pierre A AD - Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Building 10, Bethesda, MD 20892, USA. Y1 - 2002/08/19/ PY - 2002 DA - 2002 Aug 19 SP - 493 EP - 503 VL - 196 IS - 4 SN - 0022-1007, 0022-1007 KW - Antigens, CD3 KW - 0 KW - CA 074 methyl ester KW - CST3 protein, human KW - Cst3 protein, mouse KW - Cystatin C KW - Cystatins KW - Cysteine Proteinase Inhibitors KW - Dipeptides KW - Ketones KW - Oligopeptides KW - benzyloxycarbonylleucyl-leucyl-tyrosine diazomethyl ketone KW - Diazomethane KW - 60A625P70P KW - MDL 201053 KW - 96922-64-4 KW - Cathepsin B KW - EC 3.4.22.1 KW - Index Medicus KW - Animals KW - Cell Membrane -- enzymology KW - Humans KW - Exocytosis KW - Mice KW - Mice, Inbred BALB C KW - Mice, Knockout KW - Antigens, CD3 -- immunology KW - Cysteine Proteinase Inhibitors -- pharmacology KW - Mice, Inbred C57BL KW - Cytotoxicity Tests, Immunologic KW - Oligopeptides -- pharmacology KW - Cystatins -- pharmacology KW - Dipeptides -- pharmacology KW - Ketones -- pharmacology KW - T-Lymphocytes, Cytotoxic -- physiology KW - Diazomethane -- pharmacology KW - Cell Degranulation -- physiology KW - Diazomethane -- analogs & derivatives KW - T-Lymphocytes, Cytotoxic -- immunology KW - Cathepsin B -- antagonists & inhibitors KW - Cathepsin B -- biosynthesis KW - T-Lymphocytes, Cytotoxic -- enzymology KW - T-Lymphocytes, Cytotoxic -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72006931?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Surface+cathepsin+B+protects+cytotoxic+lymphocytes+from+self-destruction+after+degranulation.&rft.au=Balaji%2C+Kithiganahalli+N%3BSchaschke%2C+Norbert%3BMachleidt%2C+Werner%3BCatalfamo%2C+Marta%3BHenkart%2C+Pierre+A&rft.aulast=Balaji&rft.aufirst=Kithiganahalli&rft.date=2002-08-19&rft.volume=196&rft.issue=4&rft.spage=493&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 - 2002-09-13 N1 - Date created - 2002-08-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1999 Dec 3;286(5446):1957-9 [10583959] J Exp Med. 2000 Sep 4;192(5):755-60 [10974040] J Biol Chem. 2000 Apr 28;275(17):12806-12 [10777578] Annu Rev Immunol. 2000;18:275-308 [10837060] FEBS Lett. 2000 Sep 29;482(1-2):91-6 [11018529] Immunity. 2000 Nov;13(5):657-64 [11114378] J Immunol. 2001 Mar 1;166(5):3218-25 [11207275] J Cell Biol. 2001 Feb 19;152(4):835-42 [11266473] Nat Immunol. 2001 Apr;2(4):293-9 [11276199] Semin Immunol. 2001 Feb;13(1):1-9 [11289794] J Immunol. 2001 Aug 15;167(4):2172-8 [11490002] EMBO J. 2001 Sep 3;20(17):4629-33 [11532926] J Immunol. 1978 Nov;121(5):1652-6 [309477] Anal Biochem. 1985 Sep;149(2):461-5 [4073501] J Exp Med. 1986 Sep 1;164(3):962-7 [3489065] J Exp Med. 1987 May 1;165(5):1371-82 [3494808] Proc Natl Acad Sci U S A. 1987 May;84(10):3375-9 [2953028] J Exp Med. 1987 Oct 1;166(4):1070-83 [3498787] J Exp Med. 1987 Nov 1;166(5):1536-47 [2445890] Nat Immun Cell Growth Regul. 1987;6(4):171-88 [2960890] Biochem J. 1988 Aug 1;253(3):751-8 [2845932] J Immunol. 1989 Jun 15;142(12):4378-84 [2723433] J Exp Med. 1989 Jun 1;169(6):2211-25 [2786549] Cell Immunol. 1989 Nov;124(1):64-76 [2478302] J Immunol. 1990 Feb 1;144(3):998-1003 [2104915] Adv Enzymol Relat Areas Mol Biol. 1990;63:271-347 [2407065] Proc Natl Acad Sci U S A. 1990 Nov;87(22):9015-9 [2123347] Immunology. 1990 Nov;71(3):428-33 [2269479] Mol Immunol. 1991 Nov;28(11):1263-70 [1961199] Int Immunol. 1992 May;4(5):571-80 [1378297] Arch Biochem Biophys. 1992 Dec;299(2):377-80 [1444478] J Immunol. 1993 Jul 15;151(2):658-67 [8335901] J Immunol. 1994 Sep 15;153(6):2470-8 [7521362] Immunity. 1994 Aug;1(5):343-6 [7882166] Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5679-83 [7777569] J Immunol. 1996 May 15;156(10):3678-86 [8621902] J Biol Chem. 1996 Nov 1;271(44):27802-9 [8910377] Immunity. 1997 Feb;6(2):209-15 [9047242] J Immunol. 1997 Apr 1;158(7):3148-54 [9120268] FEBS Lett. 1997 Apr 1;405(3):253-9 [9108299] FEBS Lett. 1998 Jan 2;421(1):80-2 [9462845] J Immunol. 1998 Mar 15;160(6):2655-64 [9510164] Biochim Biophys Acta. 1998 Feb 4;1401(2):146-56 [9531970] J Immunol. 1998 Sep 15;161(6):2810-6 [9743340] Mol Cell Biol. 1998 Nov;18(11):6387-98 [9774654] Leukemia. 1998 Nov;12(11):1771-81 [9823953] Immunity. 1998 Nov;9(5):711-20 [9846492] J Immunol. 1999 Jan 15;162(2):1192-9 [9916752] J Virol. 1999 Mar;73(3):2527-36 [9971838] Ann Intern Med. 1999 Apr 6;130(7):591-601 [10189330] Biochem Biophys Res Commun. 1999 Jun 7;259(2):401-7 [10362521] Biopolymers. 1999;51(1):99-107 [10380357] Annu Rev Biophys Biomol Struct. 1999;28:181-204 [10410800] Eur J Biochem. 2000 Jul;267(13):4165-70 [10866820] Blood. 2000 Jul 15;96(2):594-600 [10887123] Biochim Biophys Acta. 2000 Mar 7;1477(1-2):215-30 [10708859] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A novel chimeric Rev, Tat, and Nef (Retanef) antigen as a component of an SIV/HIV vaccine. AN - 71989649; 12163269 AB - The human immunodeficiency virus type 1 (HIV-1) regulatory proteins Rev, Tat, and Nef are expressed at early time post-infection and represent attractive targets to be included in a vaccine candidate for AIDS. However, the putative immunosuppressive activities of some of these proteins may limit their immunogenicity. To circumvent these issues, a novel chimeric polyprotein vaccine candidate (Retanef), comprising genetically modified and re-assorted rev, tat, and nef open reading frames of simian immunodeficiency virus (SIV), was constructed and optimized for its expression in mammalian cells. Retanef encodes a protein of approximately 55 kDa localized primarily in the cytoplasm of transfected cells. The Retanef gene expressed in context of an eucaryotic expression vector (DNA-SIV-Retanef) or cloned into a highly attenuated poxvirus-based NYVAC vector (NYVAC-SIV-Retanef) was used to immunize either naive rhesus macaques or macaques chronically infected with SIVmac251 undergoing anti-retroviral therapy (ART). Three immunizations of naive macaques with DNA-SIV-Retanef followed by a single NYVAC-SIV-Retanef boost induced a response to the Mamu-A(*)01-restricted Tat epitope (Tat_SL8, TTPESANL) demonstrated by staining with a specific tetramer and by direct cytolytic activity assays, as well as responses to Rev, Tat and Nef proteins demonstrated by ELISPOT assays using overlapping peptide pools encompassing the entire proteins. Immunization of infected macaques with either DNA-SIV-Retanef or NYVAC-SIV-Retanef expanded the frequency of Tat-specific tetramer-staining cells by two- to seven-fold. No adverse effects were observed in either naive or SIV-infected rhesus macaques. Thus, an analogous HIV-1-based chimeric vaccine may represent useful component of an HIV-1 vaccine. Copyright 2002 Elsevier Science Ltd. JF - Vaccine AU - Hel, Zdenek AU - Johnson, Julie M AU - Tryniszewska, Elzbieta AU - Tsai, Wen-Po AU - Harrod, Robert AU - Fullen, Jake AU - Tartaglia, Jim AU - Franchini, Genoveffa AD - Basic Research Laboratory, National Cancer Institute, 41/D804, Bethesda, MD 20892, USA. zdenek@mail.nih.gov Y1 - 2002/08/19/ PY - 2002 DA - 2002 Aug 19 SP - 3171 EP - 3186 VL - 20 IS - 25-26 SN - 0264-410X, 0264-410X KW - AIDS Vaccines KW - 0 KW - Antigens, Viral KW - HIV Antigens KW - Immunotoxins KW - Proteins KW - Recombinant Fusion Proteins KW - SAIDS Vaccines KW - Vaccines, Synthetic KW - retanef KW - Index Medicus KW - Animals KW - Recombinant Fusion Proteins -- immunology KW - HeLa Cells KW - Open Reading Frames KW - Humans KW - Amino Acid Sequence KW - HIV Antigens -- immunology KW - Vaccination KW - Base Sequence KW - Transfection KW - Antigens, Viral -- immunology KW - Vaccines, Synthetic -- immunology KW - Cercopithecus aethiops KW - Genes, env KW - Recombinant Fusion Proteins -- genetics KW - Molecular Sequence Data KW - Vero Cells KW - Vaccines, Synthetic -- genetics KW - Macaca mulatta KW - Vaccines, Synthetic -- adverse effects KW - Antigens, Viral -- genetics KW - Genetic Vectors -- genetics KW - HIV Antigens -- genetics KW - Simian Immunodeficiency Virus -- genetics KW - SAIDS Vaccines -- adverse effects KW - Simian Immunodeficiency Virus -- immunology KW - SAIDS Vaccines -- immunology KW - HIV-1 -- genetics KW - HIV-1 -- immunology KW - SAIDS Vaccines -- genetics KW - AIDS Vaccines -- immunology KW - AIDS Vaccines -- adverse effects KW - Genes, nef KW - AIDS Vaccines -- biosynthesis KW - Immunotoxins -- immunology KW - AIDS Vaccines -- genetics KW - Genes, rev KW - Immunotoxins -- genetics KW - Genes, tat UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71989649?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Vaccine&rft.atitle=A+novel+chimeric+Rev%2C+Tat%2C+and+Nef+%28Retanef%29+antigen+as+a+component+of+an+SIV%2FHIV+vaccine.&rft.au=Hel%2C+Zdenek%3BJohnson%2C+Julie+M%3BTryniszewska%2C+Elzbieta%3BTsai%2C+Wen-Po%3BHarrod%2C+Robert%3BFullen%2C+Jake%3BTartaglia%2C+Jim%3BFranchini%2C+Genoveffa&rft.aulast=Hel&rft.aufirst=Zdenek&rft.date=2002-08-19&rft.volume=20&rft.issue=25-26&rft.spage=3171&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-28 N1 - Date created - 2002-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bacteria-triggered CD4 super(+) T Regulatory Cells Suppress Helicobacter hepaticus-induced Colitis AN - 18497010; 5463357 AB - We have previously demonstrated that interleukin (IL)-10-deficient (IL-10 knockout [KO]) but not wild-type (WT) mice develop colitis after infection with Helicobacter hepaticus. Here, we show that infected recombination activating gene (RAG) KO mice develop intestinal inflammation after reconstitution with CD4 super(+) T cells from IL-10 KO animals and that the cotransfer of CD4 super(+) T cells from H. hepaticus-infected but not uninfected WT mice prevents this colitis. The disease-protective WT CD4 super(+) cells are contained within the CD45RB super(low) fraction and unexpectedly were found in both the CD25 super(+) and the CD25 super(-) subpopulations of these cells, their frequency being higher in the latter. The mechanism by which CD25 super(+) and CD25 super(-) CD45RB super(low) CD4 super(+) cells block colitis involves IL-10 and not transforming growth factor (TGF)- beta , as treatment with anti-IL-10R but not anti-TGF- beta monoclonal antibody abrogated their protective effect. In vitro, CD45RB super(low) CD4 super(+) cells from infected WT mice were shown to produce IL-10 and suppress interferon- gamma production by IL-10 KO CD4 super(+) cells in an H. hepaticus antigen-specific manner. Together, our data support the concept that H. hepaticus infection results in the induction in WT mice of regulatory T cells that prevent bacteria-induced colitis. The induction of such cells in response to gut flora may be a mechanism protecting normal individuals against inflammatory bowel disease. JF - Journal of Experimental Medicine AU - Kullberg, M C AU - Jankovic, D AU - Gorelick, P L AU - Caspar, P AU - Letterio, J J AU - Cheever, A W AU - Sher, A AD - Immunobiology Section, Laboratory of Parasitic Diseases, NIAID, NIH, Building 50, Room 6146, 50 South Drive, Bethesda, MD 20892, USA, MKullberg@niaid.nih.gov Y1 - 2002/08/19/ PY - 2002 DA - 2002 Aug 19 SP - 505 EP - 515 VL - 196 IS - 4 SN - 0022-1007, 0022-1007 KW - CD25 antigen KW - CD4 antigen KW - RAG gene KW - knockout mice KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts; Immunology Abstracts KW - F 06880:Gastrointestinal tract & liver KW - G 07240:Immunogenetics KW - F 06801:Bacteria KW - F 06756:Function KW - J 02846:Gastrointestinal tract UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18497010?accountid=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=Bacteria-triggered+CD4+super%28%2B%29+T+Regulatory+Cells+Suppress+Helicobacter+hepaticus-induced+Colitis&rft.au=Kullberg%2C+M+C%3BJankovic%2C+D%3BGorelick%2C+P+L%3BCaspar%2C+P%3BLetterio%2C+J+J%3BCheever%2C+A+W%3BSher%2C+A&rft.aulast=Kullberg&rft.aufirst=M&rft.date=2002-08-19&rft.volume=196&rft.issue=4&rft.spage=505&rft.isbn=&rft.btitle=&rft.title=Journal+of+Experimental+Medicine&rft.issn=00221007&rft_id=info:doi/10.1084%2Fjem.20020556 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1084/jem.20020556 ER - TY - JOUR T1 - Hepatic vascular isolation and perfusion for patients with progressive unresectable liver metastases from colorectal carcinoma refractory to previous systemic and regional chemotherapy. AN - 72059562; 12209715 AB - Many patients with colorectal carcinoma develop unresectable metastases confined to the liver that remain the life-limiting component of disease despite best available systemic or regional chemotherapy. In the current study, the authors present their results using vascular isolation and perfusion of the liver for individuals with progressive, unresectable liver metastases from colorectal carcinoma that were refractory to both previous systemic and regional chemotherapy. Seven patients with refractory, progressive, unresectable colorectal carcinoma metastases confined to the liver underwent a 60-minute hyperthermic (39-40 degrees C) isolated hepatic perfusion (IHP) and were followed for toxicity, response, and survival. There was no surgical- or treatment-related mortality; all patients experienced transient Grade 3-4 (according to National Cancer Institute common toxicity criteria) hepatic toxicity. At a median potential follow-up of 16 months, the overall objective radiographic response rate (all partial responses) was 71% (5 of 7 assessable patients). It is interesting to note that two patients who were treated with tumor necrosis factor (TNF) alone demonstrated no response to therapy compared with all five patients who were treated with melphalan and TNF (three patients) or melphalan alone (two patients). For the 5 patients who responded to treatment, the median duration of response was 10 months (range, 10-13 months) and in all 7 patients the mean overall survival was 19.7 months (range, 2-33 months), including 5 months and 7.5 months, respectively, for the 2 patients treated with TNF alone. The results of the current study demonstrate that IHP using melphalan with or without TNF has significant antitumor activity in this patient population. IHP deserves continued clinical evaluation as a therapeutic modality for patients with unresectable colorectal carcinoma metastases to the liver. JF - Cancer AU - Alexander, H Richard AU - Libutti, Steven K AU - Bartlett, David L AU - Pingpank, James F AU - Kranda, Karen AU - Helsabeck, Cynthia AU - Beresnev, Tatiana AD - Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Richard_Alexander@nih.gov Y1 - 2002/08/15/ PY - 2002 DA - 2002 Aug 15 SP - 730 EP - 736 VL - 95 IS - 4 SN - 0008-543X, 0008-543X KW - Antineoplastic Agents KW - 0 KW - Tumor Necrosis Factor-alpha KW - Melphalan KW - Q41OR9510P KW - Abridged Index Medicus KW - Index Medicus KW - Tumor Necrosis Factor-alpha -- administration & dosage KW - Melphalan -- administration & dosage KW - Humans KW - Chemotherapy, Cancer, Regional Perfusion KW - Cohort Studies KW - Aged KW - Middle Aged KW - Hepatic Veins KW - Drug Resistance, Neoplasm KW - Male KW - Antineoplastic Agents -- administration & dosage KW - Colorectal Neoplasms -- pathology KW - Liver Neoplasms -- drug therapy KW - Carcinoma -- drug therapy KW - Liver Neoplasms -- secondary KW - Colorectal Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72059562?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Hepatic+vascular+isolation+and+perfusion+for+patients+with+progressive+unresectable+liver+metastases+from+colorectal+carcinoma+refractory+to+previous+systemic+and+regional+chemotherapy.&rft.au=Alexander%2C+H+Richard%3BLibutti%2C+Steven+K%3BBartlett%2C+David+L%3BPingpank%2C+James+F%3BKranda%2C+Karen%3BHelsabeck%2C+Cynthia%3BBeresnev%2C+Tatiana&rft.aulast=Alexander&rft.aufirst=H&rft.date=2002-08-15&rft.volume=95&rft.issue=4&rft.spage=730&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-09-23 N1 - Date created - 2002-09-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic basis of attenuation of dengue virus type 4 small plaque mutants with restricted replication in suckling mice and in SCID mice transplanted with human liver cells. AN - 72047686; 12202213 AB - Mutations that restrict replication of dengue virus have been sought for the generation of recombinant live-attenuated dengue virus vaccines. Dengue virus type 4 (DEN4) was previously grown in Vero cells in the presence of 5-fluorouracil, and the characterization of 1248 mutagenized, Vero cell passaged clones identified 20 temperature-sensitive (ts) mutant viruses that were attenuated (att) in suckling mouse brain (J. E. Blaney, Jr., D. H. Johnson, C. Y. Firestone, C. T. Hanson, B. R. Murphy, and S. S. Whitehead, 2001, J. Virol. 75(20), 9731-9740). The present investigation has extended these studies by identifying an additional 22 DEN4 mutant viruses which have a small plaque size (sp) phenotype in Vero cells and/or the liver cell line, HuH-7. Five mutant viruses have a sp phenotype in both Vero and HuH-7 cells, three of which are also ts. Seventeen mutant viruses have a sp phenotype in only HuH-7 cells, 13 of which are also ts. Each of the sp viruses was growth restricted in the suckling mouse brain, exhibiting a wide range of reduction in replication (9- to 100,000-fold). Complete nucleotide sequence was determined for the 22 DEN4 sp mutant viruses, and nucleotide substitutions were found in the 3'-untranslated region (UTR) as well as in all coding regions except NS4A. Identical mutations have been identified in multiple virus clones, suggesting that they may be involved in the adaptation of DEN4 virus to efficient growth in Vero cells. Six of the 22 sp 5-FU mutant viruses lacked coding mutations in the structural genes, and 17 recombinant DEN4 viruses were generated which separately encoded each of the mutations observed in these six sp viruses. Analysis of the recombinant DEN4 viruses defined the genetic basis of the sp, ts, and att phenotypes observed in the six sp viruses. Mutations in NS1, NS3, and the 3'-UTR were found to confer a greater than 100-fold, 10,000-fold, and 1000-fold reduction in replication of rDEN4 virus in SCID mice transplanted with HuH-7 cells, respectively, which serves as a novel small animal model for DEN4 infection. JF - Virology AU - Blaney, Joseph E AU - Johnson, Daniel H AU - Manipon, Gracielle G AU - Firestone, Cai-Yen AU - Hanson, Christopher T AU - Murphy, Brian R AU - Whitehead, Stephen S AD - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-8007, USA. jblaney@niaid.nih.gov Y1 - 2002/08/15/ PY - 2002 DA - 2002 Aug 15 SP - 125 EP - 139 VL - 300 IS - 1 SN - 0042-6822, 0042-6822 KW - Index Medicus KW - Phenotype KW - Animals, Suckling KW - Animals KW - Viral Plaque Assay KW - Humans KW - Recombination, Genetic KW - Cercopithecus aethiops KW - Transplantation, Heterologous KW - Vero Cells KW - Mice KW - Mice, SCID KW - Liver Transplantation KW - Virus Replication -- physiology KW - Dengue Virus -- genetics KW - Cell Transplantation KW - Mutation KW - Dengue Virus -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72047686?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Genetic+basis+of+attenuation+of+dengue+virus+type+4+small+plaque+mutants+with+restricted+replication+in+suckling+mice+and+in+SCID+mice+transplanted+with+human+liver+cells.&rft.au=Blaney%2C+Joseph+E%3BJohnson%2C+Daniel+H%3BManipon%2C+Gracielle+G%3BFirestone%2C+Cai-Yen%3BHanson%2C+Christopher+T%3BMurphy%2C+Brian+R%3BWhitehead%2C+Stephen+S&rft.aulast=Blaney&rft.aufirst=Joseph&rft.date=2002-08-15&rft.volume=300&rft.issue=1&rft.spage=125&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-10-04 N1 - Date created - 2002-08-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lethal shock induced by streptococcal pyrogenic exotoxin A in mice transgenic for human leukocyte antigen-DQ8 and human CD4 receptors: implications for development of vaccines and therapeutics. AN - 72030518; 12195377 AB - Streptococcal and staphylococcal infections result in significant human morbidity and mortality. This study used a transgenic murine model expressing human major histocompatibility complex (MHC) class II and human CD4 in which, without additional toxic sensitization, human-like responses to the bacterial superantigen (SAg) streptococcal pyrogenic exotoxin A (SpeA) could be simulated, as determined by studying multiple biologic effects of the SAgs in vivo. Expression of human leukocyte antigen (HLA)-DQ8 rendered the mice susceptible to SpeA-induced lethal shock that was accompanied by massive cytokine production and marked elevation of serum alanine and aspartate aminotransferase levels. Of importance, this model enabled examination of the efficacy of an engineered non-SAg vaccine candidate against SpeA in the context of HLA. This report is thought to be the first of a lethal shock triggered in mice by bacterial SAgs without prior sensitization and examination of a vaccine against streptococcal SAg in the context of human MHC receptors. JF - The Journal of infectious diseases AU - Welcher, Brent C AU - Carra, John H AU - DaSilva, Luis AU - Hanson, Juli AU - David, Chella S AU - Aman, M Javad AU - Bavari, Sina AD - Department of Cell Biology and Biochemistry, US Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA. bwelche@mail.nih.gov Y1 - 2002/08/15/ PY - 2002 DA - 2002 Aug 15 SP - 501 EP - 510 VL - 186 IS - 4 SN - 0022-1899, 0022-1899 KW - Antigens, CD4 KW - 0 KW - Bacterial Proteins KW - Cytokines KW - Exotoxins KW - HLA-DQ Antigens KW - HLA-DQ8 antigen KW - Membrane Proteins KW - Receptors, Antigen, T-Cell, alpha-beta KW - SpeA protein, Streptococcus pyogenes KW - Streptococcal Vaccines KW - Superantigens KW - erythrogenic toxin KW - Abridged Index Medicus KW - Index Medicus KW - Cytokines -- blood KW - Animals KW - Liver -- enzymology KW - Receptors, Antigen, T-Cell, alpha-beta -- metabolism KW - Humans KW - Transgenes KW - Mice KW - Streptococcal Infections -- prevention & control KW - Streptococcus pyogenes -- immunology KW - Mice, Inbred BALB C KW - Mice, Transgenic KW - Streptococcal Infections -- etiology KW - Mice, Inbred C57BL KW - Streptococcal Vaccines -- immunology KW - T-Lymphocytes -- immunology KW - Streptococcal Vaccines -- administration & dosage KW - Exotoxins -- genetics KW - HLA-DQ Antigens -- metabolism KW - HLA-DQ Antigens -- genetics KW - Shock, Septic -- etiology KW - Disease Models, Animal KW - Exotoxins -- immunology KW - Superantigens -- immunology KW - Superantigens -- toxicity KW - Antigens, CD4 -- metabolism KW - Shock, Septic -- immunology KW - Antigens, CD4 -- genetics KW - Exotoxins -- toxicity KW - Shock, Septic -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72030518?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Lethal+shock+induced+by+streptococcal+pyrogenic+exotoxin+A+in+mice+transgenic+for+human+leukocyte+antigen-DQ8+and+human+CD4+receptors%3A+implications+for+development+of+vaccines+and+therapeutics.&rft.au=Welcher%2C+Brent+C%3BCarra%2C+John+H%3BDaSilva%2C+Luis%3BHanson%2C+Juli%3BDavid%2C+Chella+S%3BAman%2C+M+Javad%3BBavari%2C+Sina&rft.aulast=Welcher&rft.aufirst=Brent&rft.date=2002-08-15&rft.volume=186&rft.issue=4&rft.spage=501&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 - 2002-09-17 N1 - Date created - 2002-08-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Altered transcriptional regulation in cells expressing the expanded polyglutamine androgen receptor. AN - 71986822; 12165558 AB - Kennedy's disease is a degenerative disease of motor neurons in which the causative mutation is expansion of a CAG/polyglutamine tract near the 5' end of the androgen receptor gene. The mutant protein misfolds, aggregates, and interacts abnormally with other proteins, leading to a novel, toxic gain of function and an alteration of normal function. We used a cell culture model to explore the mechanisms underlying the alterations in androgen receptor function conferred by the mutation. Here we show that cells expressing the wild-type androgen receptor with 24 CAG repeats respond to ligand by showing trophic effects including prolonged survival in low serum, whereas cells expressing the mutant receptor with 65 CAG repeats do not show a robust trophic response. This partial loss of function correlates with decreased levels of the mutant protein due to its preferential degradation by the ubiquitin-proteasome pathway. Expression analysis using oligonucleotide arrays confirms that the mutant receptor has undergone a partial loss of function, and fails to regulate a subset of genes whose expression is normally affected by ligand activation of the wild-type receptor. The mutant receptor has also undergone several functionally important post-translational modifications in the absence of ligand that the wild-type receptor undergoes in the presence of ligand, including acetylation and phosphorylation. These modifications correlate with a ligand-independent gain of function exhibited by the mutant receptor in expression analysis. Our findings suggest that polyglutamine expansion alters androgen receptor function by promoting its degradation and by modifying its activity as a transcription factor. JF - Human molecular genetics AU - Lieberman, Andrew P AU - Harmison, George AU - Strand, Andrew D AU - Olson, James M AU - Fischbeck, Kenneth H AD - Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. liebermn@umich.edu Y1 - 2002/08/15/ PY - 2002 DA - 2002 Aug 15 SP - 1967 EP - 1976 VL - 11 IS - 17 SN - 0964-6906, 0964-6906 KW - Peptides KW - 0 KW - Receptors, Androgen KW - Testosterone Congeners KW - Ubiquitin KW - polyglutamine KW - 26700-71-0 KW - Peptide Hydrolases KW - EC 3.4.- KW - Index Medicus KW - Trinucleotide Repeat Expansion -- genetics KW - Animals KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - Mice KW - Transcription, Genetic KW - Models, Biological KW - Cell Survival KW - Mutagenesis, Site-Directed KW - Gene Expression Profiling KW - Ubiquitin -- metabolism KW - Cells, Cultured KW - Peptide Hydrolases -- metabolism KW - Testosterone Congeners -- pharmacology KW - Motor Neurons -- pathology KW - Motor Neurons -- metabolism KW - Muscular Atrophy, Spinal -- metabolism KW - Gene Expression Regulation -- physiology KW - Receptors, Androgen -- genetics KW - Receptors, Androgen -- metabolism KW - Muscular Atrophy, Spinal -- pathology KW - Peptides -- metabolism KW - Peptides -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71986822?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Altered+transcriptional+regulation+in+cells+expressing+the+expanded+polyglutamine+androgen+receptor.&rft.au=Lieberman%2C+Andrew+P%3BHarmison%2C+George%3BStrand%2C+Andrew+D%3BOlson%2C+James+M%3BFischbeck%2C+Kenneth+H&rft.aulast=Lieberman&rft.aufirst=Andrew&rft.date=2002-08-15&rft.volume=11&rft.issue=17&rft.spage=1967&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 - 2003-02-03 N1 - Date created - 2002-08-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A Model of Prefrontal Cortex Dopaminergic Modulation during the Delayed Alternation Task AN - 18593324; 5451600 AB - Working memory performance is modulated by the level of dopamine (DA) D1 receptors stimulation in the prefrontal cortex (PFC). This modulation is exerted at different time scales. Injection of D1 agonists/antagonists exerts a long-lasting influence (several minutes or hours) on PFC pyramidal neurons. In contrast, during performance of a cognitive task, the duration of the postsynaptic effect of phasic DA release is short lasting. The functional relationships of these two time scales of DA modulation remain poorly understood. Here we propose a model that combines these two time scales of DA modulation on a prefrontal neural network. The model links the cellular and behavioral levels during performance of the delayed alternation task. The network, which represents the activity of deep-layer pyramidal neurons with intrinsic neuronal properties, exhibits two stable states of activity that can be switched on and off by excitatory inputs from long-distance cortical areas arriving in superficial layers. These stable states allow PFC neurons to maintain representations during the delay period. The role of an increase of DA receptors stimulation is to restrict inputs arriving on the prefrontal network. The model explains how the level of working memory performance follows an inverted U-shape with an increased stimulation of DA D1 receptors. The model predicts that (1) D1 receptor agonists increase perseverations, (2) D1 antagonists increase distractability, and (3) the duration of the postsynaptic effect of phasic DA release in the PFC is adjusted to the delay period of the task. These results show how the precise duration of the postsynaptic effect of phasic DA release influences behavioral performance during a simple cognitive task. JF - Journal of Cognitive Neuroscience AU - Dreher, J-C AU - Guigon, E AU - Burnod, Y AD - Clinical Brain Disorder Branch, NIMH, Room 4C108, MSC 1440, Bethesda, MD 20892-1440, USA, dreherj@intra.nimh.nih.gov Y1 - 2002/08/15/ PY - 2002 DA - 2002 Aug 15 SP - 853 EP - 865 VL - 14 IS - 6 SN - 0898-929X, 0898-929X KW - delayed alternation task KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; CSA Neurosciences Abstracts KW - W4 340:Neurocomputing & Neural Networks KW - W 30965:Miscellaneous, Reviews KW - N3 11026:Mathematical models and computer simulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18593324?accountid=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+Cognitive+Neuroscience&rft.atitle=A+Model+of+Prefrontal+Cortex+Dopaminergic+Modulation+during+the+Delayed+Alternation+Task&rft.au=Dreher%2C+J-C%3BGuigon%2C+E%3BBurnod%2C+Y&rft.aulast=Dreher&rft.aufirst=J-C&rft.date=2002-08-15&rft.volume=14&rft.issue=6&rft.spage=853&rft.isbn=&rft.btitle=&rft.title=Journal+of+Cognitive+Neuroscience&rft.issn=0898929X&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 - Operator-bound GalR dimers close DNA loops by direct interaction: tetramerization and inducer binding AN - 18488593; 5457635 AB - The assembly of the Gal repressosome, a higher order nucleoprotein complex that represses transcription of the gal operon in Escherichia coli, involves the formation of a DNA loop encompassing the promoter segment. GalR dimers bound to two spatially separated operators, O sub(E) and O sub(I), specifically interact with the histone-like protein HU and close the loop in supercoiled DNA. We isolated and characterized a GalR mutant containing an amino acid substitution (R282L) that can repress transcription in the absence of HU and supercoiled DNA both in vivo and in vitro. Repression involves the same DNA looping; deletion of either O sub(E) or O sub(I) makes the mutant GalR ineffective in repression. This and other results suggest that the R282L substitution increases the normal affinity between two DNA-bound GalR dimers, allowing looping. We conclude that GalR dimers interact directly and do not use HU as an adaptor in loop closure; HU and DNA supercoiling act in concert to stabilize the GalR tetramer. The stronger GalR GalR interaction also made the gal transcription non-inducible, suggesting that the inducer binding acts by modulating tetramerization. JF - EMBO Journal AU - Semsey, S AU - Geanacopoulos, M AU - Lewis, DEA AU - Adhya, S AD - Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4264, USA, sadhya@helix.nih.gov Y1 - 2002/08/15/ PY - 2002 DA - 2002 Aug 15 SP - 4349 EP - 4356 VL - 21 IS - 16 SN - 0261-4189, 0261-4189 KW - GalR protein KW - double prime HU protein KW - tetramerization KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - J 02726:RNA and ribosomes KW - N 14930:Transcription factors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18488593?accountid=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=Operator-bound+GalR+dimers+close+DNA+loops+by+direct+interaction%3A+tetramerization+and+inducer+binding&rft.au=Semsey%2C+S%3BGeanacopoulos%2C+M%3BLewis%2C+DEA%3BAdhya%2C+S&rft.aulast=Semsey&rft.aufirst=S&rft.date=2002-08-15&rft.volume=21&rft.issue=16&rft.spage=4349&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 ER - TY - JOUR T1 - Malaria: Thermoregulation in a parasite's life cycle AN - 18476316; 5437967 AB - The life cycle of the malaria parasite Plasmodium falciparum goes through three developmental stages (schizogony, gametogony and sporogony), each of which presents different environmental constraints that must be met by an adaptive response in the parasite. Here we show that thermoregulation, in which the transcription of select RNAs is upregulated at cooler temperatures, is crucial to the developmental transition that occurs during the transmission of P. falciparum from human to mosquito. Our findings offer new insight into how the malaria parasite senses and reacts to its environment. JF - Nature AU - Fang, J AU - McCutchan, T F AD - Growth and Development Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0425, USA, tmccutchan@niaid.nih.gov Y1 - 2002/08/15/ PY - 2002 DA - 2002 Aug 15 SP - 742 PB - Macmillan Publishers Ltd. VL - 418 IS - 6899 SN - 0028-0836, 0028-0836 KW - Mosquitoes KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; ASFA 3: Aquatic Pollution & Environmental Quality; ASFA 1: Biological Sciences & Living Resources KW - Freshwater KW - Q5 01524:Public health, medicines, dangerous organisms KW - K 03090:Protozoa: human KW - Q1 01484:Species interactions: parasites and diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18476316?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=Malaria%3A+Thermoregulation+in+a+parasite%27s+life+cycle&rft.au=Fang%2C+J%3BMcCutchan%2C+T+F&rft.aulast=Fang&rft.aufirst=J&rft.date=2002-08-15&rft.volume=418&rft.issue=6899&rft.spage=742&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 - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Freshwater ER - TY - JOUR T1 - Drug abuse's smallest victims: in utero drug exposure. AN - 72062891; 12208017 AB - The social and economic impact of drug use on our global population continues to increase leaving no geographical, social or cultural group untouched. The National Institute on Drug Abuse (NIDA), in one of the few large surveys of maternal abuse, found that 5.5% of mothers reported taking an illicit substance during gestation. These figures certainly are underestimates due to the stigma of drug use during pregnancy and the accompanying legal, ethical and economic issues. Although drugs of choice and routes of administration vary by country, exposure of our most valuable resource, our children, to the developmental effects of drugs is an enormous problem. In utero drug exposure can have a severe impact not only on the development of the fetus, but also on the child during later stages of life. More than 75% of infants exposed to drugs have major medical problems as compared to 27% of unexposed infants. The cost of treating drug-affected infants was twice the cost of non-affected infants. Obstetrical complications including placental insufficiency, miscarriage, intrauterine death, and increased incidence of infectious and sexually-transmitted diseases are higher in the drug-abusing mother. Treatment for pregnant addicts should be a high priority for our governments. Increased awareness and improvement in our understanding of drug abuse in the medical, legal and social realms will enable us to reduce the barriers to treatment for this important population.Accurate identification of in utero drug exposure has important implications for the care of the mother and child, but can raise difficult legal issues. Society discourages prenatal care with the infliction of harsh criminal penalties. Maternal drug use during pregnancy can be monitored with urine, sweat, oral fluid and/or hair testing. Detection of in utero drug exposure has traditionally been accomplished through urine testing; however, the window of detection is short, reflecting drug use for only a few days before delivery. Monitoring exposure through testing of alternative matrices, such as neonatal meconium and hair, offers advantages including non-invasive collection and detection earlier in gestation. There are many unresolved issues in monitoring in utero drug exposure that urgently require research. These can be divided into research to definitively differentiate drug exposed and non-drug-exposed fetuses, determine the most efficient methods to routinely monitor women's drug use, and determine how these drug test results relate to neonatal and maternal outcomes. Research in this area is difficult and expensive to perform, but necessary to assess accurately drug effects on the fetus. By increasing our understanding of the physiological, biochemical and behavioral effects of gestational drug exposure, we may ultimately provide solutions for better drug prevention, treatment and a reduction in the number of drug-exposed children. JF - Forensic science international AU - Huestis, Marilyn A AU - Choo, Robin E AD - Intramural Research Program, Chemistry and Drug Metabolism Section, National Institute on Drug Abuse, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. mhuestis@intra.nida.nih.gov Y1 - 2002/08/14/ PY - 2002 DA - 2002 Aug 14 SP - 20 EP - 30 VL - 128 IS - 1-2 SN - 0379-0738, 0379-0738 KW - Index Medicus KW - Humans KW - Infant, Newborn KW - Female KW - Pregnancy KW - Infant, Newborn, Diseases -- diagnosis KW - Substance-Related Disorders -- diagnosis KW - Maternal-Fetal Exchange KW - Fetus -- drug effects KW - Infant, Newborn, Diseases -- chemically induced KW - Substance-Related Disorders -- complications KW - Infant, Newborn, Diseases -- economics KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72062891?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Drug+abuse%27s+smallest+victims%3A+in+utero+drug+exposure.&rft.au=Huestis%2C+Marilyn+A%3BChoo%2C+Robin+E&rft.aulast=Huestis&rft.aufirst=Marilyn&rft.date=2002-08-14&rft.volume=128&rft.issue=1-2&rft.spage=20&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 - 2002-10-18 N1 - Date created - 2002-09-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - ACC/AHA/NHLBI clinical advisory on the use and safety of statins. AN - 71952703; 12142128 JF - Journal of the American College of Cardiology AU - Pasternak, Richard C AU - Smith, Sidney C AU - Bairey-Merz, C Noel AU - Grundy, Scott M AU - Cleeman, James I AU - Lenfant, Claude AU - American College of Cardiology AU - American Heart Association AU - National Heart, Lung and Blood Institute AD - American College of Cardiology ; American Heart Association ; National Heart, Lung and Blood Institute Y1 - 2002/08/07/ PY - 2002 DA - 2002 Aug 07 SP - 567 EP - 572 VL - 40 IS - 3 SN - 0735-1097, 0735-1097 KW - Anticholesteremic Agents KW - 0 KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors KW - Pyridines KW - cerivastatin KW - AM91H2KS67 KW - Creatine Kinase KW - EC 2.7.3.2 KW - Abridged Index Medicus KW - Index Medicus KW - Drug Interactions KW - Humans KW - Aged KW - Monitoring, Physiologic KW - Muscular Diseases -- prevention & control KW - Coronary Disease -- drug therapy KW - Creatine Kinase -- blood KW - Muscular Diseases -- chemically induced KW - Aged, 80 and over KW - Risk Factors KW - Middle Aged KW - Female KW - Male KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors -- contraindications KW - Anticholesteremic Agents -- contraindications KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors -- therapeutic use KW - Pyridines -- therapeutic use KW - Anticholesteremic Agents -- therapeutic use KW - Pyridines -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71952703?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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+College+of+Cardiology&rft.atitle=ACC%2FAHA%2FNHLBI+clinical+advisory+on+the+use+and+safety+of+statins.&rft.au=Pasternak%2C+Richard+C%3BSmith%2C+Sidney+C%3BBairey-Merz%2C+C+Noel%3BGrundy%2C+Scott+M%3BCleeman%2C+James+I%3BLenfant%2C+Claude%3BAmerican+College+of+Cardiology%3BAmerican+Heart+Association%3BNational+Heart%2C+Lung+and+Blood+Institute&rft.aulast=Pasternak&rft.aufirst=Richard&rft.date=2002-08-07&rft.volume=40&rft.issue=3&rft.spage=567&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+College+of+Cardiology&rft.issn=07351097&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-08-30 N1 - Date created - 2002-07-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Am Coll Cardiol. 2003 Feb 5;41(3):519-20 [12575989] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evidence for the role of glycosylation in accessibility of the extracellular domains of human MRP1 (ABCC1). AN - 71953307; 12146977 AB - To enable cell surface localization of the human multidrug resistance protein (MRP1, ABCC1) and to assess the role of the extracellular domains of this transporter, the FLAG epitope tag was introduced into different extracellular loops of the three membrane-spanning domains (MSDs) of the transporter. We constructed and expressed various partially and fully glycosylation-deficient, FLAG-tagged MRP1 proteins in a Vaccinia virus-based transient expression system, and the cell surface expression level of MRP1 on intact cells was followed by flow cytometry, using the FLAG tag specific monoclonal antibody M2. We also expressed the wild-type MRP1 protein and some of the FLAG-tagged mutants in stably transfected HEK293 cells, and followed the cell surface expression and the transport function of MRP1 both by monitoring the efflux of fluorescent substrate and by their ability to confer resistance to HEK293 transfectants to anticancer agents such as daunorubicin and etoposide. When we inserted the FLAG epitope in extracellular loops of the MSD1 or MSD3, the tag was accessible upon removal of N-glycosylation sites (N --> Q at positions 17, 23, and 1006, respectively), whereas the FLAG epitope placed in the MSD2 was not accessible even after removal of all three N-glycosylation sites, indicating that MSD2 region is deeply buried in the plasma membrane. However, all FLAG tagged MRP1 mutants were expressed at the cell surface to the same extent as the wild-type protein and also exhibited normal transport function. Our results demonstrate that the accessibility of the external FLAG epitope is strongly dependent on the position of the tag and the glycosylation state of the different FLAG-tagged MRP1s, and the conformation of extracellular loops in MSD1 and MDS3 does not appear to contribute to the functional status of MRP1. JF - Biochemistry AU - Müller, Marianna AU - Yong, Michelle AU - Peng, Xiang-Hong AU - Petre, Ben AU - Arora, Sonia AU - Ambudkar, Suresh V AD - Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive MSC 4254, Bethesda, MD 20892-4254, USA. Y1 - 2002/08/06/ PY - 2002 DA - 2002 Aug 06 SP - 10123 EP - 10132 VL - 41 IS - 31 SN - 0006-2960, 0006-2960 KW - DNA Primers KW - 0 KW - Multidrug Resistance-Associated Proteins KW - multidrug resistance-associated protein 1 KW - Y49M64GZ4Q KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Transfection KW - HeLa Cells KW - Electrophoresis, Polyacrylamide Gel KW - Humans KW - Glycosylation KW - Plasmids KW - Multidrug Resistance-Associated Proteins -- metabolism KW - Multidrug Resistance-Associated Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71953307?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Evidence+for+the+role+of+glycosylation+in+accessibility+of+the+extracellular+domains+of+human+MRP1+%28ABCC1%29.&rft.au=M%C3%BCller%2C+Marianna%3BYong%2C+Michelle%3BPeng%2C+Xiang-Hong%3BPetre%2C+Ben%3BArora%2C+Sonia%3BAmbudkar%2C+Suresh+V&rft.aulast=M%C3%BCller&rft.aufirst=Marianna&rft.date=2002-08-06&rft.volume=41&rft.issue=31&rft.spage=10123&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-09-05 N1 - Date created - 2002-07-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lexical Access Rate of Closed-Class Elements during Auditory Sentence Comprehension in Adults with Aphasia AN - 85564380; 200302141 AB - One hypothesis regarding the underlying impairment in agrammatic comprehension suggests that individuals with this disorder suffer from a reduction in lexical activation of closed-class words & therefore cannot appropriately construct a syntactic frame on which lexical semantic information can be applied (Friederici, 1988). Given the temporally based hypothesis, this investigation examined the effects of increased inter-word intervals (IWI) following closed-class words on auditory comprehension of various sentence types by individuals with agrammatic comprehension. It was hypothesized that providing a longer temporal window for access & processing of closed-class words would improve sentence structure comprehension. Adults with aphasia (N = 12) participated in an agent identification task given varying auditory sentence stimuli. Six sentence types & six IWI durations served as independent variables while accuracy & response times were measured. Results indicated that auditory sentence comprehension performance improves when IWIs are increased. However, differences exist among individuals in response to specific IWI durations. Implications of delayed access rates of closed-class words in agrammatic comprehension are discussed. 14 Tables, 40 References. Adapted from the source document JF - Aphasiology AU - Park, Grace H AU - McNeil, Malcolm R AU - Doyle, Patrick J AD - National Instits Health, NIDCD, Bethesda, MD parkgrac@nidcd.nih.gov Y1 - 2002/08// PY - 2002 DA - August 2002 SP - 801 EP - 814 VL - 16 IS - 8 SN - 0268-7038, 0268-7038 KW - Agrammatism (01200) KW - Aphasia (03400) KW - Syntactic Processing (86760) KW - Lexical Access (46630) KW - article UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85564380?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Allba&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Aphasiology&rft.atitle=Lexical+Access+Rate+of+Closed-Class+Elements+during+Auditory+Sentence+Comprehension+in+Adults+with+Aphasia&rft.au=Park%2C+Grace+H%3BMcNeil%2C+Malcolm+R%3BDoyle%2C+Patrick+J&rft.aulast=Park&rft.aufirst=Grace&rft.date=2002-08-01&rft.volume=16&rft.issue=8&rft.spage=801&rft.isbn=&rft.btitle=&rft.title=Aphasiology&rft.issn=02687038&rft_id=info:doi/ LA - English DB - Linguistics and Language Behavior Abstracts (LLBA) N1 - Date revised - 2003-10-01 N1 - Last updated - 2016-09-27 N1 - CODEN - APHAEA N1 - SubjectsTermNotLitGenreText - Lexical Access (46630); Aphasia (03400); Agrammatism (01200); Syntactic Processing (86760) ER - TY - JOUR T1 - Naturalistic Language Sampling in Typically Developing Children AN - 85563898; 200300020 AB - This study compares naturalistic samples of three features of language - total utterances, word roots, & MLU - in two-year-olds (N = 30) in the home in three contrasting situations: the child observed playing by her/himself with the mother nearby, the child & mother observed in direct-play interaction, & the child & mother unobserved at a time the mother judged would provide a sample of the child's "optimal" language. Children produced more utterances & word roots & expressed themselves in longer MLU when in interaction than when playing "alone," but children's utterances, word roots, & MLU were greatest in the optimal language production situation. Girls used more word roots & spoke in longer MLU (especially in the optimal language situation) than did boys. Despite mean-level differences, children maintained their rank orders across the three situations in use of word roots & in MLU. These findings have implications for understanding children's language & the representativeness of sampling child language. 1 Table, 3 Figures, 36 References. Adapted from the source document JF - Journal of Child Language AU - Bornstein, Marc H AU - Painter, Kathleen M AU - Park, Jaihyun AD - National Instit Child Health & Human Development, Bethesda, MD Marc_H_Bornstein@nih.gov Y1 - 2002/08// PY - 2002 DA - August 2002 SP - 687 EP - 699 VL - 29 IS - 3 SN - 0305-0009, 0305-0009 KW - Parent Child Interaction (62760) KW - Mean Length of Utterance (52100) KW - Child Language (11800) KW - Sex Differences (77850) KW - Research Design (72950) KW - Roots (Morphology) (74200) KW - article KW - 4015: psycholinguistics; child language acquisition UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85563898?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Allba&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Child+Language&rft.atitle=Naturalistic+Language+Sampling+in+Typically+Developing+Children&rft.au=Bornstein%2C+Marc+H%3BPainter%2C+Kathleen+M%3BPark%2C+Jaihyun&rft.aulast=Bornstein&rft.aufirst=Marc&rft.date=2002-08-01&rft.volume=29&rft.issue=3&rft.spage=687&rft.isbn=&rft.btitle=&rft.title=Journal+of+Child+Language&rft.issn=03050009&rft_id=info:doi/ LA - English DB - Linguistics and Language Behavior Abstracts (LLBA) N1 - Date revised - 2003-10-01 N1 - Last updated - 2016-09-27 N1 - CODEN - JCLGBJ N1 - SubjectsTermNotLitGenreText - Child Language (11800); Sex Differences (77850); Mean Length of Utterance (52100); Roots (Morphology) (74200); Parent Child Interaction (62760); Research Design (72950) ER - TY - JOUR T1 - Percutaneous embolization of mandibular hemangioma: a case report. AN - 85360081; pmid-12149745 JF - Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons AU - Jayakumar, P N AU - Desai, Sunali V AU - Kovoor, J M E AU - Vasudev, M K AD - Department of Neuroimaging and Intervention Radiology, National Institute of Mental Health and Neurosciences, Bangalore, India. jayakumarpn@nimhans.kar.nic.in Y1 - 2002/08// PY - 2002 DA - Aug 2002 SP - 945 EP - 948 VL - 60 IS - 8 SN - 0278-2391, 0278-2391 KW - National Library of Medicine KW - Angiography KW - Child KW - Contrast Media KW - *Embolization, Therapeutic KW - *Enbucrilate: analogs & derivatives KW - Enbucrilate: therapeutic use KW - Fluoroscopy KW - Hemangioma: blood supply KW - *Hemangioma: therapy KW - Humans KW - Iophendylate: diagnostic use KW - Male KW - Mandibular Neoplasms: blood supply KW - *Mandibular Neoplasms: therapy KW - Tissue Adhesives: therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85360081?accountid=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+oral+and+maxillofacial+surgery+%3A+official+journal+of+the+American+Association+of+Oral+and+Maxillofacial+Surgeons&rft.atitle=Percutaneous+embolization+of+mandibular+hemangioma%3A+a+case+report.&rft.au=Jayakumar%2C+P+N%3BDesai%2C+Sunali+V%3BKovoor%2C+J+M+E%3BVasudev%2C+M+K&rft.aulast=Jayakumar&rft.aufirst=P&rft.date=2002-08-01&rft.volume=60&rft.issue=8&rft.spage=945&rft.isbn=&rft.btitle=&rft.title=Journal+of+oral+and+maxillofacial+surgery+%3A+official+journal+of+the+American+Association+of+Oral+and+Maxillofacial+Surgeons&rft.issn=02782391&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Cocaine-induced oronasal fistulas with external nasal erosion but without palate involvement. AN - 85358012; pmid-12199175 AB - The effects of chronic cocaine abuse have been widely described in the literature. Common complications include nasal septal perforation, saddle-nose deformity, and palatal perforation. Erosion of the external structures of the face has not been as extensively described, nor have oronasal fistulas that involve structures other than the hard or soft palate. In this article, we present the first reported case of cocaine-induced external nasal erosion that included multiple oronasal fistulas in the anterior gingival sulcus but did not involve the hard or soft palate. We stress the importance of a thorough history in such patients and consideration of all possible diagnoses, including drug abuse. JF - Ear, nose, & throat journal AU - Vilela, Ronald J AU - Langford, Carol AU - McCullagh, Linda AU - Kass, Erik S AD - National Institute of Deafness and Other Communication Disorders, National Institutes of Health, Bldg. 10, Room 5C400, 10 Center Dr., MSC 1750, Bethesda, MD 20892-1750, USA. Y1 - 2002/08// PY - 2002 DA - Aug 2002 SP - 562 EP - 563 VL - 81 IS - 8 SN - 0145-5613, 0145-5613 KW - Index Medicus KW - National Library of Medicine KW - Adult KW - Biopsy, Needle KW - *Cocaine: adverse effects KW - *Cocaine-Related Disorders: diagnosis KW - Cocaine-Related Disorders: surgery KW - Female KW - Follow-Up Studies KW - Humans KW - Nose Deformities, Acquired: diagnosis KW - Nose Deformities, Acquired: etiology KW - Nose Deformities, Acquired: surgery KW - *Nose Diseases: chemically induced KW - Nose Diseases: complications KW - Nose Diseases: surgery KW - *Oral Fistula: chemically induced KW - Oral Fistula: complications KW - Oral Fistula: surgery KW - Palate, Hard: physiopathology KW - Palate, Soft: physiopathology KW - Risk Assessment KW - Severity of Illness Index KW - Tomography, X-Ray Computed UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85358012?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Ear%2C+nose%2C+%26+throat+journal&rft.atitle=Cocaine-induced+oronasal+fistulas+with+external+nasal+erosion+but+without+palate+involvement.&rft.au=Vilela%2C+Ronald+J%3BLangford%2C+Carol%3BMcCullagh%2C+Linda%3BKass%2C+Erik+S&rft.aulast=Vilela&rft.aufirst=Ronald&rft.date=2002-08-01&rft.volume=81&rft.issue=8&rft.spage=562&rft.isbn=&rft.btitle=&rft.title=Ear%2C+nose%2C+%26+throat+journal&rft.issn=01455613&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Progression of late-stage chronic maxillary atelectasis. AN - 85357496; pmid-12184602 JF - The Annals of otology, rhinology, and laryngology AU - Ende, Kevin AU - Mah, Linda AU - Kass, Erik S AD - National Institutes of Health, Bethesda, Maryland 20892-1750, USA. Y1 - 2002/08// PY - 2002 DA - Aug 2002 SP - 759 EP - 762 VL - 111 IS - 8 SN - 0003-4894, 0003-4894 KW - National Library of Medicine KW - Adult KW - Disease Progression KW - Female KW - Follow-Up Studies KW - Humans KW - Maxillary Diseases: epidemiology KW - *Maxillary Diseases: radiography KW - Photography KW - Time Factors KW - Tomography, X-Ray Computed UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85357496?accountid=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+Annals+of+otology%2C+rhinology%2C+and+laryngology&rft.atitle=Progression+of+late-stage+chronic+maxillary+atelectasis.&rft.au=Ende%2C+Kevin%3BMah%2C+Linda%3BKass%2C+Erik+S&rft.aulast=Ende&rft.aufirst=Kevin&rft.date=2002-08-01&rft.volume=111&rft.issue=8&rft.spage=759&rft.isbn=&rft.btitle=&rft.title=The+Annals+of+otology%2C+rhinology%2C+and+laryngology&rft.issn=00034894&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Structural cell biology: Rapid renewal of auditory hair bundles. AN - 85177939; pmid-12192399 AB - Stereocilia, also known as hair bundles, are mechanosensitive organelles of the sensory hair cells of the inner ear that can detect displacements on a nanometre scale and are supported by a rigid, dense core of actin filaments. Here we show that these actin-filament arrays are continuously remodelled by the addition of actin monomers to the stereocilium tips, and that the entire core of the stereocilium is renewed every 48 hours. This unexpected dynamic feature of stereocilia will help our understanding of how auditory sensory function develops and is maintained. JF - Nature AU - Schneider, Mark E AU - Belyantseva, Inna A AU - Azevedo, Ricardo B AU - Kachar Bechara AD - National Institute on Deafness and Other Communication Disorders PY - 2002 SP - 837 EP - 838 VL - 418 IS - 6900 SN - 0028-0836, 0028-0836 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85177939?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=Structural+cell+biology%3A+Rapid+renewal+of+auditory+hair+bundles.&rft.au=Schneider%2C+Mark+E%3BBelyantseva%2C+Inna+A%3BAzevedo%2C+Ricardo+B%3BKachar+Bechara&rft.aulast=Schneider&rft.aufirst=Mark&rft.date=2002-08-01&rft.volume=418&rft.issue=6900&rft.spage=837&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) AN - 759317360; 13686000 AB - MOLECULAR PSYCHIATRY: (2002) 7, S24-S25. doi:10.1038/sj.mp.4001170 JF - Molecular Psychiatry AU - Swedo, S E AD - Pediatrics and Developmental Neuropsychiatry Branch, National Institute of Mental Health, Bethesda, MD, USA Y1 - 2002/08// PY - 2002 DA - Aug 2002 SP - S24 EP - S25 PB - Nature Publishing Group, The Macmillan Building London N1 9XW UK VL - 7 IS - s2 SN - 1359-4184, 1359-4184 KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts; CSA Neurosciences Abstracts KW - Streptococcus KW - Mental disorders KW - Pediatrics KW - Infection KW - Psychiatry KW - N3 11001:Behavioral and Cognitive Neuroscience KW - F 06960:Molecular Immunology KW - J 02490:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/759317360?accountid=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+Psychiatry&rft.atitle=Pediatric+autoimmune+neuropsychiatric+disorders+associated+with+streptococcal+infections+%28PANDAS%29&rft.au=Swedo%2C+S+E&rft.aulast=Swedo&rft.aufirst=S&rft.date=2002-08-01&rft.volume=7&rft.issue=s2&rft.spage=S24&rft.isbn=&rft.btitle=&rft.title=Molecular+Psychiatry&rft.issn=13594184&rft_id=info:doi/10.1038%2Fsj.mp.4001170 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-10-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Mental disorders; Pediatrics; Infection; Psychiatry; Streptococcus DO - http://dx.doi.org/10.1038/sj.mp.4001170 ER - TY - JOUR T1 - An evidence-based approach to cancer prevention clinical trials. AN - 72843396; 12570334 AB - Research on carcinogenesis and its inhibition has made significant progress in the last 30 years, providing an impressive body of evidence that supports various strategies for cancer prevention. Innovative studies have helped to identify potential causes of cancer, including environmental factors such as diet, and provided valuable information about their mechanisms of action. Hundreds of epidemiologic and experimental studies have focused on possible associations between dietary factors and different types of cancer. During the same period, potential inhibitors of cancer that appeared able to prevent, arrest or reverse cancer development by interfering with one or more steps in the process of carcinogenesis were identified, and the term 'chemoprevention' was coined for this pharmacological approach to cancer prevention. Promising compounds were systematically evaluated for their potential as chemopreventive agents. Numerous agents were determined to be safe and effective in preclinical trials, including naturally occurring vitamins, minerals and phytochemicals as well as synthetic compounds. Based on preclinical results, selected agents have been and are now being evaluated in phase I, II and III clinical interventions for various cancers. Development of valid surrogate end point biomarkers for clinical disease that can be modulated by interventions is essential to accelerate progress in cancer prevention clinical trials. JF - European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) AU - Greenwald, Peter AU - McDonald, Sharon S AU - Anderson, Darrell E AD - Division of Cancer Prevention, National Cancer Institute, 6130 Executive Boulevard, Suite 2040, Bethesda, MD 20892-7309, USA. pg37g@nih.gov Y1 - 2002/08// PY - 2002 DA - August 2002 SP - S43 EP - S47 VL - 11 Suppl 2 SN - 0959-8278, 0959-8278 KW - Anticarcinogenic Agents KW - 0 KW - Index Medicus KW - Sensitivity and Specificity KW - Evidence-Based Medicine KW - Humans KW - Prognosis KW - Research KW - Primary Prevention -- methods KW - Patient Selection KW - Male KW - Female KW - Clinical Trials as Topic KW - Chemoprevention -- methods KW - Neoplasms -- prevention & control KW - Anticarcinogenic Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72843396?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+prevention+%3A+the+official+journal+of+the+European+Cancer+Prevention+Organisation+%28ECP%29&rft.atitle=An+evidence-based+approach+to+cancer+prevention+clinical+trials.&rft.au=Greenwald%2C+Peter%3BMcDonald%2C+Sharon+S%3BAnderson%2C+Darrell+E&rft.aulast=Greenwald&rft.aufirst=Peter&rft.date=2002-08-01&rft.volume=11+Suppl+2&rft.issue=&rft.spage=S43&rft.isbn=&rft.btitle=&rft.title=European+journal+of+cancer+prevention+%3A+the+official+journal+of+the+European+Cancer+Prevention+Organisation+%28ECP%29&rft.issn=09598278&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-02 N1 - Date created - 2003-02-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phenotypes of the COX-deficient mice indicate physiological and pathophysiological roles for COX-1 and COX-2. AN - 72683643; 12432917 AB - The development of mice deficient in either cyclooxygenase-1 (COX-1) or COX-2, as well as mice deficient in both COX isoforms, has provided models to elucidate the physiological and pathophysiological roles of these enzymes. The findings obtained with the COX-deficient mice suggest that COX-2 may be more important than COX-1 for supplying prostaglandins (PGs) to maintain tissue homeostasis. Furthermore, both isoforms may be involved in the development of diseases, such as inflammation and cancer. Therefore, the contribution of each isoform to the prevention or development of disease is more complex than originally described. Studies with the COX-deficient mice suggest that in addition to COX-2-selective inhibition, therapeutic advances may also be achieved with COX-1-selective inhibitors which lack gastrointestinal side effects. JF - Prostaglandins & other lipid mediators AU - Loftin, Charles D AU - Tiano, Howard F AU - Langenbach, Robert AD - Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 2002/08// PY - 2002 DA - August 2002 SP - 177 EP - 185 VL - 68-69 SN - 1098-8823, 1098-8823 KW - Isoenzymes KW - 0 KW - Membrane Proteins KW - Cyclooxygenase 1 KW - EC 1.14.99.1 KW - Cyclooxygenase 2 KW - Prostaglandin-Endoperoxide Synthases KW - Ptgs1 protein, mouse KW - Index Medicus KW - Peptic Ulcer -- enzymology KW - Animals KW - Ductus Arteriosus -- metabolism KW - Intestinal Neoplasms -- metabolism KW - Cell Division -- physiology KW - Kidney -- physiology KW - Mice KW - Mice, Knockout KW - Phenotype KW - Reproduction -- physiology KW - Inflammation -- metabolism KW - Female KW - Prostaglandin-Endoperoxide Synthases -- metabolism KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - Isoenzymes -- genetics KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72683643?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+%26+other+lipid+mediators&rft.atitle=Phenotypes+of+the+COX-deficient+mice+indicate+physiological+and+pathophysiological+roles+for+COX-1+and+COX-2.&rft.au=Loftin%2C+Charles+D%3BTiano%2C+Howard+F%3BLangenbach%2C+Robert&rft.aulast=Loftin&rft.aufirst=Charles&rft.date=2002-08-01&rft.volume=68-69&rft.issue=&rft.spage=177&rft.isbn=&rft.btitle=&rft.title=Prostaglandins+%26+other+lipid+mediators&rft.issn=10988823&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-10 N1 - Date created - 2002-11-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of rewarding effect of toluene by the conditioned place preference procedure in mice. AN - 72176259; 12379437 AB - Toluene and many toluene-containing products are abused via inhalation. Previous investigations have used the place preference paradigm to evaluate the rewarding effects of commonly abused drugs such as morphine, cocaine, and amphetamine. A conditioning paradigm of toluene inhalation was developed in order to estimate the rewarding effect in mice. Conditioning sessions (five for toluene, five for air) were conducted twice daily for 5 days using a newly developed airtight inhalation shuttlebox (15x30x15 cm: wxlxh), which was divided into two compartments of equal size. One compartment was white with a textured floor, and the other was black with a smooth floor. All conditioning sessions were 20 min in duration, with a minimum of 7 h between sessions. Test sessions were carried out 1 day after the final training session with mice in a drug-free state. The time spent in each compartment during a 20-min session was measured using a digital video camera. Exposure to toluene vapors (700-3200 ppm) produced a significant conditioned place preference in mice. These results suggest that the conditioned place preference procedure using the newly developed airtight inhalation shuttlebox constitutes an important tool for studying the rewarding effect of abused solvents. Copyright 2002 Elsevier Science B.V. JF - Brain research. Brain research protocols AU - Funada, Masahiko AU - Sato, Mio AU - Makino, Yukiko AU - Wada, Kiyoshi AD - Section of Addictive Drugs Research, Division of Drug Dependence, National Institute of Mental Health, National Center of Neurology and Psychiatry, 1-7-3 Kohnodai, Ichikawa, Chiba 272-0827, Japan. mfunada@ncnp-k.go.jp Y1 - 2002/08// PY - 2002 DA - August 2002 SP - 47 EP - 54 VL - 10 IS - 1 SN - 1385-299X, 1385-299X KW - Toluene KW - 3FPU23BG52 KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Brain -- drug effects KW - Body Weight -- physiology KW - Hyperkinesis -- physiopathology KW - Mice KW - Brain -- metabolism KW - Housing, Animal -- standards KW - Behavior, Animal -- drug effects KW - Environment, Controlled KW - Drug Tolerance -- physiology KW - Hyperkinesis -- chemically induced KW - Body Weight -- drug effects KW - Atmosphere Exposure Chambers KW - Behavior, Animal -- physiology KW - Administration, Inhalation KW - Male KW - Substance-Related Disorders -- physiopathology KW - Drug Delivery Systems -- instrumentation KW - Toluene -- pharmacology KW - Mice, Inbred ICR -- psychology KW - Reward KW - Conditioning (Psychology) -- physiology KW - Drug Delivery Systems -- methods KW - Neuropsychological Tests -- standards KW - Mice, Inbred ICR -- physiology KW - Conditioning (Psychology) -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72176259?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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.+Brain+research+protocols&rft.atitle=Evaluation+of+rewarding+effect+of+toluene+by+the+conditioned+place+preference+procedure+in+mice.&rft.au=Funada%2C+Masahiko%3BSato%2C+Mio%3BMakino%2C+Yukiko%3BWada%2C+Kiyoshi&rft.aulast=Funada&rft.aufirst=Masahiko&rft.date=2002-08-01&rft.volume=10&rft.issue=1&rft.spage=47&rft.isbn=&rft.btitle=&rft.title=Brain+research.+Brain+research+protocols&rft.issn=1385299X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-01-03 N1 - Date created - 2002-10-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemokine release is associated with the protective action of PACAP-38 against HIV envelope protein neurotoxicity. AN - 72161031; 12372701 AB - The envelope protein (gp120) of the human immunodeficiency virus produces neuronal cell death in cultures that can be prevented by co-treatment with pituitary adenylate activating peptide-38 (PACAP-38) or chemokines. To investigate the hypothesis that a functional relationship exists between these two protectants, the release of chemokines was measured in rat astrocyte cultures after PACAP-38 treatment. Chemokine analyses were performed by immunoaffinity capillary electrophoresis. Bell-shaped dose-responses for PACAP-mediated release of chemokines into the culture medium were observed with EC(50)'s of 3 x 10(15) M (RANTES: regulated upon activation normal T cell expressed and secreted), 3 x 10(-11) M (MIP-1 beta) and 10(-7)M (MIP-1 alpha). In addition, PACAP-mediated depletion of chemokines from cultured astrocytes exhibited inverted bell-shaped curves, with similar EC(50)'s to those observed for chemokine measurements of the medium. Comparative studies with structurally related peptides (vasoactive intestinal peptide [VIP] and secretin) revealed that PACAP was the most potent secretagogue for RANTES on astrocyte cultures. Gp120-mediated neuronal cell death was prevented by co-treatment with PACAP-38, although the efficacy of protection varied significantly among the gp120 isolates. A bi-model dose-response was observed with EC(50)'s of 3 x 10(-15) and 3 x 10(-11) M. Co-treatment with neutralizing antiserum to RANTES attenuated PACAP-mediated protection from toxicity associated with gp120. In contrast to previous studies with VIP and gp120 toxicity, co-treatment with anti-MIP-1 alpha did not affect PACAP-induced protection. These studies support the hypothesis that PACAP produces neuroprotection from gp120 toxicity, in part, through the release of RANTES and this mechanism is distinct from that observed with VIP. Copyright 2002 Elsevier Science Ltd. JF - Neuropeptides AU - Brenneman, Douglas E AU - Hauser, Janet M AU - Spong, CatherineY AU - Phillips, Terry M AD - Section on Developmental and Molecular Pharmacology, Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Building 49, Room 5A38, Bethesda, MD 20892, USA. dbrenn@codon.nih.gov Y1 - 2002/08// PY - 2002 DA - August 2002 SP - 271 EP - 280 VL - 36 IS - 4 SN - 0143-4179, 0143-4179 KW - Adcyap1 protein, rat KW - 0 KW - Chemokine CCL4 KW - Chemokine CCL5 KW - Chemokines KW - HIV Envelope Protein gp120 KW - Indicators and Reagents KW - Macrophage Inflammatory Proteins KW - Neuropeptides KW - Neuroprotective Agents KW - Pituitary Adenylate Cyclase-Activating Polypeptide KW - Vasoactive Intestinal Peptide KW - 37221-79-7 KW - Index Medicus KW - Vasoactive Intestinal Peptide -- pharmacology KW - Animals KW - Dose-Response Relationship, Drug KW - Astrocytes -- drug effects KW - Macrophage Inflammatory Proteins -- pharmacology KW - Chemokine CCL5 -- metabolism KW - Rats KW - Animals, Newborn KW - Cell Survival -- drug effects KW - Astrocytes -- metabolism KW - Neuropeptides -- pharmacology KW - Chemokines -- metabolism KW - HIV Envelope Protein gp120 -- toxicity KW - Neuroprotective Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72161031?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chemokine+release+is+associated+with+the+protective+action+of+PACAP-38+against+HIV+envelope+protein+neurotoxicity.&rft.au=Brenneman%2C+Douglas+E%3BHauser%2C+Janet+M%3BSpong%2C+CatherineY%3BPhillips%2C+Terry+M&rft.aulast=Brenneman&rft.aufirst=Douglas&rft.date=2002-08-01&rft.volume=36&rft.issue=4&rft.spage=271&rft.isbn=&rft.btitle=&rft.title=Neuropeptides&rft.issn=01434179&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-01-10 N1 - Date created - 2002-10-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Experimental and clinical psychopharmacology: National Institute on Drug Abuse's clinical research agenda. AN - 72093340; 12233978 AB - Studies of drugs and behavior are a core component of virtually every portfolio within the broad purview of the National Institute on Drug Abuse (NIDA). Moreover, psychopharmacological research is an important vehicle for advancing understanding of how drugs of abuse produce their effects, particularly including addiction. However, as with all major public health issues, simply understanding the issue is not enough. NIDA's psychopharmacology projects, therefore, span basic, clinical, and applied (e.g., medication development) research activities. These include the establishment of a nationwide clinical trials network designed to provide an infrastructure to test both behavioral and psychopharmacological treatments in a real-life practice setting with diverse patients. JF - Experimental and clinical psychopharmacology AU - Leshner, Alan I AD - National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland, USA. aleshner@aaas.org Y1 - 2002/08// PY - 2002 DA - August 2002 SP - 159 EP - 161 VL - 10 IS - 3 SN - 1064-1297, 1064-1297 KW - Index Medicus KW - United States KW - Acquired Immunodeficiency Syndrome -- physiopathology KW - Behavior Therapy KW - Humans KW - Acquired Immunodeficiency Syndrome -- psychology KW - Behavior, Addictive -- physiopathology KW - Substance-Related Disorders -- therapy KW - Biomedical Research KW - National Institutes of Health (U.S.) KW - Substance-Related Disorders -- drug therapy KW - Substance-Related Disorders -- psychology KW - Psychopharmacology -- trends UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72093340?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+and+clinical+psychopharmacology&rft.atitle=Experimental+and+clinical+psychopharmacology%3A+National+Institute+on+Drug+Abuse%27s+clinical+research+agenda.&rft.au=Leshner%2C+Alan+I&rft.aulast=Leshner&rft.aufirst=Alan&rft.date=2002-08-01&rft.volume=10&rft.issue=3&rft.spage=159&rft.isbn=&rft.btitle=&rft.title=Experimental+and+clinical+psychopharmacology&rft.issn=10641297&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-10 N1 - Date created - 2002-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oxidative stress and its role in skin disease. AN - 72087159; 12230879 AB - Skin is a major target of oxidative stress due to reactive oxygen species (ROS) that originate in the environment and in the skin itself. ROS are generated during normal metabolism, are an integral part of normal cellular function, and are usually of little harm because of intracellular mechanisms that reduce their damaging effects. Antioxidants attenuate the damaging effects of ROS and can impair and/or reverse many of the events that contribute to epidermal toxicity and disease. However, increased or prolonged free radical action can overwhelm ROS defense mechanisms, contributing to the development of cutaneous diseases and disorders. Although ROS play a role in diseases such as skin cancer, their biological targets and pathogenic mode of action are still not fully understood. In addition, strategies useful in the therapeutic management of ROS action in human skin are still lacking. This review is intended to give investigators an introduction to ROS, antioxidants, two skin disorders influenced by ROS action (skin cancer and psoriasis), and relevant model systems used to study ROS action. JF - Antioxidants & redox signaling AU - Trouba, Kevin J AU - Hamadeh, Hisham K AU - Amin, Rupesh P AU - Germolec, Dori R AD - National Institute of Environmental Health Sciences, Laboratory of Molecular Toxicology, Research Triangle Park, NC 27709, USA. Y1 - 2002/08// PY - 2002 DA - August 2002 SP - 665 EP - 673 VL - 4 IS - 4 SN - 1523-0864, 1523-0864 KW - Antioxidants KW - 0 KW - Reactive Oxygen Species KW - Index Medicus KW - Signal Transduction -- physiology KW - Animals KW - DNA Damage KW - Humans KW - Disease Models, Animal KW - Immune System -- physiology KW - Models, Biological KW - Reactive Oxygen Species -- metabolism KW - Antioxidants -- metabolism KW - Oxidative Stress KW - Skin Neoplasms -- metabolism KW - Psoriasis -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72087159?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antioxidants+%26+redox+signaling&rft.atitle=Oxidative+stress+and+its+role+in+skin+disease.&rft.au=Trouba%2C+Kevin+J%3BHamadeh%2C+Hisham+K%3BAmin%2C+Rupesh+P%3BGermolec%2C+Dori+R&rft.aulast=Trouba&rft.aufirst=Kevin&rft.date=2002-08-01&rft.volume=4&rft.issue=4&rft.spage=665&rft.isbn=&rft.btitle=&rft.title=Antioxidants+%26+redox+signaling&rft.issn=15230864&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-21 N1 - Date created - 2002-09-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of metastatic osteosarcoma with the somatostatin analog OncoLar: significant reduction of insulin-like growth factor-1 serum levels. AN - 72079556; 12218590 AB - Insulin-like growth factor-1 (IGF-1) has been implicated in the growth and/or metastasis of osteosarcoma (OS) and chondrosarcoma based on in vitro and experimental animal studies. To determine the degree of growth hormone (GH), IGF-1 axis blockade, toxicities, and antitumor effect of OncoLar (ONC) (Novartis, East Hanover, NJ, U.S.A.) in OS. A phase 1 study with ONC enrolled 21 OS patients (median age 19 y) in four cohorts: ONC 60 mg or 90 mg intramuscularly every 4 weeks with/without tamoxifen (TAM) 20 mg oral daily. There were no dose-limiting toxicities. Nineteen percent of patients had grade III drug-related toxicities including: 62% of patients showed progressive disease after two courses (8 wk). Nineteen percent received four courses. No clinical responses were observed. At weeks two and eight of therapy, IGF-1 serum levels dropped 46% ( < 0.0001, n = 21) and 53% ( = 0.003, n = 10). The difference of the area under the curve (AUC) minus baseline AUC (DeltaAUC) for arginine-stimulated GH serum levels at week two was lower than baseline ( < 0.01). At weeks two and eight, GH peak values were lower than baseline ( < 0.0001 and = 0.002, respectively). A long-acting somatostatin analog was able to lower IGF-1 levels of OS patients. IGF-BP-3 and GH were only transiently reduced. Although ONC was well tolerated, no sustained clinical responses were observed. The pathophysiology of serum versus tissue concentrations of IGF-1 as well as the interplay of IGFs, IGF-binding proteins, and other growth factors and cytokines in osteosarcoma warrants further investigation. A better understanding of these processes should lead to a more effective exploitation of these pathways for the targeted therapy of OS. JF - Journal of pediatric hematology/oncology AU - Mansky, Patrick J AU - Liewehr, David J AU - Steinberg, Seth M AU - Chrousos, George P AU - Avila, Nilo A AU - Long, Lauren AU - Bernstein, Donna AU - Mackall, Crystal L AU - Hawkins, Douglas S AU - Helman, Lee J AD - Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-2669, USA. Mansky@mail.nih.gov PY - 2002 SP - 440 EP - 446 VL - 24 IS - 6 SN - 1077-4114, 1077-4114 KW - Antineoplastic Agents, Hormonal KW - 0 KW - Insulin-Like Growth Factor Binding Proteins KW - Tamoxifen KW - 094ZI81Y45 KW - Polyglactin 910 KW - 34346-01-5 KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Insulin-Like Growth Factor II KW - 67763-97-7 KW - Growth Hormone KW - 9002-72-6 KW - Octreotide KW - RWM8CCW8GP KW - Index Medicus KW - Dose-Response Relationship, Drug KW - Polyglactin 910 -- therapeutic use KW - Tamoxifen -- therapeutic use KW - Growth Hormone -- blood KW - Humans KW - Child KW - Insulin-Like Growth Factor Binding Proteins -- blood KW - Insulin-Like Growth Factor II -- metabolism KW - Drug Therapy, Combination KW - Adult KW - Treatment Outcome KW - Tamoxifen -- adverse effects KW - Adolescent KW - Female KW - Male KW - Osteosarcoma -- drug therapy KW - Bone Neoplasms -- blood KW - Octreotide -- analogs & derivatives KW - Osteosarcoma -- secondary KW - Octreotide -- therapeutic use KW - Octreotide -- adverse effects KW - Bone Neoplasms -- drug therapy KW - Insulin-Like Growth Factor I -- metabolism KW - Osteosarcoma -- blood KW - Bone Neoplasms -- pathology KW - Antineoplastic Agents, Hormonal -- therapeutic use KW - Antineoplastic Agents, Hormonal -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72079556?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Treatment+of+metastatic+osteosarcoma+with+the+somatostatin+analog+OncoLar%3A+significant+reduction+of+insulin-like+growth+factor-1+serum+levels.&rft.au=Mansky%2C+Patrick+J%3BLiewehr%2C+David+J%3BSteinberg%2C+Seth+M%3BChrousos%2C+George+P%3BAvila%2C+Nilo+A%3BLong%2C+Lauren%3BBernstein%2C+Donna%3BMackall%2C+Crystal+L%3BHawkins%2C+Douglas+S%3BHelman%2C+Lee+J&rft.aulast=Mansky&rft.aufirst=Patrick&rft.date=2002-08-01&rft.volume=24&rft.issue=6&rft.spage=440&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 - 2002-12-09 N1 - Date created - 2002-09-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glucosylsphingosine accumulation in tissues from patients with Gaucher disease: correlation with phenotype and genotype. AN - 72065196; 12208131 AB - Gaucher disease, the inherited deficiency of lysosomal glucocerebrosidase, presents with a wide spectrum of clinical manifestations including neuronopathic and non-neuronopathic forms. While the lipid glucosylceramide is stored in both patients with Gaucher disease and in a null allele mouse model of Gaucher disease, elevated levels of a second potentially toxic substrate, glucosylsphingosine, are also found. Using high performance liquid chromatography, glucosylsphingosine levels were measured in tissues from patients with type 1, 2, and 3 Gaucher disease. Glucosylsphingosine was measured in 16 spleen samples (8 type 1; 4 type 2; and 4, type 3) and levels ranged from 54 to 728 ng/mg protein in the patients with type 1 disease, 133 to 1200 ng/mg protein in the patients with type 2, and 109 to 1298 ng/mg protein in the type 3 samples. The levels of splenic glucosylsphingosine bore no relation to the type of Gaucher disease, the age of the patient, the genotype, nor the clinical course. In the same patients, hepatic glucosylsphingosine levels were lower than in spleen. Glucosylsphingosine was also measured in brains from 13 patients (1 type 1; 8 type 2; and 4 type 3). While the glucosylsphingosine level in the brain from the type 1 patient, 1.0 ng/mg protein, was in the normal range, the levels in the type 3 samples ranged from 14 to 32 ng/mg protein, and in the type 2 samples from 24 to 437 ng/mg protein, with the highest values detected in two fetuses with hydrops fetalis. The elevated levels found in brains from patients with neuronopathic Gaucher disease support the hypothesis that glucosylsphingosine may contribute to the nervous system involvement in these patients. JF - Molecular genetics and metabolism AU - Orvisky, Eduard AU - Park, Joseph K AU - LaMarca, Mary E AU - Ginns, Edward I AU - Martin, Brian M AU - Tayebi, Nahid AU - Sidransky, Ellen AD - Clinical Neuroscience Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2002/08// PY - 2002 DA - August 2002 SP - 262 EP - 270 VL - 76 IS - 4 SN - 1096-7192, 1096-7192 KW - Psychosine KW - 2238-90-6 KW - sphingosyl beta-glucoside KW - 52050-17-6 KW - Sphingosine KW - NGZ37HRE42 KW - Index Medicus KW - Spleen -- metabolism KW - Humans KW - Spleen -- pathology KW - Psychosine -- analogs & derivatives KW - Liver -- metabolism KW - Organ Specificity KW - Brain -- metabolism KW - Child KW - Chromatography, High Pressure Liquid KW - Structure-Activity Relationship KW - Child, Preschool KW - Phenotype KW - Genotype KW - Infant KW - Adult KW - Middle Aged KW - Adolescent KW - Female KW - Male KW - Sphingosine -- metabolism KW - Sphingosine -- analysis KW - Sphingosine -- analogs & derivatives KW - Gaucher Disease -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72065196?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+genetics+and+metabolism&rft.atitle=Glucosylsphingosine+accumulation+in+tissues+from+patients+with+Gaucher+disease%3A+correlation+with+phenotype+and+genotype.&rft.au=Orvisky%2C+Eduard%3BPark%2C+Joseph+K%3BLaMarca%2C+Mary+E%3BGinns%2C+Edward+I%3BMartin%2C+Brian+M%3BTayebi%2C+Nahid%3BSidransky%2C+Ellen&rft.aulast=Orvisky&rft.aufirst=Eduard&rft.date=2002-08-01&rft.volume=76&rft.issue=4&rft.spage=262&rft.isbn=&rft.btitle=&rft.title=Molecular+genetics+and+metabolism&rft.issn=10967192&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-10 N1 - Date created - 2002-09-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Using an interleukin-6 challenge to evaluate neuropsychological performance in chronic fatigue syndrome. AN - 72064675; 12214788 AB - Individuals with acute infections experience a range of symptoms including fatigue, malaise, muscle aches, and difficulties with concentration and memory that are usually self-limited. This cluster of symptoms is otherwise, similar to those that characterize chronic fatigue syndrome (CFS). The goal of the present study was to evaluate the cognitive and psychological functioning of CFS patients and normal controls (NCs) when they both were experiencing acute influenza-like symptoms. To induce influenza-like symptoms, we administered interleukin-6 (IL-6), a cytokine that temporarily activates the acute phase immunological and endocrine responses. Nineteen patients who met the 1994 International CFS Study Group Criteria and ten normal controls (NCs) completed routine clinical evaluations, neuropsychological tests of short-term memory, selective attention, and executive control, and self-ratings of somatic symptoms and psychological mood before, shortly following, and 1 day after IL-6 administration. CFS patients consistently reported more somatic symptoms, even when both groups perceived that they were ill. Both groups somatic symptoms increased during the IL-6 challenge, but the CFS patients symptoms increased more rapidly than controls. In general, the CFS patients performed similarly to NCs on the cognitive measures before, during, and after the IL-6. In contrast to predictions, IL-6 provocation did not impair the cognitive performance of either CFS patients or NCs. The IL-6 provocation exacerbated the patients self-reported symptoms but did not reveal notable cognitive impairments between patients and controls during cytokine-induced acute influenza-like symptoms. JF - Psychological medicine AU - Arnold, M C AU - Papanicolaou, D A AU - O'Grady, J A AU - Lotsikas, A AU - Dale, J K AU - Straus, S E AU - Grafman, J AD - National Institute of Neurological Disorders and Stroke, National Institute of Child Health and Human Development and National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1440, USA. Y1 - 2002/08// PY - 2002 DA - August 2002 SP - 1075 EP - 1089 VL - 32 IS - 6 SN - 0033-2917, 0033-2917 KW - Interleukin-6 KW - 0 KW - Index Medicus KW - Memory KW - Cognition Disorders -- diagnosis KW - Humans KW - Adult KW - Task Performance and Analysis KW - Middle Aged KW - Cognition Disorders -- chemically induced KW - Affect KW - Neuropsychological Tests KW - Male KW - Female KW - Cognition Disorders -- psychology KW - Fatigue Syndrome, Chronic -- diagnosis KW - Fatigue Syndrome, Chronic -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72064675?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Using+an+interleukin-6+challenge+to+evaluate+neuropsychological+performance+in+chronic+fatigue+syndrome.&rft.au=Arnold%2C+M+C%3BPapanicolaou%2C+D+A%3BO%27Grady%2C+J+A%3BLotsikas%2C+A%3BDale%2C+J+K%3BStraus%2C+S+E%3BGrafman%2C+J&rft.aulast=Arnold&rft.aufirst=M&rft.date=2002-08-01&rft.volume=32&rft.issue=6&rft.spage=1075&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 - 2003-02-05 N1 - Date created - 2002-09-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modulation of multiple experimental arthritis models by collagen-induced arthritis quantitative trait loci isolated in congenic rat lines: different effects of non-major histocompatibility complex quantitative trait loci in males and females. AN - 72059345; 12209529 AB - Collagen-induced arthritis (CIA) is a model of inflammatory arthritis with many similarities to rheumatoid arthritis (RA). We previously mapped in F(2) offspring of CIA-susceptible DA and CIA-resistant F344 rats, 5 quantitative trait loci (QTLs) for which F344 alleles were associated with reduced CIA severity. In the present study, we sought to characterize the independent arthritis-modulating effects of these 5 QTLs. CIA-regulatory regions were transferred from the F344 genome to the DA background or vice versa by repeated backcrossing. The arthritis-modulating effects of the transferred alleles were determined by comparing the severity of experimentally induced arthritis in congenic rats with that in DA rats. Congenic lines with either the F344 major histocompatibility complex (MHC) on the DA background or the DA MHC on the F344 background were resistant to CIA, confirming both MHC and non-MHC contributions to the genetic regulation of CIA. F344 alleles at the Cia3 and Cia5 regions of chromosomes 4 and 10 reduced CIA severity relative to that observed in DA rats. F344 Cia4 and Cia6 regions of chromosomes 7 and 8 failed to significantly alter CIA severity. Arthritis-modifying effects of Cia4 and Cia6 were, however, detected in pristane-induced and/or Freund's incomplete adjuvant oil-induced arthritis. The arthritis-modifying effects of the non-MHC CIA-regulatory loci differed in males and females. These congenic lines confirmed the existence and location of genes that regulate the severity of experimental arthritis in rats. Mechanisms responsible for the sex-specificity of individual arthritis-regulatory loci may explain some of the sex differences observed in RA and other autoimmune diseases in humans. JF - Arthritis and rheumatism AU - Remmers, Elaine F AU - Joe, Bina AU - Griffiths, Marie M AU - Dobbins, David E AU - Dracheva, Svetlana V AU - Hashiramoto, Akira AU - Furuya, Takefumi AU - Salstrom, Jennifer L AU - Wang, JianPing AU - Gulko, Pércio S AU - Cannon, Grant W AU - Wilder, Ronald L AD - National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland20892, USA. remmerse@mail.nih.gov Y1 - 2002/08// PY - 2002 DA - August 2002 SP - 2225 EP - 2234 VL - 46 IS - 8 SN - 0004-3591, 0004-3591 KW - Terpenes KW - 0 KW - pristane KW - 26HZV48DT1 KW - Collagen KW - 9007-34-5 KW - Freund's Adjuvant KW - 9007-81-2 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Sex Factors KW - Disease Models, Animal KW - Freund's Adjuvant -- immunology KW - Terpenes -- immunology KW - Rats KW - Freund's Adjuvant -- pharmacology KW - Rats, Inbred F344 KW - Collagen -- immunology KW - Terpenes -- pharmacology KW - Collagen -- pharmacology KW - Time Factors KW - Female KW - Male KW - Quantitative Trait, Heritable KW - Major Histocompatibility Complex -- immunology KW - Major Histocompatibility Complex -- genetics KW - Arthritis, Experimental -- genetics KW - Antigenic Modulation -- immunology KW - Animals, Congenic -- immunology KW - Animals, Congenic -- genetics KW - Arthritis, Experimental -- physiopathology KW - Antigenic Modulation -- genetics KW - Arthritis, Experimental -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72059345?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Modulation+of+multiple+experimental+arthritis+models+by+collagen-induced+arthritis+quantitative+trait+loci+isolated+in+congenic+rat+lines%3A+different+effects+of+non-major+histocompatibility+complex+quantitative+trait+loci+in+males+and+females.&rft.au=Remmers%2C+Elaine+F%3BJoe%2C+Bina%3BGriffiths%2C+Marie+M%3BDobbins%2C+David+E%3BDracheva%2C+Svetlana+V%3BHashiramoto%2C+Akira%3BFuruya%2C+Takefumi%3BSalstrom%2C+Jennifer+L%3BWang%2C+JianPing%3BGulko%2C+P%C3%A9rcio+S%3BCannon%2C+Grant+W%3BWilder%2C+Ronald+L&rft.aulast=Remmers&rft.aufirst=Elaine&rft.date=2002-08-01&rft.volume=46&rft.issue=8&rft.spage=2225&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 - 2002-09-19 N1 - Date created - 2002-09-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reduction of gradient acoustic noise in MRI using SENSE-EPI. AN - 72041801; 12202101 AB - A new approach to reduce gradient acoustic noise levels in EPI experiments is presented. Using multichannel RF receive coils, combined with SENSE data acquisition and reconstruction, gradient slew-rates in single-shot EPI were reduced fourfold for rate-2 and ninefold for rate-3 SENSE. Multislice EPI experiments were performed on three different scanner platforms. With 3.4 mm in-plane resolution, measuring 6 slices per second (12 slices with 2000 ms TR), this resulted in average sound pressure level reductions of 11.3 dB(A) and 16.5 dB(A) for rate-2 and rate-3 SENSE, respectively. BOLD fMRI experiments, using visually paced finger-tapping paradigms, showed no detrimental effect of the acoustic noise reduction strategy on temporal noise levels and t scores. JF - NeuroImage AU - de Zwart, Jacco A AU - van Gelderen, Peter AU - Kellman, Peter AU - Duyn, Jeff H AD - Advanced MRI, Laboratory of Functional and Molecular Imaging, NINDS, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2002/08// PY - 2002 DA - August 2002 SP - 1151 EP - 1155 VL - 16 IS - 4 SN - 1053-8119, 1053-8119 KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Magnetic Resonance Imaging KW - Oxygen -- blood KW - Humans KW - Adult KW - Fingers -- physiology KW - Male KW - Female KW - Echo-Planar Imaging KW - Motor Cortex -- physiology KW - Noise KW - Image Processing, Computer-Assisted UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72041801?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NeuroImage&rft.atitle=Reduction+of+gradient+acoustic+noise+in+MRI+using+SENSE-EPI.&rft.au=de+Zwart%2C+Jacco+A%3Bvan+Gelderen%2C+Peter%3BKellman%2C+Peter%3BDuyn%2C+Jeff+H&rft.aulast=de+Zwart&rft.aufirst=Jacco&rft.date=2002-08-01&rft.volume=16&rft.issue=4&rft.spage=1151&rft.isbn=&rft.btitle=&rft.title=NeuroImage&rft.issn=10538119&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-10-09 N1 - Date created - 2002-08-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Occupational dust exposure and the risk of laryngeal cancer in Turkey. AN - 72037345; 12199430 AB - A hospital-based case-referent study was conducted to identify occupational risk factors for laryngeal cancer. In a previous report an association was found between laryngeal cancer and occupations with potential dust exposure; a job-exposure matrix was developed to aid further evaluation of laryngeal cancer risks from five occupational dust exposures. Among 7631 cancer cases from the Okmeydani Hospital, Istanbul, between 1979 and 1984, 958 larynx cancer cases were identified among men. After exclusions, 940 laryngeal cancer cases and 1519 referents were available. A standardized questionnaire was used to obtain basic information on the patients. Seven-digit standard occupational and industrial codes were created to classify the job and industrial titles. A job-exposure matrix was developed for occupational dusts, including silica, asbestos, wood, cotton, and grain, and age-, smoking-, and alcohol-adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were calculated to evaluate risks of laryngeal cancer. An excess of laryngeal cancer occurred for workers potentially exposed to silica and cotton dust, particularly for supraglottic cancer (OR 1.8, 95% CI 1.3-2.3, for silica and OR 1.6, 95% CI 1.1-2.5, for cotton dust), and there was a significant dose-response relationship with silica exposure. No relationship was found between laryngeal cancer and asbestos, grain, or wood dust exposures. Laryngeal cancer, especially supraglottic tumors, is associated with silica and cotton dust exposures in Turkey. JF - Scandinavian journal of work, environment & health AU - Elci, Omur Cinar AU - Akpinar-Elci, Muge AU - Blair, Aaron AU - Dosemeci, Mustafa AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, United States. oae3@cdc.gov Y1 - 2002/08// PY - 2002 DA - August 2002 SP - 278 EP - 284 VL - 28 IS - 4 SN - 0355-3140, 0355-3140 KW - Dust KW - 0 KW - Index Medicus KW - Humans KW - Turkey -- epidemiology KW - Male KW - Occupational Exposure -- adverse effects KW - Laryngeal Neoplasms -- epidemiology KW - Dust -- adverse effects KW - Inhalation Exposure -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72037345?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Occupational+dust+exposure+and+the+risk+of+laryngeal+cancer+in+Turkey.&rft.au=Elci%2C+Omur+Cinar%3BAkpinar-Elci%2C+Muge%3BBlair%2C+Aaron%3BDosemeci%2C+Mustafa&rft.aulast=Elci&rft.aufirst=Omur&rft.date=2002-08-01&rft.volume=28&rft.issue=4&rft.spage=278&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 - 2002-09-17 N1 - Date created - 2002-08-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Epileptiform activity extinguished by amygdala infusion of the neurotoxin ibotenate in a rat model of temporal lobe epilepsy. AN - 72015476; 12186475 AB - The long-term antiseizure effects of local convection-enhanced infusion of the excitotoxin ibotenate were examined in a rat model of temporal lobe epilepsy. A single injection of kainate, an epileptogenic excitatory amino acid, into the left amygdala elicited chronic spontaneous recurrent seizure activity for at least 36 days after the injection. Two weeks after the injection, infusion of ibotenate, a nonepileptogenic excitatory amino acid that is an axon-sparing neuronal cell toxin, into the left amygdala and piriform lobe induced immediate and permanent extinction of electrical and behavioral seizure activity. Lesioning of an epileptic focus by convective distribution of ibotenate can produce an enduring suppression of seizure activity, indicating a chemical neurosurgical approach for epilepsy therapy. JF - Journal of neurosurgery AU - Pace, John R AU - Lonser, Russell R AU - Kirkby, R Duncan AU - Jeffries, Neal AU - Rogawski, Michael A AU - Oldfield, Edward H AD - Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/08// PY - 2002 DA - August 2002 SP - 450 EP - 454 VL - 97 IS - 2 SN - 0022-3085, 0022-3085 KW - Excitatory Amino Acid Agonists KW - 0 KW - Neurotoxins KW - Ibotenic Acid KW - 2552-55-8 KW - Kainic Acid KW - SIV03811UC KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Kainic Acid -- administration & dosage KW - Animals KW - Rats, Sprague-Dawley KW - Electroencephalography KW - Kainic Acid -- therapeutic use KW - Disease Models, Animal KW - Injections KW - Time Factors KW - Male KW - Epilepsy, Temporal Lobe -- physiopathology KW - Amygdala -- physiopathology KW - Ibotenic Acid -- therapeutic use KW - Ibotenic Acid -- administration & dosage KW - Excitatory Amino Acid Agonists -- therapeutic use KW - Neurotoxins -- administration & dosage KW - Excitatory Amino Acid Agonists -- administration & dosage KW - Neurotoxins -- therapeutic use KW - Amygdala -- drug effects KW - Epilepsy, Temporal Lobe -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72015476?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Epileptiform+activity+extinguished+by+amygdala+infusion+of+the+neurotoxin+ibotenate+in+a+rat+model+of+temporal+lobe+epilepsy.&rft.au=Pace%2C+John+R%3BLonser%2C+Russell+R%3BKirkby%2C+R+Duncan%3BJeffries%2C+Neal%3BRogawski%2C+Michael+A%3BOldfield%2C+Edward+H&rft.aulast=Pace&rft.aufirst=John&rft.date=2002-08-01&rft.volume=97&rft.issue=2&rft.spage=450&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 - 2002-09-04 N1 - Date created - 2002-08-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cyclooxygenase-1-selective inhibition prolongs gestation in mice without adverse effects on the ductus arteriosus. AN - 72011039; 12189249 AB - Preterm delivery is the leading cause of neonatal mortality and contributes significantly to infant morbidity. Classical cyclooxygenase (COX) inhibitors, such as indomethacin, which inhibit both COX-1 and COX-2, are effective for delaying premature labor, but their use is limited by serious complications to the fetus and neonate, including adverse effects on the ductus arteriosus (DA). Using isoform-selective inhibitors, we characterized the roles of the COX isoforms in the initiation of labor and the regulation of fetal and neonatal DA closure in mice. Chronic inhibition of COX-2 during pregnancy (gestation days 15-18) significantly increased neonatal mortality by preventing closure of the DA after birth, whereas acute COX-2 inhibition near the end of term (gestation day 18) constricted the fetal DA. In contrast, the inhibition of COX-1 during pregnancy lacked these prenatal and postnatal adverse effects on the DA and effectively delayed the initiation of full-term labor and LPS-induced preterm labor. These findings suggest that premature fetal DA closure or neonatal patent DA observed following indomethacin tocolysis in women may result from the inhibition of COX-2. Therefore, COX-1-selective inhibitors may provide effective treatment to delay preterm labor with fewer adverse effects on fetal or neonatal health than nonselective or COX-2-selective inhibitors. JF - The Journal of clinical investigation AU - Loftin, Charles D AU - Trivedi, Darshini B AU - Langenbach, Robert AD - Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. langenbach@niehs.nih.gov Y1 - 2002/08// PY - 2002 DA - August 2002 SP - 549 EP - 557 VL - 110 IS - 4 SN - 0021-9738, 0021-9738 KW - Cyclooxygenase 2 Inhibitors KW - 0 KW - Cyclooxygenase Inhibitors KW - Isoenzymes KW - Membrane Proteins KW - Pyrazoles KW - Receptors, Thromboxane KW - SC 560 KW - Cyclooxygenase 1 KW - EC 1.14.99.1 KW - Cyclooxygenase 2 KW - Prostaglandin-Endoperoxide Synthases KW - Ptgs1 protein, mouse KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Fetus -- drug effects KW - Gestational Age KW - Constriction, Pathologic -- chemically induced KW - Mice KW - Fetus -- enzymology KW - Ductus Arteriosus, Patent -- pathology KW - Pregnancy KW - Mice, Knockout KW - Maternal-Fetal Exchange KW - Animals, Newborn KW - Kinetics KW - Constriction, Pathologic -- pathology KW - Mice, Inbred C57BL KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - Ductus Arteriosus, Patent -- chemically induced KW - Receptors, Thromboxane -- agonists KW - Female KW - Survival Analysis KW - Ductus Arteriosus, Patent -- enzymology KW - Labor, Obstetric -- drug effects KW - Isoenzymes -- antagonists & inhibitors KW - Pyrazoles -- toxicity KW - Pyrazoles -- pharmacology KW - Ductus Arteriosus -- pathology KW - Ductus Arteriosus -- drug effects KW - Cyclooxygenase Inhibitors -- toxicity KW - Pregnancy, Animal -- drug effects KW - Isoenzymes -- genetics KW - Cyclooxygenase Inhibitors -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72011039?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Cyclooxygenase-1-selective+inhibition+prolongs+gestation+in+mice+without+adverse+effects+on+the+ductus+arteriosus.&rft.au=Loftin%2C+Charles+D%3BTrivedi%2C+Darshini+B%3BLangenbach%2C+Robert&rft.aulast=Loftin&rft.aufirst=Charles&rft.date=2002-08-01&rft.volume=110&rft.issue=4&rft.spage=549&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 - 2002-09-06 N1 - Date created - 2002-08-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1995 Nov 3;83(3):473-82 [8521477] Cell. 1995 Nov 3;83(3):483-92 [8521478] Nature. 1995 Nov 23;378(6555):406-9 [7477380] J Med Chem. 1997 Apr 25;40(9):1347-65 [9135032] Science. 1997 Aug 1;277(5326):681-3 [9235889] Am J Obstet Gynecol. 1997 Aug;177(2):256-9; discussion 259-61 [9290437] Cell. 1997 Oct 17;91(2):197-208 [9346237] Nature. 1997 Nov 6;390(6655):78-81 [9363893] Teratology. 1997 Oct;56(4):282-92 [9408979] Pharmacol Rev. 1998 Mar;50(1):35-58 [9549757] Biochem Biophys Res Commun. 1998 May 8;246(1):7-12 [9600059] J Pharm Pharmacol. 1998 Jun;50(6):681-5 [9680081] Proc Natl Acad Sci U S A. 1998 Sep 29;95(20):11875-9 [9751758] Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13313-8 [9789085] Pediatrics. 1998 Nov;102(5):E56 [9794986] Inflamm Res. 1998 Oct;47 Suppl 2:S78-87 [9831328] Early Hum Dev. 1999 Apr;54(3):271-94 [10321793] N Engl J Med. 1999 Aug 26;341(9):660-6 [10460818] J Toxicol Sci. 1995 Feb;20(1):29-32 [7595972] Am J Obstet Gynecol. 2000 Feb;182(2):370-6 [10694339] Placenta. 2000 Jan;21(1):54-7 [10692251] Endocrinology. 2000 Apr;141(4):1554-9 [10746663] Am J Physiol Regul Integr Comp Physiol. 2000 Jun;278(6):R1415-23 [10848506] Am J Physiol Regul Integr Comp Physiol. 2000 Jun;278(6):R1496-505 [10848516] Paediatr Drugs. 1999 Apr-Jun;1(2):81-92 [10937444] Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9759-64 [10944235] Arch Dis Child Fetal Neonatal Ed. 2000 Sep;83(2):F79-85 [10952696] Proc Natl Acad Sci U S A. 2001 Jan 30;98(3):1059-64 [11158594] Circulation. 2001 Apr 3;103(13):1806-12 [11282914] Mol Hum Reprod. 2001 Jun;7(6):595-602 [11385116] Exp Physiol. 2001 Mar;86(2):213-22 [11429638] Exp Physiol. 2001 Mar;86(2):297-302 [11429647] Circ Res. 2001 Oct 12;89(8):650-60 [11597987] Am J Physiol. 1980 May;238(5):H631-8 [6990790] Biochim Biophys Acta. 1983 Feb 7;750(2):330-3 [6860685] Can J Biochem Cell Biol. 1983 May;61(5):240-7 [6411303] Thromb Res. 1986 Feb 15;41(4):471-81 [3008368] Pediatr Res. 1987 Nov;22(5):567-72 [3684384] N Engl J Med. 1988 Aug 11;319(6):327-31 [3393194] J Pharmacol Exp Ther. 1989 Nov;251(2):557-62 [2530338] Am J Obstet Gynecol. 1990 Feb;162(2):549-54 [2309841] Early Hum Dev. 1992 Jun-Jul;29(1-3):63-73 [1327713] Am J Obstet Gynecol. 1993 May;168(5):1350-3 [8498410] Pediatr Res. 1993 Jun;33(6):615-9 [8378121] N Engl J Med. 1993 Nov 25;329(22):1602-7 [8232428] Circ Res. 1994 Feb;74(2):197-205 [8293559] Am J Obstet Gynecol. 1995 Mar;172(3):886-90 [7892880] J Cardiovasc Pharmacol. 1995 Jan;25(1):113-8 [7723339] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Measuring complications of cancer treatment using the SEER-Medicare data. AN - 72004312; 12187170 AB - The linkage of SEER registry data with Medicare claims allows the longitudinal tracking of health care and outcomes for patients after a cancer diagnosis. One category of outcomes amenable to research using Medicare claims is complications of cancer treatments: the unintentional, adverse side effects or sequelae of interventions used to treat or palliate cancer patients. The authors review some of the methods and limitations of using Medicare claims to identify both acute and chronic complications of cancer treatments, and present an original analysis comparing survey-based and claims-based complications following radical prostatectomy for prostate cancer to illustrate some of the potential limitations inherent in using claims for this purpose. Utility of the Medicare claims for identifying postdischarge complications varies by the patient type, the initial treatment used, and any subsequent treatment of complications. For patients undergoing surgical interventions, Medicare claims can be used to identify most acute inpatient complications. However, claims data cannot be used as effectively in the long-term to capture chronic complications, particularly when the complication does not consistently prompt an intervention. Researchers who use the SEER-Medicare-linked database to assess long-term complications of cancer treatments should exercise caution when designing and interpreting studies. Ideally, for studies of most chronic complications of cancer care, validation studies similar to the one performed here would provide valuable additional evidence to assess the credibility of conclusions based on claims data. JF - Medical care AU - Potosky, Arnold L AU - Warren, Joan L AU - Riedel, Elyn R AU - Klabunde, Carrie N AU - Earle, Craig C AU - Begg, Colin B AD - Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Maryland 20892-7344, USA. potosky@nih.gov Y1 - 2002/08// PY - 2002 DA - August 2002 SP - IV EP - 62-8 VL - 40 IS - 8 Suppl SN - 0025-7079, 0025-7079 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Medical Record Linkage KW - Postoperative Complications KW - Humans KW - Health Services Research KW - Insurance Claim Reporting KW - Aged KW - United States -- epidemiology KW - Male KW - Female KW - Radiotherapy -- adverse effects KW - Antineoplastic Agents -- adverse effects KW - SEER Program KW - Neoplasms -- epidemiology KW - Medicare KW - Outcome Assessment (Health Care) KW - Neoplasms -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72004312?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Medical+care&rft.atitle=Measuring+complications+of+cancer+treatment+using+the+SEER-Medicare+data.&rft.au=Potosky%2C+Arnold+L%3BWarren%2C+Joan+L%3BRiedel%2C+Elyn+R%3BKlabunde%2C+Carrie+N%3BEarle%2C+Craig+C%3BBegg%2C+Colin+B&rft.aulast=Potosky&rft.aufirst=Arnold&rft.date=2002-08-01&rft.volume=40&rft.issue=8+Suppl&rft.spage=IV&rft.isbn=&rft.btitle=&rft.title=Medical+care&rft.issn=00257079&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-09-11 N1 - Date created - 2002-08-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Caffeine potentiates the discriminative-stimulus effects of nicotine in rats. AN - 71999979; 12172692 AB - Caffeine and nicotine are the main psychoactive ingredients of coffee and tobacco, respectively, with a high frequency of concurrent use in humans. The aim of the present study was to examine the interaction of caffeine and nicotine in rats trained to discriminate nicotine from saline. Two groups of male Sprague-Dawley rats ( n=8 per group) were trained to discriminate 0.4 mg/kg nicotine, SC, from saline under a fixed ratio schedule of food presentation. One group of rats was chronically exposed to caffeine (1.0 mg/ml) dissolved in their drinking water whereas the other group was exposed to tap water. Effects of IP injections of caffeine on nicotine-lever selection were subsequently examined. In separate groups of rats exposed to the same caffeine-drinking or water-drinking regimen, effects of caffeine pretreatment on nicotine plasma levels were evaluated. Although caffeine (1.0-30.0 mg/kg) did not generalize to nicotine when administered alone, it markedly potentiated discriminative-stimulus effects of the threshold dose of nicotine (0.05 mg/kg) in both water- and caffeine-drinking rats. Nicotine plasma levels were, however, not affected by acute or chronic caffeine exposure. Caffeine appears to enhance the discriminative-stimulus effects of the threshold dose of nicotine by a pharmacodynamic rather than a pharmacokinetic interaction. This suggests that caffeine consumption may be a contributing factor in the onset, maintenance of and relapse to tobacco dependence. JF - Psychopharmacology AU - Gasior, Maciej AU - Jaszyna, Maria AU - Munzar, Patrik AU - Witkin, Jeffrey M AU - Goldberg, Steven R AD - National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA. mgasior@mclean.harvard.edu Y1 - 2002/08// PY - 2002 DA - August 2002 SP - 385 EP - 395 VL - 162 IS - 4 SN - 0033-3158, 0033-3158 KW - Central Nervous System Stimulants KW - 0 KW - Ganglionic Stimulants KW - Vasodilator Agents KW - Caffeine KW - 3G6A5W338E KW - Nicotine KW - 6M3C89ZY6R KW - Theophylline KW - C137DTR5RG KW - Theobromine KW - OBD445WZ5P KW - 1,7-dimethylxanthine KW - Q3565Y41V7 KW - Index Medicus KW - Animals KW - Generalization, Stimulus -- drug effects KW - Reinforcement Schedule KW - Differential Threshold KW - Dose-Response Relationship, Drug KW - Theobromine -- pharmacology KW - Vasodilator Agents -- pharmacology KW - Rats KW - Rats, Sprague-Dawley KW - Theophylline -- pharmacology KW - Motor Activity -- drug effects KW - Drug Synergism KW - Male KW - Discrimination Learning -- drug effects KW - Caffeine -- blood KW - Ganglionic Stimulants -- blood KW - Central Nervous System Stimulants -- pharmacology KW - Central Nervous System Stimulants -- blood KW - Caffeine -- pharmacology KW - Nicotine -- administration & dosage KW - Nicotine -- blood KW - Ganglionic Stimulants -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71999979?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Caffeine+potentiates+the+discriminative-stimulus+effects+of+nicotine+in+rats.&rft.au=Gasior%2C+Maciej%3BJaszyna%2C+Maria%3BMunzar%2C+Patrik%3BWitkin%2C+Jeffrey+M%3BGoldberg%2C+Steven+R&rft.aulast=Gasior&rft.aufirst=Maciej&rft.date=2002-08-01&rft.volume=162&rft.issue=4&rft.spage=385&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-01-07 N1 - Date created - 2002-08-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gemcitabine (2',2'-difluoro-2'-deoxycytidine), an antimetabolite that poisons topoisomerase I. AN - 71998836; 12171875 AB - Gemcitabine-containing regimens are among standard therapies for the treatment of advanced non-small cell lung,pancreatic, or bladder cancers. Gemcitabine is a nucleoside analogue and its cytotoxicity is correlated with incorporation into genomic DNA and concomitant inhibition of DNA synthesis. However, it is still unclear by which mechanism(s) gemcitabine incorporation leads to cell death. We used purified oligodeoxynucleotides to study the effects of gemcitabine incorporation on topoisomerase I (top1) activity and tested the role of top1 poisoning in gemcitabine-induced cytotoxicity in cancer cells. We found that top1-mediated DNA cleavage was enhanced when gemcitabine was incorporated immediately 3' from a top1 cleavage site on the nonscissile strand. This position-specific enhancement was attributable to an increased DNA cleavage by top1 and was likely to have resulted from a combination of gemcitabine-induced conformational and electrostatic effects. Gemcitabine also enhanced camptothecin-induced cleavage complexes. We also detected top1 cleavage complexes in human leukemia CEM cells treated with gemcitabine and a 5-fold resistance of P388/CPT45 top1-deficient cells to gemcitabine, indicating that poisoning of top1 can contribute to the antitumor activity of gemcitabine. The present results extend our recent finding that incorporation of 1-beta-D-arabinofuranosylcytosine into DNA can induce top1 cleavage complexes [P. Pourquier et al. Proc. Natl. Acad. Sci. USA, 97: 1885-1890, 2000]. The enhancement of camptothecin-induced top1 cleavage complexes may, at least in part, contribute to the synergistic or additive effects of gemcitabine in combination with topotecan and irinotecan in human breast or lung cancer cells. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Pourquier, Philippe AU - Gioffre, Christopher AU - Kohlhagen, Glenda AU - Urasaki, Yoshimasa AU - Goldwasser, François AU - Hertel, Lary W AU - Yu, Shuyuan AU - Pon, Richard T AU - Gmeiner, William H AU - Pommier, Yves AD - Laboratory of Molecular Pharmacology, Division of Basic Sciences, NCI, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 2002/08// PY - 2002 DA - August 2002 SP - 2499 EP - 2504 VL - 8 IS - 8 SN - 1078-0432, 1078-0432 KW - Antimetabolites, Antineoplastic KW - 0 KW - Enzyme Inhibitors KW - Oligonucleotides KW - Topoisomerase I Inhibitors KW - Deoxycytidine KW - 0W860991D6 KW - gemcitabine KW - B76N6SBZ8R KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured KW - Oligonucleotides -- chemistry KW - Dose-Response Relationship, Drug KW - Humans KW - Models, Chemical KW - Mice KW - Time Factors KW - Deoxycytidine -- analogs & derivatives KW - Enzyme Inhibitors -- pharmacology KW - Deoxycytidine -- pharmacology KW - Antimetabolites, Antineoplastic -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71998836?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Gemcitabine+%282%27%2C2%27-difluoro-2%27-deoxycytidine%29%2C+an+antimetabolite+that+poisons+topoisomerase+I.&rft.au=Pourquier%2C+Philippe%3BGioffre%2C+Christopher%3BKohlhagen%2C+Glenda%3BUrasaki%2C+Yoshimasa%3BGoldwasser%2C+Fran%C3%A7ois%3BHertel%2C+Lary+W%3BYu%2C+Shuyuan%3BPon%2C+Richard+T%3BGmeiner%2C+William+H%3BPommier%2C+Yves&rft.aulast=Pourquier&rft.aufirst=Philippe&rft.date=2002-08-01&rft.volume=8&rft.issue=8&rft.spage=2499&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 - 2003-02-26 N1 - Date created - 2002-08-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular pathogenesis of human hepatocellular carcinoma. AN - 71997108; 12149612 AB - Hepatocarcinogenesis is a slow process during which genomic changes progressively alter the hepatocellular phenotype to produce cellular intermediates that evolve into hepatocellular carcinoma. During the long preneoplastic stage, in which the liver is often the site of chronic hepatitis, cirrhosis, or both, hepatocyte cycling is accelerated by upregulation of mitogenic pathways, in part through epigenetic mechanisms. This leads to the production of monoclonal populations of aberrant and dysplastic hepatocytes that have telomere erosion and telomerase re-expression, sometimes microsatellite instability, and occasionally structural aberrations in genes and chromosomes. Development of dysplastic hepatocytes in foci and nodules and emergence of hepatocellular carcinoma are associated with the accumulation of irreversible structural alterations in genes and chromosomes, but the genomic basis of the malignant phenotype is heterogeneous. The malignant hepatocyte phenotype may be produced by the disruption of a number of genes that function in different regulatory pathways, producing several molecular variants of hepatocellular carcinoma. New strategies should enable these variants to be characterized. JF - Nature genetics AU - Thorgeirsson, Snorri S AU - Grisham, Joe W AD - Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. snorri_thorgeirsson@nih.gov Y1 - 2002/08// PY - 2002 DA - August 2002 SP - 339 EP - 346 VL - 31 IS - 4 SN - 1061-4036, 1061-4036 KW - Transforming Growth Factor alpha KW - 0 KW - Insulin-Like Growth Factor II KW - 67763-97-7 KW - Index Medicus KW - Gene Expression Regulation, Neoplastic KW - Precancerous Conditions -- genetics KW - Transforming Growth Factor alpha -- genetics KW - DNA Methylation KW - Precancerous Conditions -- etiology KW - Humans KW - Chromosome Aberrations KW - Insulin-Like Growth Factor II -- genetics KW - Precancerous Conditions -- pathology KW - Genetic Heterogeneity KW - Liver Neoplasms -- pathology KW - Carcinoma, Hepatocellular -- genetics KW - Carcinoma, Hepatocellular -- pathology KW - Liver Neoplasms -- etiology KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71997108?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Molecular+pathogenesis+of+human+hepatocellular+carcinoma.&rft.au=Thorgeirsson%2C+Snorri+S%3BGrisham%2C+Joe+W&rft.aulast=Thorgeirsson&rft.aufirst=Snorri&rft.date=2002-08-01&rft.volume=31&rft.issue=4&rft.spage=339&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 - 2002-09-06 N1 - Date created - 2002-07-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Downstream E-box-mediated regulation of the human telomerase reverse transcriptase (hTERT) gene transcription: evidence for an endogenous mechanism of transcriptional repression. AN - 71992260; 12181331 AB - Regulation of the hTERT gene encoding the telomerase catalytic subunit plays an important role in human cell senescence, immortalization, and carcinogenesis. By examining the activity of various deleted or mutated hTERT promoter fragments, we show that an E-box element downstream of the transcription initiation site is critical to differential hTERT transcription between the telomerase/hTERT-positive renal cell carcinoma cell line (RCC23) and its telomerase/hTERT-negative counterpart containing a transferred, normal chromosome 3 (RCC23+3). This E-box element mediated repression of hTERT transcription in RCC23+3 but not in RCC23. A copy number-dependent enhancement of the repression suggested active repression, rather than loss of activation, in RCC23+3. Endogenous expression levels of c-Myc or Mad1, which could activate or repress hTERT transcription when overexpressed, did not account for the differential hTERT transcription. Gel mobility shift assays identified the upstream stimulatory factors (USFs) as a major E-box-binding protein complex in both RCC23 and RCC23+3 and, importantly, detected an RCC23+3-specific, E-box-binding factor that was distinct from the USF and Myc/Mad families. The E-box-mediated repression was also active in normal human fibroblasts and epithelial cells and inactive in some, but not all, telomerase/hTERT-positive cancer cells. These findings provide evidence for an endogenous, repressive mechanism that actively functions in telomerase/hTERT-negative normal cells and becomes defective during carcinogenic processes, e.g., by an inactivation of the telomerase repressor gene on chromosome 3. JF - Molecular biology of the cell AU - Horikawa, Izumi AU - Cable, P LouAnn AU - Mazur, Sharlyn J AU - Appella, Ettore AU - Afshari, Cynthia A AU - Barrett, J Carl AD - Laboratory of Biosystems and Cancer, Cancer and Aging Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. horikawi@mail.nih.gov Y1 - 2002/08// PY - 2002 DA - August 2002 SP - 2585 EP - 2597 VL - 13 IS - 8 SN - 1059-1524, 1059-1524 KW - Cell Cycle Proteins KW - 0 KW - DNA-Binding Proteins KW - MAD1L1 protein, human KW - Nuclear Proteins KW - Phosphoproteins KW - Proto-Oncogene Proteins c-myc KW - Repressor Proteins KW - Telomerase KW - EC 2.7.7.49 KW - Index Medicus KW - Phosphoproteins -- genetics KW - Humans KW - Repressor Proteins -- metabolism KW - Proto-Oncogene Proteins c-myc -- genetics KW - Proto-Oncogene Proteins c-myc -- metabolism KW - Repressor Proteins -- genetics KW - Mutagenesis, Site-Directed KW - Chromosomes, Human, Pair 3 KW - Promoter Regions, Genetic KW - Telomere -- metabolism KW - Tumor Cells, Cultured KW - Genes, Reporter KW - DNA-Binding Proteins -- metabolism KW - Phosphoproteins -- metabolism KW - Transcription, Genetic KW - Telomerase -- genetics KW - Gene Expression Regulation KW - E-Box Elements -- genetics KW - Telomerase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71992260?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+biology+of+the+cell&rft.atitle=Downstream+E-box-mediated+regulation+of+the+human+telomerase+reverse+transcriptase+%28hTERT%29+gene+transcription%3A+evidence+for+an+endogenous+mechanism+of+transcriptional+repression.&rft.au=Horikawa%2C+Izumi%3BCable%2C+P+LouAnn%3BMazur%2C+Sharlyn+J%3BAppella%2C+Ettore%3BAfshari%2C+Cynthia+A%3BBarrett%2C+J+Carl&rft.aulast=Horikawa&rft.aufirst=Izumi&rft.date=2002-08-01&rft.volume=13&rft.issue=8&rft.spage=2585&rft.isbn=&rft.btitle=&rft.title=Molecular+biology+of+the+cell&rft.issn=10591524&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-09 N1 - Date created - 2002-08-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Gene Ther. 2001 Apr;8(7):568-78 [11319624] Nat Med. 1999 Oct;5(10):1164-70 [10502820] Gene. 2001 May 16;269(1-2):1-12 [11376932] J Biol Chem. 2001 Jun 22;276(25):22016-23 [11279234] Oncogene. 2001 May 3;20(20):2600-5 [11420670] Cell Mol Life Sci. 2001 May;58(5-6):721-7 [11437233] J Biol Chem. 2001 Aug 10;276(32):29994-30001 [11402027] J Cell Biochem. 2001;82(3):415-21 [11500918] Cancer Res. 2001 Sep 1;61(17):6340-4 [11522622] Cancer Res. 2001 Oct 15;61(20):7594-602 [11606399] Oncogene. 2002 Jan 24;21(5):769-77 [11850805] Cell. 1991 Jun 28;65(7):1243-53 [1829647] Science. 1994 Dec 23;266(5193):2011-5 [7605428] J Biol Chem. 1996 Jan 19;271(3):1405-15 [8576131] Oncogene. 1996 Sep 19;13(6):1249-57 [8808699] Mol Cell Biol. 1997 Jan;17(1):18-23 [8972181] Oncogene. 1997 Feb 6;14(5):589-94 [9053857] Proc Soc Exp Biol Med. 1997 Feb;214(2):99-106 [9034126] Trends Biochem Sci. 1997 Feb;22(2):43-7 [9048479] Science. 1997 Aug 15;277(5328):955-9 [9252327] Cell. 1997 Aug 22;90(4):785-95 [9288757] Oncol Res. 1997;9(6-7):313-25 [9406237] Nat Genet. 1998 Jan;18(1):65-8 [9425903] Science. 1998 Jan 16;279(5349):349-52 [9454332] J Biol Chem. 1998 Mar 20;273(12):6632-42 [9506959] Mol Carcinog. 1998 Jun;22(2):65-72 [9655250] Genes Chromosomes Cancer. 1998 Oct;23(2):123-33 [9739015] Biochem J. 1999 Nov 15;344 Pt 1:145-52 [10548544] J Biol Chem. 1999 Dec 24;274(52):37473-8 [10601322] Oncogene. 1999 Dec 2;18(51):7200-11 [10602473] Cancer Res. 1999 Dec 15;59(24):6087-90 [10626795] Nucleic Acids Res. 2000 Feb 1;28(3):669-77 [10637317] Oncogene. 2000 Mar 9;19(11):1485-90 [10723141] Cancer Res. 2000 Apr 15;60(8):2116-21 [10786671] Mol Cell Biol. 2000 Jun;20(11):3764-71 [10805720] Nucleic Acids Res. 2000 Jul 1;28(13):2557-62 [10871406] J Clin Oncol. 2000 Jul;18(13):2626-34 [10893296] Hum Gene Ther. 2000 Jul 1;11(10):1397-406 [10910137] Cancer Res. 2000 Oct 1;60(19):5359-64 [11034071] Oncogene. 2000 Oct 26;19(45):5123-33 [11064449] Cancer Res. 2000 Nov 1;60(21):5922-8 [11085504] J Biol Chem. 2000 Nov 17;275(46):35665-8 [10986277] In Vitro Cell Dev Biol Anim. 2000 Nov-Dec;36(10):620-4 [11229591] Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):3826-31 [11274400] Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4498-503 [11287649] J Natl Cancer Inst. 1999 Jan 6;91(1):37-45 [9890168] Nat Genet. 1999 Feb;21(2):220-4 [9988278] Oncogene. 1999 Feb 4;18(5):1219-26 [10022128] Cancer Res. 1999 Feb 15;59(4):826-30 [10029071] Curr Opin Cell Biol. 1999 Jun;11(3):318-24 [10395557] Biochim Biophys Acta. 2001 Feb 16;1517(3):398-409 [11342218] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Autosomal dominant hypocalcemia caused by a novel mutation in the loop 2 region of the human calcium receptor extracellular domain. AN - 71988082; 12162500 AB - We report a novel missense mutation N124K in the extracellular calcium receptor (CaR) identified in two related subjects with the phenotypic features of autosomal dominant hypocalcemia (ADH). Expression of the N124K mutant receptor created by site-directed mutagenesis and transfected into HEK-293 cells was comparable with that of the wild-type (WT) receptor and two other mutant receptors N118K and L125P identified in subjects with ADH. Functional characterization by the extracellular Ca2+ ion ([Ca2+]0)-stimulated phosphoinositide (PI) hydrolysis in transfected HEK-293 cells showed that the N124K mutant receptor was left-shifted in Ca2+ sensitivity. This biochemical gain-of-function is comparable with that seen in other missense mutations of the CaR identified in subjects with ADH. We tested a series of missense substitutions (R, Q, E, and G) in addition to K for N124 and found that only the N124K mutation and to a much lesser extent N124R caused a left shift in Ca2+ sensitivity. Thus, a specific substitution, not merely a mutation of the N124 residue, is required for receptor activation. The N124K mutation is one of eight naturally occurring mutations in subjects with ADH identified in a short segment A116-C129 of the CaR extracellular domain (ECD). We present a hypothesis to explain receptor activation by mutations in this region based on the recently described three-dimensional structure of the related metabotropic glutamate type 1 receptor (mGluR1). JF - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research AU - Hu, Jianxin AU - Mora, Stefano AU - Colussi, Giacomo AU - Proverbio, Maria Carla AU - Jones, Kendra A AU - Bolzoni, Laura AU - De Ferrari, Maria E AU - Civati, Giovanni AU - Spiegel, Allen M AD - Molecular Pathophysiology Section, National Institute on Deafness and other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/08// PY - 2002 DA - August 2002 SP - 1461 EP - 1469 VL - 17 IS - 8 SN - 0884-0431, 0884-0431 KW - Calcium-Binding Proteins KW - 0 KW - Parathyroid Hormone KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Calcium -- blood KW - Humans KW - Adult KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Parathyroid Hormone -- blood KW - Female KW - Cell Line KW - Genes, Dominant KW - Point Mutation KW - Hypocalcemia -- genetics KW - Calcium-Binding Proteins -- genetics KW - Calcium-Binding Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71988082?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Autosomal+dominant+hypocalcemia+caused+by+a+novel+mutation+in+the+loop+2+region+of+the+human+calcium+receptor+extracellular+domain.&rft.au=Hu%2C+Jianxin%3BMora%2C+Stefano%3BColussi%2C+Giacomo%3BProverbio%2C+Maria+Carla%3BJones%2C+Kendra+A%3BBolzoni%2C+Laura%3BDe+Ferrari%2C+Maria+E%3BCivati%2C+Giovanni%3BSpiegel%2C+Allen+M&rft.aulast=Hu&rft.aufirst=Jianxin&rft.date=2002-08-01&rft.volume=17&rft.issue=8&rft.spage=1461&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 - 2003-01-22 N1 - Date created - 2002-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - PMA activation of macrophages alters macrophage metabolism of aggregated LDL. AN - 71985021; 12177171 AB - Aggregation of LDL may contribute to its retention in atherosclerotic lesions. Previously, we showed that aggregated LDL induces and enters surface-connected compartments (SCCs) in human monocyte-derived macrophages by a process we have named patocytosis. Aggregated LDL was disaggregated and released from SCCs of macrophages when exposed to human lipoprotein-deficient serum. The serum factor that mediated aggregated LDL release and disaggregation was plasmin generated from plasminogen by macrophage urokinase plasminogen activator. We now show that activation of macrophages with PMA inhibits plasmin-mediated release of aggregated LDL from macrophages. With macrophage activation, plasminogen released about 60% less cholesterol and 63% less TCA-insoluble (125)I-aggregated LDL than when macrophages were not activated. Electron microscopy showed that PMA did not cause SCCs to close, which could have trapped aggregated LDL within the SCCs and limited protease access to aggregated LDL. Rather, PMA decreased macrophage generation of plasmin by 61%, and stimulated lysosomal degradation of aggregated LDL by more than 2-fold. Degradation was mediated by protein kinase C, shown by the finding that degradation was inhibited by the protein kinase C inhibitor Gö6976. PMA-stimulated degradation of aggregated LDL was associated with a 3-fold increase in cholesterol esterification, consistent with hydrolysis and re-esterification of aggregated LDL-derived cholesteryl ester. In conclusion, macrophage activation with PMA causes more of the aggregated LDL that enters macrophage SCCs to be metabolized by lysosomes. This results in more cholesterol to be stored in macrophages and less aggregated LDL to be available for plasmin-mediated release from macrophage SCCs. JF - Journal of lipid research AU - Huang, Wei AU - Ishii, Itsuko AU - Zhang, Wei-Yang AU - Sonobe, Miyahiko AU - Kruth, Howard S AD - Section of Experimental Atherosclerosis, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10, Room 5N-113, 10 Center Drive MSC 1422, Bethesda, MD 20892, USA. Y1 - 2002/08// PY - 2002 DA - August 2002 SP - 1275 EP - 1282 VL - 43 IS - 8 SN - 0022-2275, 0022-2275 KW - Lipoproteins, LDL KW - 0 KW - Plasminogen KW - 9001-91-6 KW - Cholesterol KW - 97C5T2UQ7J KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Esterification KW - Cholesterol -- metabolism KW - Cells, Cultured KW - Humans KW - Plasminogen -- metabolism KW - Microscopy, Electron KW - Hydrolysis KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Lipoproteins, LDL -- metabolism KW - Macrophages -- metabolism KW - Macrophage Activation -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71985021?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+lipid+research&rft.atitle=PMA+activation+of+macrophages+alters+macrophage+metabolism+of+aggregated+LDL.&rft.au=Huang%2C+Wei%3BIshii%2C+Itsuko%3BZhang%2C+Wei-Yang%3BSonobe%2C+Miyahiko%3BKruth%2C+Howard+S&rft.aulast=Huang&rft.aufirst=Wei&rft.date=2002-08-01&rft.volume=43&rft.issue=8&rft.spage=1275&rft.isbn=&rft.btitle=&rft.title=Journal+of+lipid+research&rft.issn=00222275&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-04 N1 - Date created - 2002-08-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Susceptibility of cyclooxygenase-2-deficient mice to pulmonary fibrogenesis. AN - 71984648; 12163371 AB - The cyclooxygenase (COX)-2 enzyme has been implicated as an important mediator of pulmonary fibrosis. In this study, the lung fibrotic responses were investigated in COX-1 or COX-2-deficient (-/-) mice following vanadium pentoxide (V(2)O(5)) exposure. Lung histology was normal in saline-instilled wild-type and COX-deficient mice. COX-2(-/-), but not COX-1(-/-) or wild-type mice, exhibited severe inflammatory responses by 3 days following V(2)O(5) exposure and developed pulmonary fibrosis 2 weeks post-V(2)O(5) exposure. Western blot analysis and immunohistochemistry showed that COX-1 protein was present in type 2 epithelial cells, bronchial epithelial cells, and airway smooth muscle cells of saline or V(2)O(5)-exposed wild-type and COX-2(-/-) mice. COX-2 protein was present in Clara cells of wild-type and COX-1(-/-) terminal bronchioles and was strongly induced 24 hours after V(2)O(5) exposure. Prostaglandin (PG) E(2) levels in the bronchoalveolar lavage (BAL) fluid from wild-type and COX-1(-/-) mice were significantly up-regulated by V(2)O(5) exposure within 24 hours, whereas PGE(2) was not up-regulated in COX-2(-/-) BAL fluid. Tumor necrosis factor-alpha was elevated in the BAL fluid from all genotypes after V(2)O(5) exposure, but was significantly and chronically elevated in the BAL fluid from COX-2(-/-) mice above wild-type or COX-1(-/-) mice. These findings indicate that the COX-2 enzyme is protective against pulmonary fibrogenesis, and we suggest that COX-2 generation of PGE(2) is an important factor in resolving inflammation. JF - The American journal of pathology AU - Bonner, James C AU - Rice, Annette B AU - Ingram, Jennifer L AU - Moomaw, Cindy R AU - Nyska, Abraham AU - Bradbury, Alyce AU - Sessoms, Alisha R AU - Chulada, Patricia C AU - Morgan, Daniel L AU - Zeldin, Darryl C AU - Langenbach, Robert AD - Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, North Carolina 27709, USA. bonnerj@niehs.nih.gov Y1 - 2002/08// PY - 2002 DA - August 2002 SP - 459 EP - 470 VL - 161 IS - 2 SN - 0002-9440, 0002-9440 KW - Isoenzymes KW - 0 KW - Vanadium Compounds KW - vanadium pentoxide KW - BVG363OH7A KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - Prostaglandin-Endoperoxide Synthases KW - Dinoprostone KW - K7Q1JQR04M KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Dinoprostone -- biosynthesis KW - Vanadium Compounds -- toxicity KW - Mice KW - Up-Regulation KW - Genetic Predisposition to Disease KW - Immunohistochemistry KW - Male KW - Female KW - Mice, Knockout KW - Prostaglandin-Endoperoxide Synthases -- deficiency KW - Isoenzymes -- deficiency KW - Pulmonary Fibrosis -- etiology KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - Isoenzymes -- genetics KW - Pulmonary Fibrosis -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71984648?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Susceptibility+of+cyclooxygenase-2-deficient+mice+to+pulmonary+fibrogenesis.&rft.au=Bonner%2C+James+C%3BRice%2C+Annette+B%3BIngram%2C+Jennifer+L%3BMoomaw%2C+Cindy+R%3BNyska%2C+Abraham%3BBradbury%2C+Alyce%3BSessoms%2C+Alisha+R%3BChulada%2C+Patricia+C%3BMorgan%2C+Daniel+L%3BZeldin%2C+Darryl+C%3BLangenbach%2C+Robert&rft.aulast=Bonner&rft.aufirst=James&rft.date=2002-08-01&rft.volume=161&rft.issue=2&rft.spage=459&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 - 2002-08-28 N1 - Date created - 2002-08-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Respir Cell Mol Biol. 2001 Oct;25(4):457-65 [11694451] Am J Pathol. 2001 Apr;158(4):1411-22 [11290559] Prostaglandins. 1987 Jun;33(6):903-13 [2823317] Nature. 1990 Mar 15;344(6263):245-7 [2156165] Am Rev Respir Dis. 1991 Oct;144(4):892-900 [1718192] J Lipid Mediat. 1993 Mar-Apr;6(1-3):175-81 [8395242] J Clin Invest. 1995 Apr;95(4):1861-8 [7706493] Cell. 1995 Nov 3;83(3):473-82 [8521477] Cell. 1995 Nov 3;83(3):483-92 [8521478] Arch Biochem Biophys. 1996 Jun 15;330(2):301-13 [8660660] Adv Immunol. 1996;62:167-215 [8781269] Am J Pathol. 1997 Nov;151(5):1303-10 [9358756] J Biol Chem. 1997 Dec 5;272(49):31065-72 [9388257] Am J Physiol. 1998 Jan;274(1 Pt 1):L72-80 [9458803] Am J Pathol. 1998 Sep;153(3):825-32 [9736031] Am J Pathol. 1998 Dec;153(6):1839-47 [9846974] Science. 1998 Dec 18;282(5397):2258-61 [9856949] FEBS Lett. 1998 Nov 27;440(1-2):76-80 [9862429] Am J Respir Cell Mol Biol. 1999 Mar;20(3):433-40 [10030841] J Biol Chem. 1999 Apr 23;274(17):11660-6 [10206978] Int J Exp Pathol. 1999 Feb;80(1):41-9 [10365086] Am J Pathol. 1999 Jul;155(1):213-21 [10393853] Biochem Pharmacol. 1999 Oct 15;58(8):1237-46 [10487525] J Clin Invest. 1999 Sep;104(6):721-32 [10491407] Mol Cell Biochem. 1999 Aug;198(1-2):193-200 [10497896] Am J Physiol. 1999 Dec;277(6 Pt 1):L1165-71 [10600887] Am J Physiol Lung Cell Mol Physiol. 2000 Jan;278(1):L209-16 [10645909] J Clin Invest. 2000 Feb;105(4):469-78 [10683376] Am J Respir Cell Mol Biol. 2000 May;22(5):628-34 [10783136] Am J Respir Crit Care Med. 2000 Aug;162(2 Pt 1):676-81 [10934105] J Occup Med. 1984 Aug;26(8):567-70 [6332888] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Influence of ritonavir on olanzapine pharmacokinetics in healthy volunteers. AN - 71979470; 12172335 AB - HIV infection and psychotic illnesses frequently coexist. The atypical antipsychotic olanzapine is metabolized primarily by CYP1A2 and glucuronosyl transferases, both of which are induced by the HIV protease inhibitor ritonavir. The purpose of this study was to determine the effect of ritonavir on the pharmacokinetics of a single dose of olanzapine. Fourteen healthy volunteers (13 men; age range, 20-28 years) participated in this open-label study. Subjects received olanzapine 10 mg and blood samples were collected over a 120-hour post-dose period. Two weeks later, subjects took ritonavir 300 mg twice daily for 3 days, 400 mg twice daily for 4 days, and 500 mg twice daily for 4 days. The next morning, after 11 days of ritonavir, olanzapine 10 mg was administered and blood sampling was repeated. Plasma samples were analyzed for olanzapine with HPLC. We compared olanzapine noncompartmental pharmacokinetic parameter values before and after ritonavir with a paired Student t test. Ritonavir reduced the area under the plasma concentration-time curve of olanzapine from 501 ng. hr/mL (443-582) to 235 ng. hr/mL (197-294) (p < 0.001), the half-life from 32 hours (28-36) to 16 hours (14-18) (p = 0.00001), and the peak concentration from 15 ng/mL (13-19) to 9 ng/mL (8-12) (p = 0.002). Olanzapine oral clearance increased from 20 L/hr (18-23) to 43 L/hr (38-51) (p < 0.001) after ritonavir. Ritonavir significantly reduced the systemic exposure of olanzapine in volunteers. Patients receiving this combination may ultimately require higher olanzapine doses to achieve desired therapeutic effects. JF - Journal of clinical psychopharmacology AU - Penzak, Scott R AU - Hon, Yuen Yi AU - Lawhorn, Walter D AU - Shirley, Kara L AU - Spratlin, Vicky AU - Jann, Michael W AD - Department of Pharmacy Practice, Mercer University, Southern School of Pharmacy, Atlanta, Georgia, USA. spenzak@mail.cc.nih.gov Y1 - 2002/08// PY - 2002 DA - August 2002 SP - 366 EP - 370 VL - 22 IS - 4 SN - 0271-0749, 0271-0749 KW - Antipsychotic Agents KW - 0 KW - HIV Protease Inhibitors KW - Benzodiazepines KW - 12794-10-4 KW - Pirenzepine KW - 3G0285N20N KW - olanzapine KW - N7U69T4SZR KW - Ritonavir KW - O3J8G9O825 KW - Index Medicus KW - Drug Interactions KW - Area Under Curve KW - Humans KW - Adult KW - Confidence Intervals KW - Male KW - Female KW - Ritonavir -- blood KW - Ritonavir -- pharmacokinetics KW - Antipsychotic Agents -- blood KW - Pirenzepine -- analogs & derivatives KW - Antipsychotic Agents -- pharmacokinetics KW - HIV Protease Inhibitors -- blood KW - HIV Protease Inhibitors -- pharmacokinetics KW - Pirenzepine -- blood KW - Pirenzepine -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71979470?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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+psychopharmacology&rft.atitle=Influence+of+ritonavir+on+olanzapine+pharmacokinetics+in+healthy+volunteers.&rft.au=Penzak%2C+Scott+R%3BHon%2C+Yuen+Yi%3BLawhorn%2C+Walter+D%3BShirley%2C+Kara+L%3BSpratlin%2C+Vicky%3BJann%2C+Michael+W&rft.aulast=Penzak&rft.aufirst=Scott&rft.date=2002-08-01&rft.volume=22&rft.issue=4&rft.spage=366&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+psychopharmacology&rft.issn=02710749&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-09-18 N1 - Date created - 2002-08-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Promotion of altered hepatic foci by 2,3,7,8-tetrachlorodibenzo-p-dioxin and 17beta-estradiol in male Sprague-Dawley rats. AN - 71970787; 12151625 AB - The determination of differences in hormonal regulation of tumor promotion-related response to 2,3,7,8-tetrachlorodibenzop-dioxin (TCDD) between males and females may identify factors contributing to the female-specific hepatocarcinogenicity of TCDD in rats. In the current study, diethylnitrosamine-initiated male Sprague-Dawley rats were exposed to TCDD or corn oil vehicle in the presence and absence of 17beta-estradiol (E2), and cell proliferation and development of preneoplastic altered hepatic foci (AHF) were determined. After 30 weeks of exposure, gamma-glutamyltranspeptidase (GGT)-positive AHF and the number of placental glutathione-s-transferase (PGST)-positive AHF were significantly higher in TCDD-treated rats than in control rats. Both the number and volume fraction of GGT-positive AHF were significantly lower in rats cotreated with E2 regardless of TCDD exposure compared with corresponding non-E2-treated groups and were unaffected by TCDD. In contrast, the number of PGST-positive AHF was significantly higher in E2-treated rats in the absence of TCDD treatment. In addition, whereas E2 had no effect on the volume fraction of PGST-positive foci, the levels in rats cotreated with both E2 and TCDD were significantly higher than in controls. No differences were observed in cell proliferation between TCDD-treated and control rats, although cell proliferation was lower in rats exposed to E2 compared with placebo controls. The weaker potency of tumor promotion and lack of induction of cell replication and DNA damage in male rats likely explain the female-specific hepatocarcinogenicity of TCDD in chronic bioassays. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Wyde, Michael E AU - Cambre, Theresa AU - Lebetkin, Mark AU - Eldridge, Sandra R AU - Walker, Nigel J AD - National Institute of Environmental Health Sciences, Environmental Toxicology Program, 111 Alexander Drive, Building 101, Room D452, MD4-01, Research Triangle Park, North Carolina 27709, USA. Y1 - 2002/08// PY - 2002 DA - August 2002 SP - 295 EP - 303 VL - 68 IS - 2 SN - 1096-6080, 1096-6080 KW - Carcinogens KW - 0 KW - Polychlorinated Dibenzodioxins KW - RNA, Messenger KW - Diethylnitrosamine KW - 3IQ78TTX1A KW - Estradiol KW - 4TI98Z838E KW - Cytochrome P-450 CYP1A1 KW - EC 1.14.14.1 KW - gamma-Glutamyltransferase KW - EC 2.3.2.2 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Animals KW - Cytochrome P-450 CYP1A1 -- genetics KW - gamma-Glutamyltransferase -- metabolism KW - Glutathione Transferase -- metabolism KW - Cell Division -- drug effects KW - Reverse Transcriptase Polymerase Chain Reaction KW - Cytochrome P-450 CYP1A1 -- biosynthesis KW - Diethylnitrosamine -- toxicity KW - Rats KW - Rats, Sprague-Dawley KW - RNA, Messenger -- metabolism KW - Carcinogenicity Tests KW - Drug Antagonism KW - Male KW - Estradiol -- administration & dosage KW - Carcinogens -- administration & dosage KW - Liver Neoplasms, Experimental -- pathology KW - Precancerous Conditions -- chemically induced KW - Polychlorinated Dibenzodioxins -- administration & dosage KW - Polychlorinated Dibenzodioxins -- toxicity KW - Liver Neoplasms, Experimental -- enzymology KW - Estradiol -- toxicity KW - Carcinogens -- toxicity KW - Liver Neoplasms, Experimental -- chemically induced KW - Precancerous Conditions -- pathology KW - Precancerous Conditions -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71970787?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Promotion+of+altered+hepatic+foci+by+2%2C3%2C7%2C8-tetrachlorodibenzo-p-dioxin+and+17beta-estradiol+in+male+Sprague-Dawley+rats.&rft.au=Wyde%2C+Michael+E%3BCambre%2C+Theresa%3BLebetkin%2C+Mark%3BEldridge%2C+Sandra+R%3BWalker%2C+Nigel+J&rft.aulast=Wyde&rft.aufirst=Michael&rft.date=2002-08-01&rft.volume=68&rft.issue=2&rft.spage=295&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-12-23 N1 - Date created - 2002-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Trends in reproductive, smoking, and other chronic disease risk factors by birth cohort and race in a large occupational study population. AN - 71970224; 12160594 AB - To illustrate the value of cohort studies to assess trends in chronic disease risk factors. In collaboration with the American Registry of Radiologic Technologists and the University of Minnesota, the National Cancer Institute initiated a cohort study of cancer among radiologic technologists. More than 90,000 technologists who responded to a mailed questionnaire were grouped into ten birth cohorts from before 1920 through 1960 and later, and stratified by self-reported racial/ethnic groups. Trends in height, smoking, and reproductive factors were analyzed. Among the trends observed were that the proportion of young men ( 26 years), highest rates of nulliparity at age 25 (>/= 63 %), and lowest mean parity levels (< or = 1.7) compared with earlier cohorts. Analyses of large cohorts can clarify birth cohort trends in chronic disease risk factors. JF - Annals of epidemiology AU - Freedman, D Michael AU - Tarone, Robert E AU - Doody, Michele M AU - Mohan, Aparna AU - Alexander, Bruce H AU - Boice, John D AU - Linet, Martha S AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-7238, USA. Y1 - 2002/08// PY - 2002 DA - August 2002 SP - 363 EP - 369 VL - 12 IS - 6 SN - 1047-2797, 1047-2797 KW - Index Medicus KW - Age Factors KW - Sex Factors KW - Humans KW - Aged KW - Age Distribution KW - Aged, 80 and over KW - Risk Factors KW - Adult KW - Cohort Studies KW - Surveys and Questionnaires KW - Middle Aged KW - United States -- epidemiology KW - Sex Distribution KW - Female KW - Male KW - Occupational Exposure KW - Smoking KW - Occupational Diseases -- ethnology KW - Body Height KW - Reproductive History KW - Occupational Diseases -- epidemiology KW - Radiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71970224?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Trends+in+reproductive%2C+smoking%2C+and+other+chronic+disease+risk+factors+by+birth+cohort+and+race+in+a+large+occupational+study+population.&rft.au=Freedman%2C+D+Michael%3BTarone%2C+Robert+E%3BDoody%2C+Michele+M%3BMohan%2C+Aparna%3BAlexander%2C+Bruce+H%3BBoice%2C+John+D%3BLinet%2C+Martha+S&rft.aulast=Freedman&rft.aufirst=D&rft.date=2002-08-01&rft.volume=12&rft.issue=6&rft.spage=363&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 - 2002-09-19 N1 - Date created - 2002-08-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pertussis toxin alters the innate and the adaptive immune responses in a pertussis-dependent model of autoimmunity. AN - 71965363; 12161029 AB - Pertussis toxin (PTX) is used to promote development of autoimmune diseases. The mechanism(s) are still incompletely understood. We dissected the innate and adaptive immune responses in a PTX-dependent model of autoimmune retinal disease, experimental autoimmune uveoretinitis (EAU), a Th1-driven disease of the neural retina elicited in F344 rats with a peptide derived from the retinal antigen interphotoreceptor retinoid binding protein (IRBP). Our results showed that optimal doses of PTX led to strongly increased innate cytokine responses, followed by enhanced adaptive Th1 immunity and disease. At supraoptimal doses of PTX, EAU was suppressed, the animals exhibited persistent lymphocytosis and had an inhibited chemotactic response to chemokines. We suggest that the suppressive effect of PTX at supraoptimal doses is due to inhibition of lymphocyte emigration from the blood into the target tissue, secondary to inhibition of Gi-protein-coupled chemokine receptor signaling, that persists into the effector phase of disease. JF - Journal of neuroimmunology AU - Agarwal, Rajeev K AU - Sun, Shu Hui AU - Su, Shao Bo AU - Chan, Chi-Chao AU - Caspi, Rachel R AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, 10 Center Drive, 10/10N222, Bethesda, MD 20892-1857, USA. Y1 - 2002/08// PY - 2002 DA - August 2002 SP - 133 EP - 140 VL - 129 IS - 1-2 SN - 0165-5728, 0165-5728 KW - Chemokine CCL5 KW - 0 KW - Chemokine CXCL12 KW - Chemokines KW - Chemokines, CXC KW - Cytokines KW - Eye Proteins KW - RNA, Messenger KW - Retinol-Binding Proteins KW - Virulence Factors, Bordetella KW - interstitial retinol-binding protein KW - Pertussis Toxin KW - EC 2.4.2.31 KW - Index Medicus KW - Animals KW - Retinol-Binding Proteins -- pharmacology KW - Cytokines -- genetics KW - Dose-Response Relationship, Drug KW - RNA, Messenger -- drug effects KW - Disease Models, Animal KW - Immune System -- immunology KW - Leukocyte Count KW - Rats KW - Chemokines, CXC -- pharmacology KW - Rats, Inbred F344 KW - Chemokine CCL5 -- immunology KW - Immune System -- drug effects KW - Retinol-Binding Proteins -- immunology KW - RNA, Messenger -- metabolism KW - Chemokine CCL5 -- pharmacology KW - Adaptation, Physiological -- immunology KW - Chemokines, CXC -- immunology KW - Female KW - Th1 Cells -- immunology KW - Chemotaxis, Leukocyte -- drug effects KW - Retinitis -- immunology KW - Retinitis -- physiopathology KW - Chemokines -- immunology KW - Uveitis -- physiopathology KW - Uveitis -- immunology KW - Retinitis -- chemically induced KW - Nervous System Autoimmune Disease, Experimental -- immunology KW - Virulence Factors, Bordetella -- pharmacology KW - Chemokines -- pharmacology KW - Virulence Factors, Bordetella -- immunology KW - Nervous System Autoimmune Disease, Experimental -- chemically induced KW - Th1 Cells -- drug effects KW - Chemotaxis, Leukocyte -- immunology KW - Nervous System Autoimmune Disease, Experimental -- physiopathology KW - Uveitis -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71965363?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Pertussis+toxin+alters+the+innate+and+the+adaptive+immune+responses+in+a+pertussis-dependent+model+of+autoimmunity.&rft.au=Agarwal%2C+Rajeev+K%3BSun%2C+Shu+Hui%3BSu%2C+Shao+Bo%3BChan%2C+Chi-Chao%3BCaspi%2C+Rachel+R&rft.aulast=Agarwal&rft.aufirst=Rajeev&rft.date=2002-08-01&rft.volume=129&rft.issue=1-2&rft.spage=133&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 - 2002-09-27 N1 - Date created - 2002-08-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DksA affects ppGpp induction of RpoS at a translational level. AN - 71952260; 12142416 AB - The RpoS sigma factor (also called sigmaS or sigma38) is known to regulate at least 50 genes in response to environmental sources of stress or during entry into stationary phase. Regulation of RpoS abundance and activity is complex, with many factors participating at multiple levels. One factor is the nutritional stress signal ppGpp. The absence of ppGpp blocks or delays the induction of rpoS during entry into stationary phase. Artificially inducing ppGpp, without starvation, is known to induce rpoS during the log phase 25- to 50-fold. Induction of ppGpp is found to have only minor effects on rpoS transcript abundance or on RpoS protein stability; instead, the efficiency of rpoS mRNA translation is increased by ppGpp as judged by both RpoS pulse-labeling and promoter-independent effects on lacZ fusions. DksA is found to affect RpoS abundance in a manner related to ppGpp. Deleting dksA blocks rpoS induction by ppGpp. Overproduction of DksA induces rpoS but not ppGpp. Deleting dksA neither alters regulation of ppGpp in response to amino acid starvation nor nullifies the inhibitory effects of ppGpp on stable RNA synthesis. Although this suggests that dksA is epistatic to ppGpp, inducing ppGpp does not induce DksA. A dksA deletion does display a subset of the same multiple-amino-acid requirements found for ppGpp(0) mutants, but overproducing DksA does not satisfy ppGpp(0) requirements. Sequenced spontaneous extragenic suppressors of dksA polyauxotrophy are frequently the same T563P rpoB allele that suppresses a ppGpp(0) phenotype. We propose that DksA functions downstream of ppGpp but indirectly regulates rpoS induction. JF - Journal of bacteriology AU - Brown, Larissa AU - Gentry, Daniel AU - Elliott, Thomas AU - Cashel, Michael AD - Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA. Y1 - 2002/08// PY - 2002 DA - August 2002 SP - 4455 EP - 4465 VL - 184 IS - 16 SN - 0021-9193, 0021-9193 KW - Bacterial Proteins KW - 0 KW - Escherichia coli Proteins KW - RNA, Messenger KW - Recombinant Fusion Proteins KW - Sigma Factor KW - dksA protein, E coli KW - sigma factor KatF protein, Bacteria KW - Guanosine Tetraphosphate KW - 33503-72-9 KW - Ligases KW - EC 6.- KW - guanosine 3',5'-polyphosphate synthetases KW - Index Medicus KW - Gene Expression Regulation, Bacterial KW - Ligases -- genetics KW - Escherichia coli -- genetics KW - Mutagenesis -- physiology KW - Gene Deletion KW - Lac Operon -- genetics KW - Phenotype KW - Genes, Suppressor -- physiology KW - RNA, Messenger -- metabolism KW - Recombinant Fusion Proteins -- genetics KW - Ligases -- metabolism KW - Escherichia coli -- growth & development KW - Gene Dosage KW - Guanosine Tetraphosphate -- metabolism KW - Sigma Factor -- genetics KW - Bacterial Proteins -- genetics KW - Protein Biosynthesis -- physiology KW - Guanosine Tetraphosphate -- deficiency UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71952260?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=DksA+affects+ppGpp+induction+of+RpoS+at+a+translational+level.&rft.au=Brown%2C+Larissa%3BGentry%2C+Daniel%3BElliott%2C+Thomas%3BCashel%2C+Michael&rft.aulast=Brown&rft.aufirst=Larissa&rft.date=2002-08-01&rft.volume=184&rft.issue=16&rft.spage=4455&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 - 2002-08-14 N1 - Date created - 2002-07-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Microbiol. 1999 Oct;34(1):112-23 [10540290] Mol Microbiol. 1994 Jul;13(2):301-12 [7984109] J Biol Chem. 2000 May 19;275(20):14795-8 [10747855] Proc Natl Acad Sci U S A. 2000 May 23;97(11):5978-83 [10811905] Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6640-5 [10829079] Mol Microbiol. 2000 Jul;37(2):371-81 [10931332] Proc Natl Acad Sci U S A. 2000 Aug 29;97(18):9919-24 [10954740] Mol Microbiol. 2000 Nov;38(4):667-72 [11115103] J Bacteriol. 2001 Mar;183(6):1997-2005 [11222598] Mol Microbiol. 2001 Feb;39(4):1069-79 [11251825] Mol Microbiol. 2001 Mar;39(5):1382-94 [11251852] J Bacteriol. 2001 Jul;183(13):4012-23 [11395466] J Bacteriol. 1974 Sep;119(3):736-47 [4604283] Cell. 1981 Jun;24(3):707-17 [6788377] J Bacteriol. 1985 Aug;163(2):534-42 [3894329] Gene. 1988 Dec 20;73(2):337-45 [2977357] EMBO J. 1989 Dec 1;8(12):3923-31 [2684651] J Bacteriol. 1995 Jun;177(12):3455-64 [7768855] J Bacteriol. 1995 Jul;177(14):4121-30 [7608087] J Bacteriol. 1995 Aug;177(16):4676-80 [7642494] J Mol Biol. 1995 Oct 6;252(5):536-49 [7563072] J Bacteriol. 1996 Jan;178(2):470-6 [8550468] J Bacteriol. 1996 Feb;178(4):1154-61 [8576052] Genes Dev. 1996 May 1;10(9):1143-51 [8654929] J Bacteriol. 1996 Jul;178(13):3763-70 [8682778] Mol Microbiol. 1996 Mar;19(6):1373-84 [8730877] Mol Microbiol. 1996 Sep;21(5):887-93 [8885260] J Bacteriol. 1997 Feb;179(3):656-62 [9006017] Mol Microbiol. 1997 May;24(3):643-51 [9179856] J Bacteriol. 1998 Feb;180(4):846-54 [9473038] J Bacteriol. 1998 Mar;180(5):1154-8 [9495753] J Bacteriol. 1998 Sep;180(17):4564-70 [9721296] Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12462-7 [9770508] EMBO J. 1998 Oct 15;17(20):6061-8 [9774349] Mol Microbiol. 1998 Aug;29(4):1039-51 [9767572] Can J Microbiol. 1998 Aug;44(8):707-17 [9830102] Proc Natl Acad Sci U S A. 1999 May 25;96(11):6439-44 [10339606] Nucleic Acids Res. 1989 Dec 11;17(23):9979-91 [2690013] Genes Dev. 1989 Sep;3(9):1462-71 [2691330] J Bacteriol. 1990 Apr;172(4):2055-64 [2180916] J Biol Chem. 1991 Mar 25;266(9):5980-90 [2005134] Mol Microbiol. 1991 Jan;5(1):49-59 [1849609] J Bacteriol. 1991 Jun;173(12):3901-3 [1711031] J Bacteriol. 1992 Jan;174(1):245-53 [1309519] Mol Microbiol. 1992 Nov;6(21):3187-98 [1453957] J Biol Chem. 1993 Feb 5;268(4):2307-11 [8428905] J Bacteriol. 1993 Jun;175(11):3401-7 [8501045] J Bacteriol. 1993 Aug;175(15):4744-55 [8393005] Biochemistry. 1993 Oct 19;32(41):11112-7 [8218173] J Bacteriol. 1993 Dec;175(24):7982-9 [8253685] Mol Gen Genet. 1994 Jun 3;243(5):525-31 [8208244] Genes Dev. 1994 Jul 1;8(13):1600-12 [7525405] Mol Microbiol. 2000 Feb;35(3):657-66 [10672187] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Substance abuse vulnerability loci: converging genome scanning data. AN - 71947759; 12142011 AB - Classical genetic studies suggest strong complex genetic contributions to a predisposition to abuse multiple addictive substances. Until recently, there were no reproducible genome scanning data identifying chromosomal positions likely to contain allelic variants that predispose the carrier to illegal substance addiction. Nominal results of linkage-based genome scanning studies for ethanol and nicotine addictions failed to display much agreement. Our recent data from association-based genome scans for illegal addictions, and reanalyses of previous results now provide a substantial body of converging results. The 15 reproducible chromosomal loci identified here are good candidates to harbor allelic variants that alter human substance abuse vulnerabilities. We discuss several approaches to identifying the specific gene variants that underlie these convergent association and linkage observations, and the impact that these convergent observations should have on understanding important human addictive disorders. JF - Trends in genetics : TIG AU - Uhl, George R AU - Liu, Qing-Rong AU - Naiman, Daniel AD - Molecular Neurobiology Branch, NIDA-IRP, NIH, Box 5180, Baltimore, MD 21224, USA. guhl@intra.nida.nih.gov Y1 - 2002/08// PY - 2002 DA - August 2002 SP - 420 EP - 425 VL - 18 IS - 8 SN - 0168-9525, 0168-9525 KW - Index Medicus KW - Genetic Linkage KW - Lod Score KW - Humans KW - Monte Carlo Method KW - Chromosome Mapping KW - Genome, Human KW - Genetic Predisposition to Disease KW - Substance-Related Disorders -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71947759?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+genetics+%3A+TIG&rft.atitle=Substance+abuse+vulnerability+loci%3A+converging+genome+scanning+data.&rft.au=Uhl%2C+George+R%3BLiu%2C+Qing-Rong%3BNaiman%2C+Daniel&rft.aulast=Uhl&rft.aufirst=George&rft.date=2002-08-01&rft.volume=18&rft.issue=8&rft.spage=420&rft.isbn=&rft.btitle=&rft.title=Trends+in+genetics+%3A+TIG&rft.issn=01689525&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-09-16 N1 - Date created - 2002-07-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Development and application of fully functional epitope-tagged forms of transforming growth factor-beta. AN - 71934053; 12133618 AB - Administration of transforming growth factor-beta (TGF-beta) has been found to be of therapeutic benefit in various mouse disease models and has potential clinical usefulness. However, the ability to track the distribution of exogenously administered, recombinant forms of these proteins has been restricted by cross-reactivity with endogenous TGF-beta and related TGF-beta isoforms. We describe novel FLAG- and hemagglutinin (HA)-tagged versions of mature TGF-beta1 that retain full biological activity as demonstrated by their ability to inhibit the growth of Mv1Lu epithelial cells, and to induce phosphorylation of the TGF-beta signaling intermediate, smad 2. Intracellular FLAG- and HA-TGF-beta1 can be detected in transfected cells by confocal immunofluorescence microscopy. We also describe sandwich ELISAs designed to specifically detect epitope-tagged TGF-beta and demonstrate the utility of these tagged ligands as probes for TGF-beta receptor expression by flow cytometry. The design of these fully functional epitope-tagged TGF-beta proteins should facilitate studies such as the evaluation of in vivo peptide pharmacodynamics and trafficking of TGF-beta ligand-receptor complexes. JF - Journal of immunological methods AU - Wolfraim, Lawrence A AU - Alkemade, Gonnie M AU - Alex, Biju AU - Sharpe, Shellyann AU - Parks, W Tony AU - Letterio, John J AD - Laboratory of Cell Regulation and Carcinogenesis, The National Cancer Institute, National Institutes of Health, Room C629, Building 41, 41 Library Drive, MSC 5055, Bethesda, MD 20892-5055, USA. Y1 - 2002/08/01/ PY - 2002 DA - 2002 Aug 01 SP - 7 EP - 18 VL - 266 IS - 1-2 SN - 0022-1759, 0022-1759 KW - Epitopes KW - 0 KW - Hemagglutinins KW - N-FLAG-TGF-beta1 KW - Oligopeptides KW - Peptides KW - Receptors, Cytoplasmic and Nuclear KW - Receptors, Transforming Growth Factor beta KW - Recombinant Fusion Proteins KW - Recombinant Proteins KW - Tgfb1 protein, mouse KW - Transforming Growth Factor beta KW - Transforming Growth Factor beta1 KW - FLAG peptide KW - 98849-88-8 KW - Index Medicus KW - Receptors, Transforming Growth Factor beta -- analysis KW - Recombinant Fusion Proteins -- analysis KW - Animals KW - COS Cells KW - Peptides -- immunology KW - Amino Acid Sequence KW - Recombinant Fusion Proteins -- chemistry KW - Flow Cytometry -- methods KW - Enzyme-Linked Immunosorbent Assay -- methods KW - Epitopes -- analysis KW - Base Sequence KW - Transfection KW - Molecular Sequence Data KW - Recombinant Fusion Proteins -- pharmacology KW - Receptors, Cytoplasmic and Nuclear -- analysis KW - Microscopy, Fluorescence -- methods KW - Peptides -- genetics KW - Hemagglutinins -- genetics KW - Microscopy, Confocal -- methods KW - Cell Line KW - Hemagglutinins -- immunology KW - Transforming Growth Factor beta -- analysis KW - Transforming Growth Factor beta -- pharmacology KW - Transforming Growth Factor beta -- physiology KW - Transforming Growth Factor beta -- chemistry KW - Transforming Growth Factor beta -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71934053?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunological+methods&rft.atitle=Development+and+application+of+fully+functional+epitope-tagged+forms+of+transforming+growth+factor-beta.&rft.au=Wolfraim%2C+Lawrence+A%3BAlkemade%2C+Gonnie+M%3BAlex%2C+Biju%3BSharpe%2C+Shellyann%3BParks%2C+W+Tony%3BLetterio%2C+John+J&rft.aulast=Wolfraim&rft.aufirst=Lawrence&rft.date=2002-08-01&rft.volume=266&rft.issue=1-2&rft.spage=7&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 completed - 2002-09-25 N1 - Date created - 2002-07-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanistic perspectives on sulfonamide-induced cutaneous drug reactions. AN - 71930948; 12130945 AB - Idiosyncratic drug reactions continue to limit the therapeutic utility of sulfonamide drugs because of their associated morbidity and mortality. Cutaneous reactions are the predominant reasons for withdrawal of such drugs from use in patients. As a consequence of the recognized metabolic and immunologic capability of the skin, an understanding of the pathogenic role of this tissue in the development of sulfonamide-induced cutaneous drug reactions may provide insight into the mechanisms and risk factors for these and other adverse drug events. In the present review we discuss currently available mechanistic information, including issues related to drug bioactivation and adduct formation, immunoresponsiveness, and immune dysregulation, for the development of sulfonamide-induced (delayed-type) cutaneous drug reactions. The potential application of findings from several related areas of research are also discussed within the context of the pathogenesis of these cutaneous reactions. Despite progress, numerous unresolved issues support the testing of novel hypotheses, the search for additional risk factors, and the need for a global approach, including links between laboratory and clinical paradigms. These issues must be addressed if we are to gain an understanding of the mechanistic bases for these cutaneous drug reactions. JF - Current opinion in allergy and clinical immunology AU - Reilly, Timothy P AU - Ju, Cynthia AD - Molecular and Cellular Toxicology Section, Laboratory of Molecular Immunology, NHLBI/NIH, 9000 Rockville Pike, Building 10, Room 8N110, Bethesda, MD 20892-2760, USA. ReillyT@nhlbi.nih.gov Y1 - 2002/08// PY - 2002 DA - August 2002 SP - 307 EP - 315 VL - 2 IS - 4 SN - 1528-4050, 1528-4050 KW - Anti-Infective Agents KW - 0 KW - Sulfonamides KW - Index Medicus KW - Humans KW - Sulfonamides -- adverse effects KW - Drug Eruptions -- etiology KW - Anti-Infective Agents -- immunology KW - Anti-Infective Agents -- adverse effects KW - Sulfonamides -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71930948?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+allergy+and+clinical+immunology&rft.atitle=Mechanistic+perspectives+on+sulfonamide-induced+cutaneous+drug+reactions.&rft.au=Reilly%2C+Timothy+P%3BJu%2C+Cynthia&rft.aulast=Reilly&rft.aufirst=Timothy&rft.date=2002-08-01&rft.volume=2&rft.issue=4&rft.spage=307&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+allergy+and+clinical+immunology&rft.issn=15284050&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-10-18 N1 - Date created - 2002-07-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytochrome P450 2E1 (CYP2E1) is essential for acrylonitrile metabolism to cyanide: comparative studies using CYP2E1-null and wild-type mice. AN - 71925465; 12124309 AB - Acrylonitrile (AN) is a rodent carcinogen and suspected human carcinogen. Metabolism of AN proceeds via conjugation with glutathione or epoxidation via cytochrome P4502E1 (CYP2E1) to cyanoethylene oxide (CEO). It was hypothesized that CEO metabolism via epoxide hydrolase (EH) is the primary pathway for cyanide formation. The objective of this work is to assess the enzymatic basis of metabolism to cyanide. Male wild-type and CYP2E1-null mice received 0, 2.5, 10, 20, or 40 mg of AN/kg by gavage, and cyanide was measured in blood and tissues. CYP2E1 and EH expression were assessed using Western blot analyses. Present results demonstrated that cyanide concentrations in blood and tissues of AN-treated wild-type mice were higher at 1 versus 3 h, increased in a dose-dependent manner, and were significantly higher in AN-treated versus vehicle-treated mice. In contrast, cyanide concentrations in the blood and tissues of AN-treated CYP2E1-null mice were not statistically different from those of vehicle-treated mice. Furthermore, this work showed that EH is expressed in CYP2E1-null and wild-type mice. In conclusion, under the current experimental conditions using CYP2E1-null mice, current work demonstrated for the first time that CYP2E1-mediated oxidation is a prerequisite for AN metabolism to cyanide. Since earlier studies showed that CYP2E1 is the only enzyme responsible for AN epoxidation, it is concluded that AN metabolism to CEO is a prerequisite for cyanide formation, and this pathway is exclusively catalyzed by CYP2E1. Finally, this work confirmed that cyanide plays an essential role in the causation of the acute toxicity/mortality of AN. JF - Drug metabolism and disposition: the biological fate of chemicals AU - Wang, Hongbing AU - Chanas, Brian AU - Ghanayem, Burhan I AD - Laboratory of Pharmacology and Chemistry, Environmental Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2002/08// PY - 2002 DA - August 2002 SP - 911 EP - 917 VL - 30 IS - 8 SN - 0090-9556, 0090-9556 KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - Epoxide Hydrolases KW - EC 3.3.2.- KW - Acrylonitrile KW - MP1U0D42PE KW - Index Medicus KW - Animals KW - Epoxide Hydrolases -- metabolism KW - Liver -- enzymology KW - Dose-Response Relationship, Drug KW - Kidney -- drug effects KW - Kidney -- enzymology KW - Microsomes -- enzymology KW - Mice KW - Tissue Distribution KW - Mice, Mutant Strains KW - Toxicity Tests, Acute KW - Lung -- drug effects KW - Lung -- enzymology KW - Species Specificity KW - Male KW - Microsomes -- drug effects KW - Acrylonitrile -- pharmacology KW - Cytochrome P-450 CYP2E1 -- metabolism KW - Acrylonitrile -- metabolism KW - Cytochrome P-450 CYP2E1 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71925465?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cytochrome+P450+2E1+%28CYP2E1%29+is+essential+for+acrylonitrile+metabolism+to+cyanide%3A+comparative+studies+using+CYP2E1-null+and+wild-type+mice.&rft.au=Wang%2C+Hongbing%3BChanas%2C+Brian%3BGhanayem%2C+Burhan+I&rft.aulast=Wang&rft.aufirst=Hongbing&rft.date=2002-08-01&rft.volume=30&rft.issue=8&rft.spage=911&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 - 2003-01-27 N1 - Date created - 2002-07-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Safety, pharmacokinetics, and pharmacodynamics of cyclodextrin itraconazole in pediatric patients with oropharyngeal candidiasis. AN - 71921035; 12121932 AB - The safety, pharmacokinetics, and pharmacodynamics of cyclodextrin itraconazole (CD-ITRA) oral suspension were investigated in an open sequential dose escalation study with 26 human immunodeficiency virus (HIV)-infected children and adolescents (5 to 18 years old; mean CD4(+)-cell count, 128/microl) with oropharyngeal candidiasis (OPC). Patients received CD-ITRA at either 2.5 mg/kg of body weight once a day (QD) or 2.5 mg/kg twice a day (BID) for a total of 15 days. Pharmacokinetic sampling was performed after the first dose and for up to 120 h after the last dose, and antifungal efficacy was evaluated by standardized scoring of the oropharynx. Apart from mild to moderate gastrointestinal disturbances in three patients (11.5%), CD-ITRA was well tolerated. Two patients (7.6%) discontinued treatment prematurely due to study drug-related adverse events. After 15 days of treatment, the peak concentration of drug in plasma (C(max)), the area under the plasma concentration-time curve (AUC) from 0 to 24 h (AUC(0-24)), the concentration in plasma at the end of the dosing interval (predose) (C(min)), and the terminal half-life of itraconazole (ITRA) were (means and standard deviations) 0.604 +/- 0.53 microg/ml, 6.80 +/- 7.4 microg. h/ml, 0.192 +/- 0.06 microg/ml, and 56.48 +/- 44 h, respectively, for the QD regimen and 1.340 +/- 0.75 microg/ml, 23.04 +/- 14.5 microg. h/ml, 0.782 +/- 0.19 microg/ml, and 104.22 +/- 94 h, respectively, for the BID regimen. The mean AUC-based accumulation factors for ITRA on day 15 were 4.14 +/- 0.9 and 3.53 +/- 0.6, respectively. A comparison of the dose-normalized median AUC of the two dosage regimens revealed a trend toward nonlinear drug disposition (P = 0.05). The mean metabolic ratios (AUC of hydroxyitraconazole/AUC of ITRA) at day 15 were 1.96 +/- 0.1 for the QD regimen and 1.29 +/- 0.2 for the BID regimen, respectively (P or =5 years old. JF - Antimicrobial agents and chemotherapy AU - Groll, Andreas H AU - Wood, Lauren AU - Roden, Maureen AU - Mickiene, Diana AU - Chiou, Christine C AU - Townley, Ellen AU - Dad, Luqman AU - Piscitelli, Stephen C AU - Walsh, Thomas J AD - Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute/NIH, Building 10, 10 Center Drive, Bethesda, MD 20892, USA. Y1 - 2002/08// PY - 2002 DA - August 2002 SP - 2554 EP - 2563 VL - 46 IS - 8 SN - 0066-4804, 0066-4804 KW - Antifungal Agents KW - 0 KW - Cyclodextrins KW - HIV Protease Inhibitors KW - cyclodextrin itraconazole KW - Itraconazole KW - 304NUG5GF4 KW - Index Medicus KW - Area Under Curve KW - Humans KW - Cyclodextrins -- adverse effects KW - Child KW - HIV Protease Inhibitors -- therapeutic use KW - CD4 Lymphocyte Count KW - Chromatography, High Pressure Liquid KW - Child, Preschool KW - Itraconazole -- pharmacokinetics KW - Itraconazole -- therapeutic use KW - Half-Life KW - Itraconazole -- adverse effects KW - Adolescent KW - Microbial Sensitivity Tests KW - Cyclodextrins -- pharmacokinetics KW - Cyclodextrins -- therapeutic use KW - Male KW - Female KW - Candida albicans -- drug effects KW - Antifungal Agents -- pharmacokinetics KW - Antifungal Agents -- adverse effects KW - HIV Infections -- complications KW - Candidiasis, Oral -- drug therapy KW - Pharyngeal Diseases -- drug therapy KW - Candidiasis, Oral -- microbiology KW - Pharyngeal Diseases -- microbiology KW - Antifungal Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71921035?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+agents+and+chemotherapy&rft.atitle=Safety%2C+pharmacokinetics%2C+and+pharmacodynamics+of+cyclodextrin+itraconazole+in+pediatric+patients+with+oropharyngeal+candidiasis.&rft.au=Groll%2C+Andreas+H%3BWood%2C+Lauren%3BRoden%2C+Maureen%3BMickiene%2C+Diana%3BChiou%2C+Christine+C%3BTownley%2C+Ellen%3BDad%2C+Luqman%3BPiscitelli%2C+Stephen+C%3BWalsh%2C+Thomas+J&rft.aulast=Groll&rft.aufirst=Andreas&rft.date=2002-08-01&rft.volume=46&rft.issue=8&rft.spage=2554&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 - 2003-01-13 N1 - Date created - 2002-07-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: AIDS Res Hum Retroviruses. 1999 Nov 1;15(16):1413-7 [10555103] Pharmacotherapy. 1999 May;19(5):603-11 [10331823] Mycoses. 1999;42(11-12):591-600 [10680434] Clin Pharmacokinet. 2000 Feb;38(2):111-80 [10709776] Med Mycol. 2000;38 Suppl 1:335-47 [11204162] Drugs. 2001;61 Suppl 1:27-37 [11219548] Lancet. 2001 Mar 3;357(9257):719 [11247583] Antimicrob Agents Chemother. 2001 May;45(5):1561-4 [11302829] Pharmacotherapy. 2001 Aug;21(8 Pt 2):133S-148S [11501987] Pediatr Clin North Am. 1989 Oct;36(5):1053-74 [2677935] J Antimicrob Chemother. 1990 Oct;26(4):561-6 [2174854] J Pediatr. 1992 Jun;120(6):987-93 [1593362] J Antimicrob Chemother. 1994 May;33(5):1071-3 [8089062] J Antimicrob Chemother. 1994 Aug;34(2):247-52 [7814285] Antimicrob Agents Chemother. 1995 Mar;39(3):757-9 [7793887] J Antimicrob Chemother. 1995 Oct;36(4):657-63 [8591940] Mycoses. 1996;39 Suppl 1:102-6 [8767280] Pharmacotherapy. 1996 May-Jun;16(3):424-8 [8726601] AIDS. 1996 Oct;10(12):1369-76 [8902066] Clin Infect Dis. 1996 Oct;23(4):685-93 [8909827] Clin Infect Dis. 1997 Feb;24(2):235-47 [9114154] J Clin Pathol. 1997 Jun;50(6):477-80 [9378812] Antimicrob Agents Chemother. 1998 Feb;42(2):404-8 [9527794] Am J Health Syst Pharm. 1998 Feb 1;55(3):279-83 [9492260] Am J Med. 1998 Jan;104(1):33-9 [9528717] J Pharm Biomed Anal. 1998 Feb;16(6):1005-12 [9547703] Adv Pharmacol. 1998;44:343-500 [9547888] Clin Infect Dis. 1998 Jun;26(6):1368-73 [9636865] Antimicrob Agents Chemother. 1998 Jul;42(7):1862-5 [9661037] Pharmacotherapy. 1999 Jan;19(1):76-87 [9917080] Med Mycol. 1998;36 Suppl 1:119-28 [9988500] Eur J Pediatr. 1999 Mar;158(3):187-99 [10094436] Bone Marrow Transplant. 1999 Nov;24(10):1089-93 [10578159] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Resistance of MCF-7 cells to dimethylbenz(a)anthracene-induced apoptosis is due to reduced CYP1A1 expression. AN - 71902798; 12118336 AB - We have developed a series of aryl hydrocarbon (AH)-resistant cell lines derived from MCF-7 human breast epithelial cancer cells by continuous exposure to the AH benzo[a]pyrene. These cell lines display cross-resistance to the mammary carcinogen dimethylbenz[a]anthracene (DMBA). Apoptosis induced by exposure to DMBA is greatly decreased in the resistant cell lines compared to the wild-type, in proportion to the level of resistance. Apoptosis induced by DMBA could be blocked by inhibitors of DMBA metabolism such as alpha-naphthoflavone and diosmetin. We therefore examined the resistant cell lines for their ability to metabolize DMBA and for the formation of DMBA-DNA adducts, and found that both parameters were decreased compared to wild-type cells in proportion to the level of resistance. When exposed to DMBA or 2,3,7,8-tetrachlorodibenzo-p-dioxin, the resistant cell lines have a diminished capacity to carry out ethoxyresorufin-O-deethylation, indicating that the induction of cytochrome P450 1A1 (CYP1A1) enzyme is impaired. We therefore examined the expression of the CYP1A1 gene, and found reduced levels of both CYP1A1 mRNA and CYP1A1-promoter controlled transcription in resistant cells compared to the wild-type. The deleterious effects of AHs are believed to be mediated by the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor which regulates CYP1A1 expression. Resistant cell lines had a reduced expression of the AhR, as measured at the mRNA and protein levels. These data demonstrate that AH resistance in these cells is mediated by changes in the signal transduction pathway which regulates CYP1A1 expression. JF - International journal of oncology AU - Ciolino, Henry P AU - Dankwah, Maame AU - Yeh, Grace Chao AD - Cellular Defense and Carcinogenesis Section, Basic Research Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, Frederick, MD 21702-1201, USA. Y1 - 2002/08// PY - 2002 DA - August 2002 SP - 385 EP - 391 VL - 21 IS - 2 SN - 1019-6439, 1019-6439 KW - 7,12-dimethylbenz(a)anthracene-DNA adduct KW - 0 KW - Carcinogens KW - DNA Adducts KW - DNA, Neoplasm KW - Polychlorinated Dibenzodioxins KW - RNA, Messenger KW - Teratogens KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Cytochrome P-450 CYP1A1 KW - EC 1.14.14.1 KW - Index Medicus KW - Blotting, Western KW - RNA, Messenger -- metabolism KW - Down-Regulation KW - Transfection KW - Humans KW - Polychlorinated Dibenzodioxins -- pharmacology KW - Cell Division -- drug effects KW - Teratogens -- pharmacology KW - Reverse Transcriptase Polymerase Chain Reaction KW - DNA, Neoplasm -- metabolism KW - DNA Adducts -- metabolism KW - Carcinogens -- pharmacology KW - Cytochrome P-450 CYP1A1 -- genetics KW - 9,10-Dimethyl-1,2-benzanthracene -- analogs & derivatives KW - 9,10-Dimethyl-1,2-benzanthracene -- pharmacology KW - Tumor Cells, Cultured -- drug effects KW - Apoptosis -- drug effects KW - Cytochrome P-450 CYP1A1 -- metabolism KW - Drug Resistance, Neoplasm KW - 9,10-Dimethyl-1,2-benzanthracene -- metabolism KW - Tumor Cells, Cultured -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71902798?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+oncology&rft.atitle=Resistance+of+MCF-7+cells+to+dimethylbenz%28a%29anthracene-induced+apoptosis+is+due+to+reduced+CYP1A1+expression.&rft.au=Ciolino%2C+Henry+P%3BDankwah%2C+Maame%3BYeh%2C+Grace+Chao&rft.aulast=Ciolino&rft.aufirst=Henry&rft.date=2002-08-01&rft.volume=21&rft.issue=2&rft.spage=385&rft.isbn=&rft.btitle=&rft.title=International+journal+of+oncology&rft.issn=10196439&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-01-27 N1 - Date created - 2002-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Altered apoptotic gene expression and acquired apoptotic resistance in cadmium-transformed human prostate epithelial cells. AN - 71893477; 12111698 AB - Cadmium is a suspected prostatic carcinogen, although the underlying mechanisms are unclear. To investigate these mechanisms, we performed molecular comparisons between the cadmium-transformed prostate epithelial cell line CTPE and the nontumorigenic parental line RWPE-1. Gene expression patterns were compared by using cDNA arrays, RNase protection assays, and Western blots. Apoptosis was analyzed by using flow cytometry to quantify apoptotic nuclei and an enzyme-linked immunosorbent assay method to measure DNA fragmentation. Caspase-3 activity was measured colorimetrically. Among the genes down-regulated in CTPE cells were those encoding several members of the caspase family of apoptotic proteases as well as the apoptotic regulator Bax. Ribonuclease protection assays confirmed global down-regulation of caspase gene expression in CTPE. Decreased Bax expression in CTPE was confirmed by Western blots, which also revealed increased expression of anti-apoptotic Bcl-2. Consistent with these changes, CTPE cells exhibited increased resistance to apoptosis induced by cadmium, cisplatin, and etoposide. CTPE cells also exhibited lower caspase-3 activity vs. RWPE-1 after etoposide treatment. CTPE cells exhibited altered expression of important apoptotic regulators as well as resistance to several apoptotic stimuli. We hypothesize that acquired apoptotic resistance may be a key aspect of cadmium-induced malignant transformation of prostate epithelial cells and that this may contribute to both tumor initiation and the acquisition of aggressive characteristics subsequent to tumor formation. Copyright 2002 Wiley-Liss, Inc. JF - The Prostate AU - Achanzar, William E AU - Webber, Mukta M AU - Waalkes, Michael P AD - Inorganic Carcinogenesis Section, National Cancer Institute at National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2002/08/01/ PY - 2002 DA - 2002 Aug 01 SP - 236 EP - 244 VL - 52 IS - 3 SN - 0270-4137, 0270-4137 KW - Cadmium KW - 00BH33GNGH KW - Etoposide KW - 6PLQ3CP4P3 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Etoposide -- poisoning KW - Epithelial Cells -- physiology KW - Epithelial Cells -- drug effects KW - Humans KW - Drug Resistance KW - Cisplatin -- poisoning KW - Cell Line, Transformed KW - Male KW - Cell Line KW - Prostate -- physiology KW - Prostate -- drug effects KW - Cadmium -- pharmacology KW - Apoptosis -- genetics KW - Gene Expression KW - Prostate -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71893477?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Prostate&rft.atitle=Altered+apoptotic+gene+expression+and+acquired+apoptotic+resistance+in+cadmium-transformed+human+prostate+epithelial+cells.&rft.au=Achanzar%2C+William+E%3BWebber%2C+Mukta+M%3BWaalkes%2C+Michael+P&rft.aulast=Achanzar&rft.aufirst=William&rft.date=2002-08-01&rft.volume=52&rft.issue=3&rft.spage=236&rft.isbn=&rft.btitle=&rft.title=The+Prostate&rft.issn=02704137&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-08-14 N1 - Date created - 2002-07-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hormones and prostate cancer: current perspectives and future directions. AN - 71893432; 12111697 AB - Prostate cancer is the most commonly diagnosed non-skin cancer in men in most western countries. Despite the high morbidity and mortality from prostate cancer, its etiology remains obscure. Although compelling laboratory data suggest a role for androgens in prostate carcinogenesis, most epidemiologic data on humans are inconclusive. To provide insights and directions for future epidemiologic research on hormones and prostate cancer, this review focuses on current perspectives of serum-based studies and polymorphisms in relevant hormone-related genes. We highlight the importance of methodologic studies and investigations of hormone levels in the prostatic tissue to help clarify the often-contradictory data on serologic studies. We recommend careful analysis and cautious interpretation of studies of genetic markers, including repeats and single nucleotide polymorphisms (SNPs), as false positive and negative results may arise in many current and future studies with limited statistical power and non-representative samples from the population. The review also highlights the reasons to perform functional analyses of SNPs, a critical and often under-appreciated component of molecular epidemiologic investigations. The time is ripe for large-scale multidisciplinary investigations that incorporate molecular genetics, biochemistry, histopathology, and endocrinology into traditional epidemiologic studies. Such collaboration will lead to a deeper understanding of the etiologic pathways of prostate cancer, ultimately yielding better preventive, diagnostic, and therapeutic strategies. JF - The Prostate AU - Hsing, Ann W AU - Reichardt, Juergen K V AU - Stanczyk, Frank Z AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20852-7234, USA. hsinga@exchange.nih.gov Y1 - 2002/08/01/ PY - 2002 DA - 2002 Aug 01 SP - 213 EP - 235 VL - 52 IS - 3 SN - 0270-4137, 0270-4137 KW - Androgens KW - 0 KW - Hormones KW - Index Medicus KW - Polymorphism, Genetic KW - Humans KW - Genetic Predisposition to Disease KW - Male KW - Androgens -- metabolism KW - Endocrinology -- trends KW - Prostatic Neoplasms -- metabolism KW - Prostatic Neoplasms -- genetics KW - Hormones -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71893432?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Prostate&rft.atitle=Hormones+and+prostate+cancer%3A+current+perspectives+and+future+directions.&rft.au=Hsing%2C+Ann+W%3BReichardt%2C+Juergen+K+V%3BStanczyk%2C+Frank+Z&rft.aulast=Hsing&rft.aufirst=Ann&rft.date=2002-08-01&rft.volume=52&rft.issue=3&rft.spage=213&rft.isbn=&rft.btitle=&rft.title=The+Prostate&rft.issn=02704137&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-08-14 N1 - Date created - 2002-07-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HRAS1 variable number of tandem repeats polymorphism and risk of bladder cancer. AN - 71892479; 12115522 AB - The HRAS1 variable number of tandem repeats (VNTR) polymorphism, 1 kb downstream from the HRAS1 gene, has been reported to be associated with risk of various cancers. To examine whether individuals with rare HRAS1 VNTR alleles are at increased risk of bladder cancer we carried out a case control study with 230 bladder cancer cases and 203 hospital-based controls frequency-matched on ethnicity, gender and age. For genotyping we used a PCR-based long-gel electrophoretic assay that provides precise allele size discrimination. We did not find evidence of a strong overall effect of the HRAS1 VNTR on bladder cancer risk. Genotype data for whites and blacks were analyzed separately, but the number of black subjects was too small to estimate meaningful odds ratios. Compared to white subjects with 2 common alleles, the odds ratio (OR) for white subjects with 1 rare allele was 0.9 (95% confidence interval (CI) = 0.5-1.4) and for those with 2 rare alleles OR = 1.7 (95% CI = 0.6-5.4). HRAS1 genotype may be related to the prognosis of bladder cancer, however, because incident cases, i.e., newly diagnosed cases had a higher frequency of rare alleles than did prevalent cases, i.e., cases already existing at the time of recruitment. Repeating the analyses with incident cases only (n = 53), the OR for subjects with 1 rare allele was 1.2 (95% CI = 0.6-2.4) and for those with 2 rare alleles 3.2 (95% CI = 0.8-13.7). The number of incident cases was too small to draw firm conclusions on a possible association with a subgroup of tumors with a poor prognosis. Published 2002 Wiley-Liss, Inc. JF - International journal of cancer AU - van Gils, Carla H AU - Conway, Kathleen AU - Li, Yu AU - Taylor, Jack A AD - Molecular and Genetic Epidemiology Section, Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 2002/08/01/ PY - 2002 DA - 2002 Aug 01 SP - 414 EP - 418 VL - 100 IS - 4 SN - 0020-7136, 0020-7136 KW - Biomarkers, Tumor KW - 0 KW - Index Medicus KW - Genotype KW - Risk Factors KW - Humans KW - Prognosis KW - Aged KW - Middle Aged KW - Male KW - Female KW - Biomarkers, Tumor -- genetics KW - Polymorphism, Genetic KW - Urinary Bladder Neoplasms -- genetics KW - Minisatellite Repeats -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71892479?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=HRAS1+variable+number+of+tandem+repeats+polymorphism+and+risk+of+bladder+cancer.&rft.au=van+Gils%2C+Carla+H%3BConway%2C+Kathleen%3BLi%2C+Yu%3BTaylor%2C+Jack+A&rft.aulast=van+Gils&rft.aufirst=Carla&rft.date=2002-08-01&rft.volume=100&rft.issue=4&rft.spage=414&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 - 2002-07-19 N1 - Date created - 2002-07-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanism of idiosyncratic drug reactions: reactive metabolite formation, protein binding and the regulation of the immune system. AN - 71879241; 12093356 AB - Drug-induced adverse reactions, especially type B reactions, represent a major clinical problem. They also impart a significant degree of uncertainty into drug development because they are often not detected until the drug has been released onto the market. Type B reactions are also termed idiosyncratic drug reactions by many investigators due to their unpredictable nature and our lack of understanding of the mechanisms involved. It is currently believed that the majority of these reactions are immune-mediated and are caused by immunogenic conjugates formed from the reaction of a reactive metabolite of a drug with cellular proteins. It has been shown that most drugs associated with idiosyncratic reactions form reactive metabolites to some degree. Covalent binding of reactive metabolites to cellular proteins has also been shown in many cases. However, studies to reveal the role of reactive metabolites and their protein-adducts in the mechanism of drug-induced idiosyncratic reactions are lacking. This review will focus on our current understanding and speculative views on how a reactive metabolite of a drug might ultimately lead to immune-mediated toxicity. JF - Current drug metabolism AU - Ju, C AU - Uetrecht, J P AD - Molecular and Cellular Toxicology Section, Laboratory of Molecular Immunology, NHLBI, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA. JuC@NHLBI.NIH.GOV Y1 - 2002/08// PY - 2002 DA - August 2002 SP - 367 EP - 377 VL - 3 IS - 4 SN - 1389-2002, 1389-2002 KW - Pharmaceutical Preparations KW - 0 KW - Index Medicus KW - Inactivation, Metabolic KW - Humans KW - Cell Communication KW - Protein Binding KW - Immune Tolerance KW - Pharmaceutical Preparations -- metabolism KW - Immune System -- drug effects KW - Drug Hypersensitivity -- immunology KW - Drug-Related Side Effects and Adverse Reactions KW - Immune System -- immunology KW - Drug Hypersensitivity -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71879241?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+drug+metabolism&rft.atitle=Mechanism+of+idiosyncratic+drug+reactions%3A+reactive+metabolite+formation%2C+protein+binding+and+the+regulation+of+the+immune+system.&rft.au=Ju%2C+C%3BUetrecht%2C+J+P&rft.aulast=Ju&rft.aufirst=C&rft.date=2002-08-01&rft.volume=3&rft.issue=4&rft.spage=367&rft.isbn=&rft.btitle=&rft.title=Current+drug+metabolism&rft.issn=13892002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-01-30 N1 - Date created - 2002-07-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Study of diverse mechanisms of cell-mediated cytotoxicity in gene-targeted mice using flow cytometric cytotoxicity assay. AN - 71800366; 12057855 AB - Cytotoxic lymphocytes kill tumor or virus-infected target cells utilizing two mechanisms-(1) release of lytic granules (containing perforin and granzymes), and (2) Fas ligand (FasL)/Fas or TNF-initiated apoptosis. We have examined mechanisms of target cell lysis by effector T cells from gene-targeted and mutant mice using a new Flow Cytometric Cytotoxicity Assay (FC Assay). Target cells were labeled with PKH67 dye. Cell death was estimated by 7-AAD inclusion and annexin V-PE binding. A direct correlation has been found between the percentage of dead target cells in FC Assay and the results of 111In release cytotoxicity assay when effector T cells from either Pfp -/- (perforin knockout) or gld (non-functional Fas Ligand) mice were used. As shown by the 4 h FC assay, the granule-mediated mechanism was utilized by T cells from gld mice. In contrast, T cells from Pfp -/- mice used death receptor-mediated lysis. Therefore, cytotoxic cells from gene-targeted and mutant mice can serve as valuable tools for studying different mechanisms of cell-mediated cytotoxicity, and the FC assay could be applied irrespective of which cytotoxic effector pathway is involved. JF - Immunology letters AU - Malyguine, Anatoli AU - Derby, Eric AU - Brooks, Alan AU - Reddy, Vasavi AU - Baseler, Michael AU - Sayers, Thomas AD - SAIC Frederick, Inc. NCI at Frederick, P.O. Box B, Frederick, MD 21702-1201, USA. amalyguine@mail.ncifcrf.gov Y1 - 2002/08/01/ PY - 2002 DA - 2002 Aug 01 SP - 55 EP - 59 VL - 83 IS - 1 SN - 0165-2478, 0165-2478 KW - Fas Ligand Protein KW - 0 KW - Fasl protein, mouse KW - Membrane Glycoproteins KW - Pore Forming Cytotoxic Proteins KW - Perforin KW - 126465-35-8 KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured KW - Mice KW - Flow Cytometry KW - Gene Targeting KW - T-Lymphocytes KW - Mice, Knockout KW - Membrane Glycoproteins -- genetics KW - Cytotoxicity, Immunologic KW - Immunity, Cellular KW - Cytotoxicity Tests, Immunologic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71800366?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Study+of+diverse+mechanisms+of+cell-mediated+cytotoxicity+in+gene-targeted+mice+using+flow+cytometric+cytotoxicity+assay.&rft.au=Malyguine%2C+Anatoli%3BDerby%2C+Eric%3BBrooks%2C+Alan%3BReddy%2C+Vasavi%3BBaseler%2C+Michael%3BSayers%2C+Thomas&rft.aulast=Malyguine&rft.aufirst=Anatoli&rft.date=2002-08-01&rft.volume=83&rft.issue=1&rft.spage=55&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 - 2003-08-12 N1 - Date created - 2002-06-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Child Maltreatment and Adulthood Violence: The Contribution of Attachment and Drug Abuse AN - 61512855; 200301947 AB - This study examined the association between child maltreatment & adult violence in a high-risk sample of women with & without a history of cocaine abuse & the contribution of working models of childhood attachment relationships in understanding this association. Results indicated that whereas childhood physical abuse was associated with adult sexual victimization for cocaine-abusing women, sexual abuse was associated with both partner violence victimization & perpetration for comparison women. Insecure working models of attachment were associated with partner violence victimization for comparison women, independent of the effect of sexual abuse. These findings suggest the importance of research focused on understanding the processes by which child maltreatment may lead to later violence & that examines both childhood & adulthood experiences in understanding pathways to adult violence. 6 Tables, 98 References. [Copyright 2002 Sage Publications, Inc.] JF - Child Maltreatment AU - Feerick, Margaret M AU - Haugaard, Jeffrey J AU - Hien, Denise A AD - Child Development & Behavior Branch, National Instit Child Health & Human Development, National Instits Health, Bethesda, MD feerickm@mail.nih.gov Y1 - 2002/08// PY - 2002 DA - August 2002 SP - 226 EP - 240 VL - 7 IS - 3 SN - 1077-5595, 1077-5595 KW - New York City, New York KW - Attachment KW - Childhood Factors KW - Females KW - Adults KW - Cocaine KW - Child Abuse KW - Victimization KW - Drug Abuse KW - Child Sexual Abuse KW - article KW - 6143: child & family welfare UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61512855?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocialservices&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Child+Maltreatment&rft.atitle=Child+Maltreatment+and+Adulthood+Violence%3A+The+Contribution+of+Attachment+and+Drug+Abuse&rft.au=Feerick%2C+Margaret+M%3BHaugaard%2C+Jeffrey+J%3BHien%2C+Denise+A&rft.aulast=Feerick&rft.aufirst=Margaret&rft.date=2002-08-01&rft.volume=7&rft.issue=3&rft.spage=226&rft.isbn=&rft.btitle=&rft.title=Child+Maltreatment&rft.issn=10775595&rft_id=info:doi/ LA - English DB - Social Services Abstracts N1 - Date revised - 2007-05-01 N1 - Last updated - 2016-09-28 N1 - CODEN - CMALFA N1 - SubjectsTermNotLitGenreText - Child Abuse; Child Sexual Abuse; Childhood Factors; Cocaine; Drug Abuse; Attachment; Victimization; Adults; Females; New York City, New York ER - TY - JOUR T1 - Up-Regulation of FPR2, a Chemotactic Receptor for Amyloid beta 1-42 (A beta 42), in Murine Microglial Cells by TNF alpha AN - 21057692; 8068218 AB - Human FPRL1 and its mouse homologue FPR2 are functional receptors for several exogenous and host-derived chemotactic peptides, including amyloid beta 42 (A beta 42), a critical pathogenic factor in Alzheimer's disease. We investigated the effect of TNF alpha on the expression and function of FPR2 in mouse microglial cells, a crucial inflammatory cell type in the CNS. Primary murine microglia and a cell line N9 in resting state expressed low levels of FPR2 gene and lacked the response to chemotactic agonists for this receptor. Incubation with TNF alpha , however, increased microglial expression of FPR2 gene, in association with potent chemotactic responses to FPR2-specific agonists including A beta 42. The effect of TNF alpha was dependent on the p55 TNF alpha receptor and activation of MAP kinase p38. TNF alpha concomitantly down-regulated microglial response to the chemokine SDF-1 alpha . Thus, by selectively up-regulating FPR2 in microglia, TNF alpha has the capacity to amplify host response in inflammatory diseases in the CNS. JF - Neurobiology of Disease AU - Cui, Y H AU - Le, Y AU - Zhang, X AU - Gong, W AU - Abe, K AU - Sun, R AU - Van Damme, J AU - Proost, P AU - Wang, J M AD - Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, Maryland, 21702 Y1 - 2002/08// PY - 2002 DA - Aug 2002 SP - 366 EP - 377 PB - Elsevier Science, The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:usinfo-f@elsevier.com], [URL:http://www.elsevier.nl] VL - 10 IS - 3 SN - 0969-9961, 0969-9961 KW - Aqualine Abstracts; CSA Neurosciences Abstracts KW - SDF-1 protein KW - Central nervous system KW - Chemokines KW - MAP kinase KW - Alzheimer's disease KW - Incubation KW - Microglia KW - Inflammation KW - Neurodegenerative diseases KW - ^b-Amyloid KW - Inflammatory diseases KW - Tumor necrosis factor-^a KW - Peptides KW - Capacity KW - Diseases KW - Microglial cells KW - AQ 00001:Water Resources and Supplies KW - N3 11027:Neurology & neuropathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21057692?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aaqualine&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurobiology+of+Disease&rft.atitle=Up-Regulation+of+FPR2%2C+a+Chemotactic+Receptor+for+Amyloid+beta+1-42+%28A+beta+42%29%2C+in+Murine+Microglial+Cells+by+TNF+alpha&rft.au=Cui%2C+Y+H%3BLe%2C+Y%3BZhang%2C+X%3BGong%2C+W%3BAbe%2C+K%3BSun%2C+R%3BVan+Damme%2C+J%3BProost%2C+P%3BWang%2C+J+M&rft.aulast=Cui&rft.aufirst=Y&rft.date=2002-08-01&rft.volume=10&rft.issue=3&rft.spage=366&rft.isbn=&rft.btitle=&rft.title=Neurobiology+of+Disease&rft.issn=09699961&rft_id=info:doi/10.1006%2Fnbdi.2002.0517 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-04-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Diseases; Capacity; Peptides; Incubation; Tumor necrosis factor-^a; ^b-Amyloid; Central nervous system; Microglia; Microglial cells; Alzheimer's disease; Inflammatory diseases; MAP kinase; Inflammation; Chemokines; Neurodegenerative diseases; SDF-1 protein DO - http://dx.doi.org/10.1006/nbdi.2002.0517 ER - TY - JOUR T1 - CDKS and CKIS: Molecular targets for tissue remodelling AN - 20641285; 7921021 AB - Effective tissue remodelling is essential to the survival of adult organs. Many of the signalling pathways that control these cellular decisions are regulated by nuclear interactions of cell-cycle proteins. Molecules that target cyclin-dependent kinases (CDKs) or CDK inhibitors (CKIs) represent a new class of therapeutic agents that influence tissue remodelling in several organ systems. An understanding of their cell-specific functions is leading to the development of exciting and bold approaches to the treatment cancer, cardiovascular disease and other diseases. JF - Nature Reviews: Drug Discovery AU - Nabel, Elizabeth G AD - Cardiovascular Branch, National Heart, Lung and Blood Institute/National Institutes of Health, Building 10/8C103, 10 Center Drive, Bethesda, Maryland 20892, USA., enabel@nih.gov Y1 - 2002/08// PY - 2002 DA - Aug 2002 SP - 587 EP - 598 PB - Nature Publishing Group, The Macmillan Building 4 Crinan Street London N1 9XW UK, [mailto:feedback@nature.com], [URL:http://www.nature.com/] VL - 1 IS - 8 SN - 1474-1784, 1474-1784 KW - Biotechnology and Bioengineering Abstracts KW - Cyclin-dependent kinase KW - Cardiovascular diseases KW - Cancer KW - Signal transduction KW - W 30915:Pharmaceuticals & Vaccines UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20641285?accountid=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+Reviews%3A+Drug+Discovery&rft.atitle=CDKS+and+CKIS%3A+Molecular+targets+for+tissue+remodelling&rft.au=Nabel%2C+Elizabeth+G&rft.aulast=Nabel&rft.aufirst=Elizabeth&rft.date=2002-08-01&rft.volume=1&rft.issue=8&rft.spage=587&rft.isbn=&rft.btitle=&rft.title=Nature+Reviews%3A+Drug+Discovery&rft.issn=14741784&rft_id=info:doi/10.1038%2Fnrd869 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-01-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Cyclin-dependent kinase; Cardiovascular diseases; Cancer; Signal transduction DO - http://dx.doi.org/10.1038/nrd869 ER - TY - JOUR T1 - The association between urban form and physical activity in U.S. adults AN - 18689366; 5580255 AB - Background: Physical inactivity is associated with multiple adverse health outcomes. Results from the transportation literature suggest that aspects of the urban environment may influence walking for transportation. In this paper we examine the association between a proxy measure of the urban environment and walking behavior. Methods: We analyzed the association between home age and walking behavior in U.S. adults using data from the Third National Health and Nutrition Examination Survey. Logistic regression was used to estimate odds ratios and 95% confidence intervals and to control for the effects of gender, race/ethnicity, age, education level, household income, and activity limitations. Results: Adults who lived in homes built before 1946 and from 1946 to 1973 were significantly more likely to walk 1+ miles greater than or equal to 20 times per month than those who lived in homes built after 1973. This association was present among people living in urban and suburban counties, but absent among those living in rural counties. The association was also found in models that controlled for gender, race/ethnicity, age, education, income, and any health-related activity limitation. Other forms of leisure-time physical activity were not independently associated with home age. Conclusions: These results support the hypothesis that environmental variables influence walking frequency and suggest that home age may be a useful proxy for features of the urban environment that influence physical activity in the form of walking. Such proxy measures could facilitate testing ecologic models of health behavior using survey data. JF - American Journal of Preventive Medicine AU - Berrigan, D AU - Troiano, R P AD - Division of Cancer Control and Population Sciences, National Institutes of Health, Bethesda, Maryland, USA Y1 - 2002/08// PY - 2002 DA - Aug 2002 SP - 74 EP - 79 VL - 23 IS - 2 SN - 0749-3797, 0749-3797 KW - Physical Education Index KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18689366?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Preventive+Medicine&rft.atitle=The+association+between+urban+form+and+physical+activity+in+U.S.+adults&rft.au=Berrigan%2C+D%3BTroiano%2C+R+P&rft.aulast=Berrigan&rft.aufirst=D&rft.date=2002-08-01&rft.volume=23&rft.issue=2&rft.spage=74&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Preventive+Medicine&rft.issn=07493797&rft_id=info:doi/10.1016%2FS0749-3797%2802%2900476-2 LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0749-3797(02)00476-2 ER - TY - JOUR T1 - Emerging measurement and statistical methods in physical activity research AN - 18680199; 5580252 AB - Although many studies have attempted to identify mediators and moderators of changes in physical activity involvement, the literature is inconclusive regarding which variable(s) relate to physical activity behavior change. The Cooper 2001 Conference series dedicated a session to discussing measurement and statistical methods that could contribute to advancing this research agenda. This article focuses on four such methodologic approaches: qualitative; psychometric; latent-variable, structural equation modeling; and multilevel modeling. The article presents a brief overview of these methods and discusses potential advantages and limitations of using them. JF - American Journal of Preventive Medicine AU - Maasse, L C AU - Dassa, C AU - Gauvin, L AU - Giles-Corti, B AU - Motl, R AD - Health Promotion Research Branch, National Cancer Institute (Maasse), Bethesda, Maryland, USA Y1 - 2002/08// PY - 2002 DA - Aug 2002 SP - 44 EP - 55 VL - 23 IS - 2 SN - 0749-3797, 0749-3797 KW - Physical Education Index KW - PE 070:Measurement & Evaluation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18680199?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Preventive+Medicine&rft.atitle=Emerging+measurement+and+statistical+methods+in+physical+activity+research&rft.au=Maasse%2C+L+C%3BDassa%2C+C%3BGauvin%2C+L%3BGiles-Corti%2C+B%3BMotl%2C+R&rft.aulast=Maasse&rft.aufirst=L&rft.date=2002-08-01&rft.volume=23&rft.issue=2&rft.spage=44&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Preventive+Medicine&rft.issn=07493797&rft_id=info:doi/10.1016%2FS0749-3797%2802%2900473-7 LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0749-3797(02)00473-7 ER - TY - JOUR T1 - Three-dimensional structure of a bacterial oxalate transporter AN - 18546975; 5508496 AB - The major facilitator superfamily (MFS) represents one of the largest classes of evolutionarily related membrane transporter proteins. Here we present the three-dimensional structure at 6.5 AA resolution of a bacterial member of this superfamily, OxIT. The structure, derived from an electron crystallographic analysis of two-dimensional crystals, reveals that the 12 helices in the OxIT molecule are arranged around a central cavity, which is widest at the center of the membrane. The helices divide naturally into three groups: a peripheral set comprising helices 3, 6, 9 and 12; a second set comprising helices 2, 5, 8 and 11 that faces the central substrate transport pathway across most of the length of the membrane; and a third set comprising helices 1, 4, 7 and 10 that participate in the pathway either on the cytoplasmic side (4 and 10) or on the periplasmic side (1 and 7). Overall, the architecture of the protein is remarkably symmetric, providing a compelling molecular explanation for the ability of such transporters to carry out bi-directional substrate transport. JF - Nature Structural Biology AU - Hirai, T AU - Heymann, JAW AU - Shi, D AU - Sarker, R AU - Maloney, P C AU - Subramaniam, S AD - Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA, ss1@nih.gov Y1 - 2002/08// PY - 2002 DA - Aug 2002 SP - 597 EP - 600 VL - 9 IS - 8 SN - 1072-8368, 1072-8368 KW - Microbiology Abstracts B: Bacteriology KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18546975?accountid=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=Nature+Structural+Biology&rft.atitle=Three-dimensional+structure+of+a+bacterial+oxalate+transporter&rft.au=Hirai%2C+T%3BHeymann%2C+JAW%3BShi%2C+D%3BSarker%2C+R%3BMaloney%2C+P+C%3BSubramaniam%2C+S&rft.aulast=Hirai&rft.aufirst=T&rft.date=2002-08-01&rft.volume=9&rft.issue=8&rft.spage=597&rft.isbn=&rft.btitle=&rft.title=Nature+Structural+Biology&rft.issn=10728368&rft_id=info:doi/10.1038%2Fnsb821 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1038/nsb821 ER - TY - JOUR T1 - Increased Serum Corticosterone and Glucose in Offspring of Chromium(III)-Treated Male Mice AN - 18502821; 5467732 AB - Preconceptional carcinogenesis occurs in animals and is suspected for humans - for example, after occupational metals exposure. Several characteristics in animal models, including high frequency and non-Mendelian inheritance patterns, have suggested an epigenetic mechanism, possibly involving hormone changes in offspring. To test this hypothesis, we treated male mice with chromium (III) chloride, a preconceptional carcinogen, 2 weeks before mating, in two separate experiments. Their 10-week-old offspring showed highly significant increases in average serum corticosterone and glucose, compared with control offspring. Average serum levels of insulin-like growth factor 1 (IGF1) showed more modest possible increases. A previous microarray experiment identified hepatic insulin-like growth factor binding protein 1 (IGF BP1) gene expression as consistently changed in correlation with serum corticosterone levels. In the present study, hepatic IGF BP1 mRNA correlated with serum IGF1 in male offspring of chromium-treated fathers, but not in controls; serum glucose correlated positively with hepatic IGF BP1 in chromium-group offspring but negatively in controls. These results support the hypothesis that preconceptional exposure effects may alter hormones, metabolism, and control of tissue gene expression, probably through epigenetic mechanisms. Risk of neoplasia may be influenced by these changes. JF - Environmental Health Perspectives AU - Cheng, RYS AU - Alvord, W G AU - Powell, D AU - Kasprzak, K S AU - Anderson, L M AD - Bldg. 538, NCI-Frederick, Ft. Detrick, Frederick, MD 21702, USA, Andersol@mail.ncifcrf.gov Y1 - 2002/08// PY - 2002 DA - Aug 2002 SP - 801 EP - 804 VL - 110 IS - 8 SN - 0091-6765, 0091-6765 KW - males KW - mice KW - Toxicology Abstracts KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18502821?accountid=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=Increased+Serum+Corticosterone+and+Glucose+in+Offspring+of+Chromium%28III%29-Treated+Male+Mice&rft.au=Cheng%2C+RYS%3BAlvord%2C+W+G%3BPowell%2C+D%3BKasprzak%2C+K+S%3BAnderson%2C+L+M&rft.aulast=Cheng&rft.aufirst=RYS&rft.date=2002-08-01&rft.volume=110&rft.issue=8&rft.spage=801&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 ER - TY - JOUR T1 - Nitric oxide trapping of the tyrosyl radical-chemistry and biochemistry AN - 18494083; 5450047 AB - The quenching of the Y sub(D) tyrosyl radical in photosystem II by nitric oxide was reported to result from the formation of a weak tyrosyl radical-nitric oxide complex. This radical/radical reaction is expected to generate an electron spin resonance (ESR)-silent nitrosocyclohexadienone species that can reversibly regenerate the tyrosyl radical and nitric oxide or undergo rearrangement to form 3-nitrosotyrosine. It has been proposed that 3-nitrosotyrosine can be oxidized by one electron to form the tyrosine iminoxyl radical ( > C = N-O super(.)). This proposal was put forth as a result of ESR detection of the iminoxyl radical intermediate when photosystem II was exposed to nitric oxide. Although the detection of the iminoxyl radical in photosystem II strongly suggested a mechanism involving 3-nitrosotyrosine, the iminoxyl radical ESR spectrum was not unequivocally identified as originating from tyrosine. Subsequently, non-protein L-tyrosine iminoxyl radical was generated by two methods: (1) peroxidase oxidation of synthetic 3-nitroso-N-acetyl-L-tyrosine; and (2) peroxidase oxidation of free L-tyrosine in the presence of nitric oxide. The determination of protein nitrotyrosine content has become a frequently used technique for the detection of nitrosative tissue damage. Protein nitration has been suggested to be a final product of the production of highly reactive nitrogen oxide intermediates (e.g. peroxynitrite) formed in reactions between nitric oxide (NO super(.)) and oxygen-derived species such as superoxide. The enzyme prostaglandin H synthase-2 also forms a tyrosyl radical during its enzymatic catalysis of prostaglandin formation. In the presence of the NO super(.) -generator diethylamine nonoate, the tyrosyl radical of prostaglandin H synthase-2 also changes to that of an iminoxyl radical. Western blot analysis of prostaglandin H synthase-2 after exposure to the NO super(.)-generator revealed nitrotyrosine formation. The results provide a mechanism for nitric oxide-dependent tyrosine nitration that does not require formation of more highly reactive nitrogen oxide intermediates such as peroxynitrite or nitrogen dioxide. JF - Toxicology AU - Gunther, M R AU - Sturgeon, B E AU - Mason, R P AD - Laboratory of Pharmacology and Chemistry, NIEHS, National Institutes of Health, Research Triangle Park, NC 27709, USA, mason4@niehs.nih.gov Y1 - 2002/08/01/ PY - 2002 DA - 2002 Aug 01 SP - 1 EP - 9 VL - 177 IS - 1 SN - 0300-483X, 0300-483X KW - Toxicology Abstracts KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18494083?accountid=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=Nitric+oxide+trapping+of+the+tyrosyl+radical-chemistry+and+biochemistry&rft.au=Gunther%2C+M+R%3BSturgeon%2C+B+E%3BMason%2C+R+P&rft.aulast=Gunther&rft.aufirst=M&rft.date=2002-08-01&rft.volume=177&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Saturation of DNA Mismatch Repair and Error Catastrophe by a Base Analogue in Escherichia coli AN - 18492079; 5457926 AB - Deoxyribosyl-dihydropyrimido[4,5- c][1,2]oxazin-7-one (dP) is a potent mutagenic deoxycytidine-derived base analogue capable of pairing with both A and G, thereby causing G super(.) C -> A super(.) T and A super(.) T -> G super(.) C transition mutations. We have found that the Escherichia coli DNA mismatch- repair system can protect cells against this mutagenic action. At a low dose, dP is much more mutagenic in mismatch-repair-defective mutH, mutL, and mutS strains than in a wild-type strain. At higher doses, the difference between the wild-type and the mutator strains becomes small, indicative of saturation of mismatch repair. Introduction of a plasmid containing the E. coli mutLu+ gene significantly reduces dP-induced mutagenesis. Together, the results indicate that the mismatch- repair system can remove dP-induced replication errors, but that its capacity to remove dP-containing mismatches can readily be saturated. When cells are cultured at high dP concentration, mutant frequencies reach exceptionally high levels and viable cell counts are reduced. The observations are consistent with a hypothesis in which dP-induced cell killing and growth impairment result from excess mutations (error catastrophe), as previously observed spontaneously in proofreading-deficient mutD (dnaQ) strains. JF - Genetics AU - Negishi, K AU - Loakes, D AU - Schaaper, R M AD - E3-01, National Institute of Environmental Health Sciences, P.O. Box 12233, 111 TW Alexander Dr., Research Triangle Park, NC 27709, USA, schaaper@niehs.nih.gov Y1 - 2002/08// PY - 2002 DA - Aug 2002 SP - 1363 EP - 1371 VL - 161 IS - 4 SN - 0016-6731, 0016-6731 KW - mismatch repair KW - mutD protein KW - mutH protein KW - mutL protein KW - mutS protein KW - mutators KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids; Genetics Abstracts KW - J 02725:DNA KW - G 07320:Bacterial genetics KW - N 14652:DNA repair UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18492079?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genetics&rft.atitle=Saturation+of+DNA+Mismatch+Repair+and+Error+Catastrophe+by+a+Base+Analogue+in+Escherichia+coli&rft.au=Negishi%2C+K%3BLoakes%2C+D%3BSchaaper%2C+R+M&rft.aulast=Negishi&rft.aufirst=K&rft.date=2002-08-01&rft.volume=161&rft.issue=4&rft.spage=1363&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Corresponding author: Roel M. Schaaper N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Serum selenium and the risk of cervical cancer among women in the United States AN - 18483503; 5454330 AB - Objective: To explore the relationship between serum selenium and cervical cancer. Methods: We conducted a case-control study of cervical cancer in five areas around Birmingham, AL; Chicago, IL; Denver, CO; Miami, FL; and Philadelphia, PA. Community controls were selected by random-digit dialing and were matched to invasive cervical cancer cases by age, race/ethnicity, and telephone exchange. Serum selenium was determined by neutron activation analysis. Logistic regression analysis controlling for known risk factors of cervical cancer, including human papillomavirus (HPV) type-16 measured serologically, was performed on 227 invasive cases, 127 in-situ cases, and 526 controls. Results: Values of serum selenium ranged from 67.5 to 185.0 ng/ml. Adjusted odds ratios for invasive cervical cancer by quintile were: 1.0 (highest selenium), 1.1, 1.0, 0.8, and 1.0 (lowest selenium), p for trend = 0.82. Similar patterns were observed for Stage I invasive, and Stages II-IV invasive cases, suggesting severity of disease did not influence the null results. Although no associations were seen among current or never smokers, a protective effect of selenium was suggested among former smokers. Effect modification was not evident for other variables examined. Conclusions: This study does not support a relationship between serum selenium and invasive cervical cancer at typical serum selenium levels in the US. JF - Cancer Causes & Control AU - Thompson, F E AU - Patterson, B H AU - Weinstein, S J AU - McAdams, M AU - Spate, V L AU - Hamman, R F AU - Levine, R S AU - Mallin, K AU - Stolley, P D AU - Brinton, LA AU - Morris, J S AU - Ziegler, R G AD - National Cancer Institute, Division of Cancer Control and Population Sciences, Applied Research Program, Risk Factor Monitoring and Methods Branch, EPN 4016, 6130 Executive Blvd MSC 7344, Bethesda, MD 20892-7344, USA Y1 - 2002/08// PY - 2002 DA - Aug 2002 SP - 517 EP - 526 VL - 13 IS - 6 SN - 0957-5243, 0957-5243 KW - epidemiology KW - man KW - Toxicology Abstracts KW - X 24162:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18483503?accountid=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=Serum+selenium+and+the+risk+of+cervical+cancer+among+women+in+the+United+States&rft.au=Thompson%2C+F+E%3BPatterson%2C+B+H%3BWeinstein%2C+S+J%3BMcAdams%2C+M%3BSpate%2C+V+L%3BHamman%2C+R+F%3BLevine%2C+R+S%3BMallin%2C+K%3BStolley%2C+P+D%3BBrinton%2C+LA%3BMorris%2C+J+S%3BZiegler%2C+R+G&rft.aulast=Thompson&rft.aufirst=F&rft.date=2002-08-01&rft.volume=13&rft.issue=6&rft.spage=517&rft.isbn=&rft.btitle=&rft.title=Cancer+Causes+%26+Control&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Tissue Compatibility of Two Biodegradable Tubular Scaffolds Implanted Adjacent to Skin or Buccal Mucosa in Mice AN - 18482139; 5444828 AB - Radiation therapy for cancer in the head and neck region leads to a marked loss of salivary gland parenchyma, resulting in a severe reduction of salivary secretions. Currently, there is no satisfactory treatment for these patients. To address this problem, we are using both tissue engineering and gene transfer principles to develop an orally implantable, artificial fluid-secreting device. In the present study, we examined the tissue compatibility of two biodegradable substrata potentially useful in fabricating such a device. We implanted in Balb/c mice tubular scaffolds of poly-L-lactic acid (PLLA), poly-glycolic acid coated with PLLA (PGA/PLLA), or nothing (sham-operated controls) either beneath the skin on the back, a site widely used in earlier toxicity and biocompatibility studies, or adjacent to the buccal mucosa, a site quite different functionally and immunologically. At 1, 3, 7, 14, and 28 days postimplantation, implant sites were examined histologically, and systemic responses were assessed by conventional clinical chemistry and hematology analyses. Inflammatory responses in the connective tissue were similar regardless of site or type of polymer implant used. However, inflammatory reactions were shorter and without epithelioid and giant cells in sham-operated controls. Also, biodegradation proceeded more slowly with the PLLA tubules than with the PGA/PLLA tubules. No significant changes in clinical chemistry and hematology were seen due to the implantation of tubular scaffolds. These results indicate that the tissue responses to PLLA and PGA/PLLA scaffolds are generally similar in areas subjacent to skin in the back and oral cavity. However, these studies also identified several potentially significant concerns that must be addressed prior to initiating any clinical applications of this device. JF - Tissue Engineering AU - Aframian, D J AU - Redman, R S AU - Yamano, S AU - Nikolovski, J AU - Cukierman, E AU - Yamada, K M AU - Kriete, M F AU - Swaim, W D AU - Mooney, D J AU - Baum, B J AD - GTTB, NIDCR, NIH, Bldg. 10, Rm. 1N113, MSC-1190, Bethesda, MD 20892, USA, bbaum@dir.nidcr.nih.gov Y1 - 2002/08// PY - 2002 DA - Aug 2002 SP - 649 EP - 659 VL - 8 IS - 4 SN - 1076-3279, 1076-3279 KW - Balb/c mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33170:Cellular based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18482139?accountid=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=Tissue+Engineering&rft.atitle=Tissue+Compatibility+of+Two+Biodegradable+Tubular+Scaffolds+Implanted+Adjacent+to+Skin+or+Buccal+Mucosa+in+Mice&rft.au=Aframian%2C+D+J%3BRedman%2C+R+S%3BYamano%2C+S%3BNikolovski%2C+J%3BCukierman%2C+E%3BYamada%2C+K+M%3BKriete%2C+M+F%3BSwaim%2C+W+D%3BMooney%2C+D+J%3BBaum%2C+B+J&rft.aulast=Aframian&rft.aufirst=D&rft.date=2002-08-01&rft.volume=8&rft.issue=4&rft.spage=649&rft.isbn=&rft.btitle=&rft.title=Tissue+Engineering&rft.issn=10763279&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 - Adhesion of viridans group streptococci to sialic acid-, galactose- and N-acetylgalactosamine-containing receptors AN - 18479102; 5444066 AB - The binding of 10 viridans group streptococci to sialic acid-, galactose (Gal)- and N-acetylgalactosamine (GalNAc)-containing receptors was defined by analysis of the interactions between these bacteria and structurally defined glycoconjugates, host cells and other streptococci. All interactions with sialic acid-containing receptors were Ca super(2+)-independent as they were not affected by ethyleneglycoltetraacetic acid (EGTA), whereas all interactions with Gal- and GalNAc-containing receptors were Ca super(2+)-dependent. Recognition of sialic acid-, Gal- and GalNAc-containing receptors varied widely among the strains examined, in a manner consistent with the association of each of the three lectin-like activities with a different bacterial cell surface component. JF - Oral Microbiology and Immunology AU - Takahashi, Y AU - Ruhl, S AU - Yoon, J-W AU - Sandberg, AL AU - Cisar, JO AD - Building 30, Room 532, NIDCR, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 2002/08// PY - 2002 DA - Aug 2002 SP - 257 EP - 262 VL - 17 IS - 4 SN - 0902-0055, 0902-0055 KW - N-Acetylgalactosamine KW - streptococci KW - Microbiology Abstracts B: Bacteriology KW - J 02730:Carbohydrates UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18479102?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oral+Microbiology+and+Immunology&rft.atitle=Adhesion+of+viridans+group+streptococci+to+sialic+acid-%2C+galactose-+and+N-acetylgalactosamine-containing+receptors&rft.au=Takahashi%2C+Y%3BRuhl%2C+S%3BYoon%2C+J-W%3BSandberg%2C+AL%3BCisar%2C+JO&rft.aulast=Takahashi&rft.aufirst=Y&rft.date=2002-08-01&rft.volume=17&rft.issue=4&rft.spage=257&rft.isbn=&rft.btitle=&rft.title=Oral+Microbiology+and+Immunology&rft.issn=09020055&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - A novel multiplex RT-PCR probe capture hybridization (RT-PCR-ELISA) for simultaneous detection of six viroids in four genera: Apscaviroid, Hostuviroid, Pelamoviroid, and Pospiviroid AN - 18472538; 5440723 AB - A rapid and sensitive assay was developed for the detection and identification of viroids by standard or multiplex reverse transcription-polymerase chain reaction (RT-PCR)-probe capture hybridization (RT-PCR-ELISA). The assay was applied successfully for the detection and identification of the following six viroid species from infected tissues: Potato spindle tuber viroid (Pospiviroid), Peach latent mosaic viroid (Pelamoviroid), Apple scar skin viroid (Apscaviroid), Apple dimple fruit viroid (Apscaviroid), Pear blister canker viroid (Apscaviroid), and Hop stunt viroid (Hostuviroid). Total RNA was obtained from infected tissue by the Qiagen RNeasy kit and, then viroid cDNA was synthesized using viroid specific complementary DNA primer. To identify and differentiate the amplicons of the six viroids, each amplicon was digoxigenin (DIG)-labelled during the amplification process, and then detected by a colorimetric system using a biotinylated cDNA capture probe specific for each viroid. The results revealed that each capture probe hybridized only to its complementary DIG-labelled amplicon. Thus the six viroids can be detected and differentiated in a multiplex RT-PCR-ELISA assay. In the multiplex assay, cDNAs of six viroids were synthesized simultaneously in one tube, DIG-labelled during amplification, then a portion of the DIG-labelled amplified products was hybridized with selected capture probe. All the six viroid capture probes hybridized to their respective complementary DIG-labelled RT-PCR-amplified product. These findings are important for viroid detection and identification for studying host-viroid interactions and for management and control viroid diseases. JF - Journal of Virological Methods AU - Shamloul, A M AU - Faggioli, F AU - Keith, J M AU - Hadidi, A AD - Vaccine and Therapeutic Development Section, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA, mshamloul@dir.nidcr.nih.gov Y1 - 2002/08// PY - 2002 DA - Aug 2002 SP - 115 EP - 121 PB - Elsevier Science B.V. VL - 105 IS - 1 SN - 0166-0934, 0166-0934 KW - host-viroid interactions KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - V 22181:Detection KW - A 01114:Viruses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18472538?accountid=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+Virological+Methods&rft.atitle=A+novel+multiplex+RT-PCR+probe+capture+hybridization+%28RT-PCR-ELISA%29+for+simultaneous+detection+of+six+viroids+in+four+genera%3A+Apscaviroid%2C+Hostuviroid%2C+Pelamoviroid%2C+and+Pospiviroid&rft.au=Shamloul%2C+A+M%3BFaggioli%2C+F%3BKeith%2C+J+M%3BHadidi%2C+A&rft.aulast=Shamloul&rft.aufirst=A&rft.date=2002-08-01&rft.volume=105&rft.issue=1&rft.spage=115&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virological+Methods&rft.issn=01660934&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 - Large-Scale Screening of Nasal Swabs for Bacillus anthracis: Descriptive Summary and Discussion of the National Institutes of Health's Experience AN - 18470071; 5431242 AB - In October 2001, a letter containing a large number of anthrax spores was sent through the Brentwood post office in Washington, D.C., to a United States Senate office on Capitol Hill, resulting in contamination in both places. Several thousand people who worked at these sites were screened for spore exposure by collecting nasal swab samples. We describe here a screening protocol which we, as a level A laboratory, used on very short notice to process a large number of specimens (3,936 swabs) in order to report preliminary results as quickly as possible. Six isolates from our screening met preliminary criteria for Bacillus anthracis identification and were referred for definitive testing. Although none of the isolates was later confirmed to be B. anthracis, we studied these isolates further to define their biochemical characteristics and 16S rRNA sequences. Four of the six isolates were identified as Bacillus megaterium, one was identified as Bacillus cereus, and one was an unidentifiable Bacillus sp. Our results suggest that large-scale nasal-swab screening for potential exposure to anthrax spores, particularly if not done immediately postexposure, may not be very effective for detecting B. anthracis but may detect a number of Bacillus spp. that are phenotypically very similar to B. anthracis. JF - Journal of Clinical Microbiology AU - Kiratisin, P AU - Fukuda, C D AU - Wong, A AU - Stock, F AU - Preuss, J C AU - Ediger, L AU - Brahmbhatt, T N AU - Fischer, SH AU - Fedorko, D P AU - Witebsky, F G AU - Gill, V J AD - Microbiology Service, Department of Laboratory Medicine, National Institutes of Health, Building 10, Room 2C385, 10 Center Dr. MSC 1508, Bethesda, MD 20892- 1508., pkiratisin@mail.cc.nih.gov Y1 - 2002/08// PY - 2002 DA - Aug 2002 SP - 3012 EP - 3016 VL - 40 IS - 8 SN - 0095-1137, 0095-1137 KW - bioterrorism KW - man KW - Microbiology Abstracts B: Bacteriology KW - J 02855:Human Bacteriology: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18470071?accountid=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=Large-Scale+Screening+of+Nasal+Swabs+for+Bacillus+anthracis%3A+Descriptive+Summary+and+Discussion+of+the+National+Institutes+of+Health%27s+Experience&rft.au=Kiratisin%2C+P%3BFukuda%2C+C+D%3BWong%2C+A%3BStock%2C+F%3BPreuss%2C+J+C%3BEdiger%2C+L%3BBrahmbhatt%2C+T+N%3BFischer%2C+SH%3BFedorko%2C+D+P%3BWitebsky%2C+F+G%3BGill%2C+V+J&rft.aulast=Kiratisin&rft.aufirst=P&rft.date=2002-08-01&rft.volume=40&rft.issue=8&rft.spage=3012&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Microbiology&rft.issn=00951137&rft_id=info:doi/10.1128%2FJCM.40.8.3012-3016.2002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/JCM.40.8.3012-3016.2002 ER - TY - JOUR T1 - Increased functional expression of transgene in primary human lymphocytes using retroviral vectors modified with IRES and splicing motifs AN - 18457049; 5434496 AB - Genetic modification of human lymphocytes is being employed in strategies to correct enzyme deficiencies, encode cytokines and to redirect lymphocytes to antigenic targets other than those encoded by their endogenous T cell receptor. However, expression of transgenes in primary lymphocytes is generally low. Reasoning that vector modification may lead to increased transgene expression and subsequent increases in function, we have performed two retroviral vector modifications and report their effect on the functional expression in primary lymphocytes. A chimeric receptor specific for the colon carcinoma-associated antigen, EGP40, was initially incorporated into the retroviral vector LXSN. In this vector, receptor expression is driven by the Moloney murine leukemia virus LTR, and neomycin phosphotransferase expression driven by the SV40 promoter. Replacement of SV40 with an internal ribosomal entry site (IRES) increased the transgene activity of a mouse T cell line and human PBL as judged by increased cytokine release in response to antigen positive target cells. A further increase in transgene function was generated by the additional incorporation of a splice acceptor motif into the construct. Human PBL transduced with vector incorporating both IRES and intron were consistently more effective at lysing antigen positive colorectal carcinoma cells. JF - Gene Therapy AU - Royal, R E AU - Kershaw, M H AU - Reeves, ME AU - Wang, G AU - Daly, T AU - Treisman, J AU - Lam, J AU - Hwu, P AD - Building 10 Room 2B42, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD, 20892, USA Y1 - 2002/08// PY - 2002 DA - Aug 2002 SP - 1085 EP - 1092 VL - 9 IS - 16 SN - 0969-7128, 0969-7128 KW - internal ribosome entry site KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18457049?accountid=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=Increased+functional+expression+of+transgene+in+primary+human+lymphocytes+using+retroviral+vectors+modified+with+IRES+and+splicing+motifs&rft.au=Royal%2C+R+E%3BKershaw%2C+M+H%3BReeves%2C+ME%3BWang%2C+G%3BDaly%2C+T%3BTreisman%2C+J%3BLam%2C+J%3BHwu%2C+P&rft.aulast=Royal&rft.aufirst=R&rft.date=2002-08-01&rft.volume=9&rft.issue=16&rft.spage=1085&rft.isbn=&rft.btitle=&rft.title=Gene+Therapy&rft.issn=09697128&rft_id=info:doi/10.1038%2Fsj.gt.3301734 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1038/sj.gt.3301734 ER - TY - JOUR T1 - Identification and Characterization of a Novel Heme-Associated Cell Surface Protein Made by Streptococcus pyogenes AN - 18451451; 5425464 AB - Analysis of the genome sequence of a serotype M1 group A Streptococcus (GAS) strain identified a gene encoding a previously undescribed putative cell surface protein. The gene was cloned from a serotype M1 strain, and the recombinant protein was overexpressed in Escherichia coli and purified to homogeneity. The purified protein was associated with heme in a 1:1 stoichiometry. This streptococcal heme-associated protein, designated Shp, was produced in vitro by GAS, located on the bacterial cell surface, and accessible to specific antibody raised against the purified recombinant protein. Mice inoculated subcutaneously with GAS and humans with invasive infections and pharyngitis caused by GAS seroconverted to Shp, indicating that Shp was produced in vivo. The blood of mice actively immunized with Shp had significantly higher bactericidal activity than the blood of unimmunized mice. The shp gene was cotranscribed with eight contiguous genes, including homologues of an ABC transporter involved in iron uptake in gram-negative bacteria. Our results indicate that Shp is a novel cell surface heme-associated protein. JF - Infection and Immunity AU - Lei, B AU - Smoot, L M AU - Menning, H M AU - Voyich, J M AU - Kala, S V AU - Deleo AU - Reid, S D AU - Musser, J M AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th St., Hamilton, MT 59840., jmusser@niaid.nih.gov Y1 - 2002/08// PY - 2002 DA - Aug 2002 SP - 4494 EP - 4500 VL - 70 IS - 8 SN - 0019-9567, 0019-9567 KW - Shp protein KW - cloning KW - shp gene KW - Microbiology Abstracts B: Bacteriology KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18451451?accountid=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=Identification+and+Characterization+of+a+Novel+Heme-Associated+Cell+Surface+Protein+Made+by+Streptococcus+pyogenes&rft.au=Lei%2C+B%3BSmoot%2C+L+M%3BMenning%2C+H+M%3BVoyich%2C+J+M%3BKala%2C+S+V%3BDeleo%3BReid%2C+S+D%3BMusser%2C+J+M&rft.aulast=Lei&rft.aufirst=B&rft.date=2002-08-01&rft.volume=70&rft.issue=8&rft.spage=4494&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.70.8.4494-4500.2002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/IAI.70.8.4494-4500.2002 ER - TY - JOUR T1 - The CXC Chemokine Murine Monokine Induced by IFN- gamma (CXC Chemokine Ligand 9) Is Made by APCs, Targets Lymphocytes Including Activated B Cells, and Supports Antibody Responses to a Bacterial Pathogen In Vivo AN - 18436173; 5413283 AB - Monokine induced by IFN- gamma (Mig; CXC chemokine ligand 9) is an IFN- gamma -inducible CXC chemokine that signals through the receptor CXCR3 and is known to function as a chemotactic factor for human T cells, particularly following T cell activation. The mig gene can be induced in multiple cell types and organs, and Mig has been shown to contribute to T cell infiltration into immune/inflammatory reactions in peripheral tissues in mice. We have investigated the expression and activities of Mig and CXCR3 in mouse cells and the role of Mig in models of host defense in mice. Murine (Mu)Mig functioned as a chemotactic factor for resting memory and activated T cells, both CD4 super(+) and CD8 super(+), and responsiveness to MuMig correlated with surface expression of MuCXCR3. Using mig super(-/-) mice, we found that MuMig was not necessary for survival after infections with a number of intracellular pathogens. Surprisingly, however, we found that mig super(-/-) mice showed reductions of 50 75% in Abs produced against the intracellular bacterium Francisella tularensis live vaccine strain. Furthermore, we found that MuMig induced both calcium signals and chemotaxis in activated B cells, and that B cell activation induced expression of MuCXCR3. In addition, IFN- gamma induced the expression of mumig in APCs, including CD8 alpha super(+) and CD8 alpha super(-) dendritic cells. Together, our data suggest that Mig and CXCR3 may be important not only to recruit T cells to peripheral inflammatory sites, but also in some cases to maximize interactions among activated T cells, B cells, and dendritic cells within lymphoid organs to provide optimal humoral responses to pathogens. JF - Journal of Immunology AU - Park, M K AU - Amichay, D AU - Love, P AU - Wick, E AU - Liao, F AU - Grinberg, A AU - Rabin, R L AU - Zhang, H H AU - Gebeyehu, S AU - Wright, T M AU - Iwasaki, A AU - Weng, Y AU - DeMartino, JA AU - Elkins, K L AU - Farber, J M AD - Inflammation Biology Section and Immune Cell Interaction Unit, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, National Institutes of Health, and Division of Bacterial, Parasitic, and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892 Y1 - 2002/08/01/ PY - 2002 DA - 2002 Aug 01 SP - 1433 EP - 1443 VL - 169 IS - 3 SN - 0022-1767, 0022-1767 KW - CXCL9 protein KW - Mig protein KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - F 06801:Bacteria KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18436173?accountid=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=The+CXC+Chemokine+Murine+Monokine+Induced+by+IFN-+gamma+%28CXC+Chemokine+Ligand+9%29+Is+Made+by+APCs%2C+Targets+Lymphocytes+Including+Activated+B+Cells%2C+and+Supports+Antibody+Responses+to+a+Bacterial+Pathogen+In+Vivo&rft.au=Park%2C+M+K%3BAmichay%2C+D%3BLove%2C+P%3BWick%2C+E%3BLiao%2C+F%3BGrinberg%2C+A%3BRabin%2C+R+L%3BZhang%2C+H+H%3BGebeyehu%2C+S%3BWright%2C+T+M%3BIwasaki%2C+A%3BWeng%2C+Y%3BDeMartino%2C+JA%3BElkins%2C+K+L%3BFarber%2C+J+M&rft.aulast=Park&rft.aufirst=M&rft.date=2002-08-01&rft.volume=169&rft.issue=3&rft.spage=1433&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunology&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Effective solutions for the pollution of river water quality--Chei-Tong River at Shin-Chu as an example AN - 16160943; 5635862 AB - The pollution of rivers will affect not only the quality of drinking water sources, public health, and environmental quality, but for those with an irrigation purpose, it may also endanger the growth of crops and cause soil contamination problems. Furthermore, the pollutants accumulated in crops may possibly influence human health. With the Chei-Tong River at Shin Chu as an example, the authors collected data from relevant past research, discussed the water quality pollution problem of the river, and finally provided effective solutions for the problems. The water in this river mostly came from the discharge of some plants along the river and the wastewater treatment plant of Shin-Chu Industrial Park. It was found that the river water appeared dark red. This was primarily due to the discharge from the treatment plant and the SO super(-) sub(4) super(2) and Cl super(-) in the water. The conductivity and SAR (Sodium Absorption Rate) of the water, in particular, were much higher than irrigation water quality standards. Therefore, it was concluded that the water of Chei-Tong River was not appropriate for irrigation purposes. To solve these problems, the authors suggested that the treatment capability of the wastewater treatment plant should be improved, the water quality standards of the river or for irrigation usage should be revised, and the relevant governmental institutions should actively look for other alternative irrigation water sources. JF - Taiwan Journal of Public Health AU - Juang, D-F AU - Kao, T-J AU - Lin, J-H AU - Chen, P-C AU - Cheng, Y-A AD - Healthcare Administration Department, Mei-Ho Institute of Technology. No. 23, Ping-Kuang Road, Nei Pu, Ping Tong, 912, Taiwan, x2060@email.meiho.edu.tw Y1 - 2002/08// PY - 2002 DA - Aug 2002 SP - 223 EP - 234 VL - 21 IS - 4 SN - 1023-2141, 1023-2141 KW - Pollution Abstracts KW - Rivers KW - Agriculture KW - Taiwan KW - Taiwan, Chei-Tong R. KW - Irrigation KW - Wastewater discharges KW - Water quality KW - Taiwan, Shin-Chu KW - Freshwater pollution KW - P 2000:FRESHWATER POLLUTION UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16160943?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Apollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Taiwan+Journal+of+Public+Health&rft.atitle=Effective+solutions+for+the+pollution+of+river+water+quality--Chei-Tong+River+at+Shin-Chu+as+an+example&rft.au=Juang%2C+D-F%3BKao%2C+T-J%3BLin%2C+J-H%3BChen%2C+P-C%3BCheng%2C+Y-A&rft.aulast=Juang&rft.aufirst=D-F&rft.date=2002-08-01&rft.volume=21&rft.issue=4&rft.spage=223&rft.isbn=&rft.btitle=&rft.title=Taiwan+Journal+of+Public+Health&rft.issn=10232141&rft_id=info:doi/ LA - Chinese DB - ProQuest Environmental Science Collection N1 - Date revised - 2003-08-01 N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Agriculture; Rivers; Irrigation; Wastewater discharges; Water quality; Freshwater pollution; Taiwan; Taiwan, Chei-Tong R.; Taiwan, Shin-Chu ER - TY - JOUR T1 - The peroxisome proliferator-activated receptor alpha (PPARalpha): role in hepatocarcinogenesis. AN - 71975199; 12161004 AB - The peroxisome proliferator-activated receptor alpha (PPARalpha) is a member of the nuclear receptor superfamily and mediates most of the known biological effects of peroxisome proliferators. The latter represents a large group of chemicals that include the fibrate hyperlipidemic drugs, the pthalate plasticizers, various solvents and degreasing agents, and endogenous hormones and fatty acids. Peroxisome proliferators are classical members of the nongenotoxic group of chemical carcinogens that do not require metabolic activation to electrophiles in order to exert their harmful effects. These chemicals are of particular concern to regulatory agencies since they can only be detected by long-term carcinogen bioassays using rodents. The mechanism of the carcinogenic action of peroxisome proliferators is beginning to emerge. PPARalpha-null mice are resistant to hepatocarcinogenesis indicating that this receptor is necessary for cancer. However, recent studies indicate that Kupffer cells, in a PPARalpha independent manor, are required for the major effects of peroxisome proliferators on cell proliferation. An interaction between PPARalpha and estrogen carcinogenesis has also been elucidated. Copyright 2002 Elsevier Science Ireland Ltd. JF - Molecular and cellular endocrinology AU - Gonzalez, Frank J AD - National Cancer Institute, National Institutes of Health, Building 37, Room 3E-24, Bethesda, MD 20892, USA. fjgonz@helix.nih.gov Y1 - 2002/07/31/ PY - 2002 DA - 2002 Jul 31 SP - 71 EP - 79 VL - 193 IS - 1-2 SN - 0303-7207, 0303-7207 KW - Carcinogens KW - 0 KW - Peroxisome Proliferators KW - Receptors, Cytoplasmic and Nuclear KW - Transcription Factors KW - Index Medicus KW - Animals KW - Peroxisome Proliferators -- adverse effects KW - Humans KW - Kupffer Cells -- metabolism KW - Carcinogens -- adverse effects KW - Receptors, Cytoplasmic and Nuclear -- physiology KW - Transcription Factors -- physiology KW - Carcinoma, Hepatocellular -- etiology KW - Carcinoma, Hepatocellular -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71975199?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+endocrinology&rft.atitle=The+peroxisome+proliferator-activated+receptor+alpha+%28PPARalpha%29%3A+role+in+hepatocarcinogenesis.&rft.au=Gonzalez%2C+Frank+J&rft.aulast=Gonzalez&rft.aufirst=Frank&rft.date=2002-07-31&rft.volume=193&rft.issue=1-2&rft.spage=71&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+endocrinology&rft.issn=03037207&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-13 N1 - Date created - 2002-08-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CPAPER T1 - Detection of slow conformational changes in proteins using NMR relaxation AN - 39575390; 3689036 AU - Ishima, R AU - Torchia, DA Y1 - 2002/07/31/ PY - 2002 DA - 2002 Jul 31 KW - CPI, Conference Papers Index KW - U 7000:Multidisciplinary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39575390?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Detection+of+slow+conformational+changes+in+proteins+using+NMR+relaxation&rft.au=Ishima%2C+R%3BTorchia%2C+DA&rft.aulast=Ishima&rft.aufirst=R&rft.date=2002-07-31&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: 43rd Experimental Nuclear Magnetic Resonance Conference, Johns Hopkins Univ Med School, 720 Rutland Ave, 217 Traylor, Baltimore, MD 21205, USA; phone: 410-614-1948; fax: 410-614-2733; email: pvanzijl@mri.jhu.edu N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Carotid intimal medial thickness is a heritable phenotype: The framingham heart study AN - 39559594; 3683335 AU - Fox, C AU - Polak, J F AU - Chazaro, I AU - Cupples, A AU - Wolf, P AU - D'Agostino, R B AU - O'Donnell, C J Y1 - 2002/07/31/ PY - 2002 DA - 2002 Jul 31 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39559594?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Carotid+intimal+medial+thickness+is+a+heritable+phenotype%3A+The+framingham+heart+study&rft.au=Fox%2C+C%3BPolak%2C+J+F%3BChazaro%2C+I%3BCupples%2C+A%3BWolf%2C+P%3BD%27Agostino%2C+R+B%3BO%27Donnell%2C+C+J&rft.aulast=Fox&rft.aufirst=C&rft.date=2002-07-31&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Louisiana State University, 433 Bolivar St., New Orleans, LA 70112-2223, USA; phone: 504-568-4808; URL: www.lsumc.edu N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Bacterial-induced IL-10-producing CD4+ CD45RBlow CD25+ and CD25- regulatory T cells suppress helicobacter hepaticus-triggered colitis AN - 39549913; 3691245 AU - Kullberg, M C Y1 - 2002/07/31/ PY - 2002 DA - 2002 Jul 31 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39549913?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Bacterial-induced+IL-10-producing+CD4%2B+CD45RBlow+CD25%2B+and+CD25-+regulatory+T+cells+suppress+helicobacter+hepaticus-triggered+colitis&rft.au=Kullberg%2C+M+C&rft.aulast=Kullberg&rft.aufirst=M&rft.date=2002-07-31&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Keystone Symposia, 21996 US Highway 6, P.O. Box 38, Keystone, CO 80435, USA; email: symposia@vailresorts.com; URL: www.keystonesymposia.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - NIH strategic plan for biodefense research AN - 39546883; 3691446 AU - Hackett, C J Y1 - 2002/07/31/ PY - 2002 DA - 2002 Jul 31 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39546883?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=NIH+strategic+plan+for+biodefense+research&rft.au=Hackett%2C+C+J&rft.aulast=Hackett&rft.aufirst=C&rft.date=2002-07-31&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Keystone Symposium, 21996 US Highway 6, P.O. Box 38, Keystone, CO 80435, USA; email: symposia@vailresorts.com; URL: www.keystonesymposia.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Hippocampal gamma oscillations and neuronal cation currents; a journey from ion channel to network phenomenon AN - 39530406; 3697603 AU - Fisahn, A Y1 - 2002/07/31/ PY - 2002 DA - 2002 Jul 31 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39530406?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Hippocampal+gamma+oscillations+and+neuronal+cation+currents%3B+a+journey+from+ion+channel+to+network+phenomenon&rft.au=Fisahn%2C+A&rft.aulast=Fisahn&rft.aufirst=A&rft.date=2002-07-31&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: University of Arizona, c/o Robert S. Sloviter; phone: 520-626-6491; fax: 520-626-8244; email: soltiver@u.arizona.edu; URL: www.u.arizona.edu/~sloviter N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Distinct NMDA receptors provide differential modes of transmission at mossy fiber-interneuron synapses AN - 39526540; 3697570 AU - McBain, C Y1 - 2002/07/31/ PY - 2002 DA - 2002 Jul 31 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39526540?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Distinct+NMDA+receptors+provide+differential+modes+of+transmission+at+mossy+fiber-interneuron+synapses&rft.au=McBain%2C+C&rft.aulast=McBain&rft.aufirst=C&rft.date=2002-07-31&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: University of Arizona, c/o Robert S. Sloviter; phone: 520-626-6491; fax: 520-626-8244; email: soltiver@u.arizona.edu; URL: www.u.arizona.edu/~sloviter N1 - Last updated - 2010-05-03 ER - TY - JOUR T1 - Solution structure and dynamics of the human-Escherichia coli thioredoxin chimera: insights into thermodynamic stability. AN - 71940443; 12135359 AB - We have determined the high-resolution solution structure of the oxidized form of a chimeric human and Escherichia coli thioredoxin (TRX(HE)) by NMR. The overall structure is well-defined with a rms difference for the backbone atoms of 0.27 +/- 0.06 A. The topology of the protein is identical to those of the human and E. coli parent proteins, consisting of a central five-stranded beta-sheet surrounded by four alpha-helices. Analysis of the interfaces between the two domains derived from the human and E. coli sequences reveals that the general hydrophobic packing is unaltered and only subtle changes in the details of side chain interactions are observed. The packing of helix alpha(4) with helix alpha(2) across the hybrid interface is less optimal than in the parent molecules, and electrostatic interactions between polar side chains are missing. In particular, lysine-glutamate salt bridges between residues on helices alpha(2) and alpha(4), which were observed in both human and E. coli proteins, are not present in the chimeric protein. The origin of the known reduced thermodynamic stability of TRX(HE) was probed by mutagenesis on the basis of these structural findings. Two mutants of TRX(HE), S44D and S44E, were created, and their thermal and chemical stabilities were examined. Improved stability toward chaotropic agents was observed for both mutants, but no increase in the denaturation temperature was seen compared to that of TRX(HE). In addition to the structural analysis, the backbone dynamics of TRX(HE) were investigated by (15)N NMR relaxation measurements. Analysis using the model free approach reveals that the protein is fairly rigid with an average S(2) of 0.88. Increased mobility is primarily present in two external loop regions comprising residues 72-74 and 92-94 that contain glycine and proline residues. JF - Biochemistry AU - Dangi, Bindi AU - Dobrodumov, Anatoliy V AU - Louis, John M AU - Gronenborn, Angela M AD - Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0560, USA. Y1 - 2002/07/30/ PY - 2002 DA - 2002 Jul 30 SP - 9376 EP - 9388 VL - 41 IS - 30 SN - 0006-2960, 0006-2960 KW - Recombinant Fusion Proteins KW - 0 KW - Thioredoxins KW - 52500-60-4 KW - Index Medicus KW - Protein Structure, Secondary KW - Models, Molecular KW - Nuclear Magnetic Resonance, Biomolecular KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Thioredoxins -- genetics KW - Thioredoxins -- chemistry KW - Escherichia coli -- chemistry KW - Recombinant Fusion Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71940443?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Solution+structure+and+dynamics+of+the+human-Escherichia+coli+thioredoxin+chimera%3A+insights+into+thermodynamic+stability.&rft.au=Dangi%2C+Bindi%3BDobrodumov%2C+Anatoliy+V%3BLouis%2C+John+M%3BGronenborn%2C+Angela+M&rft.aulast=Dangi&rft.aufirst=Bindi&rft.date=2002-07-30&rft.volume=41&rft.issue=30&rft.spage=9376&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-08-22 N1 - Date created - 2002-07-23 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 1M7T; PDB N1 - SuppNotes - Erratum In: Biochemistry 2002 Oct 8;41(40):12270 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lys 43 and Asp 46 in alpha-helix 3 of uteroglobin are essential for its phospholipase A2 inhibitory activity. AN - 71929075; 12127976 AB - Uteroglobin (UG) is an anti-inflammatory, secreted protein with soluble phospholipase A2 (sPLA2)-inhibitory activity. However, the mechanism by which UG inhibits sPLA2 activity is unknown. UG is a homodimer in which each of the 70-amino acid subunits forms four alpha-helices. We previously reported that sPLA2-inhibitory activity of UG may reside in a segment of alpha-helix 3 that is exposed to the solvent. In addition, it has been suggested that UG may inhibit sPLA2 activity by binding and sequestering Ca++, essential for sPLA2 activation. By site-specific mutation, we demonstrate here that Lys 43 Glu, Asp 46 Lys or a combination of the two mutations in the full-length, recombinant human UG (rhUG) abrogates its sPLA2-inhibitory activity. We demonstrate further that recombinant UG does not bind Ca++ although when it is expressed with histidine-tag (H-tag) it is capable of binding Ca++. Taken together our results show that: (i) Lys 43 and Asp 46 in rhUG are critical residues for the sPLA2-inhibitory activity of UG and (ii) Ca++-sequestration by rhUG is not likely to be one of the mechanisms responsible for its sPLA2-inhibitory activity. JF - Biochemical and biophysical research communications AU - Chowdhury, Bhabadeb AU - Mantile-Selvaggi, Giuditta AU - Miele, Lucio AU - Cordella-Miele, Eleonora AU - Zhang, Zhongjian AU - Mukherjee, Anil B AD - Section on Developmental Genetics, Heritable Disorders Branch, NICHD, Bethesda, MD 20892-1830, USA. Y1 - 2002/07/26/ PY - 2002 DA - 2002 Jul 26 SP - 877 EP - 883 VL - 295 IS - 4 SN - 0006-291X, 0006-291X KW - DNA, Complementary KW - 0 KW - Recombinant Proteins KW - Aspartic Acid KW - 30KYC7MIAI KW - Glutamic Acid KW - 3KX376GY7L KW - Uteroglobin KW - 9060-09-7 KW - Phospholipases A KW - EC 3.1.1.32 KW - Phospholipases A2 KW - EC 3.1.1.4 KW - Lysine KW - K3Z4F929H6 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Protein Structure, Secondary KW - Glutamic Acid -- metabolism KW - Dose-Response Relationship, Drug KW - Dimerization KW - Protein Binding KW - Aspartic Acid -- chemistry KW - Calcium -- metabolism KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- metabolism KW - DNA, Complementary -- metabolism KW - Chromatography, Thin Layer KW - Protein Structure, Tertiary KW - Mutation KW - Lysine -- chemistry KW - Uteroglobin -- chemistry KW - Uteroglobin -- physiology KW - Uteroglobin -- isolation & purification KW - Lysine -- metabolism KW - Phospholipases A -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71929075?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Lys+43+and+Asp+46+in+alpha-helix+3+of+uteroglobin+are+essential+for+its+phospholipase+A2+inhibitory+activity.&rft.au=Chowdhury%2C+Bhabadeb%3BMantile-Selvaggi%2C+Giuditta%3BMiele%2C+Lucio%3BCordella-Miele%2C+Eleonora%3BZhang%2C+Zhongjian%3BMukherjee%2C+Anil+B&rft.aulast=Chowdhury&rft.aufirst=Bhabadeb&rft.date=2002-07-26&rft.volume=295&rft.issue=4&rft.spage=877&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 - 2002-09-04 N1 - Date created - 2002-07-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inositol lipid binding and membrane localization of isolated pleckstrin homology (PH) domains. Studies on the PH domains of phospholipase C delta 1 and p130. AN - 71926512; 12019260 AB - The relationship between the ability of isolated pleckstrin homology (PH) domains to bind inositol lipids or soluble inositol phosphates in vitro and to localize to cellular membranes in live cells was examined by comparing the PH domains of phospholipase Cdelta(1) (PLCdelta(1)) and the recently cloned PLC-like protein p130 fused to the green fluorescent protein (GFP). The prominent membrane localization of PLCdelta(1)PH-GFP was paralleled with high affinity binding to inositol 1,4,5-trisphosphate (InsP(3)) as well as to phosphatidylinositol 4,5-bisphosphate-containing lipid vesicles or nitrocellulose membrane strips. In contrast, no membrane localization was observed with p130PH-GFP despite its InsP(3) and phosphatidylinositol 4,5-bisphosphate-binding properties being comparable with those of PLCdelta(1)PH-GFP. The N-terminal ligand binding domain of the type I InsP(3) receptor also failed to localize to the plasma membrane despite its 5-fold higher affinity to InsP(3) than the PH domains. By using a chimeric approach and cassette mutagenesis, the C-terminal alpha-helix and the short loop between the beta6-beta7 sheets of the PLCdelta(1)PH domain, in addition to its InsP(3)-binding region, were identified as critical components for membrane localization in intact cells. These data indicate that binding to the inositol phosphate head group is necessary but may not be sufficient for membrane localization of the PLCdelta(1)PH-GFP fusion protein, and motifs located within the C-terminal half of the PH domain provide auxiliary contacts with additional membrane components. JF - The Journal of biological chemistry AU - Várnai, Péter AU - Lin, Xuena AU - Lee, Sang Bong AU - Tuymetova, Galina AU - Bondeva, Tzvetanka AU - Spät, Andras AU - Rhee, Sue Goo AU - Hajnóczky, György AU - Balla, Tamas AD - Endocrinology and Reproduction Research Branch, NICHD/National Institutes of Health, 49 Convent Drive, Bldg. 49, Bethesda, MD 20892, USA. Y1 - 2002/07/26/ PY - 2002 DA - 2002 Jul 26 SP - 27412 EP - 27422 VL - 277 IS - 30 SN - 0021-9258, 0021-9258 KW - Blood Proteins KW - 0 KW - Isoenzymes KW - Lipids KW - Luminescent Proteins KW - Phosphoproteins KW - Recombinant Fusion Proteins KW - Recombinant Proteins KW - platelet protein P47 KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Inositol KW - 4L6452S749 KW - DNA KW - 9007-49-2 KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Type C Phospholipases KW - EC 3.1.4.- KW - PLCD1 protein, human KW - EC 3.1.4.11 KW - Phospholipase C delta KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Microscopy, Confocal KW - Animals KW - Phosphoproteins -- chemistry KW - Spectrometry, Fluorescence KW - COS Cells KW - Humans KW - Inositol -- metabolism KW - Isoenzymes -- metabolism KW - Type C Phospholipases -- metabolism KW - Recombinant Fusion Proteins -- metabolism KW - Calcium -- metabolism KW - Microscopy, Fluorescence KW - Recombinant Proteins -- metabolism KW - Molecular Sequence Data KW - Inhibitory Concentration 50 KW - Sequence Homology, Amino Acid KW - Time Factors KW - Signal Transduction KW - Lipid Metabolism KW - Escherichia coli -- metabolism KW - Energy Transfer KW - Phosphatidylinositol 3-Kinases -- metabolism KW - Dose-Response Relationship, Drug KW - Models, Molecular KW - DNA -- metabolism KW - Blood Proteins -- chemistry KW - Amino Acid Sequence KW - Luminescent Proteins -- metabolism KW - Protein Binding KW - Transfection KW - Protein Structure, Tertiary KW - Lipids -- chemistry KW - Cell Membrane -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71926512?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Inositol+lipid+binding+and+membrane+localization+of+isolated+pleckstrin+homology+%28PH%29+domains.+Studies+on+the+PH+domains+of+phospholipase+C+delta+1+and+p130.&rft.au=V%C3%A1rnai%2C+P%C3%A9ter%3BLin%2C+Xuena%3BLee%2C+Sang+Bong%3BTuymetova%2C+Galina%3BBondeva%2C+Tzvetanka%3BSp%C3%A4t%2C+Andras%3BRhee%2C+Sue+Goo%3BHajn%C3%B3czky%2C+Gy%C3%B6rgy%3BBalla%2C+Tamas&rft.aulast=V%C3%A1rnai&rft.aufirst=P%C3%A9ter&rft.date=2002-07-26&rft.volume=277&rft.issue=30&rft.spage=27412&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 - 2002-08-22 N1 - Date created - 2002-07-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genome sequence of a serotype M3 strain of group A Streptococcus: phage-encoded toxins, the high-virulence phenotype, and clone emergence. AN - 71946921; 12122206 AB - Genome sequences are available for many bacterial strains, but there has been little progress in using these data to understand the molecular basis of pathogen emergence and differences in strain virulence. Serotype M3 strains of group A Streptococcus (GAS) are a common cause of severe invasive infections with unusually high rates of morbidity and mortality. To gain insight into the molecular basis of this high-virulence phenotype, we sequenced the genome of strain MGAS315, an organism isolated from a patient with streptococcal toxic shock syndrome. The genome is composed of 1,900,521 bp, and it shares approximately 1.7 Mb of related genetic material with genomes of serotype M1 and M18 strains. Phage-like elements account for the great majority of variation in gene content relative to the sequenced M1 and M18 strains. Recombination produces chimeric phages and strains with previously uncharacterized arrays of virulence factor genes. Strain MGAS315 has phage genes that encode proteins likely to contribute to pathogenesis, such as streptococcal pyrogenic exotoxin A (SpeA) and SpeK, streptococcal superantigen (SSA), and a previously uncharacterized phospholipase A(2) (designated Sla). Infected humans had anti-SpeK, -SSA, and -Sla antibodies, indicating that these GAS proteins are made in vivo. SpeK and SSA were pyrogenic and toxic for rabbits. Serotype M3 strains with the phage-encoded speK and sla genes increased dramatically in frequency late in the 20th century, commensurate with the rise in invasive disease caused by M3 organisms. Taken together, the results show that phage-mediated recombination has played a critical role in the emergence of a new, unusually virulent clone of serotype M3 GAS. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Beres, Stephen B AU - Sylva, Gail L AU - Barbian, Kent D AU - Lei, Benfang AU - Hoff, Jessica S AU - Mammarella, Nicole D AU - Liu, Meng-Yao AU - Smoot, James C AU - Porcella, Stephen F AU - Parkins, Larye D AU - Campbell, David S AU - Smith, Todd M AU - McCormick, John K AU - Leung, Donald Y M AU - Schlievert, Patrick M AU - Musser, James M AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Disease, National Institutes of Health, Hamilton, MT 59840, USA. Y1 - 2002/07/23/ PY - 2002 DA - 2002 Jul 23 SP - 10078 EP - 10083 VL - 99 IS - 15 SN - 0027-8424, 0027-8424 KW - Bacterial Toxins KW - 0 KW - Enterotoxins KW - Superantigens KW - enterotoxin F, Staphylococcal KW - Phospholipases A KW - EC 3.1.1.32 KW - Index Medicus KW - Phylogeny KW - Animals KW - Humans KW - Serotyping KW - Antibody Formation KW - Enterotoxins -- genetics KW - Amino Acid Sequence KW - Rabbits KW - Cloning, Molecular KW - Virulence KW - Phenotype KW - Shock, Septic -- microbiology KW - Sequence Alignment KW - Kinetics KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Phospholipases A -- metabolism KW - Bacterial Toxins -- genetics KW - Streptococcus -- pathogenicity KW - Streptococcus -- genetics KW - Genome, Bacterial KW - Streptococcus Phages -- physiology KW - Streptococcus -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71946921?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Genome+sequence+of+a+serotype+M3+strain+of+group+A+Streptococcus%3A+phage-encoded+toxins%2C+the+high-virulence+phenotype%2C+and+clone+emergence.&rft.au=Beres%2C+Stephen+B%3BSylva%2C+Gail+L%3BBarbian%2C+Kent+D%3BLei%2C+Benfang%3BHoff%2C+Jessica+S%3BMammarella%2C+Nicole+D%3BLiu%2C+Meng-Yao%3BSmoot%2C+James+C%3BPorcella%2C+Stephen+F%3BParkins%2C+Larye+D%3BCampbell%2C+David+S%3BSmith%2C+Todd+M%3BMcCormick%2C+John+K%3BLeung%2C+Donald+Y+M%3BSchlievert%2C+Patrick+M%3BMusser%2C+James+M&rft.aulast=Beres&rft.aufirst=Stephen&rft.date=2002-07-23&rft.volume=99&rft.issue=15&rft.spage=10078&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 - 2002-09-04 N1 - Date created - 2002-07-24 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AE014074; GENBANK N1 - SuppNotes - Cited By: Infect Immun. 2001 Nov;69(11):7169-72 [11598096] Nat Med. 1999 Aug;5(8):924-9 [10426317] Clin Infect Dis. 2002 Feb 15;34(4):454-60 [11797171] Trends Microbiol. 2001 Nov;9(11):547-53 [11825715] Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4668-73 [11917108] J Clin Microbiol. 2002 May;40(5):1805-10 [11980963] Infect Immun. 1978 Sep;21(3):753-63 [361577] Ann N Y Acad Sci. 1980;354:484-90 [6452848] Zentralbl Bakteriol Mikrobiol Hyg A. 1987 Aug;266(1-2):104-15 [3122461] J Bacteriol. 1989 Oct;171(10):5531-5 [2477359] Infect Immun. 1991 Mar;59(3):879-84 [1997438] Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2668-72 [1672766] Anal Biochem. 1992 Jul;204(1):190-7 [1514686] J Infect Dis. 1993 Feb;167(2):337-46 [8093623] Biochim Biophys Acta. 1993 Feb 13;1161(2-3):223-9 [8431471] J Infect Dis. 1993 Mar;167(3):759-62 [8440944] Infect Immun. 1994 May;62(5):1867-74 [8168951] J Bacteriol. 1994 Jun;176(11):3393-6 [8195098] Gene. 1994 Dec 2;150(1):135-40 [7959039] Microb Pathog. 1994 Jun;16(6):443-50 [7830531] Infect Immun. 1995 Mar;63(3):994-1003 [7868273] J Bacteriol. 1995 Mar;177(5):1123-8 [7868582] Infect Immun. 1995 Aug;63(8):3015-20 [7622224] Infect Immun. 1996 Apr;64(4):1161-5 [8606073] Infect Immun. 1996 Jun;64(6):2122-9 [8675316] J Immunol. 1996 Sep 15;157(6):2479-87 [8805648] Emerg Infect Dis. 1996 Jan-Mar;2(1):1-17 [8903193] Trends Genet. 2000 Jun;16(6):276-7 [10827456] Clin Microbiol Rev. 2000 Jul;13(3):470-511 [10885988] J Immunol. 2000 Aug 15;165(4):2306-12 [10925320] Infect Immun. 2000 Dec;68(12):6542-53 [11083763] Infect Immun. 2000 Dec;68(12):6807-18 [11083799] J Clin Invest. 2001 Feb;107(4):391-2 [11181636] J Clin Invest. 2001 Feb;107(4):393-9 [11181637] Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4658-63 [11296296] Infect Immun. 2001 Jun;69(6):4019-26 [11349071] Protein Eng. 1997 Jan;10(1):1-6 [9051728] J Clin Microbiol. 1997 May;35(5):1231-5 [9114412] J Clin Invest. 1997 Jun 1;99(11):2574-80 [9169486] J Infect Dis. 1997 Feb;175(2):392-9 [9203660] J Infect Dis. 1998 Apr;177(4):967-76 [9534970] Infect Immun. 1998 Jul;66(7):3449-53 [9632622] Emerg Infect Dis. 1999 Mar-Apr;5(2):254-63 [10221878] Nat Med. 2001 Dec;7(12):1298-305 [11726969] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular basis for the dichotomy in Plasmodium falciparum adhesion to CD36 and chondroitin sulfate A. AN - 71940378; 12096191 AB - Plasmodium falciparum-infected erythrocytes adhere dichotomously to the host receptors CD36 and chondroitin sulfate A (CSA). This dichotomy is associated with parasite sequestration to microvasculature beds (CD36) or placenta (CSA), leading to site-specific pathogenesis. Both properties are mediated by members of the variant P. falciparum erythrocyte membrane protein 1 (PfEMP-1) family and reside on nonoverlapping domains of the molecule. To identify the molecular basis for the apparent dichotomy, we expressed various domains of PfEMP-1 individually or in combination and tested their binding properties. We found that the CD36-binding mode of the cysteine-rich interdomain region-1 (CIDR1) ablates the ability of the Duffy binding-like gamma domain to bind CSA. In contrast, neither a non-CD36-binding CIDR1 nor an intercellular adhesion molecule 1 binding domain had any affect on CSA binding. Our findings point out that interactions between different domains of PfEMP-1 can alter the adhesion phenotype of infected erythrocytes and provide a molecular basis for the apparent dichotomy in adhesion. We suggest that the basis for the dichotomy is structural and that mutually exclusive conformations of PfEMP-1 are involved in binding to CD36 or CSA. Furthermore, we propose a model explaining the requirement for structural dichotomy between placental and nonplacental isolates. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Gamain, Benoit AU - Gratepanche, Sylvie AU - Miller, Louis H AU - Baruch, Dror I AD - Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. bgamain@niaid.nih.gov Y1 - 2002/07/23/ PY - 2002 DA - 2002 Jul 23 SP - 10020 EP - 10024 VL - 99 IS - 15 SN - 0027-8424, 0027-8424 KW - Antigens, CD36 KW - 0 KW - Protozoan Proteins KW - Recombinant Proteins KW - erythrocyte membrane protein 1, Plasmodium falciparum KW - Chondroitin Sulfates KW - 9007-28-7 KW - Index Medicus KW - Genetic Variation KW - Animals KW - Mammals KW - Recombinant Proteins -- metabolism KW - Erythrocyte Membrane -- parasitology KW - CHO Cells KW - Recombinant Proteins -- chemistry KW - Cell Line KW - Mutagenesis KW - Cricetinae KW - Protozoan Proteins -- chemistry KW - Erythrocytes -- parasitology KW - Chondroitin Sulfates -- physiology KW - Antigens, CD36 -- physiology KW - Plasmodium falciparum -- genetics KW - Protozoan Proteins -- genetics KW - Protozoan Proteins -- physiology KW - Plasmodium falciparum -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71940378?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Molecular+basis+for+the+dichotomy+in+Plasmodium+falciparum+adhesion+to+CD36+and+chondroitin+sulfate+A.&rft.au=Gamain%2C+Benoit%3BGratepanche%2C+Sylvie%3BMiller%2C+Louis+H%3BBaruch%2C+Dror+I&rft.aulast=Gamain&rft.aufirst=Benoit&rft.date=2002-07-23&rft.volume=99&rft.issue=15&rft.spage=10020&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 - 2002-09-04 N1 - Date created - 2002-07-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nat Med. 1998 Mar;4(3):358-60 [9500614] Blood. 1997 Nov 1;90(9):3766-75 [9345064] EMBO J. 1998 Sep 15;17(18):5418-26 [9736619] Nature. 1998 Oct 29;395(6705):851-2 [9804416] Br Med Bull. 1998;54(2):293-309 [9830198] Mol Biochem Parasitol. 1998 Nov 30;97(1-2):133-48 [9879893] Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5198-202 [10220443] J Infect Dis. 1999 Aug;180(2):464-72 [10395863] Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12743-8 [10535993] Nat Med. 2000 Jan;6(1):86-90 [10613830] Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1766-71 [10677532] Clin Microbiol Rev. 2000 Jul;13(3):439-50 [10885986] J Immunol. 2000 Sep 15;165(6):3309-16 [10975848] J Exp Med. 2000 Oct 16;192(8):1205-11 [11034611] Mol Biochem Parasitol. 2000 Oct;110(2):293-310 [11071284] Trends Parasitol. 2001 Mar;17(3):145-9 [11286800] Blood. 2001 May 15;97(10):3268-74 [11342458] Science. 2001 Sep 14;293(5537):2098-100 [11557894] Trans R Soc Trop Med Hyg. 1979;73(6):716-9 [395729] Proc Natl Acad Sci U S A. 1983 Aug;80(16):5075-9 [6348780] J Exp Med. 1984 Jun 1;159(6):1567-75 [6374009] Science. 1986 Jan 10;231(4734):150-3 [2417315] Am J Trop Med Hyg. 1992 Nov;47(5):621-32 [1449203] J Exp Med. 1995 Jul 1;182(1):15-20 [7790815] Cell. 1995 Jul 14;82(1):77-87 [7541722] Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3497-502 [8622965] Science. 1996 Jun 7;272(5267):1502-4 [8633247] Am J Trop Med Hyg. 1996 Jul;55(1):76-80 [8702026] Ann Trop Med Parasitol. 1997 Jul;91(5):551-7 [9329992] Am J Trop Med Hyg. 1997 Oct;57(4):389-98 [9347951] J Mol Med (Berl). 1998 Mar;76(3-4):162-71 [9535549] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Amino acid residue 184 of yeast Hsp104 chaperone is critical for prion-curing by guanidine, prion propagation, and thermotolerance. AN - 71936917; 12105276 AB - Inactivation of Hsp104 by guanidine is contended to be the mechanism by which guanidine cures yeast prions. We now find an Hsp104 mutation (D184N) that confers resistance to guanidine-curing of the yeast [PSI(+)] prion. In an independent screen we isolated an HSP104 allele altered in the same residue (D184Y) that dramatically impairs [PSI(+)] propagation in a temperature-dependent manner. Directed mutagenesis of HSP104 produced additional alleles that conferred varying degrees of resistance to guanidine-curing or impaired [PSI(+)] propagation. The mutations similarly affected propagation of the [URE3] prion. Basal and induced abundance of all mutant proteins was normal. Thermotolerance of cells expressing mutant proteins was variably resistant to guanidine, and the degree of thermotolerance did not correlate with [PSI(+)] stability. We thus show that guanidine cures yeast prions by inactivating Hsp104 and identify a highly conserved Hsp104 residue that is critical for yeast prion propagation. Our data suggest that Hsp104 activity can be reduced substantially without affecting [PSI(+)] stability, and that Hsp104 interacts differently with prion aggregates than with aggregates of thermally denatured protein. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Jung, Giman AU - Jones, Gary AU - Masison, Daniel C AD - Laboratory of Biochemistry and Genetics, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Building 8, Room 407, Bethesda, MD 20892-0851, USA. Y1 - 2002/07/23/ PY - 2002 DA - 2002 Jul 23 SP - 9936 EP - 9941 VL - 99 IS - 15 SN - 0027-8424, 0027-8424 KW - Heat-Shock Proteins KW - 0 KW - Prions KW - Saccharomyces cerevisiae Proteins KW - HsP104 protein, S cerevisiae KW - 143012-44-6 KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - Guanidine KW - JU58VJ6Y3B KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Temperature KW - Amino Acid Sequence KW - Plasmids KW - Amino Acid Substitution KW - Saccharomyces cerevisiae -- genetics KW - Prions -- physiology KW - Prions -- drug effects KW - Guanidine -- pharmacology KW - Saccharomyces cerevisiae Proteins -- genetics KW - Adenosine Triphosphatases -- chemistry KW - Saccharomyces cerevisiae Proteins -- chemistry KW - Adenosine Triphosphatases -- genetics KW - Heat-Shock Proteins -- genetics KW - Heat-Shock Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71936917?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Amino+acid+residue+184+of+yeast+Hsp104+chaperone+is+critical+for+prion-curing+by+guanidine%2C+prion+propagation%2C+and+thermotolerance.&rft.au=Jung%2C+Giman%3BJones%2C+Gary%3BMasison%2C+Daniel+C&rft.aulast=Jung&rft.aufirst=Giman&rft.date=2002-07-23&rft.volume=99&rft.issue=15&rft.spage=9936&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 - 2002-09-04 N1 - Date created - 2002-07-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Cell. 2000 Jan;5(1):163-72 [10678178] Trends Biochem Sci. 1996 Aug;21(8):289-96 [8772382] Genetics. 2000 Oct;156(2):559-70 [11014806] Mol Cell Biol. 2000 Dec;20(23):8916-22 [11073991] Curr Biol. 2000 Nov 16;10(22):1443-6 [11102806] Curr Microbiol. 2001 Jul;43(1):7-10 [11375656] Mol Cell Biol. 2001 Jul;21(14):4656-69 [11416143] Mol Microbiol. 2001 Jun;40(6):1357-69 [11442834] Cell. 2001 Jul 27;106(2):171-82 [11511345] Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12503-8 [9356479] Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13938-43 [9391131] J Biol Chem. 1998 Jun 19;273(25):15546-52 [9624144] Cell. 1998 Jul 10;94(1):13-6 [9674422] Cell. 1998 Jul 10;94(1):73-82 [9674429] Mol Cell Biol. 1999 Feb;19(2):1325-33 [9891066] Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1498-503 [9990052] EMBO J. 1999 Apr 1;18(7):1974-81 [10202160] EMBO J. 2002 Jan 15;21(1-2):12-21 [11782421] Mol Cell Biol. 2002 Jun;22(11):3590-8 [11997496] J Bacteriol. 1971 May;106(2):519-22 [5573734] Mol Gen Genet. 1977 Feb 15;150(3):265-70 [321935] Genetics. 1981 Aug;98(4):691-711 [7037537] Genetics. 1987 Aug;116(4):541-5 [3305158] Genetics. 1988 Nov;120(3):681-95 [3066684] Genetics. 1989 May;122(1):19-27 [2659436] Science. 1990 Jun 1;248(4959):1112-5 [2188365] Methods Enzymol. 1991;194:302-18 [2005795] Nature. 1991 Sep 19;353(6341):270-3 [1896074] EMBO J. 1992 Jun;11(6):2357-64 [1600951] J Biol Chem. 1994 Feb 11;269(6):4480-7 [8308017] Science. 1994 Apr 22;264(5158):566-9 [7909170] Nature. 1994 Dec 1;372(6505):475-8 [7984243] Science. 1995 May 12;268(5212):880-4 [7754373] Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):240-4 [10618402] EMBO J. 2000 Feb 1;19(3):324-31 [10654931] Cell. 2000 Jan 21;100(2):277-88 [10660050] EMBO J. 1995 Aug 15;14(16):4065-72 [7664746] EMBO J. 1995 Sep 1;14(17):4365-73 [7556078] Proc Natl Acad Sci U S A. 1996 May 28;93(11):5301-6 [8643570] EMBO J. 1996 Jun 17;15(12):3127-34 [8670813] Science. 1996 Aug 2;273(5275):622-6 [8662547] EMBO J. 2000 May 2;19(9):1942-52 [10790361] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Designed to penetrate: Time-resolved interaction of single antibiotic molecules with bacterial pores AN - 18438784; 5415092 AB - Membrane permeability barriers are among the factors contributing to the intrinsic resistance of bacteria to antibiotics. We have been able to resolve single ampicillin molecules moving through a channel of the general bacterial porin, OmpF (outer membrane protein F), believed to be the principal pathway for the beta -lactam antibiotics. With ion channel reconstitution and high-resolution conductance recording, we find that ampicillin and several other efficient penicillins and cephalosporins strongly interact with the residues of the constriction zone of the OmpF channel. Therefore, we hypothesize that, in analogy to substrate-specific channels that evolved to bind certain metabolite molecules, antibiotics have "evolved" to be channel-specific. Molecular modeling suggests that the charge distribution of the ampicillin molecule complements the charge distribution at the narrowest part of the bacterial porin. Interaction of these charges creates a region of attraction inside the channel that facilitates drug translocation through the constriction zone and results in higher permeability rates. JF - Proceedings of the National Academy of Sciences, USA AU - Nestorovich, E M AU - Danelon, C AU - Winterhalter, M AU - Bezrukov, S M AD - Laboratory of Physical and Structural Biology, National Institute of Child Health and Human Development, National Institutes of Health, Building 9, Room 1E-122, Bethesda, MD 20892-0924, USA, bezrukov@helix.nih.gov Y1 - 2002/07/23/ PY - 2002 DA - 2002 Jul 23 SP - 9789 EP - 9794 VL - 99 IS - 15 SN - 0027-8424, 0027-8424 KW - OmpF protein KW - Microbiology Abstracts B: Bacteriology KW - J 02785:Beta-lactam antibiotics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18438784?accountid=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=Designed+to+penetrate%3A+Time-resolved+interaction+of+single+antibiotic+molecules+with+bacterial+pores&rft.au=Nestorovich%2C+E+M%3BDanelon%2C+C%3BWinterhalter%2C+M%3BBezrukov%2C+S+M&rft.aulast=Nestorovich&rft.aufirst=E&rft.date=2002-07-23&rft.volume=99&rft.issue=15&rft.spage=9789&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.152206799 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1073/pnas.152206799 ER - TY - JOUR T1 - Alcohol use and HIV pharmacotherapy. AN - 71985255; 12167267 AB - Alcohol consumption by individuals infected with HIV is an important medical management issue with significant implications for the effectiveness of antiretroviral therapy as well as an important evolving field of HIV research. Alcohol consumption is a risk factor for poor medication adherence and can modify liver drug metabolism, both of which can lead to the emergence of drug-resistant virus. Research indicates that alcohol consumption greater than 50 g/day (four or five drinks) is a risk factor for liver disease progression among patients with HIV/HCV coinfection. In addition, alcohol-induced cirrhosis can result in changes in drug metabolism in the liver through compromised liver function. More research studies are needed to elucidate the biological and molecular basis of the clinical changes induced by alcohol consumption in HIV-infected individuals and on the relationship of these changes to the effectiveness of HIV pharmacotherapy. Specifically, research areas that are of particular importance are (1) determining alcohol consumption levels and patterns and its impact on antiretroviral medication adherence, efficacy, and physician prescribing practices; (2) identifying behavioral interventions to enhance adherence to HIV medications and reduce alcohol consumption; (3) clarifying the relationships and interactions among alcohol metabolism, HIV drug metabolism, and pharmacogenetics; (4) elucidating the extent of liver toxicity due to antiretroviral therapy and drug-drug interactions in individuals who consume alcohol; and (5) delineating the contribution of alcohol consumption to end-stage organ damage, particularly in HIV/HCV coinfection. JF - AIDS research and human retroviruses AU - Kresina, Thomas F AU - Flexner, Charles W AU - Sinclair, Jacqueline AU - Correia, Maria Almira AU - Stapleton, Jack T AU - Adeniyi-Jones, Samuel AU - Cargill, Victoria AU - Cheever, Laura W AD - National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2002/07/20/ PY - 2002 DA - 2002 Jul 20 SP - 757 EP - 770 VL - 18 IS - 11 SN - 0889-2229, 0889-2229 KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - AIDS/HIV KW - Liver -- physiopathology KW - Drug Interactions KW - Risk-Taking KW - Patient Compliance KW - Hepatitis C -- complications KW - Risk Factors KW - Humans KW - Ethanol -- metabolism KW - Liver Diseases, Alcoholic -- complications KW - Male KW - Female KW - HIV Infections -- complications KW - HIV Infections -- drug therapy KW - Alcoholism -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71985255?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Alcohol+use+and+HIV+pharmacotherapy.&rft.au=Kresina%2C+Thomas+F%3BFlexner%2C+Charles+W%3BSinclair%2C+Jacqueline%3BCorreia%2C+Maria+Almira%3BStapleton%2C+Jack+T%3BAdeniyi-Jones%2C+Samuel%3BCargill%2C+Victoria%3BCheever%2C+Laura+W&rft.aulast=Kresina&rft.aufirst=Thomas&rft.date=2002-07-20&rft.volume=18&rft.issue=11&rft.spage=757&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 - 2002-09-19 N1 - Date created - 2002-08-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutating conserved residues in the ribonuclease H domain of Ty3 reverse transcriptase affects specialized cleavage events. AN - 71907704; 11994277 AB - The reverse transcriptase-associated ribonuclease H (RT/RNase H) domains from the gypsy group of retrotransposons, of which Ty3 is a member, share considerable sequence homology with their retroviral counterparts. However, the gypsy elements have a conserved tyrosine (position 459 in Ty3 RT) instead of the conserved histidine in the catalytic center of retroviral RTs such as at position 539 of HIV-1. In addition, the gypsy group shows conservation of histidine adjacent to the third of the metal-chelating carboxylate residues, which is Asp-426 of Ty3 RT. The role of these and additional catalytic residues was assessed with purified recombinant enzymes and through the ability of Ty3 mutants to support transposition in Saccaromyces cerevisiae. Although all mutations had minimal impact on DNA polymerase function, amidation of Asp-358, Glu-401, and Asp-426 eliminated Mg(2+)- and Mn(2+)-dependent RNase H function. Replacing His-427 and Tyr-459 with Ala and Asp-469 with Asn resulted in reduced RNase H activity in the presence of Mg(2+), whereas in the presence of Mn(2+) these mutants displayed a lack of turnover. Despite this, mutations at all positions were lethal for transposition. To reconcile these apparently contradictory findings, the efficiency of specialized RNase H-mediated events was examined for each enzyme. Mutants retaining RNase H activity on a heteropolymeric RNA.DNA hybrid failed to support DNA strand transfer and release of the (+) strand polypurine tract primer from (+) RNA, suggesting that interrupting one or both of these events might account for the transposition defect. JF - The Journal of biological chemistry AU - Lener, Daniela AU - Budihas, Scott R AU - Le Grice, Stuart F J AD - Reverse Transcriptase Biochemistry Section, Resistance Mechanisms Laboratory, HIV Drug Resistance Program, NCI-Frederick, National Institutes of Health, Frederick, Maryland 21702, USA. Y1 - 2002/07/19/ PY - 2002 DA - 2002 Jul 19 SP - 26486 EP - 26495 VL - 277 IS - 29 SN - 0021-9258, 0021-9258 KW - Retroelements KW - 0 KW - Manganese KW - 42Z2K6ZL8P KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - Ribonuclease H KW - EC 3.1.26.4 KW - Magnesium KW - I38ZP9992A KW - Index Medicus KW - Manganese -- metabolism KW - Models, Molecular KW - Amino Acid Sequence KW - Protein Binding KW - Structure-Activity Relationship KW - Saccharomyces cerevisiae KW - Magnesium -- metabolism KW - Mutagenesis, Site-Directed KW - Conserved Sequence KW - Cells, Cultured KW - Escherichia coli KW - Molecular Sequence Data KW - Mutation KW - Amino Acid Substitution KW - Protein Conformation KW - HIV Reverse Transcriptase -- metabolism KW - HIV Reverse Transcriptase -- chemistry KW - Ribonuclease H -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71907704?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Mutating+conserved+residues+in+the+ribonuclease+H+domain+of+Ty3+reverse+transcriptase+affects+specialized+cleavage+events.&rft.au=Lener%2C+Daniela%3BBudihas%2C+Scott+R%3BLe+Grice%2C+Stuart+F+J&rft.aulast=Lener&rft.aufirst=Daniela&rft.date=2002-07-19&rft.volume=277&rft.issue=29&rft.spage=26486&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 - 2002-09-06 N1 - Date created - 2002-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic diversity and chloroquine selective sweeps in Plasmodium falciparum AN - 18436251; 5419792 AB - Widespread use of antimalarial agents can profoundly influence the evolution of the human malaria parasite Plasmodium falciparum. Recent selective sweeps for drug-resistant genotypes may have restricted the genetic diversity of this parasite, resembling effects attributed in current debates to a historic population bottleneck. Chloroquine-resistant (CQR) parasites were initially reported about 45 years ago from two foci in southeast Asia and South America, but the number of CQR founder mutations and the impact of chlorquine on parasite genomes worldwide have been difficult to evaluate. Using 342 highly polymorphic microsatellite markers from a genetic map, here we show that the level of genetic diversity varies substantially among different regions of the parasite genome, revealing extensive linkage disequilibrium surrounding the key CQR gene pfcrt and at least four CQR founder events. This disequilibrium and its decay rate in the pfcrt-flanking region are consistent with strong directional selective sweeps occurring over only similar to 20--80 sexual generations, especially a single resistant pfcrt haplotype spreading to very high frequencies throughout most of Asia and Africa. The presence of linkage disequilibrium provides a basis for mapping genes under drug selection in P. falciparum. JF - Nature AU - Wootton, J C AU - Feng, X AU - Ferdig, M T AU - Cooper, R A AU - Mu, J AU - Baruch, DI AU - Magill, A J AU - Su, X-Z AD - Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0425, USA, xsu@niaid.nih.gov Y1 - 2002/07/18/ PY - 2002 DA - 2002 Jul 18 SP - 320 EP - 323 PB - Macmillan Publishers Ltd. VL - 418 IS - 6895 SN - 0028-0836, 0028-0836 KW - Mosquitoes KW - natural selection KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; Genetics Abstracts; ASFA 3: Aquatic Pollution & Environmental Quality KW - Freshwater KW - Q5 01524:Public health, medicines, dangerous organisms KW - K 03090:Protozoa: human KW - G 07361:Protozoans/slime molds UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18436251?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=Genetic+diversity+and+chloroquine+selective+sweeps+in+Plasmodium+falciparum&rft.au=Wootton%2C+J+C%3BFeng%2C+X%3BFerdig%2C+M+T%3BCooper%2C+R+A%3BMu%2C+J%3BBaruch%2C+DI%3BMagill%2C+A+J%3BSu%2C+X-Z&rft.aulast=Wootton&rft.aufirst=J&rft.date=2002-07-18&rft.volume=418&rft.issue=6895&rft.spage=320&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 - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Freshwater ER - TY - JOUR T1 - Chromosome-wide SNPs reveal an ancient origin for Plasmodium falciparum AN - 18435304; 5419793 AB - The Malaria's Eve hypothesis, proposing a severe recent population bottleneck (about 3,000--5,000 years ago) of the human malaria parasite Plasmodium falciparum, has prompted a debate about the origin and evolution of the parasite. The hypothesis implies that the parasite population is relatively homogeneous, favouring malaria control measures. Other studies, however, suggested an ancient origin and large effective population size. To test the hypothesis, we analysed single nucleotide polymorphisms (SNPs) from 204 genes on chromosome 3 of P. falciparum. We have identified 403 polymorphic sites, including 238 SNPs and 165 microsatellites, from five parasite clones, establishing chromosome-wide haplotypes and a dense map with one polymorphic marker per similar to 2.3 kilobases. On the basis of synonymous SNPs and non-coding SNPs, we estimate the time to the most recent common ancestor to be similar to 100,000--180,000 years, significantly older than the proposed bottleneck. Our estimated divergence time coincides approximately with the start of human population expansion, and is consistent with a genetically complex organism able to evade host immunity and other antimalarial efforts. JF - Nature AU - Mu, J AU - Duan, J AU - Makova, K D AU - Joy, DA AU - Huynh, C Q AU - Branch, OH AU - Li, W-H AU - Su, X-Z AD - Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0425, USA, xsu@niaid.nih.gov Y1 - 2002/07/18/ PY - 2002 DA - 2002 Jul 18 SP - 323 EP - 324 PB - Macmillan Publishers Ltd. VL - 418 IS - 6895 SN - 0028-0836, 0028-0836 KW - Mosquitoes KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; ASFA 3: Aquatic Pollution & Environmental Quality; Genetics Abstracts KW - Freshwater KW - Q5 01524:Public health, medicines, dangerous organisms KW - G 07270:Ecological genetics KW - G 07361:Protozoans/slime molds KW - K 03091:Protozoa: animal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18435304?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=Chromosome-wide+SNPs+reveal+an+ancient+origin+for+Plasmodium+falciparum&rft.au=Mu%2C+J%3BDuan%2C+J%3BMakova%2C+K+D%3BJoy%2C+DA%3BHuynh%2C+C+Q%3BBranch%2C+OH%3BLi%2C+W-H%3BSu%2C+X-Z&rft.aulast=Mu&rft.aufirst=J&rft.date=2002-07-18&rft.volume=418&rft.issue=6895&rft.spage=323&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 - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Freshwater ER - TY - JOUR T1 - Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women. Principal Results From the Women's Health Initiative Randomized Controlled Trial AN - 18478750; 5443959 AB - Despite decades of accumulated observational evidence, the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain. To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States. Estrogen plus progestin component of the Women's Health Initiative, a randomized controlled primary prevention trial (planned duration, 8.5 years) in which 16608 postmenopausal women aged 50-79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993-1998. Participants received conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102). The primary outcome was coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the primary adverse outcome. A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, and death due to other causes. On May 31, 2002, after a mean of 5.2 years of follow-up, the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits. This report includes data on the major clinical outcomes through April 30, 2002. Estimated hazard ratios (HRs) (nominal 95% confidence intervals [CIs]) were as follows: CHD, 1.29 (1.02-1.63) with 286 cases; breast cancer, 1.26 (1.00-1.59) with 290 cases; stroke, 1.41 (1.07-1.85) with 212 cases; PE, 2.13 (1.39-3.25) with 101 cases; colorectal cancer, 0.63 (0.43-0.92) with 112 cases; endometrial cancer, 0.83 (0.47-1.47) with 47 cases; hip fracture, 0.66 (0.45-0.98) with 106 cases; and death due to other causes, 0.92 (0.74-1.14) with 331 cases. Corresponding HRs (nominal 95% CIs) for composite outcomes were 1.22 (1.09-1.36) for total cardiovascular disease (arterial and venous disease), 1.03 (0.90-1.17) for total cancer, 0.76 (0.69-0.85) for combined fractures, 0.98 (0.82-1.18) for total mortality, and 1.15 (1.03-1.28) for the global index. Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures. The absolute excess risk of events included in the global index was 19 per 10 000 person-years. Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women. All-cause mortality was not affected during the trial. The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD. JF - Journal of the American Medical Association AU - Rossouw, JE AU - Anderson, G L AU - Prentice, R L AU - LaCroix, A Z AU - Kooperberg, C AU - Stefanick, M L AU - Jackson, R D AU - Beresford, SAA AU - Howard, B V AU - Johnson, K C AU - Kotchen, J M AU - Ockene, J AD - Division of Women's Health Initiative, National Heart, Lung, and Blood Institute, 6705 Rockledge Dr, One Rockledge Ctr, Suite 300, MS/7966, Bethesda, MD 20817, USA, rossouw@nih.gov Y1 - 2002/07/17/ PY - 2002 DA - 2002 Jul 17 SP - 321 EP - 333 VL - 288 IS - 3 SN - 0098-7484, 0098-7484 KW - hormone replacement therapy KW - post-menopause KW - Health & Safety Science Abstracts KW - H 4000:Food and Drugs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18478750?accountid=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+the+American+Medical+Association&rft.atitle=Risks+and+Benefits+of+Estrogen+Plus+Progestin+in+Healthy+Postmenopausal+Women.+Principal+Results+From+the+Women%27s+Health+Initiative+Randomized+Controlled+Trial&rft.au=Rossouw%2C+JE%3BAnderson%2C+G+L%3BPrentice%2C+R+L%3BLaCroix%2C+A+Z%3BKooperberg%2C+C%3BStefanick%2C+M+L%3BJackson%2C+R+D%3BBeresford%2C+SAA%3BHoward%2C+B+V%3BJohnson%2C+K+C%3BKotchen%2C+J+M%3BOckene%2C+J&rft.aulast=Rossouw&rft.aufirst=JE&rft.date=2002-07-17&rft.volume=288&rft.issue=3&rft.spage=321&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Medical+Association&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Menopausal Hormone Replacement Therapy and Risk of Ovarian Cancer AN - 18477842; 5443958 AB - The association between menopausal hormone replacement therapy and ovarian cancer is unclear. To determine whether hormone replacement therapy using estrogen only, estrogen-progestin only, or both estrogen only and estrogen-progestin increases ovarian cancer risk. A 1979-1998 cohort study of former participants in the Breast Cancer Detection Demonstration Project, a nationwide breast cancer screening program. Twenty-nine US clinical centers. A total of 44 241 postmenopausal women (mean age at start of follow-up, 56.6 years). Incident ovarian cancer. We identified 329 women who developed ovarian cancer during follow-up. In time-dependent analyses adjusted for age, menopause type, and oral contraceptive use, ever use of estrogen only was significantly associated with ovarian cancer (rate ratio [RR], 1.6; 95% confidence interval [CI], 1.2-2.0). Increasing duration of estrogen-only use was significantly associated with ovarian cancer: RRs for 10 to 19 years and 20 or more years were 1.8 (95% CI, 1.1-3.0) and 3.2 (95% CI, 1.7-5.7), respectively (P value for trend <.001), and we observed a 7% (95% CI, 2%-13%) increase in RR per year of use. We observed significantly elevated RRs with increasing duration of estrogen-only use across all strata of other ovarian cancer risk factors, including women with hysterectomy. The RR for estrogen-progestin use after prior estrogen-only use was 1.5 (95% CI, 0.91-2.4), but the RR for estrogen-progestin-only use was 1.1 (95% CI, 0.64-1.7). The RRs for less than 2 years and 2 or more years of estrogen-progestin-only use were 1.6 (95% CI, 0.78-3.3) and 0.80 (95% CI, 0.35-1.8), respectively, and there was no evidence of a duration response (P value for trend = .30). Women who used estrogen-only replacement therapy, particularly for 10 or more years, were at significantly increased risk of ovarian cancer in this study. Women who used short-term estrogen-progestin-only replacement therapy were not at increased risk, but risk associated with short-term and longer-term estrogen-progestin replacement therapy warrants further investigation. JF - Journal of the American Medical Association AU - Lacey, JV Jr AU - Mink, P J AU - Lubin, J H AU - Sherman, ME AU - Troisi, R AU - Hartge, P AU - Schatzkin, A AU - Schairer, C AD - National Cancer Institute, Division of Cancer Epidemiology and Genetics, 6120 Executive Blvd, MSC 7234, Rockville, MD 20852, USA, jimlacey@nih.gov Y1 - 2002/07/17/ PY - 2002 DA - 2002 Jul 17 SP - 334 EP - 341 VL - 288 IS - 3 SN - 0098-7484, 0098-7484 KW - hormone replacement therapy KW - ovarian carcinoma KW - Health & Safety Science Abstracts; Risk Abstracts KW - R2 23060:Medical and environmental health KW - H 4000:Food and Drugs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18477842?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Medical+Association&rft.atitle=Menopausal+Hormone+Replacement+Therapy+and+Risk+of+Ovarian+Cancer&rft.au=Lacey%2C+JV+Jr%3BMink%2C+P+J%3BLubin%2C+J+H%3BSherman%2C+ME%3BTroisi%2C+R%3BHartge%2C+P%3BSchatzkin%2C+A%3BSchairer%2C+C&rft.aulast=Lacey&rft.aufirst=JV&rft.date=2002-07-17&rft.volume=288&rft.issue=3&rft.spage=334&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Medical+Association&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Safety and efficacy of liposomal amphotericin B compared with conventional amphotericin B for induction therapy of histoplasmosis in patients with AIDS. AN - 71915161; 12118965 AB - In patients with moderate to severe histoplasmosis associated with AIDS, the preferred treatment has been the deoxycholate formulation of amphotericin B. However, serious side effects are associated with use of amphotericin B. To compare amphotericin B with liposomal amphotericin B for induction therapy of moderate to severe disseminated histoplasmosis in patients with AIDS. Randomized, double-blind, multicenter clinical trial. 21 sites of the U.S. National Institute of Allergy and Infectious Diseases Mycoses Study Group. 81 patients with AIDS and moderate to severe disseminated histoplasmosis. Clinical success, conversion of baseline blood cultures to negative, and acute toxicities that necessitated discontinuation of treatment. Clinical success was achieved in 14 of 22 patients (64%) treated with amphotericin B compared with 45 of 51 patients (88%) receiving liposomal amphotericin B (difference, 24 percentage points [95% CI, 1 to 52 percentage points]). Culture conversion rates were similar. Three patients treated with amphotericin B and one treated with liposomal amphotericin B died during induction (P = 0.04). Infusion-related side effects were greater with amphotericin B (63%) than with liposomal amphotericin B (25%) (P = 0.002). Nephrotoxicity occurred in 37% of patients treated with amphotericin B and 9% of patients treated with liposomal amphotericin B (P = 0.003). Liposomal amphotericin B seems to be a less toxic alternative to amphotericin B and is associated with improved survival. JF - Annals of internal medicine AU - Johnson, Philip C AU - Wheat, L Joseph AU - Cloud, Gretchen A AU - Goldman, Mitchell AU - Lancaster, Dan AU - Bamberger, David M AU - Powderly, William G AU - Hafner, Richard AU - Kauffman, Carol A AU - Dismukes, William E AU - U.S. National Institute of Allergy and Infectious Diseases Mycoses Study Group AD - Division of General Medicine, University of Texas-Houston Medical School, 6431 Fannin, MSB 1.122, Houston, TX 77030, USA. Philip.C.Johnson@uth.tmc.edu ; U.S. National Institute of Allergy and Infectious Diseases Mycoses Study Group Y1 - 2002/07/16/ PY - 2002 DA - 2002 Jul 16 SP - 105 EP - 109 VL - 137 IS - 2 KW - Antifungal Agents KW - 0 KW - Liposomes KW - Amphotericin B KW - 7XU7A7DROE KW - Abridged Index Medicus KW - Index Medicus KW - Chemical and Drug Induced Liver Injury -- etiology KW - Double-Blind Method KW - Humans KW - Safety KW - AIDS-Related Opportunistic Infections -- drug therapy KW - Antifungal Agents -- adverse effects KW - Amphotericin B -- adverse effects KW - Amphotericin B -- administration & dosage KW - Antifungal Agents -- administration & dosage KW - Histoplasmosis -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71915161?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Safety+and+efficacy+of+liposomal+amphotericin+B+compared+with+conventional+amphotericin+B+for+induction+therapy+of+histoplasmosis+in+patients+with+AIDS.&rft.au=Johnson%2C+Philip+C%3BWheat%2C+L+Joseph%3BCloud%2C+Gretchen+A%3BGoldman%2C+Mitchell%3BLancaster%2C+Dan%3BBamberger%2C+David+M%3BPowderly%2C+William+G%3BHafner%2C+Richard%3BKauffman%2C+Carol+A%3BDismukes%2C+William+E%3BU.S.+National+Institute+of+Allergy+and+Infectious+Diseases+Mycoses+Study+Group&rft.aulast=Johnson&rft.aufirst=Philip&rft.date=2002-07-16&rft.volume=137&rft.issue=2&rft.spage=105&rft.isbn=&rft.btitle=&rft.title=Annals+of+internal+medicine&rft.issn=1539-3704&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-24 N1 - Date created - 2002-07-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Summary For Patients In: Ann Intern Med. 2002 Jul 16;137(2):I54 [12118987] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - LC/MS analysis of NAD biosynthesis using stable isotope pyridine precursors. AN - 71924352; 12123656 AB - A liquid chromatographic-electrospray ionization ion trap mass spectrometry (LC/MS) method has been developed to measure the biosynthetic incorporation of specific precursors into NAD. The stable isotope-labeled precursors tryptophan, quinolinic acid, nicotinic acid, and nicotinamide were added to the media of human liver tumor cells (SK-HEP) grown in culture. The cells were harvested, the NAD was extracted, and the ratio of labeled to unlabeled NAD was measured using the newly developed LC/MS assay. The quantity of NAD formed from each precursor relative to an internal standard (fully labeled 13C, 15N-labeled NAD prepared from baker's yeast) was measured. The detection limit (signal-to-noise ratio 5:1) of the LC/MS method was 37 fmol (25 pg) of NAD and was linear from 20.0 ng to 25 pg. All reported NAD levels were normalized relative to cellular protein measurements. At 50 microM precursor concentrations, nicotinamide was the dominant precursor and NAD levels in the cell rose well above normal levels. Other precursors were minimally incorporated. The same methods were applied to NAD biosynthesized by macrophages derived from peripheral blood monocytes. However, the NAD concentration in macrophages was about 5% of that in SK-HEP cells and the incorporation of stable isotope-labeled substrates remained below measurable levels. JF - Analytical biochemistry AU - Evans, Jason AU - Wang, Tao Chin AU - Heyes, Melvyn P AU - Markey, S P AD - Laboratory of Neurotoxicology, National Institute of Mental Health, Bethesda, Maryland 20892-1262, USA. Y1 - 2002/07/15/ PY - 2002 DA - 2002 Jul 15 SP - 197 EP - 203 VL - 306 IS - 2 SN - 0003-2697, 0003-2697 KW - Carbon Isotopes KW - 0 KW - Isotopes KW - Pyridines KW - NAD KW - 0U46U6E8UK KW - Niacinamide KW - 25X51I8RD4 KW - pyridine KW - NH9L3PP67S KW - Index Medicus KW - Isotopes -- metabolism KW - Niacinamide -- metabolism KW - Macrophages -- metabolism KW - Mass Spectrometry KW - Chromatography, Liquid KW - NAD -- biosynthesis KW - Pyridines -- metabolism KW - NAD -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71924352?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=LC%2FMS+analysis+of+NAD+biosynthesis+using+stable+isotope+pyridine+precursors.&rft.au=Evans%2C+Jason%3BWang%2C+Tao+Chin%3BHeyes%2C+Melvyn+P%3BMarkey%2C+S+P&rft.aulast=Evans&rft.aufirst=Jason&rft.date=2002-07-15&rft.volume=306&rft.issue=2&rft.spage=197&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 - 2002-12-10 N1 - Date created - 2002-07-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Average midrange ultraviolet radiation flux and time outdoors predict melanoma risk. AN - 71920809; 12124332 AB - Sunlight is the major environmental risk factor for melanoma. Descriptive studies have shown latitudinal variation in population incidence and mortality rates [D. C. Whiteman and A. C. Green, Int. J. Dermatol., 38: 481-489, 1999, and B. K. Armstrong, Australian J. Dermatol., 38 (Suppl. 1): 51-56, 1997]. In analytic studies, individual exposure has been particularly difficult to quantify. Lifetime residential history was coupled with levels of midrange UV radiation (UVB flux) to provide a measure of individual exposure to sunlight thought to be less subject to misclassification and recall bias. Data were analyzed from 718 non-Hispanic white patients with invasive cutaneous melanoma from melanoma clinics in Philadelphia and San Francisco. Matched controls were 945 patients from outpatient clinics with similar catchment areas. The association of melanoma risk and history of UVB flux along with the usual outdoor exposure risk factors were studied. A 10% increase in the average annual UVB flux was associated with a 19% [95% confidence interval (CI), 5-35%] increase in individual odds for melanoma for men and 16% (95% CI, 2-32%) for women. In men, a 10% increase in hours outdoors was associated with a 2.8% (95% CI, 1.2-4.5%) increase in odds. Even in women who could develop a deep tan, a 10% increase in hours outdoors was associated with a 5.8% increase in odds (95% CI, 1.4-10.4%). The association between melanoma risk and average annual UVB flux was strong and consistent for men and for women. The association with total adult hours outdoors was notable for men of all skin types and women who develop a suntan. JF - Cancer research AU - Fears, Thomas R AU - Bird, Cameron C AU - Guerry, DuPont AU - Sagebiel, Richard W AU - Gail, Mitchell H AU - Elder, David E AU - Halpern, Allan AU - Holly, Elizabeth A AU - Hartge, Patricia AU - Tucker, Margaret A AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. fears@epndce.nci.nih.gov Y1 - 2002/07/15/ PY - 2002 DA - 2002 Jul 15 SP - 3992 EP - 3996 VL - 62 IS - 14 SN - 0008-5472, 0008-5472 KW - Index Medicus KW - Risk Factors KW - Humans KW - Adult KW - Environmental Exposure KW - Case-Control Studies KW - Aged KW - San Francisco -- epidemiology KW - Middle Aged KW - Residence Characteristics KW - Time Factors KW - Philadelphia -- epidemiology KW - Male KW - Female KW - Neoplasms, Radiation-Induced -- etiology KW - Sunlight -- adverse effects KW - Skin Neoplasms -- etiology KW - Neoplasms, Radiation-Induced -- epidemiology KW - Melanoma -- etiology KW - Ultraviolet Rays -- adverse effects KW - Skin Neoplasms -- epidemiology KW - Melanoma -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71920809?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Average+midrange+ultraviolet+radiation+flux+and+time+outdoors+predict+melanoma+risk.&rft.au=Fears%2C+Thomas+R%3BBird%2C+Cameron+C%3BGuerry%2C+DuPont%3BSagebiel%2C+Richard+W%3BGail%2C+Mitchell+H%3BElder%2C+David+E%3BHalpern%2C+Allan%3BHolly%2C+Elizabeth+A%3BHartge%2C+Patricia%3BTucker%2C+Margaret+A&rft.aulast=Fears&rft.aufirst=Thomas&rft.date=2002-07-15&rft.volume=62&rft.issue=14&rft.spage=3992&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 - 2002-08-13 N1 - Date created - 2002-07-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adenovirus-mediated endostatin delivery results in inhibition of mammary gland tumor growth in C3(1)/SV40 T-antigen transgenic mice. AN - 71918882; 12124322 AB - We demonstrate the efficacy of systemic administration of a replication-defective adenovirus expressing endostatin (Ad-mEndo) administered during the preinvasive stage of mammary tumor development in C3(1)/T antigen transgenic mice. Mean serum levels of endostatin increased about 8-fold above that of controls and resulted in a significant decrease in tumor growth and an increase in survival. The inhibitory effect of endostatin occurred during or after the progression to invasive carcinoma. Reduced levels of vascular endothelial growth factor mRNA were found in association with high levels of endostatin. Our results demonstrate that the adenoviral induction of high levels of circulating endostatin significantly inhibits mammary tumor growth during the period when the "angiogenic switch" occurs. JF - Cancer research AU - Calvo, Alfonso AU - Feldman, Andrew L AU - Libutti, Steven K AU - Green, Jeffrey E AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 2002/07/15/ PY - 2002 DA - 2002 Jul 15 SP - 3934 EP - 3938 VL - 62 IS - 14 SN - 0008-5472, 0008-5472 KW - Antigens, Polyomavirus Transforming KW - 0 KW - Endostatins KW - Endothelial Growth Factors KW - Lymphokines KW - Peptide Fragments KW - RNA, Messenger KW - Vascular Endothelial Growth Factor A KW - Vascular Endothelial Growth Factors KW - Collagen KW - 9007-34-5 KW - Index Medicus KW - Animals KW - Endothelial Growth Factors -- biosynthesis KW - Cell Division -- physiology KW - Endothelial Growth Factors -- genetics KW - Mice KW - Mice, Hairless KW - RNA, Messenger -- genetics KW - Mice, Transgenic KW - Antigens, Polyomavirus Transforming -- genetics KW - RNA, Messenger -- biosynthesis KW - Adenoviridae -- genetics KW - Lymphokines -- biosynthesis KW - Lymphokines -- genetics KW - Female KW - Collagen -- genetics KW - Peptide Fragments -- biosynthesis KW - Peptide Fragments -- genetics KW - Neovascularization, Pathologic -- blood KW - Mammary Neoplasms, Experimental -- blood supply KW - Collagen -- blood KW - Mammary Neoplasms, Experimental -- genetics KW - Genetic Therapy -- methods KW - Peptide Fragments -- blood KW - Collagen -- biosynthesis KW - Neovascularization, Pathologic -- therapy KW - Mammary Neoplasms, Experimental -- blood KW - Mammary Neoplasms, Experimental -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71918882?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Adenovirus-mediated+endostatin+delivery+results+in+inhibition+of+mammary+gland+tumor+growth+in+C3%281%29%2FSV40+T-antigen+transgenic+mice.&rft.au=Calvo%2C+Alfonso%3BFeldman%2C+Andrew+L%3BLibutti%2C+Steven+K%3BGreen%2C+Jeffrey+E&rft.aulast=Calvo&rft.aufirst=Alfonso&rft.date=2002-07-15&rft.volume=62&rft.issue=14&rft.spage=3934&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 - 2002-08-13 N1 - Date created - 2002-07-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pooled analysis and meta-analysis of glutathione S-transferase M1 and bladder cancer: a HuGE review. AN - 71907477; 12117698 AB - Smoking is a known risk factor for bladder cancer. The product of the GSTM1 gene, glutathione S-transferase M1 (GSTM1), is involved in the detoxification of polycyclic aromatic hydrocarbons found in tobacco smoke; a homozygous deletion of this gene in approximately 50% of Caucasians and Asians results in a lack of GSTM1 enzyme activity. Most studies examining the relation between bladder cancer and GSTM1 have reported an increased risk associated with a lack of GSTM1 activity. The authors performed meta- and pooled analyses of published and unpublished, case-control, genotype-based studies that examined this association (17 studies, 2,149 cases, 3,646 controls) and excluded studies conducted in populations with a high prevalence of exposure to known bladder cancer risk factors other than tobacco smoke. Using random effects models in the meta-analysis, the authors obtained a summary odds ratio of 1.44 (95% confidence interval (CI): 1.23, 1.68) for GSTM1 null status with all studies included. Results from studies with at least 100 cases and 100 controls produced a summary odds ratio of 1.42 (95% CI: 1.26, 1.60). Pooled analyses using original data sets from 10 studies (1,496 cases and 1,444 controls) and adjusting for age, sex, and race produced similar results. There was no evidence of multiplicative interaction between the GSTM1 null genotype and ever smoking in relation to bladder cancer, although there was a suggestion of additive interaction (additive interaction = 0.45, 95% CI: -0.03, 0.93). These results indicate that, among populations studied to date, GSTM1 null status is associated with a modest increase in the risk of bladder cancer. JF - American journal of epidemiology AU - Engel, Lawrence S AU - Taioli, Emanuela AU - Pfeiffer, Ruth AU - Garcia-Closas, Montserrat AU - Marcus, Pamela M AU - Lan, Qing AU - Boffetta, Paolo AU - Vineis, Paolo AU - Autrup, Herman AU - Bell, Douglas A AU - Branch, Robert A AU - Brockmöller, Jürgen AU - Daly, Ann K AU - Heckbert, Susan R AU - Kalina, Ivan AU - Kang, Daehee AU - Katoh, Takahiko AU - Lafuente, Amalia AU - Lin, Henry J AU - Romkes, Marjorie AU - Taylor, Jack A AU - Rothman, Nathaniel AD - Occupational Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-7240, USA. engell@mail.nih.gov Y1 - 2002/07/15/ PY - 2002 DA - 2002 Jul 15 SP - 95 EP - 109 VL - 156 IS - 2 SN - 0002-9262, 0002-9262 KW - Carcinogens KW - 0 KW - Benzo(a)pyrene KW - 3417WMA06D KW - Glutathione Transferase KW - EC 2.5.1.18 KW - glutathione S-transferase M1 KW - Index Medicus KW - Odds Ratio KW - Humans KW - Europe -- epidemiology KW - Genotype KW - Japan -- epidemiology KW - Korea -- epidemiology KW - Carcinogens -- metabolism KW - United Kingdom -- epidemiology KW - Risk Factors KW - Case-Control Studies KW - Confidence Intervals KW - United States -- epidemiology KW - Benzo(a)pyrene -- metabolism KW - Urinary Bladder Neoplasms -- genetics KW - Glutathione Transferase -- metabolism KW - Urinary Bladder Neoplasms -- enzymology KW - Smoking -- adverse effects KW - Glutathione Transferase -- genetics KW - Urinary Bladder Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71907477?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Pooled+analysis+and+meta-analysis+of+glutathione+S-transferase+M1+and+bladder+cancer%3A+a+HuGE+review.&rft.au=Engel%2C+Lawrence+S%3BTaioli%2C+Emanuela%3BPfeiffer%2C+Ruth%3BGarcia-Closas%2C+Montserrat%3BMarcus%2C+Pamela+M%3BLan%2C+Qing%3BBoffetta%2C+Paolo%3BVineis%2C+Paolo%3BAutrup%2C+Herman%3BBell%2C+Douglas+A%3BBranch%2C+Robert+A%3BBrockm%C3%B6ller%2C+J%C3%BCrgen%3BDaly%2C+Ann+K%3BHeckbert%2C+Susan+R%3BKalina%2C+Ivan%3BKang%2C+Daehee%3BKatoh%2C+Takahiko%3BLafuente%2C+Amalia%3BLin%2C+Henry+J%3BRomkes%2C+Marjorie%3BTaylor%2C+Jack+A%3BRothman%2C+Nathaniel&rft.aulast=Engel&rft.aufirst=Lawrence&rft.date=2002-07-15&rft.volume=156&rft.issue=2&rft.spage=95&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 - 2002-07-25 N1 - Date created - 2002-07-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Am J Epidemiol 2002 Sep 1;156(5):492 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization and expression of human bifunctional 3'-phosphoadenosine 5'-phosphosulphate synthase isoforms. AN - 71879749; 11931637 AB - Sulphonation, a fundamental process essential for normal growth and development, requires the sulphonate donor molecule 3'-phosphoadenosine 5'-phosphosulphate (PAPS), which is produced from ATP and inorganic sulphate by the bifunctional enzyme PAPS synthase. In humans, two genes encode isoenzymes that are 77% identical at the amino acid level, and alternative splicing creates two subtypes of PAPS synthase 2. The question as to whether distinctions in amino acid composition are reflected in differences in activity has been examined. The specific activity of the PAPS synthase 2 subtypes is 10- to 15-fold higher than that for PAPS synthase 1. The greater catalytic efficiency of the PAPS synthase 2 subtypes is demonstrated further by the 3- to 6-fold higher k(cat)/K(m) ratios for ATP and inorganic sulphate as compared with the ratios for PAPS synthase 1. In humans, PAPS synthase 1 is expressed ubiquitously, and is the dominant isoform in most tissues, whereas expression of the PAPS synthase 2 subtypes is variable and tissue-specific. It is noteworthy that, similar to other human tissues, PAPS synthase 1 also appears to be the dominant isoform expressed in cartilage. The latter finding initially created a conundrum, since there is a specific human dwarfing disorder that is known to be caused by a mutation in the PAPS synthase 2 gene. This apparent enigma would seem to be resolved by examination of cartilage from guinea-pigs as an animal model. Similar to humans, cartilage from mature animals predominantly expresses PAPS synthase 1. In contrast, expression of PAPS synthase 1 is relatively low in the cartilage of immature guinea-pigs, including the growth plate of long bones, whereas PAPS synthase 2 is the highly expressed isoenzyme. JF - The Biochemical journal AU - Fuda, Hirotoshi AU - Shimizu, Chikara AU - Lee, Young C AU - Akita, Harukuni AU - Strott, Charles A AD - Section on Steroid Regulation, Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-4510, USA. Y1 - 2002/07/15/ PY - 2002 DA - 2002 Jul 15 SP - 497 EP - 504 VL - 365 SN - 0264-6021, 0264-6021 KW - DNA Primers KW - 0 KW - Isoenzymes KW - RNA, Messenger KW - Sulfatases KW - EC 3.1.6.- KW - phosphoadenylylsulfatase KW - EC 3.6.2.2 KW - Index Medicus KW - Animals KW - Guinea Pigs KW - Humans KW - Amino Acid Sequence KW - Reverse Transcriptase Polymerase Chain Reaction KW - RNA, Messenger -- genetics KW - Mutagenesis, Site-Directed KW - Cartilage -- enzymology KW - Base Sequence KW - Kinetics KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Catalysis KW - Isoenzymes -- chemistry KW - Sulfatases -- metabolism KW - Sulfatases -- chemistry KW - Sulfatases -- genetics KW - Isoenzymes -- genetics KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71879749?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Characterization+and+expression+of+human+bifunctional+3%27-phosphoadenosine+5%27-phosphosulphate+synthase+isoforms.&rft.au=Fuda%2C+Hirotoshi%3BShimizu%2C+Chikara%3BLee%2C+Young+C%3BAkita%2C+Harukuni%3BStrott%2C+Charles+A&rft.aulast=Fuda&rft.aufirst=Hirotoshi&rft.date=2002-07-15&rft.volume=365&rft.issue=&rft.spage=497&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 - 2002-09-05 N1 - Date created - 2002-07-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1999 Nov 19;274(47):33306-12 [10559207] Annu Rev Biochem. 1960;29:347-64 [13851709] Biochem Biophys Res Commun. 2000 Feb 16;268(2):437-44 [10679223] Biochem Biophys Res Commun. 2001 Jun 15;284(3):763-70 [11396968] Pharmacogenetics. 2002 Jan;12(1):11-21 [11773860] Biochem J. 2002 Apr 15;363(Pt 2):263-71 [11931653] Dev Biol. 1976 May;50(1):82-94 [1269836] Annu Rev Physiol. 1988;50:363-76 [3288098] Endocrinology. 1993 Nov;133(5):2284-91 [8404682] Biochemistry. 1994 Jun 7;33(22):6822-7 [8204616] J Biol Chem. 1995 Dec 8;270(49):29453-9 [7493984] Gene. 1995 Nov 20;165(2):243-8 [8522184] Chem Biol Interact. 1998 Feb 20;109(1-3):143-51 [9566742] FASEB J. 1998 May;12(7):603-12 [9576487] Biosci Biotechnol Biochem. 1998 May;62(5):1037-40 [9648242] J Biol Chem. 1998 Jul 24;273(30):19311-20 [9668121] Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8681-5 [9671738] Nat Genet. 1998 Oct;20(2):157-62 [9771708] Chem Biol. 1999 Jan;6(1):R9-R22 [9889154] Science. 1958 Sep 12;128(3324):575-80 [13580219] FASEB J. 2000 Feb;14(2):345-54 [10657990] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanism in the reaction of cytochrome c oxidase with organic hydroperoxides: an ESR spin-trapping investigation. AN - 71878974; 11931642 AB - Organic hydroperoxides are of great utility in probing the reaction mechanism and the toxicological consequences of lipid peroxidation. In the present study, ESR spin-trapping was employed to investigate the peroxidation of mitochondrial cytochrome c oxidase (CcO) with t-butyl hydroperoxide (t-BuOOH) and cumene hydroperoxide (CumOOH). The spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) was used to detect the radical species formed from the reaction of CcO with t-BuOOH. The presence of t-BuOOH-derived alkoxyl radical (t-BuO*) as the primary radical indicates reductive scission of the O-O bond by CcO. The ESR signal of DMPO/*Ot-Bu can be partially abolished by cyanide, implying that the reductive cleavage involved the haem a(3)Cu(B) binuclear site of CcO. A nitroso spin trap, 2-methyl-2-nitrosopropane (MNP), was used to detect and identify radical species from the reaction of CcO with CumOOH. In addition to the t-BuOOH-derived methyl, hydroxylmethyl and tertiary carbon-centred radicals, a protein-derived radical was detected. The intensity of the ESR signal from the protein radical increased with the CumOOH concentration at low CumOOH/CcO ratios, with maximal intensity at a ratio of 100 mol of CumOOH/mol of CcO. The immobilized protein radical adduct of MNP was stable and persistent after dialysis; it was also resistant to proteolytic digestion, suggesting that it was formed in the transmembrane region, a region that is not accessible to proteases. Its signal was greatly enhanced when CcO cysteine residues were chemically modified by N-ethylmaleimide, when the tryptophan residues in CcO were oxidized by N-bromosuccimide, and when tyrosine residues on the surface of CcO were iodinated, showing that a radical equilibrium was established among the cysteine, tryptophan and tyrosine residues of the protein-centred radical. Pre-treatment of CcO with cyanide prevented detectable MNP adduct formation, confirming that the haem a(3)-Cu(B) binuclear centre was the initial reaction site. When the CcO was pre-treated with 10 mM (100 equivalents) of CumOOH, the enzyme activity decreased by more than 20%. This inhibition was persistent after dialysis, suggesting that the detected protein-centred radical was, in part, involved in the irreversible inactivation by CumOOH. Visible spectroscopic analysis revealed that the haem a of CcO was not affected during the reaction. However, the addition of pyridine to the reaction mixture under alkaline conditions resulted in the destruction of the haem centre of CcO, suggesting that its protein matrix rather than its haem a is the target of oxidative damage by the organic hydroperoxide. JF - The Biochemical journal AU - Chen, Yeong-Renn AU - Mason, Ronald P AD - The Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. chen6@niehs.nih.gov Y1 - 2002/07/15/ PY - 2002 DA - 2002 Jul 15 SP - 461 EP - 469 VL - 365 SN - 0264-6021, 0264-6021 KW - Spin Labels KW - 0 KW - Tyrosine KW - 42HK56048U KW - Tryptophan KW - 8DUH1N11BX KW - tert-Butylhydroperoxide KW - 955VYL842B KW - Electron Transport Complex IV KW - EC 1.9.3.1 KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Cysteine -- metabolism KW - Electron Spin Resonance Spectroscopy KW - Oxidative Stress KW - Tyrosine -- metabolism KW - Tryptophan -- metabolism KW - Electron Transport Complex IV -- chemistry KW - tert-Butylhydroperoxide -- metabolism KW - Electron Transport Complex IV -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71878974?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Mechanism+in+the+reaction+of+cytochrome+c+oxidase+with+organic+hydroperoxides%3A+an+ESR+spin-trapping+investigation.&rft.au=Chen%2C+Yeong-Renn%3BMason%2C+Ronald+P&rft.aulast=Chen&rft.aufirst=Yeong-Renn&rft.date=2002-07-15&rft.volume=365&rft.issue=&rft.spage=461&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 - 2002-09-05 N1 - Date created - 2002-07-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Arch Biochem Biophys. 1988 Sep;265(2):267-71 [2844117] Anal Biochem. 1987 Feb 15;161(1):1-15 [3578775] Ann N Y Acad Sci. 1988;550:150-60 [2854387] J Biol Chem. 1989 May 15;264(14):7889-99 [2542250] J Biol Chem. 1990 Sep 25;265(27):16330-6 [2168888] Free Radic Res Commun. 1990;10(6):361-70 [2175284] FEBS Lett. 1992 Feb 3;297(1-2):63-6 [1312951] J Magn Reson B. 1994 Jun;104(2):105-10 [8049862] J Biol Chem. 1995 May 26;270(21):12709-16 [7759524] Science. 1995 Aug 25;269(5227):1069-74 [7652554] Biochim Biophys Acta. 1995 Oct 4;1239(1):45-50 [7548143] Science. 1996 May 24;272(5265):1136-44 [8638158] J Biol Chem. 1996 Jun 28;271(26):15498-503 [8663160] Biochem J. 1997 Dec 1;328 ( Pt 2):565-71 [9371716] Biochemistry. 1998 Mar 3;37(9):3062-7 [9485459] Biochem J. 1998 Mar 15;330 ( Pt 3):1293-9 [9494099] J Biol Chem. 1999 Feb 5;274(6):3308-14 [9920871] Science. 1999 Mar 5;283(5407):1482-8 [10066162] Biochim Biophys Acta. 1999 Feb 9;1410(2):159-70 [10076024] Biochim Biophys Acta. 1999 Feb 9;1410(2):171-82 [10076025] Biochim Biophys Acta. 1999 Feb 9;1410(2):183-93 [10076026] Biochim Biophys Acta. 1999 Feb 9;1410(2):99-102 [10084814] Biochim Biophys Acta. 1999 May 5;1411(2-3):378-84 [10320670] Biochemistry. 1999 Jul 20;38(29):9179-84 [10413492] J Biol Chem. 1999 Aug 27;274(35):24611-6 [10455126] Free Radic Biol Med. 1999 Oct;27(7-8):864-72 [10515591] Free Radic Res Commun. 1993;18(6):353-67 [8397147] Biochemistry. 2000 Apr 18;39(15):4415-22 [10757991] Biochim Biophys Acta. 2000 Jul 20;1459(1):125-30 [10924905] Science. 2000 Nov 24;290(5496):1588-91 [11090359] Biochem J. 1972 Jul;128(3):617-30 [4404507] Biochem J. 1973 Jul;134(3):707-16 [4749271] J Biol Chem. 1975 Aug 25;250(16):6218-21 [169233] Arch Biochem Biophys. 1977 Apr 30;180(2):248-57 [195520] Biochem J. 1980 Nov 1;191(2):421-7 [6263247] Anal Biochem. 1982 Sep 15;125(2):427-32 [6758629] Arch Biochem Biophys. 1985 Mar;237(2):408-14 [2983613] Biochem Biophys Res Commun. 1986 Jul 31;138(2):533-9 [3017331] Ann N Y Acad Sci. 1988;550:124-38 [2854384] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of retinoid X receptor responsive element-dependent transcription in T lymphocytes by Ser/Thr phosphatases: functional divergence of protein kinase C (PKC)theta; and PKC alpha in mediating calcineurin-induced transactivation. AN - 71877374; 12097375 AB - T lymphocyte activation signals regulate the expression and transactivation function of retinoid X receptor (RXR) alpha through an interplay of complex signaling cascades that are not yet fully understood. We show that cellular Ser/Thr protein phosphatases (PPs) play an important role in mediating these processes. Inhibitors specific for PP1 and PP2A decreased basal expression of RXR alpha RNA and protein in T lymphocyte leukemia Jurkat cells and prevented activation-induced RXR alpha accumulation in these cells. In addition, these inhibitors attenuated the RXR responsive element (RXRE)-dependent transcriptional activation in transient transfection assays. Inhibitors of calcineurin (CN), by contrast, did not have any effect on the basal RXR alpha expression and even augmented activation-induced RXR alpha expression. Expression of a dominant-active (DA) mutant of CN together with a DA mutant of protein kinase C (PKC)theta;, a novel PKC isoform, significantly increased RXRE-dependent transcription. Expression of catalytically inactive PKC theta; or a dominant-negative mutant of PKC theta; failed to synergize with CN and did not increase RXRE-dependent transcription. Expression of a DA mutant of PKC alpha or treatment with PMA was found to attenuate PKC theta; and CN synergism. We conclude that PP1, PP2A, and CN regulate levels and transcriptional activation function of RXR alpha in T cells. In addition, CN synergizes with PKC theta; to induce RXRE-dependent activation, a cooperative function that is antagonized by the activation of the conventional PKC alpha isoform. Thus, PKC theta; and PKC alpha may function as positive and negative modulators, respectively, of CN-regulated RXRE-dependent transcription during T cell activation. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Ishaq, Mohammad AU - Fan, Ming AU - Wigmore, Kip AU - Gaddam, Arunasri AU - Natarajan, Ven AD - Laboratory of Molecular Cell Biology, Science Applications International Corporation-Frederick, Frederick Cancer Research and Development Center, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA. mishaq@nih.gov Y1 - 2002/07/15/ PY - 2002 DA - 2002 Jul 15 SP - 732 EP - 738 VL - 169 IS - 2 SN - 0022-1767, 0022-1767 KW - Calcineurin Inhibitors KW - 0 KW - Enzyme Inhibitors KW - Isoenzymes KW - Receptors, Retinoic Acid KW - Retinoid X Receptors KW - Transcription Factors KW - PRKCQ protein, human KW - 148374-93-0 KW - Okadaic Acid KW - 1W21G5Q4N2 KW - PRKCA protein, human KW - EC 2.7.11.13 KW - Protein Kinase C KW - Protein Kinase C-alpha KW - Calcineurin KW - EC 3.1.3.16 KW - Phosphoprotein Phosphatases KW - Protein Phosphatase 1 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Jurkat Cells KW - Okadaic Acid -- pharmacology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Drug Synergism KW - Phosphoprotein Phosphatases -- antagonists & inhibitors KW - Receptors, Retinoic Acid -- genetics KW - Receptors, Retinoic Acid -- metabolism KW - Calcineurin -- physiology KW - Calcineurin -- metabolism KW - Transcription, Genetic -- drug effects KW - Transcription Factors -- metabolism KW - Transcriptional Activation -- drug effects KW - Response Elements -- immunology KW - Transcription, Genetic -- immunology KW - Transcription Factors -- genetics KW - T-Lymphocytes -- enzymology KW - Isoenzymes -- antagonists & inhibitors KW - T-Lymphocytes -- metabolism KW - Phosphoprotein Phosphatases -- physiology KW - Protein Kinase C -- antagonists & inhibitors KW - Transcriptional Activation -- immunology KW - Isoenzymes -- physiology KW - T-Lymphocytes -- drug effects KW - Protein Kinase C -- physiology KW - Response Elements -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71877374?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Regulation+of+retinoid+X+receptor+responsive+element-dependent+transcription+in+T+lymphocytes+by+Ser%2FThr+phosphatases%3A+functional+divergence+of+protein+kinase+C+%28PKC%29theta%3B+and+PKC+alpha+in+mediating+calcineurin-induced+transactivation.&rft.au=Ishaq%2C+Mohammad%3BFan%2C+Ming%3BWigmore%2C+Kip%3BGaddam%2C+Arunasri%3BNatarajan%2C+Ven&rft.aulast=Ishaq&rft.aufirst=Mohammad&rft.date=2002-07-15&rft.volume=169&rft.issue=2&rft.spage=732&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 - 2002-08-28 N1 - Date created - 2002-07-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Noncholinesterase Mechanisms of Chlorpyrifos Neurotoxicity: Altered Phosphorylation of Ca super(2+)/cAMP Response Element Binding Protein in Cultured Neurons AN - 18452266; 5429902 AB - Previous studies suggest that low doses of the organophosphate insecticide chlorpyrifos (CPF) disrupt brain development and cognitive function by mechanisms that do not involve the inhibition of acetylcholinesterase (AChE). In the present study we tested the hypothesis that CPF and its metabolites alter the Ca super(2+)/cAMP response element binding protein (CREB), a critical molecule in brain development and cognitive function. We further tested the hypothesis that changes in CREB occur independent of AChE inhibition. Western blot analysis of lysates from primary cultures of cortical neurons exposed to CPF, CPF-oxon, or trichloropyridinol (TCP) for 1 h and cultures exposed to trichloropyridinol (TCP) for 7 days indicated that all exposures increased the level of the phosphorylated (activated) form of CREB (pCREB), without significant changes in total CREB or alpha -tubulin. Remarkably, pCREB in cortical neurons was elevated by 300-400% of control levels with estimated EC50s of 60 pM, <30 fM, and <30 pM for CPF, CPF-oxon, and TCP, respectively. AChE activity and cell viability were not affected by organophosphate concentrations that caused significant increases in pCREB (up to 100 nM, 100 pM, and 10 mu M of CPF, CPF-oxon, and TCP, respectively). The level of pCREB in hippocampal neurons was also elevated after exposure to CPF, but pCREB in cultured astrocytes was not affected. Inclusion of the cytochrome P-450 inhibitor SKF-525A did not inhibit the effects of CPF on pCREB levels, indicating that metabolism of CPF to CPF-oxon was not necessary to cause the increase in pCREB. The increases in neuronal pCREB observed in this study provide biochemical evidence that CPF and its metabolites are active at critical sites within the nervous system at levels far below those required to inhibit AChE, which could explain many of the reported neurodevelopmental and behavioral changes attributed to CPF toxicity. [copy ] 2002 Elsevier Science (USA). JF - Toxicology and Applied Pharmacology AU - Schuh, R A AU - Lein, P J AU - Beckles, R A AU - Jett, DA AD - Department of Environmental Health Science, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, 21205, dj140o@nih.gov Y1 - 2002/07/15/ PY - 2002 DA - 2002 Jul 15 SP - 176 EP - 185 PB - Academic Press VL - 182 IS - 2 SN - 0041-008X, 0041-008X KW - CREB protein KW - chloropyriphos KW - Toxicology Abstracts KW - X 24135:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18452266?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+Applied+Pharmacology&rft.atitle=Noncholinesterase+Mechanisms+of+Chlorpyrifos+Neurotoxicity%3A+Altered+Phosphorylation+of+Ca+super%282%2B%29%2FcAMP+Response+Element+Binding+Protein+in+Cultured+Neurons&rft.au=Schuh%2C+R+A%3BLein%2C+P+J%3BBeckles%2C+R+A%3BJett%2C+DA&rft.aulast=Schuh&rft.aufirst=R&rft.date=2002-07-15&rft.volume=182&rft.issue=2&rft.spage=176&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+Applied+Pharmacology&rft.issn=0041008X&rft_id=info:doi/10.1006%2Ftaap.2002.9445 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1006/taap.2002.9445 ER - TY - JOUR T1 - Haemopoietic stem-cell transplantation: improving immune reconstitution, avoiding graft-versus-host disease. AN - 71942021; 12126813 JF - Lancet (London, England) AU - Dickinson, Anne AU - Cant, Andrew AD - University Department of Haematology, Royal Victoria Infirmary, Newcastle upon Tyne NEI 4LP, UK. a.m.dickinson@ncl.ac.uk Y1 - 2002/07/13/ PY - 2002 DA - 2002 Jul 13 SP - 98 EP - 99 VL - 360 IS - 9327 SN - 0140-6736, 0140-6736 KW - Immunotoxins KW - 0 KW - Receptors, Interleukin-2 KW - Abridged Index Medicus KW - Index Medicus KW - Receptors, Interleukin-2 -- therapeutic use KW - Humans KW - Immunotoxins -- therapeutic use KW - Receptors, Interleukin-2 -- immunology KW - Graft vs Host Disease -- immunology KW - Graft vs Host Disease -- prevention & control KW - Hematopoietic Stem Cell Transplantation -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71942021?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Haemopoietic+stem-cell+transplantation%3A+improving+immune+reconstitution%2C+avoiding+graft-versus-host+disease.&rft.au=Dickinson%2C+Anne%3BCant%2C+Andrew&rft.aulast=Dickinson&rft.aufirst=Anne&rft.date=2002-07-13&rft.volume=360&rft.issue=9327&rft.spage=98&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 - 2002-07-30 N1 - Date created - 2002-07-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Lancet. 2002 Jul 13;360(9327):130-7 [12126823] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparative genome analysis of potential regulatory elements in the ABCG5-ABCG8 gene cluster. AN - 71980625; 12150943 AB - The excretion of sterols from the liver and intestine is regulated by the ABCG5 and ABCG8 transporters. To identify potential regulatory elements, 152 kb of the human ABCG5-ABCG8 gene cluster was sequenced and comparative genome analysis was performed. The two genes are oriented in a head-to-head configuration and are separated by a 374-bp intergenic region, which is highly conserved among several species. Using a reporter construct, the intergenic region was found to act as a bidirectional promoter. A conserved GATA site in the intergenic region was shown by site-directed mutagenesis to act as a repressor for the ABCG5 promoter. The intergenic region was also shown to be partially responsive to treatment by LXR agonists. In summary, several potential regulatory elements were found for the ABCG5 and ABCG8 genes, and the intergenic region was found to act as a bidirectional promoter. JF - Biochemical and biophysical research communications AU - Remaley, Alan T AU - Bark, Samantha AU - Walts, Avram D AU - Freeman, Lita AU - Shulenin, Sergey AU - Annilo, Tarmo AU - Elgin, Eric AU - Rhodes, Hope E AU - Joyce, Charles AU - Dean, Michael AU - Santamarina-Fojo, Silvia AU - Brewer, H Bryan AD - National Heart, Lung and Blood Institute, National Institutes of Health, Bldg. 10/2C-433, 10 Center Drive, Bethesda, MD 20892, USA. aremaley@nih.gov Y1 - 2002/07/12/ PY - 2002 DA - 2002 Jul 12 SP - 276 EP - 282 VL - 295 IS - 2 SN - 0006-291X, 0006-291X KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Promoter Regions, Genetic KW - Base Sequence KW - Sequence Homology, Nucleic Acid KW - Humans KW - Molecular Sequence Data KW - Mice KW - Regulatory Sequences, Nucleic Acid KW - Multigene Family KW - Genome UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71980625?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Comparative+genome+analysis+of+potential+regulatory+elements+in+the+ABCG5-ABCG8+gene+cluster.&rft.au=Remaley%2C+Alan+T%3BBark%2C+Samantha%3BWalts%2C+Avram+D%3BFreeman%2C+Lita%3BShulenin%2C+Sergey%3BAnnilo%2C+Tarmo%3BElgin%2C+Eric%3BRhodes%2C+Hope+E%3BJoyce%2C+Charles%3BDean%2C+Michael%3BSantamarina-Fojo%2C+Silvia%3BBrewer%2C+H+Bryan&rft.aulast=Remaley&rft.aufirst=Alan&rft.date=2002-07-12&rft.volume=295&rft.issue=2&rft.spage=276&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 - 2002-08-29 N1 - Date created - 2002-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An estrogen receptor repressor induces cataract formation in transgenic mice. AN - 71899141; 12082175 AB - Despite the high prevalence of age-related cataracts, there are currently no known therapies to delay or prevent their occurrence. Studies in humans and rodent models suggest that estrogen may provide protection against age-related cataracts. The discovery of ocular estrogen receptors (ERs) indicates that estrogen protection may result from direct interactions with its receptors in the eye, instead an indirect consequence from effects on another tissue. Studies in our transgenic mouse model validate the concept that estrogen is beneficial for the eye. These mice express ER Delta , a dominant-negative form of ER alpha that inhibits ER alpha function. In the ER Delta 3 transgenic mice, cortical cataracts spontaneously form in ER Delta 3 females after puberty and progress with age. The cataracts initiate in the equatorial region of the lens where the epithelial cells differentiate into elongating fiber cells. Cataract formation can be prevented if the females are ovariectomized before, but not after, sexual maturity. Both male and female ER Delta 3 mice develop cataracts after neonatal treatment with the potent estrogen diethylstilbestrol (DES). The incidence of spontaneous and DES-induced cataracts in ER Delta 3 mice is 100%, yet these cataracts are absent from the wild-type mice. These data suggest that repression of estrogen action induces cortical cataract formation because estrogen is required to activate the ER Delta 3 repressor. Evidence of DES-induced cataracts in the ER Delta 3 males as well as the females suggests that estrogen is important in lens physiology in both sexes. The ER Delta 3 mice provide a powerful model for assessing the role of estrogen in maintaining the transparency of the lens. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Davis, Vicki L AU - Chan, Chi-Chao AU - Schoen, Timothy J AU - Couse, John F AU - Chader, Gerald J AU - Korach, Kenneth S AD - Receptor Biology Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. vicki.davis@cshs.org Y1 - 2002/07/09/ PY - 2002 DA - 2002 Jul 09 SP - 9427 EP - 9432 VL - 99 IS - 14 SN - 0027-8424, 0027-8424 KW - Estrogen Receptor alpha KW - 0 KW - Receptors, Estrogen KW - Repressor Proteins KW - Diethylstilbestrol KW - 731DCA35BT KW - Index Medicus KW - Animals, Newborn KW - Animals KW - Humans KW - Diethylstilbestrol -- toxicity KW - Ovariectomy KW - Mice KW - Mice, Transgenic KW - Models, Biological KW - Male KW - Female KW - Sexual Maturation KW - Receptors, Estrogen -- antagonists & inhibitors KW - Cataract -- pathology KW - Cataract -- metabolism KW - Receptors, Estrogen -- genetics KW - Repressor Proteins -- metabolism KW - Cataract -- genetics KW - Cataract -- etiology KW - Repressor Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71899141?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=An+estrogen+receptor+repressor+induces+cataract+formation+in+transgenic+mice.&rft.au=Davis%2C+Vicki+L%3BChan%2C+Chi-Chao%3BSchoen%2C+Timothy+J%3BCouse%2C+John+F%3BChader%2C+Gerald+J%3BKorach%2C+Kenneth+S&rft.aulast=Davis&rft.aufirst=Vicki&rft.date=2002-07-09&rft.volume=99&rft.issue=14&rft.spage=9427&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 - 2002-08-08 N1 - Date created - 2002-07-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 2001 Oct 5;276(40):36869-72 [11459850] Invest Ophthalmol Vis Sci. 1999 Aug;40(9):1906-11 [10440242] Exp Eye Res. 1989 Feb;48(2):215-24 [2924809] Endocr Rev. 1990 May;11(2):201-20 [2194782] Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2065-9 [1848692] Mol Endocrinol. 1991 Nov;5(11):1707-15 [1779972] Cancer. 1992 Jun 15;69(12):2961-4 [1591689] Int Ophthalmol Clin. 1993 Fall;33(4):9-29 [8258501] Arch Ophthalmol. 1994 Jan;112(1):85-91 [8285900] Endocrinology. 1994 Jul;135(1):379-86 [8013372] Biotechniques. 1994 Dec;17(6):1030-2 [7873170] Ophthalmic Res. 1996;28 Suppl 1:1-7 [8727957] Annu Rev Public Health. 1996;17:159-77 [8724222] Am J Epidemiol. 1997 Feb 1;145(3):242-9 [9012597] J Exp Med. 1997 Jan 20;185(2):273-80 [9016876] Endocrinology. 1997 Mar;138(3):863-70 [9048584] Ophthalmology. 1997 Jun;104(6):970-3 [9186438] J Natl Cancer Inst. 1998 Sep 16;90(18):1371-88 [9747868] Invest Ophthalmol Vis Sci. 1998 Oct;39(11):2105-10 [9761289] Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9328-32 [10430942] Cell. 1988 Oct 7;55(1):145-56 [3167974] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutations in the RNase H domain of HIV-1 reverse transcriptase affect the initiation of DNA synthesis and the specificity of RNase H cleavage in vivo. AN - 71896434; 12093908 AB - Retroviral reverse transcriptases contain a DNA polymerase activity that can copy an RNA or DNA template and an RNase H activity that degrades the viral RNA genome during reverse transcription. RNase H makes both specific and nonspecific cleavages; specific cleavages are used to generate and remove the polypurine tract primer used for plus-strand DNA synthesis and to remove the tRNA primer used for minus-strand DNA synthesis. We generated mutations in an HIV-1-based vector to change amino acids in the RNase H domain that contact either the RNA and DNA strands. Some of these mutations affected the initiation of DNA synthesis, demonstrating an interdependence of the polymerase and RNase H activities of HIV-1 reverse transcription during viral DNA synthesis. The ends of the linear DNA form of the HIV-1 genome are defined by the specific RNase H cleavages that remove the plus- and minus-strand primers; these ends can be joined to form two-long-terminal repeat circles. Analysis of two-long-terminal repeat circle junctions showed that mutations in the RNase H domain affect the specificity of RNase H cleavage. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Julias, John G AU - McWilliams, Mary Jane AU - Sarafianos, Stefan G AU - Arnold, Edward AU - Hughes, Stephen H AD - HIV Drug Resistance Program, National Cancer Institute, National Institutes of Health, P.O. Box B, Frederick, MD 21702-1201, USA. Y1 - 2002/07/09/ PY - 2002 DA - 2002 Jul 09 SP - 9515 EP - 9520 VL - 99 IS - 14 SN - 0027-8424, 0027-8424 KW - DNA, Viral KW - 0 KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - Ribonuclease H KW - EC 3.1.26.4 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - HIV Long Terminal Repeat KW - Base Sequence KW - Models, Molecular KW - Humans KW - Molecular Sequence Data KW - Transcription, Genetic KW - Substrate Specificity KW - Protein Structure, Tertiary KW - Cell Line KW - Ribonuclease H -- chemistry KW - HIV Reverse Transcriptase -- genetics KW - HIV-1 -- metabolism KW - HIV-1 -- genetics KW - DNA, Viral -- biosynthesis KW - HIV Reverse Transcriptase -- metabolism KW - HIV Reverse Transcriptase -- chemistry KW - Ribonuclease H -- genetics KW - Ribonuclease H -- metabolism KW - Mutation KW - DNA, Viral -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71896434?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutations+in+the+RNase+H+domain+of+HIV-1+reverse+transcriptase+affect+the+initiation+of+DNA+synthesis+and+the+specificity+of+RNase+H+cleavage+in+vivo.&rft.au=Julias%2C+John+G%3BMcWilliams%2C+Mary+Jane%3BSarafianos%2C+Stefan+G%3BArnold%2C+Edward%3BHughes%2C+Stephen+H&rft.aulast=Julias&rft.aufirst=John&rft.date=2002-07-09&rft.volume=99&rft.issue=14&rft.spage=9515&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 - 2002-08-08 N1 - Date created - 2002-07-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 2000 Apr 21;275(16):12306-12 [10766870] J Virol. 1999 Oct;73(10):8185-95 [10482569] EMBO J. 2001 Jun 15;20(12):3272-81 [11406603] J Virol. 2001 Jul;75(14):6537-46 [11413321] Biochemistry. 2002 Apr 16;41(15):4856-65 [11939780] Proc Natl Acad Sci U S A. 1988 Feb;85(4):1218-22 [2448794] J Virol. 1989 Mar;63(3):1460-4 [2464706] Virology. 1990 Apr;175(2):575-80 [1691564] J Virol. 1990 Oct;64(10):4903-6 [1697909] J Virol. 1991 Jan;65(1):551-5 [1985217] J Gen Virol. 1991 Jan;72 ( Pt 1):59-66 [1703563] Biochemistry. 1991 Jul 23;30(29):7041-6 [1713059] J Virol. 1992 Jan;66(1):367-73 [1370087] J Virol. 1992 Feb;66(2):1031-9 [1370546] J Biol Chem. 1992 Jul 25;267(21):15071-9 [1378844] J Virol. 1992 Dec;66(12):7533-7 [1279205] Annu Rev Cell Biol. 1992;8:275-306 [1282352] Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6320-4 [7687065] EMBO J. 1993 Nov;12(11):4433-8 [7693456] J Mol Biol. 1994 Oct 28;243(3):472-83 [7525967] J Mol Biol. 1998 Dec 11;284(4):1095-111 [9837729] EMBO J. 1999 Feb 15;18(4):1038-48 [10022845] EMBO J. 2001 Mar 15;20(6):1449-61 [11250910] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of cerebral ischemia in mice deficient in Persephin. AN - 71895233; 12093930 AB - Persephin (Pspn), a recently cloned member of the transforming growth factor-beta superfamily (TGF-beta) and glial cell line-derived neurotrophic factor (GDNF) subfamily, is distributed throughout the nervous system at extremely low levels and is thought to function as a survival factor for midbrain dopaminergic and spinal motor neurons in vivo. Here, we report that mice lacking Pspn by homologous recombination show normal development and behavior, but are hypersensitive to cerebral ischemia. A 300% increase in infarction volume was observed after middle cerebral artery occlusion. We find that glutamate-induced Ca(2+) influx, thought to be a major component of ischemic neuronal cell death, can be regulated directly by the Persephin protein (PSP) and that PSP can reduce hypoxia/reperfusion cell death in vitro. Neuronal cell death can be prevented or markedly attenuated by administration of recombinant human PSP in vivo before ischemia in both mouse and rat models. Taken together, these data indicate that PSP is a potent modulator of excitotoxicity in the central nervous system with pronounced neuroprotective activity. Our findings support the view that PSP signaling can exert an important control function in the context of stroke and glutamate-mediated neurotoxicity, and also suggest that future therapeutic approaches may involve this novel trophic protein. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Tomac, Andreas C AU - Agulnick, Alan D AU - Haughey, Norman AU - Chang, Chen-Fu AU - Zhang, Yajun AU - Bäckman, Cristina AU - Morales, Marisela AU - Mattson, Mark P AU - Wang, Yun AU - Westphal, Heiner AU - Hoffer, Barry J AD - National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 2002/07/09/ PY - 2002 DA - 2002 Jul 09 SP - 9521 EP - 9526 VL - 99 IS - 14 SN - 0027-8424, 0027-8424 KW - Nerve Growth Factors KW - 0 KW - Nerve Tissue Proteins KW - Recombinant Proteins KW - persephin KW - Glutamic Acid KW - 3KX376GY7L KW - Index Medicus KW - Rats KW - Animals KW - Calcium Signaling -- drug effects KW - Recombinant Proteins -- pharmacology KW - Humans KW - In Vitro Techniques KW - Stroke -- etiology KW - Mice KW - Cell Death -- drug effects KW - Glutamic Acid -- pharmacology KW - Behavior, Animal KW - Mice, Knockout KW - Nerve Tissue Proteins -- physiology KW - Nerve Tissue Proteins -- deficiency KW - Nerve Growth Factors -- genetics KW - Brain Ischemia -- pathology KW - Brain Ischemia -- prevention & control KW - Brain Ischemia -- etiology KW - Nerve Growth Factors -- deficiency KW - Nerve Growth Factors -- physiology KW - Nerve Tissue Proteins -- genetics KW - Brain Ischemia -- physiopathology KW - Nerve Tissue Proteins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71895233?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effects+of+cerebral+ischemia+in+mice+deficient+in+Persephin.&rft.au=Tomac%2C+Andreas+C%3BAgulnick%2C+Alan+D%3BHaughey%2C+Norman%3BChang%2C+Chen-Fu%3BZhang%2C+Yajun%3BB%C3%A4ckman%2C+Cristina%3BMorales%2C+Marisela%3BMattson%2C+Mark+P%3BWang%2C+Yun%3BWestphal%2C+Heiner%3BHoffer%2C+Barry+J&rft.aulast=Tomac&rft.aufirst=Andreas&rft.date=2002-07-09&rft.volume=99&rft.issue=14&rft.spage=9521&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 - 2002-08-08 N1 - Date created - 2002-07-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Exp Neurol. 2000 Feb;161(2):664-75 [10686085] Neuroscience. 2000;95(4):1011-23 [10682708] Glia. 2000 Nov;32(2):155-64 [11008215] Neuroreport. 2000 Sep 28;11(14):3289-93 [11043566] J Neurotrauma. 2000 Oct;17(10):857-69 [11063053] J Biol Chem. 2000 Dec 15;275(50):39159-66 [10995764] J Biol Chem. 2000 Dec 15;275(50):39427-34 [10958791] J Neurosci. 2001 Mar 1;21(5):1464-72 [11222636] J Biol Chem. 2001 Mar 23;276(12):9344-51 [11116144] Exp Neurol. 2001 Aug;170(2):283-9 [11476594] Science. 1993 May 21;260(5111):1130-2 [8493557] Science. 1994 Nov 11;266(5187):1062-4 [7973664] Nature. 1995 Jan 26;373(6512):335-9 [7830766] Methods Cell Biol. 1995;46:187-216 [7541884] Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8274-8 [7667281] Nature. 1996 Jul 4;382(6586):70-3 [8657306] Nature. 1996 Jul 4;382(6586):73-6 [8657307] Nature. 1996 Jul 4;382(6586):76-9 [8657308] Nature. 1996 Dec 5;384(6608):467-70 [8945474] J Neurosci. 1997 Jun 1;17(11):4341-8 [9151750] Eur J Biochem. 1998 Feb 1;251(3):622-30 [9490034] Neuron. 1998 Feb;20(2):245-53 [9491986] Neuron. 1998 Jul;21(1):53-62 [9697851] J Neurosci Res. 1998 Aug 15;53(4):494-501 [9710270] J Neurosci Res. 1998 Sep 1;53(5):593-604 [9726430] Neuron. 1998 Aug;21(2):317-24 [9728913] Ann Neurol. 1998 Sep;44(3 Suppl 1):S110-4 [9749581] Amino Acids. 1998;14(1-3):69-74 [9871444] Neuron. 1998 Dec;21(6):1291-302 [9883723] Neuron. 1999 Feb;22(2):243-52 [10069331] Neuron. 1999 Feb;22(2):253-63 [10069332] Mol Cell Neurosci. 1999 May;13(5):326-36 [10356295] Nature. 1999 Jun 24;399(6738 Suppl):A7-14 [10392575] J Biol Chem. 1999 Jul 23;274(30):20885-94 [10409632] Neuron. 1999 Aug;23(4):725-36 [10482239] N Engl J Med. 1999 Nov 11;341(20):1543-4 [10559458] FEBS Lett. 1999 Dec 10;463(1-2):63-6 [10601639] Mol Cell Neurosci. 2000 Feb;15(2):199-214 [10673327] Mol Cell Neurosci. 2000 Jun;15(6):522-33 [10860579] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Direct detection of potential selenium delivery proteins by using an Escherichia coli strain unable to incorporate selenium from selenite into proteins AN - 18427533; 5406763 AB - Selenium can be metabolized for protein synthesis by two major pathways in vivo. In a specific pathway it can be inserted into polypeptide chains as the amino acid selenocysteine, as directed by the UGA codon. Alternatively, selenium can be substituted for sulfur to generate the free amino acids selenocysteine and selenomethionine, and these are incorporated nonspecifically into proteins in place of cysteine and methionine, respectively. A mutant strain of Escherichia coli was constructed that is deficient in utilization of inorganic selenium for both specific and nonspecific pathways of selenoprotein synthesis. Disruption of the cysK gene prevented synthesis of free cysteine and selenocysteine from inorganic S and Se precursors. Inactivation of the selD gene prevented synthesis of selenophosphate, the reactive selenium donor, required for the specific incorporation pathway. As expected, the double mutant strain, RL165 Delta selD, when grown anaerobically in LB + glucose medium containing super(75)SeO sub(3) super(2-), failed to synthesize selenium-dependent formate dehydrogenase H and seleno-tRNAs. However, it incorporated 24% as much selenium as the wild-type strain. Selenium in the deficient strain was bound to five different proteins. A 39-kDa species was identified as glyceraldehyde-3-phosphate dehydrogenase. It is possible that selenium was bound as a perselenide derivative to the reactive cysteine residue of this enzyme. A 28-kDa protein identified as deoxyribose phosphate aldolase also contained bound selenium. These super(75)Se-labeled proteins may have alternate roles as selenium delivery proteins. JF - Proceedings of the National Academy of Sciences, USA AU - Lacourciere, G M AU - Levine, R L AU - Stadtman, T C AD - Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA, tcstadtman@nih.gov Y1 - 2002/07/09/ PY - 2002 DA - 2002 Jul 09 SP - 9150 EP - 9153 VL - 99 IS - 14 SN - 0027-8424, 0027-8424 KW - cysK gene KW - glyceraldehyde-3-phosphate dehydrogenase KW - selD gene KW - selenocysteine KW - selenomethione KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18427533?accountid=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=Direct+detection+of+potential+selenium+delivery+proteins+by+using+an+Escherichia+coli+strain+unable+to+incorporate+selenium+from+selenite+into+proteins&rft.au=Lacourciere%2C+G+M%3BLevine%2C+R+L%3BStadtman%2C+T+C&rft.aulast=Lacourciere&rft.aufirst=G&rft.date=2002-07-09&rft.volume=99&rft.issue=14&rft.spage=9150&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.142291199 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1073/pnas.142291199 ER - TY - JOUR T1 - WY14,643, a peroxisome proliferator-activated receptor alpha (PPARalpha ) agonist, improves hepatic and muscle steatosis and reverses insulin resistance in lipoatrophic A-ZIP/F-1 mice. AN - 71865053; 11994294 AB - WY14,643 is a specific peroxisome proliferator-activated receptor alpha (PPARalpha) agonist with strong hypolipidemic effects. Here we have examined the effect of WY14,643 in the A-ZIP/F-1 mouse, a model of severe lipoatrophic diabetes. With 1 week of treatment, all doses of WY14,643 that were tested normalized serum triglyceride and fatty acid levels. Glucose and insulin levels also improved but only with high doses and longer treatment duration. WY14,643 reduced liver and muscle triglyceride content and increased levels of mRNA encoding fatty acid oxidation enzymes. In liver, the elevated lipogenic mRNA profile (including PPARgamma) in A-ZIP/F-1 mice remained unchanged. These results suggest that WY14,643 acts by increasing beta-oxidation rather by than decreasing lipogenesis or lipid uptake. Hyperinsulinemic euglycemic clamp studies indicated that WY14,643 treatment improved liver more than muscle insulin sensitivity and that hepatic mRNA levels of gluconeogenic enzymes were reduced. Combination treatment with both WY14,643 and a PPARgamma ligand, rosiglitazone, did not lower glucose levels more effectively than did treatment with WY14,643 alone. These data support the hypothesis that reducing intracellular triglycerides in non-adipose tissues improves insulin sensitivity and suggest that further investigation of the role of PPARalpha agonists in the treatment of lipoatrophic diabetes is warranted. JF - The Journal of biological chemistry AU - Chou, Chieh J AU - Haluzik, Martin AU - Gregory, Charmaine AU - Dietz, Kelly R AU - Vinson, Charles AU - Gavrilova, Oksana AU - Reitman, Marc L AD - Diabetes Branch, NIDDK and the Metabolism Branch, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/07/05/ PY - 2002 DA - 2002 Jul 05 SP - 24484 EP - 24489 VL - 277 IS - 27 SN - 0021-9258, 0021-9258 KW - Blood Glucose KW - 0 KW - Fatty Acids, Nonesterified KW - Glucose Transporter Type 4 KW - Hypolipidemic Agents KW - Insulin KW - Monosaccharide Transport Proteins KW - Muscle Proteins KW - Pyrimidines KW - Receptors, Cytoplasmic and Nuclear KW - Slc2a4 protein, mouse KW - Transcription Factors KW - Triglycerides KW - pirinixic acid KW - 86C4MRT55A KW - Glycogen Synthase KW - EC 2.4.1.11 KW - Acetyl-CoA Carboxylase KW - EC 6.4.1.2 KW - Index Medicus KW - Animals KW - Necrosis KW - Mice, Mutant Strains KW - Blood Glucose -- metabolism KW - Insulin -- blood KW - Glycogen Synthase -- genetics KW - Blood Glucose -- drug effects KW - Hypolipidemic Agents -- pharmacology KW - Mice KW - Monosaccharide Transport Proteins -- genetics KW - Acetyl-CoA Carboxylase -- genetics KW - Receptors, Cytoplasmic and Nuclear -- physiology KW - Triglycerides -- blood KW - Transcription Factors -- physiology KW - Muscle, Skeletal -- pathology KW - Liver -- pathology KW - Liver -- drug effects KW - Pyrimidines -- pharmacology KW - Fatty Acids, Nonesterified -- blood KW - Muscle, Skeletal -- drug effects KW - Insulin Resistance -- physiology KW - Diabetes Mellitus, Lipoatrophic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71865053?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=WY14%2C643%2C+a+peroxisome+proliferator-activated+receptor+alpha+%28PPARalpha+%29+agonist%2C+improves+hepatic+and+muscle+steatosis+and+reverses+insulin+resistance+in+lipoatrophic+A-ZIP%2FF-1+mice.&rft.au=Chou%2C+Chieh+J%3BHaluzik%2C+Martin%3BGregory%2C+Charmaine%3BDietz%2C+Kelly+R%3BVinson%2C+Charles%3BGavrilova%2C+Oksana%3BReitman%2C+Marc+L&rft.aulast=Chou&rft.aufirst=Chieh&rft.date=2002-07-05&rft.volume=277&rft.issue=27&rft.spage=24484&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 - 2002-08-27 N1 - Date created - 2002-07-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease AN - 18423245; 5408053 AB - Parkinson's disease is a widespread condition caused by the loss of midbrain neurons that synthesize the neurotransmitter dopamine. Cells derived from the fetal midbrain can modify the course of the disease, but they are an inadequate source of dopamine-synthesizing neurons because their ability to generate these neurons is unstable. In contrast, embryonic stem (ES) cells proliferate extensively and can generate dopamine neurons. If ES cells are to become the basis for cell therapies, we must develop methods of enriching for the cell of interest and demonstrate that these cells show functions that will assist in treating the disease. Here we show that a highly enriched population of midbrain neural stem cells can be derived from mouse ES cells. The dopamine neurons generated by these stem cells show electrophysiological and behavioural properties expected of neurons from the midbrain. Our results encourage the use of ES cells in cell-replacement therapy for Parkinson's disease. JF - Nature AU - Kim, J H AU - Auerbach, J M AU - Rodriguez-Gomez, JA AU - Velasco, I AU - Gavin, D AU - Lumelsky, N AU - Lee, S-H AU - Nguyen, J AU - Sanchez-Pernaute, R AU - Bankiewicz, K AU - McKay, R AD - Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institute of Health, Bethesda, Maryland 20892, USA, mckay@codon.nih.gov Y1 - 2002/07/04/ PY - 2002 DA - 2002 Jul 04 SP - 50 EP - 56 PB - Macmillan Publishers Ltd. VL - 418 IS - 6893 SN - 0028-0836, 0028-0836 KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; CSA Neurosciences Abstracts KW - N3 11057:Neural transplantation and regeneration KW - W3 33170:Cellular based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18423245?accountid=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=Dopamine+neurons+derived+from+embryonic+stem+cells+function+in+an+animal+model+of+Parkinson%27s+disease&rft.au=Kim%2C+J+H%3BAuerbach%2C+J+M%3BRodriguez-Gomez%2C+JA%3BVelasco%2C+I%3BGavin%2C+D%3BLumelsky%2C+N%3BLee%2C+S-H%3BNguyen%2C+J%3BSanchez-Pernaute%2C+R%3BBankiewicz%2C+K%3BMcKay%2C+R&rft.aulast=Kim&rft.aufirst=J&rft.date=2002-07-04&rft.volume=418&rft.issue=6893&rft.spage=50&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 - 2011-12-13 ER - TY - JOUR T1 - Gene expression profiles of BRCA1-linked, BRCA2-linked, and sporadic ovarian cancers. AN - 71878514; 12096084 AB - Germline mutations in BRCA1 and BRCA2 are responsible for 5%-10% of epithelial ovarian cancers, but the molecular pathways affected by these mutations are unknown. We used complementary DNA (cDNA) microarrays to compare gene expression patterns in ovarian cancers associated with BRCA1 or BRCA2 mutations with gene expression patterns in sporadic epithelial ovarian cancers and to identify patterns common to both hereditary and sporadic tumors. Tumor samples from 61 patients with pathologically confirmed epithelial ovarian adenocarcinoma with matched clinicopathologic features were studied, including 18 with BRCA1 founder mutations, 16 with BRCA2 founder mutations, and 27 without either founder mutation (termed sporadic cancers). The cDNA microarrays contained 7651 sequence-verified features. Gene expression data were analyzed with a modified two-sided F test, with P<.0001 considered statistically significant. The expression level of six genes was also studied with reverse transcription-polymerase chain reaction. The greatest contrast in gene expression was observed between tumors with BRCA1 mutations and those with BRCA2 mutations; 110 genes showed statistically significantly different expression levels (P<.0001). This group of genes could segregate sporadic tumors into two subgroups, "BRCA1-like" and "BRCA2-like," suggesting that BRCA1-related and BRCA2-related pathways are also involved in sporadic ovarian cancers. Fifty-three genes were differentially expressed between tumors with BRCA1 mutations and sporadic tumors; six of the 53 mapped to Xp11.23 and were expressed at higher levels in tumors with BRCA1 mutations than in sporadic tumors. Compared with the immortalized ovarian surface epithelial cells used as reference, several interferon-inducible genes were overexpressed in the majority of tumors with a BRCA mutation and in sporadic tumors. Mutations in BRCA1 and BRCA2 may lead to carcinogenesis through distinct molecular pathways that also appear to be involved in sporadic cancers. Sporadic carcinogenic pathways may result from epigenetic aberrations of BRCA1 and BRCA2 or their downstream effectors. JF - Journal of the National Cancer Institute AU - Jazaeri, Amir A AU - Yee, Cindy J AU - Sotiriou, Christos AU - Brantley, Kelly R AU - Boyd, Jeff AU - Liu, Edison T AD - Division of Clinical Sciences of the National Cancer Institute, Gaithersburg, MD,USA. Y1 - 2002/07/03/ PY - 2002 DA - 2002 Jul 03 SP - 990 EP - 1000 VL - 94 IS - 13 SN - 0027-8874, 0027-8874 KW - BRCA1 Protein KW - 0 KW - BRCA2 Protein KW - DNA Primers KW - RNA, Messenger KW - RNA, Neoplasm KW - Index Medicus KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - RNA, Messenger -- analysis KW - Aged KW - Reverse Transcriptase Polymerase Chain Reaction KW - RNA, Neoplasm -- analysis KW - RNA, Messenger -- genetics KW - Gene Expression Regulation, Neoplastic KW - Genotype KW - Gene Expression Profiling KW - Middle Aged KW - Germ-Line Mutation KW - Female KW - DNA Primers -- chemistry KW - Adenocarcinoma, Clear Cell -- genetics KW - Ovarian Neoplasms -- metabolism KW - Adenocarcinoma, Mucinous -- genetics KW - Carcinoma, Endometrioid -- genetics KW - Carcinoma, Endometrioid -- metabolism KW - Adenocarcinoma, Mucinous -- metabolism KW - Ovarian Neoplasms -- genetics KW - BRCA1 Protein -- genetics KW - Adenocarcinoma, Clear Cell -- metabolism KW - Cystadenocarcinoma, Serous -- genetics KW - Cystadenocarcinoma, Serous -- metabolism KW - BRCA2 Protein -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71878514?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Gene+expression+profiles+of+BRCA1-linked%2C+BRCA2-linked%2C+and+sporadic+ovarian+cancers.&rft.au=Jazaeri%2C+Amir+A%3BYee%2C+Cindy+J%3BSotiriou%2C+Christos%3BBrantley%2C+Kelly+R%3BBoyd%2C+Jeff%3BLiu%2C+Edison+T&rft.aulast=Jazaeri&rft.aufirst=Amir&rft.date=2002-07-03&rft.volume=94&rft.issue=13&rft.spage=990&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 - 2002-07-25 N1 - Date created - 2002-07-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Natl Cancer Inst. 2002 Oct 2;94(19):1506-7 [12359861] J Natl Cancer Inst. 2002 Jul 3;94(13):960-1 [12096075] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanisms underlying the cytotoxic effects of Tachpyr--a novel metal chelator. AN - 71868716; 12090935 AB - Tachpyr (N,N'N"-tris(2-pyridylmethyl)-cis,cis-1,3,5-triaminocyclohexane), a novel metal chelator, was previously shown to deplete intracellular iron and exert a cytotoxic effect on cultured bladder cancer cells. Tachpyr binds Fe(II) and readily reduces Fe(III). The iron(II)-Tachpyr chelate undergoes intramolecular oxidative dehydrogenation resulting in mono- and diimino Fe(II) complexes. The present study investigates the redox-activity of the Tachpyr-iron complex to better define the mechanism of Tachpyr's cytotoxicity. Tachpyr's mechanism of cytotoxicity was studied using cell-free solutions, isolated DNA, and cultured mammalian cells by employing UV-VIS spectrophotometry, oximetry, spin-trapping technique, and electron paramagnetic resonance (EPR) spectrometry. The results show that: (1) Tachpyr by itself after 24 h of incubation had a cytotoxic effect on cultured cells; (2) fully oxidized Tachpyr had no cytotoxic effects on cultured cells even after 24 h of incubation; (3) Tachpyr protected isolated DNA against H(2)O(2)-induced damage, but not against HX/XO-induced damage; and (4) Tachpyr-Fe(II) chelate slows down but does not block oxidation of Fe(II), allows O*(-)(2)-induced or Tachpyr-induced reduction of Fe(III), and consequently promotes production of *OH through the Haber-Weiss reaction cycle. The results indicate that Tachpyr can protect cells against short-term, metal-mediated damage. However, upon prolonged incubation, Tachpyr exerts cytotoxic effects. Therefore, in addition to iron depletion, low-level oxidative stress, which in part occurs because of redox cycling of the coordinated iron ion, may contribute to the cytotoxic effects of Tachpyr. JF - Biochimica et biophysica acta AU - Samuni, Ayelet M AU - Krishna, Murali C AU - DeGraff, William AU - Russo, Angelo AU - Planalp, Roy P AU - Brechbiel, Martin W AU - Mitchell, James B AD - Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892-1002, USA. Y1 - 2002/07/03/ PY - 2002 DA - 2002 Jul 03 SP - 211 EP - 218 VL - 1571 IS - 3 SN - 0006-3002, 0006-3002 KW - Antineoplastic Agents KW - 0 KW - Chelating Agents KW - Cyclohexylamines KW - DNA, Single-Stranded KW - Macromolecular Substances KW - Pyridines KW - tachpyr KW - DNA KW - 9007-49-2 KW - Iron KW - E1UOL152H7 KW - Catalase KW - EC 1.11.1.6 KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Oxygen Consumption -- drug effects KW - DNA, Single-Stranded -- drug effects KW - Oxidation-Reduction -- drug effects KW - Plasmids -- genetics KW - Dose-Response Relationship, Drug KW - Humans KW - Iron -- chemistry KW - Catalase -- pharmacology KW - DNA -- drug effects KW - Superoxide Dismutase -- pharmacology KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - DNA, Single-Stranded -- chemistry KW - Oxygen -- chemistry KW - DNA -- chemistry KW - Tumor Stem Cell Assay KW - Antineoplastic Agents -- pharmacology KW - Cell-Free System KW - Chelating Agents -- pharmacology KW - Carcinoma -- pathology KW - Pyridines -- toxicity KW - Carcinoma -- drug therapy KW - Lung Neoplasms -- drug therapy KW - Cyclohexylamines -- toxicity KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71868716?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mechanisms+underlying+the+cytotoxic+effects+of+Tachpyr--a+novel+metal+chelator.&rft.au=Samuni%2C+Ayelet+M%3BKrishna%2C+Murali+C%3BDeGraff%2C+William%3BRusso%2C+Angelo%3BPlanalp%2C+Roy+P%3BBrechbiel%2C+Martin+W%3BMitchell%2C+James+B&rft.aulast=Samuni&rft.aufirst=Ayelet&rft.date=2002-07-03&rft.volume=1571&rft.issue=3&rft.spage=211&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 - 2002-08-12 N1 - Date created - 2002-07-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation of Kinetically Distinct Synaptic Conductances on Inhibitory Interneurons by Electrotonically Overlapping Afferents AN - 18467331; 5427655 AB - Mossy fiber (MF) and CA3 collateral (CL) axons activate common interneurons via synapses comprised of different AMPA receptors to provide feedforward and feedback inhibitory control of the CA3 hippocampal network. Because synapses potentially occur over variable electrotonic distances that distort somatically recorded synaptic currents, it is not known whether the underlying afferent-specific synaptic conductances are associated with different time courses. Using a somatic voltage jump technique to alter the driving force at the site of the synapse, we demonstrate that MF and CL synapses overlap in electrotonic location yet differ in conductance time course. Thus, afferent-specific conductance time courses allow single interneurons to differentially integrate feedforward and feedback information without the need to segregate distinct AMPA receptor subunits to different electrotonic domains. JF - Neuron AU - Walker, H C AU - Lawrence, J J AU - McBain, C J AD - Laboratory of Cellular and Synaptic Neurophysiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892 USA, mcbainc@mail.nih.gov Y1 - 2002/07/03/ PY - 2002 DA - 2002 Jul 03 SP - 161 EP - 171 VL - 35 IS - 1 SN - 0896-6273, 0896-6273 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; CSA Neurosciences Abstracts KW - W4 340:Neurocomputing & Neural Networks KW - N3 11065:Central nervous system KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18467331?accountid=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=Neuron&rft.atitle=Activation+of+Kinetically+Distinct+Synaptic+Conductances+on+Inhibitory+Interneurons+by+Electrotonically+Overlapping+Afferents&rft.au=Walker%2C+H+C%3BLawrence%2C+J+J%3BMcBain%2C+C+J&rft.aulast=Walker&rft.aufirst=H&rft.date=2002-07-03&rft.volume=35&rft.issue=1&rft.spage=161&rft.isbn=&rft.btitle=&rft.title=Neuron&rft.issn=08966273&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 - Does place of birth influence endogenous hormone levels in Asian-American women? AN - 954575778; 13759031 AB - In 1983-87, we conducted a population-based case-control study of breast cancer in Asian women living in California and Hawaii, in which migration history (a composite of the subject's place of birth, usual residence in Asia (urban/rural), length of time living in the West, and grandparents' place of birth) was associated with a six-fold risk gradient that paralleled the historical differences in incidence rates between the US and Asian countries. This provided the opportunity to determine whether endogenous hormones vary with migration history in Asian-American women. Plasma obtained from 316 premenopausal and 177 naturally premenopausal study controls was measured for levels of estrone (E1), estradiol (E2), estrone sulphate (E1S), androstenedione (A), testosterone (T), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS), progesterone (PROG) and sex hormone-binding globulin (SHBG). Levels of the oestrogens and sex hormone-binding globulin did not differ significantly between Asian- and Western-born women, although among premenopausal women, those least westernised had the lowest levels of E1, E2, and E1S. Androgen levels, particularly DHEA, were lower in women born in the West. Among premenopausal women, age-adjusted geometric mean levels of DHEA were 16.5 and 13.8nmoll super(-1) in Asian- and Western-born women respectively; in postmenopausal women these values were 11.8 and 9.2nmoll super(-1), (P<0.001) respectively. Among postmenopausal women, androgens tended to be highest among the least westernised women and declined as the degree of westernisation increased. Our findings suggest that aspects of hormone metabolism play a role in population differences in breast cancer incidence.BRITISH JOURNAL OF CANCER: (2002) 87, 54-60. doi:10.1038/sj.bjc.6600339 www.bjcancer.com[copy 2002 Cancer Research UK JF - British Journal of Cancer AU - Falk, R T AU - Fears, T R AU - Hoover, R N AU - Pike, M C AU - Wu, A H AU - Nomura, A M Y AU - Kolonel, L N AU - West, D W AU - Ziegler, R G AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, MD 20892, USA Y1 - 2002/07/01/ PY - 2002 DA - 2002 Jul 01 SP - 54 EP - 60 PB - Nature Publishing Group, The Macmillan Building London N1 9XW UK VL - 87 IS - 1 SN - 0007-0920, 0007-0920 KW - Risk Abstracts KW - British Isles KW - Sulfates KW - Historical account KW - migration KW - post-menopause KW - USA, Hawaii KW - Hormones KW - Cancer KW - Breast cancer KW - USA, California KW - Females KW - Asia KW - Metabolism KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/954575778?accountid=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=British+Journal+of+Cancer&rft.atitle=Does+place+of+birth+influence+endogenous+hormone+levels+in+Asian-American+women%3F&rft.au=Falk%2C+R+T%3BFears%2C+T+R%3BHoover%2C+R+N%3BPike%2C+M+C%3BWu%2C+A+H%3BNomura%2C+A+M+Y%3BKolonel%2C+L+N%3BWest%2C+D+W%3BZiegler%2C+R+G&rft.aulast=Falk&rft.aufirst=R&rft.date=2002-07-01&rft.volume=87&rft.issue=1&rft.spage=54&rft.isbn=&rft.btitle=&rft.title=British+Journal+of+Cancer&rft.issn=00070920&rft_id=info:doi/10.1038%2Fsj.bjc.6600339 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2012-03-01 N1 - Last updated - 2012-03-30 N1 - SubjectsTermNotLitGenreText - Sulfates; migration; Historical account; post-menopause; Breast cancer; Females; Hormones; Metabolism; Cancer; British Isles; USA, Hawaii; USA, California; Asia DO - http://dx.doi.org/10.1038/sj.bjc.6600339 ER - TY - JOUR T1 - Bridging the Divide? Complementary Perspectives on Property AN - 918037386; 13501225 AB - In a recent paper, we argued for the need to develop an understanding of property development processes which combines a sensitivity to the economic and social framing of development strategies with a fine-grain treatment of the locally contingent responses of property actors. This is a response to Ball's criticisms of that paper, which offer a misleading characterisation of our methodological and theoretical position with regard to property research. JF - Urban Studies AU - Guy, Simon AU - Henneberry, John AD - School of Architecture and Plarming and Landscape, University of NewcastLe, Claremont Tower, Newcastle upon Tyne, NEI 7RU, UK Y1 - 2002/07// PY - 2002 DA - Jul 2002 SP - 1471 EP - 1478 PB - Sage Publications, Inc., 2455 Teller Road Thousand Oaks CA 91320 USA VL - 39 IS - 8 SN - 0042-0980, 0042-0980 KW - Environment Abstracts KW - Sensitivity KW - Economics KW - ENA 07:General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/918037386?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aenvabstractsmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Urban+Studies&rft.atitle=Bridging+the+Divide%3F+Complementary+Perspectives+on+Property&rft.au=Guy%2C+Simon%3BHenneberry%2C+John&rft.aulast=Guy&rft.aufirst=Simon&rft.date=2002-07-01&rft.volume=39&rft.issue=8&rft.spage=1471&rft.isbn=&rft.btitle=&rft.title=Urban+Studies&rft.issn=00420980&rft_id=info:doi/10.1080%2F00420980220142736 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2012-01-01 N1 - Last updated - 2012-03-29 N1 - SubjectsTermNotLitGenreText - Sensitivity; Economics DO - http://dx.doi.org/10.1080/00420980220142736 ER - TY - JOUR T1 - Genetics of parkinsonism. AN - 85358966; pmid-12210852 AB - Parkinson's disease (PD) was noted to have a familial component as early as 1880 (Leroux, 1880). More recently, the discovery of several genetic factors influencing parkinsonism has emphasized the importance of heredity in PD. The clinical spectrum of familial parkinsonism is wide; it includes not only PD, but also dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP), essential tremor, and other disorders. In the general population, it is likely that PD results from combined genetic and environmental factors, most of which are not yet known. The discovery of causal mutations in the gene for alpha-synuclein, parkin, and of genetic linkages to chromosomes 2p4, 4p5, and three loci on 1q6-8 have revolutionized PD research. This review focuses on recent progress in the Mendelian genetics of PD and those diseases in which parkinsonism is a prominent feature, and considers how these discoveries modify our beliefs regarding the etiology and pathogenesis of these disorders. JF - Movement disorders : official journal of the Movement Disorder Society AU - Gwinn-Hardy, Katrina AD - Division of Intramural Research, Neurogenetics Laboratories, National Institute of Neurological Disease and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. gwinnk@ninds.nih.gov Y1 - 2002/07// PY - 2002 DA - Jul 2002 SP - 645 EP - 656 VL - 17 IS - 4 SN - 0885-3185, 0885-3185 KW - Index Medicus KW - National Library of Medicine KW - Chromosome Mapping KW - Essential Tremor: diagnosis KW - Essential Tremor: genetics KW - Humans KW - Lewy Body Disease: diagnosis KW - Lewy Body Disease: genetics KW - Ligases: genetics KW - Nerve Tissue Proteins: genetics KW - Parkinson Disease: diagnosis KW - *Parkinson Disease: genetics KW - Parkinsonian Disorders: diagnosis KW - *Parkinsonian Disorders: genetics KW - Supranuclear Palsy, Progressive: diagnosis KW - Supranuclear Palsy, Progressive: genetics KW - Synucleins KW - *Ubiquitin-Protein Ligases KW - alpha-Synuclein UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85358966?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.atitle=Genetics+of+parkinsonism.&rft.au=Gwinn-Hardy%2C+Katrina&rft.aulast=Gwinn-Hardy&rft.aufirst=Katrina&rft.date=2002-07-01&rft.volume=17&rft.issue=4&rft.spage=645&rft.isbn=&rft.btitle=&rft.title=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.issn=08853185&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Semantic clustering in verbal fluency: schizophrenic patients versus control participants. AN - 85259712; pmid-12171385 AB - BACKGROUND: Schizophrenic patients generate fewer words than healthy controls during verbal fluency tasks. The structure of output may explain why patients generate fewer exemplars. METHODS: Twenty-four healthy controls and 24 patients with schizophrenia participated in six, 3 min semantic fluency tasks. In a subsequent session, participants were given cards, each printed with one of their own words generated from previous fluency tasks. Participants were to sort the cards into categories (e.g. subcategories of 'animals'), thus defining their own semantic subcategories of words, and thereby eliminating experimenter assumptions about word relatedness. These clusters were matched with fluency output of each participant. The time spent searching through semantic networks within clusters and switching to other clusters when locating and producing associated words were measured. RESULTS: Patients produced fewer words and spent more time switching to words within clusters and to different clusters than controls, but otherwise response profiles were similar. Although controls returned more frequently to clusters and consequently made more switches between these clusters than patients, this group difference disappeared when the total number of words produced was covaried. CONCLUSIONS: Consistent with previous literature, patients produced fewer words and made more errors than controls. The absence of a group difference in number of different clusters or mean number of items per cluster suggests that patients are similar to controls with respect to number of ideas in their semantic network. Patients' longer between-cluster switching times indicate a general slowness that may be attributed to difficulties finding new words within a semantic field. JF - Psychological Medicine AU - Elvevåg B AU - Fisher, J E AU - Gurd, J M AU - Goldberg, T E AD - Clinical Brain Disorders Branch, National Institute of Mental Health/National Institutes of Health, Bethesda, MD 20892, USA. PY - 2002 SP - 909 EP - 917 VL - 32 IS - 5 SN - 0033-2917, 0033-2917 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85259712?accountid=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=Psychological+Medicine&rft.atitle=Semantic+clustering+in+verbal+fluency%3A+schizophrenic+patients+versus+control+participants.&rft.au=Elvev%C3%A5g+B%3BFisher%2C+J+E%3BGurd%2C+J+M%3BGoldberg%2C+T+E&rft.aulast=Elvev%C3%A5g+B&rft.aufirst=&rft.date=2002-07-01&rft.volume=32&rft.issue=5&rft.spage=909&rft.isbn=&rft.btitle=&rft.title=Psychological+Medicine&rft.issn=00332917&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. AN - 85237229; pmid-12117397 AB - CONTEXT: Despite decades of accumulated observational evidence, the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain. OBJECTIVE: To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States. DESIGN: Estrogen plus progestin component of the Women's Health Initiative, a randomized controlled primary prevention trial (planned duration, 8.5 years) in which 16608 postmenopausal women aged 50-79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993-1998. INTERVENTIONS: Participants received conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102). MAIN OUTCOMES MEASURES: The primary outcome was coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the primary adverse outcome. A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, and death due to other causes. RESULTS: On May 31, 2002, after a mean of 5.2 years of follow-up, the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits. This report includes data on the major clinical outcomes through April 30, 2002. Estimated hazard ratios (HRs) (nominal 95% confidence intervals [CIs]) were as follows: CHD, 1.29 (1.02-1.63) with 286 cases; breast cancer, 1.26 (1.00-1.59) with 290 cases; stroke, 1.41 (1.07-1.85) with 212 cases; PE, 2.13 (1.39-3.25) with 101 cases; colorectal cancer, 0.63 (0.43-0.92) with 112 cases; endometrial cancer, 0.83 (0.47-1.47) with 47 cases; hip fracture, 0.66 (0.45-0.98) with 106 cases; and death due to other causes, 0.92 (0.74-1.14) with 331 cases. Corresponding HRs (nominal 95% CIs) for composite outcomes were 1.22 (1.09-1.36) for total cardiovascular disease (arterial and venous disease), 1.03 (0.90-1.17) for total cancer, 0.76 (0.69-0.85) for combined fractures, 0.98 (0.82-1.18) for total mortality, and 1.15 (1.03-1.28) for the global index. Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures. The absolute excess risk of events included in the global index was 19 per 10 000 person-years. CONCLUSIONS: Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women. All-cause mortality was not affected during the trial. The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD. JF - JAMA AU - Rossouw, Jacques E AU - Anderson, Garnet L AU - Prentice, Ross L AU - LaCroix, Andrea Z AU - Kooperberg, Charles AU - Stefanick, Marcia L AU - Jackson, Rebecca D AU - Beresford Shirley A A AU - Howard, Barbara V AU - Johnson, Karen C AU - Kotchen Jane Morley AU - Ockene, Judith AD - Division of Women's Health Initiative, National Heart, Lung, and Blood Institute, 6705 Rockledge Dr, One Rockledge Ctr, Suite 300, Bethesda, MD 20817, PY - 2002 SP - 321 EP - 333 VL - 288 IS - 3 SN - 0098-7484, 0098-7484 KW - Medroxyprogesterone 17-Acetate KW - Pulmonary Embolism KW - Humans KW - Fractures KW - Aged KW - Breast Neoplasms KW - Thrombosis KW - Research Support, U.S. Gov't, P.H.S. KW - Coronary Disease KW - Risk KW - Estrogens, Conjugated (USP) KW - Cerebrovascular Accident KW - Endometrial Neoplasms KW - Postmenopause KW - Progesterone Congeners KW - Clinical Trials Data Monitoring Committees KW - Treatment Outcome KW - Middle Aged KW - Myocardial Infarction KW - Female KW - Colorectal Neoplasms KW - Proportional Hazards Models KW - Survival Analysis KW - Estrogen Replacement Therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85237229?accountid=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=Risks+and+benefits+of+estrogen+plus+progestin+in+healthy+postmenopausal+women%3A+principal+results+From+the+Women%27s+Health+Initiative+randomized+controlled+trial.&rft.au=Rossouw%2C+Jacques+E%3BAnderson%2C+Garnet+L%3BPrentice%2C+Ross+L%3BLaCroix%2C+Andrea+Z%3BKooperberg%2C+Charles%3BStefanick%2C+Marcia+L%3BJackson%2C+Rebecca+D%3BBeresford+Shirley+A+A%3BHoward%2C+Barbara+V%3BJohnson%2C+Karen+C%3BKotchen+Jane+Morley%3BOckene%2C+Judith&rft.aulast=Rossouw&rft.aufirst=Jacques&rft.date=2002-07-01&rft.volume=288&rft.issue=3&rft.spage=321&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 - Controlled study of citrate effects and response to i.v. calcium administration during allogeneic peripheral blood progenitor cell donation. AN - 72169064; 12375668 AB - Leukapheresis procedures are generally performed at citrate anticoagulation rates extrapolated from shorter plateletpheresis procedures. However, neither the metabolic effects nor the management of associated symptoms have been critically evaluated during leukapheresis in healthy donors. Symptom assessments (n = 315) and laboratory analyses (n = 49) were performed during 244 procedures performed with and 71 without prophylactic calcium (Ca) chloride or Ca gluconate given at a dose linked to the citrate infusion rate (1.0-2.2 mg/kg/min). During leukapheresis of 12 to 25 L processed, ionized Ca and ionized magnesium (Mg) decreased as much as 35 and 56 percent, respectively, each exhibiting a tight negative correlation with marked increases in serum citrate levels. Significant increases in urinary Ca and Mg excretion accompanied the renal excretion of a large citrate load. Serum divalent cation levels remained depressed 24 hours after leukapheresis. Symptoms were more frequent in donors who were women, had low initial total Mg levels, and underwent procedures in which larger volumes were processed at higher citrate infusion rates. Ca infusions reduced clinically significant paresthesias by 96 percent and also attenuated decreases in serum potassium. Ca chloride maintained higher Ca levels than Ca gluconate. Prophylactic Ca infusions safely attenuate the marked metabolic effects of citrate administration and promote faster, more comfortable, leukapheresis procedures. JF - Transfusion AU - Bolan, Charles D AU - Cecco, Stacey A AU - Wesley, Robert A AU - Horne, McDonald AU - Yau, Yu Ying AU - Remaley, Alan T AU - Childs, Richard W AU - Barrett, A John AU - Rehak, Nadja N AU - Leitman, Susan F AD - Department of Transfusion Medicine, Warren Grant Magnuson Clinical Center, Hematology Branch, National Heart, Lung and Blood Institute, NIH, Bethesda, MD 20892-1184, USA. cbolan@mail.cc.nih.gov Y1 - 2002/07// PY - 2002 DA - July 2002 SP - 935 EP - 946 VL - 42 IS - 7 SN - 0041-1132, 0041-1132 KW - Citric Acid KW - 2968PHW8QP KW - Magnesium KW - I38ZP9992A KW - Calcium Chloride KW - M4I0D6VV5M KW - Calcium Gluconate KW - SQE6VB453K KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Calcium Gluconate -- administration & dosage KW - Infusions, Intravenous KW - Magnesium -- blood KW - Hematopoietic Stem Cells KW - Humans KW - Paresthesia -- chemically induced KW - Transplantation, Homologous KW - Calcium Chloride -- pharmacokinetics KW - Calcium Chloride -- administration & dosage KW - Paresthesia -- etiology KW - Magnesium -- urine KW - Calcium Gluconate -- pharmacokinetics KW - Female KW - Male KW - Citric Acid -- pharmacology KW - Citric Acid -- pharmacokinetics KW - Leukapheresis -- methods KW - Citric Acid -- blood KW - Calcium -- pharmacokinetics KW - Calcium -- administration & dosage KW - Calcium -- urine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72169064?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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&rft.atitle=Controlled+study+of+citrate+effects+and+response+to+i.v.+calcium+administration+during+allogeneic+peripheral+blood+progenitor+cell+donation.&rft.au=Bolan%2C+Charles+D%3BCecco%2C+Stacey+A%3BWesley%2C+Robert+A%3BHorne%2C+McDonald%3BYau%2C+Yu+Ying%3BRemaley%2C+Alan+T%3BChilds%2C+Richard+W%3BBarrett%2C+A+John%3BRehak%2C+Nadja+N%3BLeitman%2C+Susan+F&rft.aulast=Bolan&rft.aufirst=Charles&rft.date=2002-07-01&rft.volume=42&rft.issue=7&rft.spage=935&rft.isbn=&rft.btitle=&rft.title=Transfusion&rft.issn=00411132&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-06 N1 - Date created - 2002-10-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - IARC monographs, industry influence, and upgrading, downgrading, and under-grading chemicals: a personal point of view. International Agency for Research on Cancer. AN - 72140684; 12358081 AB - The first IARC Monographs Volume was distributed in 1972, and over the 23 years through 1993, under the leadership of Dr Lorenzo Tomatis, 59 IARC Monographs were completed. During 1977-1979 the author was privileged to lead the program for Volumes 15-22, and participated in the pioneering development of the LARC Preamble and Categories of Evidence. During this era other Chiefs of the IARC Monographs included Claus Agthe, Harri Vainio, Antero Aitio, and Julian Wilbourn. Since then (starting with Volume 62: 1995), a new attitude seems to have pervaded the IARC Monographs program, resulting in an increasing influence of or partiality for industry and a diminishing dedication to public and occupational health and safety concerns, and for primary prevention. Some of this attitude comes from an apparent misguided scientific zest prematurely to endorse purported or hypothetical mechanisms of chemical carcinogenesis or modes of action of chemicals causing cancer in experimental animals. These speculations are in turn used cavalierly to discount the value of experimental evidence for predicting probable carcinogenicity to humans. Most often this is accomplished by opining that the mechanism(s) of carcinogenicity in animals would not be operative in humans. End of explanation. Examples whereby the IARC has recently "down-graded" or "under-graded" the available evidence of carcinogenicity include: acrylonitrile; atrazine; benzidine-based dyes; 1,3-butadiene, dichloromethane (methylene chloride); di (2-ethylhexyl) phthalate; glass wool insulation; MtBE [methyl tertiary butyl ether]; ochratoxin A; saccharin; sunlamps and sunbeds (use of); trichloroethylene; sulfamethazine; and others more inclusively mentioned in the text and tables. Further impeding or compromising public health, chemicals causing site-specific cancers in animals attendant with calculi/precipitate in the urinary bladder, goiter and thyroid gland, kidney and alpha-2mu globulin, peroxisome proliferation and liver tumors, and cell proliferation in general have led the IARC to discount these car- cinogenic effects. To stem this tide at the IARC, new leadership, with more objectivity and public health perspective, is needed. JF - International journal of occupational and environmental health AU - Huff, James AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. huff1@niehs.nih.gov PY - 2002 SP - 249 EP - 270 VL - 8 IS - 3 SN - 1077-3525, 1077-3525 KW - Carcinogens KW - 0 KW - Hazardous Substances KW - Index Medicus KW - Peer Review, Research KW - Occupational Health KW - Animals KW - Public Health KW - Humans KW - Scientific Misconduct KW - Periodicals as Topic KW - Hazardous Substances -- classification KW - Hazardous Substances -- adverse effects KW - Environmental Health KW - Carcinogens -- classification KW - Publication Bias KW - International Agencies -- standards KW - Conflict of Interest KW - Chemical Industry KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72140684?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+occupational+and+environmental+health&rft.atitle=IARC+monographs%2C+industry+influence%2C+and+upgrading%2C+downgrading%2C+and+under-grading+chemicals%3A+a+personal+point+of+view.+International+Agency+for+Research+on+Cancer.&rft.au=Huff%2C+James&rft.aulast=Huff&rft.aufirst=James&rft.date=2002-07-01&rft.volume=8&rft.issue=3&rft.spage=249&rft.isbn=&rft.btitle=&rft.title=International+journal+of+occupational+and+environmental+health&rft.issn=10773525&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-07 N1 - Date created - 2002-10-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Int J Occup Environ Health. 2003 Jan-Mar;9(1):90 [12749642] Int J Occup Environ Health. 2003 Jan-Mar;9(1):78-9; author reply 82 [12749635] Comment On: Int J Occup Environ Health. 2002 Apr-Jun;8(2):144-52 [12019681] Erratum In: Int J Occup Environ Health. 2003 Jan-Mar;9(1):84 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The IARC evaluation of di(2-ethylhexyl)phthalate (DEHP): a flawed decision based on an untested hypothesis. AN - 72135871; 12358086 JF - International journal of occupational and environmental health AU - Melnick, Ronald L AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. PY - 2002 SP - 284 EP - 286 VL - 8 IS - 3 SN - 1077-3525, 1077-3525 KW - Carcinogens KW - 0 KW - Peroxisome Proliferators KW - Diethylhexyl Phthalate KW - C42K0PH13C KW - Index Medicus KW - Occupational Health KW - Animals KW - Reproducibility of Results KW - Peroxisome Proliferators -- adverse effects KW - Humans KW - Peroxisome Proliferators -- classification KW - Liver Neoplasms, Experimental -- chemically induced KW - Decision Making, Organizational KW - Diethylhexyl Phthalate -- classification KW - Environmental Health KW - Carcinogens -- classification KW - International Agencies -- standards KW - Diethylhexyl Phthalate -- adverse effects KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72135871?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+occupational+and+environmental+health&rft.atitle=The+IARC+evaluation+of+di%282-ethylhexyl%29phthalate+%28DEHP%29%3A+a+flawed+decision+based+on+an+untested+hypothesis.&rft.au=Melnick%2C+Ronald+L&rft.aulast=Melnick&rft.aufirst=Ronald&rft.date=2002-07-01&rft.volume=8&rft.issue=3&rft.spage=284&rft.isbn=&rft.btitle=&rft.title=International+journal+of+occupational+and+environmental+health&rft.issn=10773525&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-07 N1 - Date created - 2002-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The use of gene transfer for the protection and repair of salivary glands. AN - 72050753; 12206399 JF - Oral diseases AU - Vitolo, J M AU - Baum, B J AD - Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2002/07// PY - 2002 DA - July 2002 SP - 183 EP - 191 VL - 8 IS - 4 SN - 1354-523X, 1354-523X KW - Recombinant Proteins KW - 0 KW - Dentistry KW - Animals KW - Radiation Protection KW - Humans KW - Radiation Injuries -- prevention & control KW - Sjogren's Syndrome -- therapy KW - Autoimmune Diseases -- therapy KW - Disease Models, Animal KW - Genetic Therapy KW - Transgenes -- genetics KW - Plasmids KW - Adenoviridae -- genetics KW - DNA Repair -- genetics KW - Genetic Vectors KW - Radiation Injuries -- therapy KW - Parvovirus -- genetics KW - Recombinant Proteins -- therapeutic use KW - Salivary Glands -- radiation effects KW - Gene Transfer Techniques KW - Salivary Gland Diseases -- therapy KW - Salivary Glands -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72050753?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oral+diseases&rft.atitle=The+use+of+gene+transfer+for+the+protection+and+repair+of+salivary+glands.&rft.au=Vitolo%2C+J+M%3BBaum%2C+B+J&rft.aulast=Vitolo&rft.aufirst=J&rft.date=2002-07-01&rft.volume=8&rft.issue=4&rft.spage=183&rft.isbn=&rft.btitle=&rft.title=Oral+diseases&rft.issn=1354523X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-20 N1 - Date created - 2002-09-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of ICCVAM in evaluating new and alternative test methods. AN - 72041164; 12200591 JF - Lab animal AU - Stokes, William S AU - Hill, Richard N AD - NTP Interagency Center for the Evaluation of Alternative Toxicological Methods, Environmental Toxicology Program, National Institute of Environmental Health Sciences, Mail Code EC-17, PO Box 1233, Research Triangle Park, NC 27709, USA. stokes@niehs.nih.gov PY - 2002 SP - 26 EP - 32 VL - 31 IS - 7 SN - 0093-7355, 0093-7355 KW - Index Medicus KW - United States KW - Animals KW - Interinstitutional Relations KW - Humans KW - Cost-Benefit Analysis KW - Safety KW - National Institutes of Health (U.S.) KW - Toxicity Tests -- methods KW - Animal Testing Alternatives KW - Animal Welfare KW - Animal Care Committees UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72041164?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lab+animal&rft.atitle=The+role+of+ICCVAM+in+evaluating+new+and+alternative+test+methods.&rft.au=Stokes%2C+William+S%3BHill%2C+Richard+N&rft.aulast=Stokes&rft.aufirst=William&rft.date=2002-07-01&rft.volume=31&rft.issue=7&rft.spage=26&rft.isbn=&rft.btitle=&rft.title=Lab+animal&rft.issn=00937355&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-25 N1 - Date created - 2002-08-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunotoxins in cancer therapy. AN - 72015093; 12186272 AB - Several antibodies have now been approved for the therapy of cancer. Two of these, rituximab (Rituxan) and alemtuzumab (CAMPATH; ILEX Oncology Inc), are capable of inducing cell death and tumor regressions when given alone. The third, trastuzumab (Herceptin), is not very effective by itself, but does potentiate the activity of paclitaxel (Taxol) and other chemotherapeutic agents. Unfortunately, most antibodies do not kill cancer cells unless they are armed with a cytotoxic agent, such as a radioisotope, a cytotoxic drug, or a protein toxin. Each of these have advantages and disadvantages. JF - Current opinion in investigational drugs (London, England : 2000) AU - Pastan, Ira AU - Kreitman, Robert J AD - Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4264, USA. pasta@helix.nih.gov Y1 - 2002/07// PY - 2002 DA - July 2002 SP - 1089 EP - 1091 VL - 3 IS - 7 SN - 1472-4472, 1472-4472 KW - Immunotoxins KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Neoplasms -- drug therapy KW - Immunotoxins -- adverse effects KW - Immunotoxins -- therapeutic use KW - Immunotoxins -- administration & dosage KW - Neoplasms -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72015093?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+investigational+drugs+%28London%2C+England+%3A+2000%29&rft.atitle=Immunotoxins+in+cancer+therapy.&rft.au=Pastan%2C+Ira%3BKreitman%2C+Robert+J&rft.aulast=Pastan&rft.aufirst=Ira&rft.date=2002-07-01&rft.volume=3&rft.issue=7&rft.spage=1089&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+investigational+drugs+%28London%2C+England+%3A+2000%29&rft.issn=14724472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-12 N1 - Date created - 2002-08-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Methapyrilene toxicity: anchorage of pathologic observations to gene expression alterations. AN - 72010343; 12187938 AB - Methapyrilene (MP) exposure of animals can result in an array of adverse pathological responses including hepatotoxicity. This study investigates gene expression and histopathological alterations in response to MP treatment in order to 1) utilize computational approaches to classify samples derived from livers of MP treated rats based on severity of toxicity incurred in the corresponding tissue, 2) to phenotypically anchor gene expression pattems, and 3) to gain insight into mechanism(s) of methapyrilene hepatotoxicity. Large-scale differential gene expression levels associated with the exposure of male Sprague-Dawley rats to the rodent hepatic carcinogen MP for 1, 3, or 7 days after daily dosage with 10 or 100 mg/kg/day were monitored. Hierarchical clustering and principal component analysis were successful in classifying samples in agreement with microscopic observations and revealed low-dose effects that were not observed histopathologically. Data from cDNA microarray analysis corroborated observed histopathological alterations such as hepatocellular necrosis, bile duct hyperplasia, microvesicular vacuolization, and portal inflammation observed in the livers of MP exposed rats and provided insight into the role of specific genes in the studied toxicological processes. JF - Toxicologic pathology AU - Hamadeh, Hisham K AU - Knight, Brian L AU - Haugen, Astrid C AU - Sieber, Stella AU - Amin, Rupesh P AU - Bushel, Pierre R AU - Stoll, Raymond AU - Blanchard, Kerry AU - Jayadev, Supriya AU - Tennant, Raymond W AU - Cunningham, Michael L AU - Afshari, Cynthia A AU - Paules, Richard S AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. PY - 2002 SP - 470 EP - 482 VL - 30 IS - 4 SN - 0192-6233, 0192-6233 KW - Histamine H1 Antagonists KW - 0 KW - Methapyrilene KW - A01LX40298 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Rats KW - Calcium -- metabolism KW - Gene Expression Profiling KW - Animals KW - Rats, Sprague-Dawley KW - Body Weight -- drug effects KW - Lipid Peroxidation -- drug effects KW - Male KW - Organ Size -- drug effects KW - Gene Expression -- drug effects KW - Liver -- pathology KW - Liver -- drug effects KW - Methapyrilene -- toxicity KW - Liver -- metabolism KW - Histamine H1 Antagonists -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72010343?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Methapyrilene+toxicity%3A+anchorage+of+pathologic+observations+to+gene+expression+alterations.&rft.au=Hamadeh%2C+Hisham+K%3BKnight%2C+Brian+L%3BHaugen%2C+Astrid+C%3BSieber%2C+Stella%3BAmin%2C+Rupesh+P%3BBushel%2C+Pierre+R%3BStoll%2C+Raymond%3BBlanchard%2C+Kerry%3BJayadev%2C+Supriya%3BTennant%2C+Raymond+W%3BCunningham%2C+Michael+L%3BAfshari%2C+Cynthia+A%3BPaules%2C+Richard+S&rft.aulast=Hamadeh&rft.aufirst=Hisham&rft.date=2002-07-01&rft.volume=30&rft.issue=4&rft.spage=470&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 - 2003-03-12 N1 - Date created - 2002-08-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Endocrine dismodulation and cancer. AN - 71991026; 12163847 AB - Carcinogenesis has generally been viewed as a genomic disease resulting from genetic mutations occurring at critical locations in the genome in a particular sequence. In the last 10 years, scientists have increasingly identified changes in the levels, frequency and types of endocrine hormones as important contributors to the major cancers faced by western populations such as breast cancer (estrogen, progesterone, prolactin), prostate cancer (estrogen, testosterone), endometrial cancer (estrogen) and thyroid cancer (TSH, T3, T4). This manuscript summarizes cancer mechanisms linked to changes in endocrine function and discusses tools for analyzing and understanding the associated data. A number of chemicals in the environment mimic the role of hormones to bind to receptors (e.g. phytoestrogens as estrogen mimics), alter signaling pathways (e.g. retinoids), inhibit steroid hormone synthesis (such as some fungicides) or alter steroid hormone metabolism (such as TCDD altering the metabolism of both estrogen and thyroid hormones). Genomic and non-genomic endocrine signaling pathways are extensively present in the body and function in a complicated fashion. In order to fully understand the basis for endocrine-induced cancers, one must simultaneously study the various receptors, ligands, enzymes, other proteins within different organs which all contribute to endocrine system function. Also, cross-talk between endocrine systems is common and is key to understanding a potential role of light-dark cycles on human cancer risks. Mechanism-based mathematical models are the only analysis tool available to address all aspects of these complicated networks. JF - Neuro endocrinology letters AU - Portier, Christopher J AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709, USA. portier@niehs.nih.gov Y1 - 2002/07// PY - 2002 DA - July 2002 SP - 43 EP - 47 VL - 23 Suppl 2 SN - 0172-780X, 0172-780X KW - Hormones KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Models, Biological KW - Hormones -- physiology KW - Neoplasms -- physiopathology KW - Neurosecretory Systems -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71991026?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuro+endocrinology+letters&rft.atitle=Endocrine+dismodulation+and+cancer.&rft.au=Portier%2C+Christopher+J&rft.aulast=Portier&rft.aufirst=Christopher&rft.date=2002-07-01&rft.volume=23+Suppl+2&rft.issue=&rft.spage=43&rft.isbn=&rft.btitle=&rft.title=Neuro+endocrinology+letters&rft.issn=0172780X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-09-12 N1 - Date created - 2002-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Role of S-adenosyl-L-methionine in the treatment of alcoholic liver disease: introduction and summary of the symposium. AN - 71990941; 12163142 AB - The National Institute on Alcohol Abuse and Alcoholism and the Office of Dietary Supplements, National Institutes of Health, sponsored a symposium on "Role of S-Adenosyl-L-Methionine (SAMe) in the Treatment of Alcoholic Liver Disease" in Bethesda, Maryland, September 2001. Alcoholic liver disease (ALD) is a major cause of illness and death in the United States. Oxidant stress plays a key role in pathogenesis of liver disease. S-Adenosyl-L-methionine, a dietary supplement, is the methyl donor for biochemical methylation reactions and a precursor of glutathione, the main hepatocellular antioxidant. S-Adenosyl-L-methionine has been shown to attenuate liver injury caused by alcohol and other hepatotoxins in some animal models. Understanding the mechanisms by which SAMe attenuates liver injury caused by alcohol may provide useful information for full-scale human clinical trials. For this symposium, seven speakers were invited to address the following issues: (1) impaired methionine metabolism in alcoholic liver injury; (2) regulation of liver function by SAMe; (3) folate deficiency, methionine metabolism, and alcoholic liver injury; (4) attenuating effect of SAMe on ALD in experimental animals; (5) SAMe and mitochondrial glutathione depletion in ALD; (6) SAMe and cytokine production in liver injury; and (7) role of SAMe in the prevention of hepatocarcinogenesis. The presentations of this symposium support the suggestion that SAMe may have potential to treat ALD by (1) acting as a precursor of antioxidant glutathione, (2) repairing mitochondrial glutathione transport system, (3) attenuating toxic effects of proinflammatory cytokines, and (4) increasing DNA methylation. Further studies are required to evaluate the safety and effectiveness of SAMe treatment. JF - Alcohol (Fayetteville, N.Y.) AU - Purohit, Vishnudutt AU - Russo, Denise Y1 - 2002/07// PY - 2002 DA - July 2002 SP - 151 EP - 154 VL - 27 IS - 3 KW - Antioxidants KW - 0 KW - S-Adenosylmethionine KW - 7LP2MPO46S KW - Index Medicus KW - Animals KW - Oxidative Stress -- physiology KW - Antioxidants -- pharmacology KW - Humans KW - Antioxidants -- therapeutic use KW - Oxidative Stress -- drug effects KW - Liver Diseases, Alcoholic -- metabolism KW - S-Adenosylmethionine -- pharmacology KW - S-Adenosylmethionine -- therapeutic use KW - S-Adenosylmethionine -- metabolism KW - Liver Diseases, Alcoholic -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71990941?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Alcohol+%28Fayetteville%2C+N.Y.%29&rft.atitle=Role+of+S-adenosyl-L-methionine+in+the+treatment+of+alcoholic+liver+disease%3A+introduction+and+summary+of+the+symposium.&rft.au=Purohit%2C+Vishnudutt%3BRusso%2C+Denise&rft.aulast=Purohit&rft.aufirst=Vishnudutt&rft.date=2002-07-01&rft.volume=27&rft.issue=3&rft.spage=151&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 - 2003-02-07 N1 - Date created - 2002-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Therapeutic and adverse actions of serotonin transporter substrates. AN - 71989116; 12163129 AB - A variety of drugs release serotonin (5-HT, 5-hydroxytryptamine) from neurons by acting as substrates for 5-HT transporter (SERT) proteins. This review summarizes the neurochemical, therapeutic, and adverse actions of substrate-type 5-HT-releasing agents. The appetite suppressant (+/-)-fenfluramine is composed of (+) and (-) isomers, which are N-de-ethylated in the liver to yield the metabolites (+)- and (-)-norfenfluramine. Fenfluramines and norfenfluramines are potent 5-HT releasers. (+/-)-3,4-Methylenedioxymethamphetamine ((+/-)-MDMA, "ecstasy") and m-chlorophenylpiperazine (mCPP) are substrate-type 5-HT releasers. Fenfluramines, (+/-)-MDMA, and mCPP release neuronal 5-HT by a common non-exocytotic diffusion-exchange mechanism involving SERTs. (+)-Norfenfluramine is a potent 5-HT(2B) and 5-HT(2C) receptor agonist. The former activity may increase the risk of valvular heart disease, whereas the latter activity is implicated in the anorexic effect of systemic fenfluramine. Appetite suppressants that increase the risk for developing primary pulmonary hypertension (PPH) are all SERT substrates, but these drugs vary considerably in their propensity to increase this risk. For example, fenfluramine and aminorex are clearly linked to the occurrence of PPH, whereas other anorectics are not. Similarly, some SERT substrates deplete brain tissue 5-HT in animals (e.g., fenfluramine), while others do not (e.g., mCPP). In addition to the established indication of obesity, 5-HT releasers may help treat psychiatric disorders, such as drug and alcohol dependence, depression, and premenstrual syndrome. Viewed collectively, we believe new medications can be developed that selectively release 5-HT without increasing the risk for adverse effects of valvular heart disease, PPH, and neurotoxicity. Such agents may be useful for treating a variety of psychiatric disorders. JF - Pharmacology & therapeutics AU - Rothman, Richard B AU - Baumann, Michael H AD - Clinical Psychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, P. O. Box 5180, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. rothman@intra.nida.nih.gov Y1 - 2002/07// PY - 2002 DA - July 2002 SP - 73 EP - 88 VL - 95 IS - 1 SN - 0163-7258, 0163-7258 KW - Appetite Depressants KW - 0 KW - Receptors, Serotonin KW - Serotonin Agents KW - Index Medicus KW - Animals KW - Synaptosomes -- drug effects KW - Hypertension, Pulmonary -- chemically induced KW - Appetite Depressants -- adverse effects KW - Brain -- cytology KW - Humans KW - Heart Valve Diseases -- chemically induced KW - Brain -- metabolism KW - Appetite Depressants -- pharmacology KW - Synaptosomes -- metabolism KW - Serotonin Agents -- pharmacology KW - Receptors, Serotonin -- metabolism KW - Serotonin Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71989116?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacology+%26+therapeutics&rft.atitle=Therapeutic+and+adverse+actions+of+serotonin+transporter+substrates.&rft.au=Rothman%2C+Richard+B%3BBaumann%2C+Michael+H&rft.aulast=Rothman&rft.aufirst=Richard&rft.date=2002-07-01&rft.volume=95&rft.issue=1&rft.spage=73&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 completed - 2003-03-05 N1 - Date created - 2002-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Relationship between cortisol and serotonin metabolites and transporters in alcoholism [correction of alcolholism]. AN - 71985647; 12163982 AB - Stress hormone activation may induce clinical depression via an interference with central serotonergic neurotransmission. In alcoholics, a reduction in serotonin transporters was associated with clinical depression, and an activation of cortisol secretion is frequently found during detoxification. We assessed the interaction between stress hormone activation, serotonin transporters, monoamine metabolites in the cerebrospinal fluid (CSF), and mood states in male and female alcoholics and healthy control subjects. The availability of serotonin transporters was measured with [I-123]beta-CIT and SPECT in the raphe area of the brainstem in 31 alcoholics after four weeks of abstinence and in 25 age-matched healthy volunteers. Concentrations of plasma cortisol were measured on the day of the SPECT scan. Within one week after the SPECT scan, we assessed monoamine metabolites and corticotropin-releasing factor (CRF) in the CSF. Clinical depression was associated with a reduction in serotonin transporter availability among male alcoholics. Among male alcoholics and healthy volunteers, CSF 5-HIAA and plasma cortisol concentrations were inversely correlated with the availability of raphe serotonin transporters and positively correlated with the severity of clinical depression. No significant correlations were observed between raphe serotonin transporters and HVA, MHPG and CRF concentrations in the CSF. Our findings support the hypothesis of an interaction between reduced serotonin transporters, stress hormone activation and clinical depression. They confirm the hypothesis that serotonergic neurotransmission dysfunction in alcoholism is limited to male alcoholics. The observed interactions between high cortisol concentrations and reduced serotonin transporter availability warrant further studies in major depression and other neuropsychiatric diseases with implied cortisol activation and serotonergic dysfunction. JF - Pharmacopsychiatry AU - Heinz, A AU - Jones, D W AU - Bissette, G AU - Hommer, D AU - Ragan, P AU - Knable, M AU - Wellek, S AU - Linnoila, M AU - Weinberger, D R AD - Intramural Research Program, Clinical Brain Disorders Branch/NIMH, Bethesda, MD, USA. andreas.heinz@charite.de Y1 - 2002/07// PY - 2002 DA - July 2002 SP - 127 EP - 134 VL - 35 IS - 4 SN - 0176-3679, 0176-3679 KW - Carrier Proteins KW - 0 KW - Iodine Radioisotopes KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - SLC6A4 protein, human KW - Serotonin Plasma Membrane Transport Proteins KW - Methoxyhydroxyphenylglycol KW - 534-82-7 KW - Hydroxyindoleacetic Acid KW - 54-16-0 KW - Corticotropin-Releasing Hormone KW - 9015-71-8 KW - Hydrocortisone KW - WI4X0X7BPJ KW - Homovanillic Acid KW - X77S6GMS36 KW - Index Medicus KW - Tomography, Emission-Computed, Single-Photon KW - Humans KW - Hydroxyindoleacetic Acid -- cerebrospinal fluid KW - Homovanillic Acid -- cerebrospinal fluid KW - Methoxyhydroxyphenylglycol -- cerebrospinal fluid KW - Adult KW - Case-Control Studies KW - Affect KW - Middle Aged KW - Depressive Disorder -- metabolism KW - Female KW - Male KW - Substance Withdrawal Syndrome -- metabolism KW - Carrier Proteins -- metabolism KW - Alcoholism -- metabolism KW - Substance Withdrawal Syndrome -- cerebrospinal fluid KW - Raphe Nuclei -- metabolism KW - Hydrocortisone -- blood KW - Corticotropin-Releasing Hormone -- cerebrospinal fluid KW - Alcoholism -- cerebrospinal fluid KW - Substance Withdrawal Syndrome -- blood KW - Alcoholism -- blood KW - Membrane Glycoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71985647?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacopsychiatry&rft.atitle=Relationship+between+cortisol+and+serotonin+metabolites+and+transporters+in+alcoholism+%5Bcorrection+of+alcolholism%5D.&rft.au=Heinz%2C+A%3BJones%2C+D+W%3BBissette%2C+G%3BHommer%2C+D%3BRagan%2C+P%3BKnable%2C+M%3BWellek%2C+S%3BLinnoila%2C+M%3BWeinberger%2C+D+R&rft.aulast=Heinz&rft.aufirst=A&rft.date=2002-07-01&rft.volume=35&rft.issue=4&rft.spage=127&rft.isbn=&rft.btitle=&rft.title=Pharmacopsychiatry&rft.issn=01763679&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-27 N1 - Date created - 2002-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genotoxicity and carcinogenicity studies of soy isoflavones. AN - 71985463; 12171629 AB - The potential cancer preventive efficacy of soy isoflavones is being investigated in preclinical and phase 1 clinical studies sponsored by the U.S. National Cancer Institute. Although 90-day oral toxicity studies with PTI G-2535 (an investigational soy isoflavone drug product) in rats and dogs, as well as teratology studies, indicated no signs of toxicity, there remains a mechanistic concern associated with the ability of isoflavones (i.e., genistein) to inhibit topoisomerase, possibly leading to DNA strand breaks. The present report describes results from two in vitro genotoxicity studies, one in vivo genotoxicity study, and a single carcinogenicity study conducted in p53 knockout mice. Bacterial mutagenesis experiments using six tester strains without metabolic activation revealed no evidence that PTI G-2535 was mutagenic. In similar experiments with exogenous metabolic activation there were statistically significant increases in revertants, but less than twofold, in a single (Salmonella typhimurium TA100) tester strain. Mouse lymphoma cell mutagenesis experiments conducted with and without metabolic activation revealed statistically significant increases in mutation frequency at PTI G-2535 concentrations > or = 0.8 and 12 microg/ml, respectively; such increases were dose related and increases in the frequency of both small and large colonies were observed. A statistically significant increase in the frequency of micronucleated polychromatic erythrocytes was also seen 24 hours after treatment in male, but not female, mice who received 500 and 1000 mg/kg body weight PTI G-2535; however,such increases were small, were not dose related, and were not observed 48 hours after treatment. In contrast, dietary genistein had no effect on survival, weight gain, or the incidence or types of tumors that developed in cancer-prone rodents lacking the p53 tumor suppressor gene, p53 knockout mice. The apparent risk/benefit of isoflavone ingestion may ultimately depend on the dose and developmental timing of exposure. JF - International journal of toxicology AU - Misra, R R AU - Hursting, S D AU - Perkins, S N AU - Sathyamoorthy, N AU - Mirsalis, J C AU - Riccio, E S AU - Crowell, J A AD - Office of Preventive Oncology, Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland, USA. PY - 2002 SP - 277 EP - 285 VL - 21 IS - 4 SN - 1091-5818, 1091-5818 KW - Carcinogens KW - 0 KW - Mutagens KW - Tumor Suppressor Protein p53 KW - Genistein KW - DH2M523P0H KW - Index Medicus KW - Administration, Oral KW - Bone Marrow Cells -- drug effects KW - Animals KW - Escherichia coli -- genetics KW - Salmonella typhimurium -- drug effects KW - Mice KW - Mice, Knockout KW - Micronucleus Tests KW - Tumor Cells, Cultured KW - Carcinogenicity Tests KW - Escherichia coli -- drug effects KW - Tumor Suppressor Protein p53 -- genetics KW - Salmonella typhimurium -- genetics KW - Mutation KW - Female KW - Male KW - Neoplasms, Experimental -- chemically induced KW - Lymphoma -- genetics KW - Neoplasms, Experimental -- genetics KW - Carcinogens -- toxicity KW - Mutagens -- toxicity KW - Lymphoma -- chemically induced KW - Genistein -- toxicity KW - Neoplasms, Experimental -- pathology KW - Lymphoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71985463?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+toxicology&rft.atitle=Genotoxicity+and+carcinogenicity+studies+of+soy+isoflavones.&rft.au=Misra%2C+R+R%3BHursting%2C+S+D%3BPerkins%2C+S+N%3BSathyamoorthy%2C+N%3BMirsalis%2C+J+C%3BRiccio%2C+E+S%3BCrowell%2C+J+A&rft.aulast=Misra&rft.aufirst=R&rft.date=2002-07-01&rft.volume=21&rft.issue=4&rft.spage=277&rft.isbn=&rft.btitle=&rft.title=International+journal+of+toxicology&rft.issn=10915818&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-05 N1 - Date created - 2002-08-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo genetics of anaesthetic action. AN - 71978573; 12173226 JF - British journal of anaesthesia AU - Nash, H A AD - Laboratory of Molecular Biology, National Institute of Mental Health, Building 36/Room 1B08, 9000 Rockville Pike, Bethesda, MD 20892-4034, USA. Y1 - 2002/07// PY - 2002 DA - July 2002 SP - 143 EP - 155 VL - 89 IS - 1 SN - 0007-0912, 0007-0912 KW - Anesthetics, Inhalation KW - 0 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Genetic Techniques KW - Gene Expression Regulation -- drug effects KW - Anesthetics, Inhalation -- pharmacology KW - Genes -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71978573?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+anaesthesia&rft.atitle=In+vivo+genetics+of+anaesthetic+action.&rft.au=Nash%2C+H+A&rft.aulast=Nash&rft.aufirst=H&rft.date=2002-07-01&rft.volume=89&rft.issue=1&rft.spage=143&rft.isbn=&rft.btitle=&rft.title=British+journal+of+anaesthesia&rft.issn=00070912&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-09-13 N1 - Date created - 2002-08-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Yeast origins establish a strand bias for replicational mutagenesis. AN - 71970905; 12150920 AB - To determine whether replicational mutagenesis in the yeast genome is influenced by the positions of active origins, a reporter gene was placed in two orientations at multiple locations within a 39,000 bp region of chromosome III possessing two strong origins. The frequency of mutations resulting from misincorporation of adenine opposite 8-hydroxyguanine in one strand and 6-hydroxylaminopurine opposite cytosine in the other strand differed by 3- to 10-fold, depending on the gene orientation and its distance from the origins. The observed patterns indicate that active origins establish a strand bias for mutations that is maintained over thousands of base pairs and results from lower nucleotide selectivity and/or less efficient proofreading or mismatch repair during leading strand DNA replication. JF - Molecular cell AU - Pavlov, Youri I AU - Newlon, Carol S AU - Kunkel, Thomas A AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2002/07// PY - 2002 DA - July 2002 SP - 207 EP - 213 VL - 10 IS - 1 SN - 1097-2765, 1097-2765 KW - DNA, Fungal KW - 0 KW - Index Medicus KW - Chromosomes, Fungal -- genetics KW - Nucleic Acid Conformation KW - Saccharomyces cerevisiae -- genetics KW - DNA Replication -- genetics KW - Mutation, Missense -- genetics KW - DNA, Fungal -- genetics KW - Replication Origin -- genetics KW - Mutagenesis -- genetics KW - DNA, Fungal -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71970905?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cell&rft.atitle=Yeast+origins+establish+a+strand+bias+for+replicational+mutagenesis.&rft.au=Pavlov%2C+Youri+I%3BNewlon%2C+Carol+S%3BKunkel%2C+Thomas+A&rft.aulast=Pavlov&rft.aufirst=Youri&rft.date=2002-07-01&rft.volume=10&rft.issue=1&rft.spage=207&rft.isbn=&rft.btitle=&rft.title=Molecular+cell&rft.issn=10972765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-08-19 N1 - Date created - 2002-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of experimental factors on nitrobenzaldehyde photoisomerization. AN - 71937125; 12137047 AB - The objective of this study was to compare the effect of various experimental factors on the photoisomerization of nitrobenzaldehyde. The experimental factors included light source, light energy, exposure time, light path distance and the concentration of nitrobenzaldehyde. The results showed that the photoisomerization of nitrobenzaldehyde increased with increasing light exposure. Different light sources and light path distances demonstrated significant impact on the reaction rate constants and half-lives of nitrobenzaldehyde. Although the light energy of UV photoreactor was 47% lower than that of xenon photoreactor, quantum yield and UV/VIS absorption pattern confirmed the finding that the effect of ultraviolet photoreactor on nitrobenzaldehyde was similar to that of xenon photoreactor with the light path of 17 cm. It was caused by the shorter wavelength of UV photoreactor mainly on 254 nn. The product of nitrobenzaldehyde photoisomerization, nitrosobenzoic acid, was detected from samples after 5 or 10 min exposure of three light sources. The concentrations of nitrosobenzoic acid increased with the increasing of exposure time up to 20 or 60 min. JF - Chemosphere AU - Lin, Yaw-Jian AU - Lee, Ampere AU - Teng, Li-Shan AU - Lin, Haw-Tarn AD - Department of Environmental Science and Engineering, National Pingtung University of Science and Technology, Nei Pu, Hsien, Taiwan. yjlin@mail.npust.edu.tw Y1 - 2002/07// PY - 2002 DA - July 2002 SP - 1 EP - 8 VL - 48 IS - 1 SN - 0045-6535, 0045-6535 KW - Aldehydes KW - 0 KW - Benzaldehydes KW - Environmental Pollutants KW - Nitrobenzenes KW - Index Medicus KW - Photochemistry KW - Ultraviolet Rays KW - Isomerism KW - Catalysis KW - Aldehydes -- chemistry KW - Nitrobenzenes -- chemistry KW - Benzaldehydes -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71937125?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemosphere&rft.atitle=Effect+of+experimental+factors+on+nitrobenzaldehyde+photoisomerization.&rft.au=Lin%2C+Yaw-Jian%3BLee%2C+Ampere%3BTeng%2C+Li-Shan%3BLin%2C+Haw-Tarn&rft.aulast=Lin&rft.aufirst=Yaw-Jian&rft.date=2002-07-01&rft.volume=48&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Chemosphere&rft.issn=00456535&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-01-08 N1 - Date created - 2002-07-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Local methotrexate and dexamethasone phosphate for the treatment of recurrent primary intraocular lymphoma. AN - 71936937; 12134997 AB - A 70-year-old patient with recurrent bilateral primary intraocular lymphoma (PIOL) was treated with local injections of methotrexate and periocular dexamethasone phosphate to both eyes over the course of 5 months. Local therapy consisted of a cycle to each eye of 3 intravitreal injections of methotrexate (200 microg in a total volume of 0.1 cc) administered on days 1, 5, and 8, followed by a subtenon injection of dexamethasone phosphate (7.5 mg in a total volume of 0.3 cc) on day 9. This treatment cycle was administered 4 times for the right eye and 3 times for the left eye, at 4 to 6 week intervals. Electroretinography was used to assess retinal function prior to and during each treatment regimen. Complete regression of the lymphomatous infiltrates and resolution of the vitritis was observed with preservation of visual acuity and no changes on electroretinography. The effect was sustained for 24 months after termination of treatment in the absence of systemic chemotherapy, radiation treatments, or maintenance intravitreal injections. Local combined chemotherapy can be used to treat recurrent PIOL, and can serve as successful palliative therapy in patients for whom further treatment with systemic chemotherapy or radiation is contraindicated. JF - Ophthalmic surgery and lasers AU - Velez, Gisela AU - Boldt, H Culver AU - Whitcup, Scott M AU - Nussenblatt, Robert B AU - Robinson, Michael R AD - Laboratory of Immunology, National Eye Institute, NIH, USA. PY - 2002 SP - 329 EP - 333 VL - 33 IS - 4 SN - 1082-3069, 1082-3069 KW - Antimetabolites, Antineoplastic KW - 0 KW - Antineoplastic Agents, Hormonal KW - Dexamethasone KW - 7S5I7G3JQL KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Fundus Oculi KW - Antimetabolites, Antineoplastic -- administration & dosage KW - Humans KW - Antineoplastic Agents, Hormonal -- administration & dosage KW - Treatment Outcome KW - Dexamethasone -- administration & dosage KW - Aged KW - Methotrexate -- administration & dosage KW - Female KW - Neoplasm Recurrence, Local -- drug therapy KW - Eye Neoplasms -- drug therapy KW - Lymphoma -- drug therapy KW - Eye Neoplasms -- pathology KW - Lymphoma -- pathology KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Neoplasm Recurrence, Local -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71936937?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Ophthalmic+surgery+and+lasers&rft.atitle=Local+methotrexate+and+dexamethasone+phosphate+for+the+treatment+of+recurrent+primary+intraocular+lymphoma.&rft.au=Velez%2C+Gisela%3BBoldt%2C+H+Culver%3BWhitcup%2C+Scott+M%3BNussenblatt%2C+Robert+B%3BRobinson%2C+Michael+R&rft.aulast=Velez&rft.aufirst=Gisela&rft.date=2002-07-01&rft.volume=33&rft.issue=4&rft.spage=329&rft.isbn=&rft.btitle=&rft.title=Ophthalmic+surgery+and+lasers&rft.issn=10823069&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-01-15 N1 - Date created - 2002-07-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gene optimization is necessary to express a bivalent anti-human anti-T cell immunotoxin in Pichia pastoris. AN - 71932331; 12135560 AB - The bivalent anti-human anti-T cell immunotoxin A-dmDT390-bisFv(G(4)S) was developed for treatment of T cell leukemia, autoimmune diseases, and tolerance induction for transplantation. The multi-domain structure of the bivalent immunotoxin hinders efficient production in Escherichia coli and most eukaryotes are sensitive to the toxin. However, Pichia pastoris has a tolerance to levels of DT (diphtheria toxin) that were previously observed to intoxicate wild type eukaryotic cells, including Saccharomyces cerevisiae. This tolerance has permitted the optimization of the secreted expression of A-dmDT390-bisFv(G(4)S) in P. pastoris under the control of AOX1 (alcohol oxidase 1) promoter. The original DNA sequence of A-dmDT390-bisFv(G(4)S) was not expressed in P. pastoris because of several AT-rich regions, which induce an early termination of transcription. After DNA rebuilding for abolishing AT-rich regions and codon optimization, the immunotoxin could be expressed up to 10mg/L in the shake flask culture. No differences in the expression levels of immunotoxin were observed by using different secretional signal sequences, Mut(s) (methanol utilization slow phenotype) or Mut(+) (methanol utilization plus phenotype) phenotypes. Buffered complex medium (pH 7.0) having 1% casamino acids provided the highest expression in shake flask culture and PMSF (phenylmethylsulfonyl fluoride) in the range of 1 to 3mM further improved the expression level presumably by inhibiting protein degradation. The immunotoxin was purified by DEAE (diethylaminoethyl) Sepharose ion exchange chromatography and Protein L affinity chromatography. The immunotoxin purified from P. pastoris culture was as fully functional as that expressed in a toxin resistant mutant CHO (Chinese hamster ovary) cell line. Our results demonstrate that P. pastoris is an ideal system for expression of toxin-based fusion proteins. JF - Protein expression and purification AU - Woo, Jung Hee AU - Liu, Yuan Yi AU - Mathias, Askale AU - Stavrou, Scott AU - Wang, Zhirui AU - Thompson, Jerry AU - Neville, David M AD - Section on Biophysical Chemistry, Laboratory of Molecular Biology, National Institute of Mental Health, National Institutes of Health, 36 RM 1B08, 36 Convent Drive, Bethesda, MD 20892-4034, USA. Y1 - 2002/07// PY - 2002 DA - July 2002 SP - 270 EP - 282 VL - 25 IS - 2 SN - 1046-5928, 1046-5928 KW - Codon KW - 0 KW - Culture Media KW - Immunoglobulin Fragments KW - Immunotoxins KW - Recombinant Fusion Proteins KW - Index Medicus KW - Animals KW - Base Composition KW - Codon -- genetics KW - Recombinant Fusion Proteins -- immunology KW - Humans KW - Immunoglobulin Fragments -- genetics KW - Immunoglobulin Fragments -- isolation & purification KW - Jurkat Cells KW - Recombinant Fusion Proteins -- toxicity KW - Recombinant Fusion Proteins -- chemistry KW - Immunoglobulin Fragments -- chemistry KW - Recombinant Fusion Proteins -- genetics KW - Molecular Sequence Data KW - Genetic Vectors -- genetics KW - Gene Dosage KW - Immunoglobulin Fragments -- immunology KW - Immunotoxins -- chemistry KW - Immunotoxins -- toxicity KW - Pichia -- genetics KW - Immunotoxins -- isolation & purification KW - Immunotoxins -- genetics KW - Antigen-Antibody Reactions -- immunology KW - T-Lymphocytes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71932331?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+expression+and+purification&rft.atitle=Gene+optimization+is+necessary+to+express+a+bivalent+anti-human+anti-T+cell+immunotoxin+in+Pichia+pastoris.&rft.au=Woo%2C+Jung+Hee%3BLiu%2C+Yuan+Yi%3BMathias%2C+Askale%3BStavrou%2C+Scott%3BWang%2C+Zhirui%3BThompson%2C+Jerry%3BNeville%2C+David+M&rft.aulast=Woo&rft.aufirst=Jung&rft.date=2002-07-01&rft.volume=25&rft.issue=2&rft.spage=270&rft.isbn=&rft.btitle=&rft.title=Protein+expression+and+purification&rft.issn=10465928&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-17 N1 - Date created - 2002-07-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A prospective study on fungal infection in children with cancer. AN - 71929371; 12132778 AB - A prospective study was conducted in 1999 at the National Cancer Institute, Cairo University, to estimate the incidence, morbidity and mortality of fungal infections along with the evaluation of risk factors influencing outcome of infections among paediatric cancer patients. Of 1917 infectious episodes, the fungal infection rate as documented both clinically and microbiologically was 3.7% (70 cases). Fungal pathogens isolated were yeasts in 55 patients (78.6%) and moulds in 15 patients (21.11%). Among yeasts, Candida parapsilosis was the commonest, followed by C. tropicalis. Pneumonia was the most common fungal infection (n = 25, 35.7%), followed by fungaemia (n = 18, 25.7%). The overall mortality rate was 40% (n = 28), with an infection-related mortality of 28.5% (n = 20). Risk factors that accompanied mortality were relapsing or recurrent disease, profound neutropenia, ADE (Ara-C, daunorubocin and etoposide) protocol of chemotherapy, C. tropicalis isolated and fungaemia as a site of infection. Early use of empirical antifungal therapy (day 4) was not associated with a better outcome. In the light of the poor outcome of patients with fungaemia and fungal pneumonia, every effort should be made to prevent these infections in paediatric cancer patients. JF - Journal of medical microbiology AU - el-Mahallawy, H A AU - Attia, I AU - Ali-el-Din, N H AU - Salem, A E AU - Abo-el-Naga, S AD - Chest Department, National Cancer Institute, Cairo University, Egypt. hadir38@hotmail.com Y1 - 2002/07// PY - 2002 DA - July 2002 SP - 601 EP - 605 VL - 51 IS - 7 SN - 0022-2615, 0022-2615 KW - Antifungal Agents KW - 0 KW - Index Medicus KW - Candidiasis -- epidemiology KW - Fungemia -- epidemiology KW - Pneumonia -- microbiology KW - Pneumonia -- mortality KW - Humans KW - Neutropenia -- complications KW - Fungemia -- drug therapy KW - Neutropenia -- chemically induced KW - Child KW - Pneumonia -- drug therapy KW - Pneumonia -- epidemiology KW - Fungemia -- mortality KW - Candidiasis -- drug therapy KW - Prospective Studies KW - Risk Factors KW - Egypt -- epidemiology KW - Treatment Outcome KW - Incidence KW - Candidiasis -- mortality KW - Female KW - Male KW - Neoplasms -- complications KW - Mycoses -- mortality KW - Mycoses -- epidemiology KW - Mycoses -- drug therapy KW - Antifungal Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71929371?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+medical+microbiology&rft.atitle=A+prospective+study+on+fungal+infection+in+children+with+cancer.&rft.au=el-Mahallawy%2C+H+A%3BAttia%2C+I%3BAli-el-Din%2C+N+H%3BSalem%2C+A+E%3BAbo-el-Naga%2C+S&rft.aulast=el-Mahallawy&rft.aufirst=H&rft.date=2002-07-01&rft.volume=51&rft.issue=7&rft.spage=601&rft.isbn=&rft.btitle=&rft.title=Journal+of+medical+microbiology&rft.issn=00222615&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-08-05 N1 - Date created - 2002-07-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of pirfenidone on the pulmonary fibrosis of Hermansky-Pudlak syndrome. AN - 71927290; 12126938 AB - Hermansky-Pudlak syndrome (HPS) consists of oculocutaneous albinism, a platelet storage pool deficiency and, in patients with HPS1 gene mutations, a progressive, fatal pulmonary fibrosis. We investigated the safety and efficacy of an antifibrotic agent, pirfenidone (800 mg, t.i.d.), in treating 21 adult Puerto Rican HPS patients, including 20 homozygous for the same HPS1 mutation. Patients were examined every 4 months for up to 44 months in a randomized, placebo-controlled trial, with rate of change in pulmonary function values as outcome parameters. Using the complete data set of 130 patient admissions, a repeated measures model showed that 11 pirfenidone-treated patients lost FVC at a rate 5% of predicted ( approximately 400 mL) per year slower than 10 placebo-treated patients (p=0.001). A random coefficients model showed no significant difference. However, using data restricted to patients with an initial FVC >50% of predicted, both models showed the pirfenidone group losing FVC (p<0.022), FEV(1) (p<0.0007), TLC (p<0.001), and DL(CO) (p<0.122) at a rate approximately 8%/year slower than the placebo group. Clinical and laboratory side effects were similar in the two groups. Pirfenidone appears to slow the progression of pulmonary fibrosis in HPS patients who have significant residual lung function. JF - Molecular genetics and metabolism AU - Gahl, William A AU - Brantly, Mark AU - Troendle, James AU - Avila, Nilo A AU - Padua, Antonio AU - Montalvo, Carlos AU - Cardona, Hilda AU - Calis, Karim Anton AU - Gochuico, Bernadette AD - Heritable Disorders Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. bgahl@helix.nih.gov Y1 - 2002/07// PY - 2002 DA - July 2002 SP - 234 EP - 242 VL - 76 IS - 3 SN - 1096-7192, 1096-7192 KW - Placebos KW - 0 KW - Pyridones KW - pirfenidone KW - D7NLD2JX7U KW - Index Medicus KW - Double-Blind Method KW - Patient Compliance KW - Humans KW - Adult KW - Treatment Outcome KW - Tomography, X-Ray Computed KW - Middle Aged KW - Male KW - Female KW - Pyridones -- adverse effects KW - Hermanski-Pudlak Syndrome -- diagnostic imaging KW - Pulmonary Fibrosis -- diagnostic imaging KW - Pulmonary Fibrosis -- drug therapy KW - Pulmonary Fibrosis -- physiopathology KW - Hermanski-Pudlak Syndrome -- physiopathology KW - Pyridones -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71927290?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+genetics+and+metabolism&rft.atitle=Effect+of+pirfenidone+on+the+pulmonary+fibrosis+of+Hermansky-Pudlak+syndrome.&rft.au=Gahl%2C+William+A%3BBrantly%2C+Mark%3BTroendle%2C+James%3BAvila%2C+Nilo+A%3BPadua%2C+Antonio%3BMontalvo%2C+Carlos%3BCardona%2C+Hilda%3BCalis%2C+Karim+Anton%3BGochuico%2C+Bernadette&rft.aulast=Gahl&rft.aufirst=William&rft.date=2002-07-01&rft.volume=76&rft.issue=3&rft.spage=234&rft.isbn=&rft.btitle=&rft.title=Molecular+genetics+and+metabolism&rft.issn=10967192&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-04 N1 - Date created - 2002-07-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Annexin 5 and apolipoprotein E2 protect against Alzheimer's amyloid-beta-peptide cytotoxicity by competitive inhibition at a common phosphatidylserine interaction site. AN - 71926768; 12128082 AB - Amyloid-beta-protein (betaA/4, AbetaP) accumulates in the brains of patients with Alzheimer's disease (AD), regardless of genetic etiology, and is thought to be the toxic principle responsible for neuronal cell death. The varepsilon4 allele of apoE has been linked closely to earlier onset of AD and increased deposition of the amyloid peptide, regardless of the clinical status of AD, while the apoE varepsilon2 allele is generally protective. We have previously hypothesized that the cell target for amyloid peptide might be the apoptotic signal molecule phosphatidylserine (PS). We report here that annexin 5, a specific ligand for PS, not only blocks amyloid peptide AbetaP[1-40] cytotoxicity, but competitively inhibits AbetaP[1-40]-dependent aggregation of PS liposomes. In addition, we find that apoE2, but not apoE4, can not only perform the same protective effect on cells exposed to AbetaP[1-40], but can also competitively inhibit PS liposome aggregation and fusion by the amyloid peptide. Altogether, the in vivo and in vitro results reported here provide fundamental insight to the process by which amyloid targets specific neurons for destruction, and suggest that PS may be a surface "receptor" site for AbetaP binding. These results also provide a biochemical mechanism by which the apoE varepsilon2 allele, but not apoE varepsilon4, can be protective towards the incidence and progression of Alzheimer's disease. JF - Peptides AU - Lee, George AU - Pollard, Harvey B AU - Arispe, Nelson AD - Laboratory of Cell Biology and Biochemistry, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2002/07// PY - 2002 DA - July 2002 SP - 1249 EP - 1263 VL - 23 IS - 7 SN - 0196-9781, 0196-9781 KW - Amyloid beta-Peptides KW - 0 KW - Annexins KW - Apolipoprotein E2 KW - Apolipoproteins E KW - Liposomes KW - Peptide Fragments KW - Phosphatidylserines KW - Protein Isoforms KW - amyloid beta-protein (1-40) KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Protein Isoforms -- metabolism KW - Humans KW - Liposomes -- metabolism KW - Protein Isoforms -- pharmacology KW - Models, Biological KW - Binding Sites KW - Rats KW - Cell Survival -- drug effects KW - Cells, Cultured KW - Protein Binding -- drug effects KW - Kinetics KW - Calcium -- physiology KW - Membrane Fusion -- drug effects KW - Cell Membrane -- metabolism KW - PC12 Cells KW - Peptide Fragments -- toxicity KW - Apolipoproteins E -- pharmacology KW - Apolipoproteins E -- metabolism KW - Annexins -- metabolism KW - Phosphatidylserines -- metabolism KW - Amyloid beta-Peptides -- toxicity KW - Peptide Fragments -- drug effects KW - Annexins -- pharmacology KW - Amyloid beta-Peptides -- drug effects KW - Alzheimer Disease -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71926768?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Peptides&rft.atitle=Annexin+5+and+apolipoprotein+E2+protect+against+Alzheimer%27s+amyloid-beta-peptide+cytotoxicity+by+competitive+inhibition+at+a+common+phosphatidylserine+interaction+site.&rft.au=Lee%2C+George%3BPollard%2C+Harvey+B%3BArispe%2C+Nelson&rft.aulast=Lee&rft.aufirst=George&rft.date=2002-07-01&rft.volume=23&rft.issue=7&rft.spage=1249&rft.isbn=&rft.btitle=&rft.title=Peptides&rft.issn=01969781&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-03 N1 - Date created - 2002-07-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of orlistat on fat-soluble vitamins in obese adolescents. AN - 71924540; 12126214 AB - To determine whether orlistat causes fat-soluble vitamin deficiencies in African-American and Caucasian adolescents. Prospective, open-label pilot study. Warren Grant Magnuson Clinical Center of the National Institutes of Health. Seventeen adolescents with body mass indexes above the 95th percentile for age, race, and gender who also had at least one obesity-related comorbid condition. Subjects received orlistat 120 mg 3 times/day and a daily multivitamin supplement containing vitamin A 5000 IU, vitamin D 400 IU, vitamin E 300 IU, and vitamin K 25 microg. During 3-6 months of orlistat treatment, acute absorption of retinol (vitamin A) was not significantly altered, but absorption of alpha-tocopherol (vitamin E) was significantly reduced compared with baseline levels (p<0.001). Serum levels of vitamins A and E did not change significantly; however, there was a nonsignificant decrease in vitamin K. Mean vitamin D levels were significantly reduced compared with baseline (p<0.02) after 1 month of orlistat, despite multivitamin supplementation. It may be prudent to monitor vitamin D concentrations in adolescents who take orlistat, even when a multivitamin is prescribed. JF - Pharmacotherapy AU - McDuffie, Jennifer R AU - Calis, Karim A AU - Booth, Sarah L AU - Uwaifo, Gabriel I AU - Yanovski, Jack A AD - Unit on Growth and Obesity, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892-1862, USA. Mcduffj@mail.nih.gov Y1 - 2002/07// PY - 2002 DA - July 2002 SP - 814 EP - 822 VL - 22 IS - 7 SN - 0277-0008, 0277-0008 KW - Lactones KW - 0 KW - Vitamin A KW - 11103-57-4 KW - Vitamin D KW - 1406-16-2 KW - Vitamin E KW - 1406-18-4 KW - orlistat KW - 95M8R751W8 KW - Index Medicus KW - Vitamin A -- blood KW - Analysis of Variance KW - Prospective Studies KW - Humans KW - Vitamin D -- blood KW - Pilot Projects KW - Child KW - Adolescent KW - Vitamin E -- blood KW - Male KW - Female KW - Obesity -- drug therapy KW - Lactones -- adverse effects KW - Lactones -- therapeutic use KW - Avitaminosis -- chemically induced KW - Avitaminosis -- blood KW - Obesity -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71924540?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacotherapy&rft.atitle=Effects+of+orlistat+on+fat-soluble+vitamins+in+obese+adolescents.&rft.au=McDuffie%2C+Jennifer+R%3BCalis%2C+Karim+A%3BBooth%2C+Sarah+L%3BUwaifo%2C+Gabriel+I%3BYanovski%2C+Jack+A&rft.aulast=McDuffie&rft.aufirst=Jennifer&rft.date=2002-07-01&rft.volume=22&rft.issue=7&rft.spage=814&rft.isbn=&rft.btitle=&rft.title=Pharmacotherapy&rft.issn=02770008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-01-07 N1 - Date created - 2002-07-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Studies on the metal binding sites in the catalytic domain of beta1,4-galactosyltransferase. AN - 71923630; 12122021 AB - The catalytic domain of bovine beta1,4-galactosyltransferase (beta4Gal-T1) has been shown to have two metal binding sites, each with a distinct binding affinity. Site I binds Mn(2+) with high affinity and does not bind Ca(2+), whereas site II binds a variety of metal ions, including Ca(2+). The catalytic region of beta4Gal-T1 has DXD motifs, associated with metal binding in glycosyltransferases, in two separate sequences: D(242)YDYNCFVFSDVD(254) (region I) and W(312)GWGGEDDD(320) (region II). Recently, the crystal structure of beta4Gal-T1 bound with UDP, Mn(2+), and alpha-lactalbumin was determined in our laboratory. It shows that in the primary metal binding site of beta4Gal-T1, the Mn(2+) ion, is coordinated to five ligands, two supplied by the phosphates of the sugar nucleotide and the other three by Asp254, His347, and Met344. The residue Asp254 in the D(252)VD(254) sequence in region I is the only residue that is coordinated to the Mn(2+) ion. Region II forms a loop structure and contains the E(317)DDD(320) sequence in which residues Asp318 and Asp319 are directly involved in GlcNAc binding. This study, using site-directed mutagenesis, kinetic, and binding affinity analysis, shows that Asp254 and His347 are strong metal ligands, whereas Met344, which coordinates less strongly, can be substituted by alanine or glutamine. Specifically, substitution of Met344 to Gln has a less severe effect on the catalysis driven by Co(2+). Glu317 and Asp320 mutants, when partially activated by Mn(2+) binding to the primary site, can be further activated by Co(2+) or inhibited by Ca(2+), an effect that is the opposite of what is observed with the wild-type enzyme. JF - Glycobiology AU - Boeggeman, Elizabeth AU - Qasba, Pradman K AD - Structural Glycobiology Section and Intramural Research Support Program-SAIC, Laboratory of Experimental and Computational Biology, NCI-CCR, Building 469, Room 221, Frederick, MD 21702-1201, USA. Y1 - 2002/07// PY - 2002 DA - July 2002 SP - 395 EP - 407 VL - 12 IS - 7 SN - 0959-6658, 0959-6658 KW - Metals KW - 0 KW - N-Acetyllactosamine Synthase KW - EC 2.4.1.90 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Cattle KW - Models, Molecular KW - Kinetics KW - Humans KW - Catalytic Domain KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Protein Conformation KW - Binding Sites KW - N-Acetyllactosamine Synthase -- genetics KW - N-Acetyllactosamine Synthase -- chemistry KW - N-Acetyllactosamine Synthase -- metabolism KW - Metals -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71923630?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Glycobiology&rft.atitle=Studies+on+the+metal+binding+sites+in+the+catalytic+domain+of+beta1%2C4-galactosyltransferase.&rft.au=Boeggeman%2C+Elizabeth%3BQasba%2C+Pradman+K&rft.aulast=Boeggeman&rft.aufirst=Elizabeth&rft.date=2002-07-01&rft.volume=12&rft.issue=7&rft.spage=395&rft.isbn=&rft.btitle=&rft.title=Glycobiology&rft.issn=09596658&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-01-22 N1 - Date created - 2002-07-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Occupational exposure to crystalline silica and risk of systemic lupus erythematosus: a population-based, case-control study in the southeastern United States. AN - 71920030; 12124868 AB - Crystalline silica may act as an immune adjuvant to increase inflammation and antibody production, and findings of occupational cohort studies suggest that silica exposure may be a risk factor for systemic lupus erythematosus (SLE). We undertook this population-based study to examine the association between occupational silica exposure and SLE in the southeastern US. SLE patients (n = 265; diagnosed between January 1, 1995 and July 31, 1999) were recruited from 4 university rheumatology practices and 30 community-based rheumatologists in 60 contiguous counties. Controls (n = 355), frequency-matched to patients by age, sex, and state of residence, were randomly selected from driver's license registries. The mean age of the patients at diagnosis was 39 years; 91% were women and 60% were African American. Detailed occupational and farming histories were collected by in-person interviews. Silica exposure was determined through blinded assessment of job histories by 3 industrial hygienists, and potential medium- or high-level exposures were confirmed through followup telephone interviews. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated by logistic regression. More patients (19%) than controls (8%) had a history of medium- or high-level silica exposure from farming or trades. We observed an association between silica and SLE (medium exposure OR 2.1 [95% CI 1.1-4.0], high exposure OR 4.6 [95% CI 1.4-15.4]) that was seen in separate analyses by sex, race, and at different levels of education. These results suggest that crystalline silica exposure may promote the development of SLE in some individuals. Additional research is recommended in other populations, using study designs that minimize potential selection bias and maximize the quality of exposure assessment. JF - Arthritis and rheumatism AU - Parks, Christine G AU - Cooper, Glinda S AU - Nylander-French, Leena A AU - Sanderson, Wayne T AU - Dement, John M AU - Cohen, Philip L AU - Dooley, Mary Anne AU - Treadwell, Edward L AU - St Clair, E William AU - Gilkeson, Gary S AU - Hoppin, Jane A AU - Savitz, David A AD - Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Durham, North Carolina 27709, USA. parks@niehs.nih.gov Y1 - 2002/07// PY - 2002 DA - July 2002 SP - 1840 EP - 1850 VL - 46 IS - 7 SN - 0004-3591, 0004-3591 KW - Silicon Dioxide KW - 7631-86-9 KW - Abridged Index Medicus KW - Index Medicus KW - Educational Status KW - Southeastern United States -- epidemiology KW - Humans KW - Continental Population Groups KW - Aged KW - Aged, 80 and over KW - Logistic Models KW - Adult KW - Case-Control Studies KW - Middle Aged KW - Adolescent KW - Female KW - Male KW - Prevalence KW - Occupational Exposure KW - Lupus Erythematosus, Systemic -- chemically induced KW - Lupus Erythematosus, Systemic -- epidemiology KW - Silicon Dioxide -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71920030?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Occupational+exposure+to+crystalline+silica+and+risk+of+systemic+lupus+erythematosus%3A+a+population-based%2C+case-control+study+in+the+southeastern+United+States.&rft.au=Parks%2C+Christine+G%3BCooper%2C+Glinda+S%3BNylander-French%2C+Leena+A%3BSanderson%2C+Wayne+T%3BDement%2C+John+M%3BCohen%2C+Philip+L%3BDooley%2C+Mary+Anne%3BTreadwell%2C+Edward+L%3BSt+Clair%2C+E+William%3BGilkeson%2C+Gary+S%3BHoppin%2C+Jane+A%3BSavitz%2C+David+A&rft.aulast=Parks&rft.aufirst=Christine&rft.date=2002-07-01&rft.volume=46&rft.issue=7&rft.spage=1840&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 - 2002-08-05 N1 - Date created - 2002-07-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Arthritis Rheum. 2004 May;50(5):1694 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of systemic and central nervous system localized inflammation on the contributions of metabolic precursors to the L-kynurenine and quinolinic acid pools in brain. AN - 71917058; 12124427 AB - L-Kynurenine and quinolinic acid are neuroactive L-tryptophan-kynurenine pathway metabolites of potential importance in pathogenesis and treatment of neurologic disease. To identify precursors of these metabolites in brain, [(2)H(3) ]-L-kynurenine was infused subcutaneously by osmotic pump into three groups of gerbils: controls, CNS-localized immune-activated, and systemically immune-activated. The specific activity of L-kynurenine and quinolinate in blood, brain and systemic tissues at equilibrium was then quantified by mass spectrometry and the results applied to a model of metabolism to differentiate the relative contributions of various metabolic precursors. In control gerbils, 22% of L-kynurenine in brain was derived via local synthesis from L-tryptophan/formylkynurenine versus 78% from L-kynurenine from blood. Quinolinate in brain was derived from several sources, including: local tissue L-tryptophan/formylkynurenine (10%), blood L-kynurenine (35%), blood 3-hydroxykynurenine/3-hydroxyanthranilate (7%), and blood quinolinate (48%). After systemic immune-activation, however, L-kynurenine in brain was derived exclusively from blood, whereas quinolinate in brain was derived from three sources: blood L-kynurenine (52%), blood 3-hydroxykynurenine or 3-hydroxyanthranilate (8%), and blood quinolinate (40%). During CNS-localized immune activation, > 98% of both L-kynurenine and quinolinate were derived via local synthesis in brain. Thus, immune activation and its site determine the sources from which L-kynurenine and quinolinate are synthesized in brain. Successful therapeutic modulation of their concentrations must take into account the metabolic and compartment sources. JF - Journal of neurochemistry AU - Kita, Tomoyuki AU - Morrison, Paul F AU - Heyes, Melvyn P AU - Markey, S P AD - Laboratory of Neurotoxicology, National Institute of Mental Health, Bethesda, Maryland 20892, USA. Y1 - 2002/07// PY - 2002 DA - July 2002 SP - 258 EP - 268 VL - 82 IS - 2 SN - 0022-3042, 0022-3042 KW - Lipopolysaccharides KW - 0 KW - Serum Albumin KW - Tritium KW - 10028-17-8 KW - Kynurenine KW - 343-65-7 KW - Tryptophan KW - 8DUH1N11BX KW - Quinolinic Acid KW - F6F0HK1URN KW - Index Medicus KW - Serum Albumin -- metabolism KW - Animals KW - Gerbillinae KW - Mass Spectrometry KW - Kidney -- metabolism KW - Body Fluid Compartments KW - Corpus Striatum -- metabolism KW - Liver -- metabolism KW - Tissue Distribution KW - Lung -- metabolism KW - Tryptophan -- metabolism KW - Models, Biological KW - Protein Binding -- physiology KW - Injections, Subcutaneous KW - Corpus Striatum -- drug effects KW - Female KW - Quinolinic Acid -- metabolism KW - Inflammation -- chemically induced KW - Kynurenine -- metabolism KW - Inflammation -- metabolism KW - Brain -- metabolism KW - Encephalitis -- metabolism KW - Kynurenine -- pharmacokinetics KW - Kynurenine -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71917058?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Effects+of+systemic+and+central+nervous+system+localized+inflammation+on+the+contributions+of+metabolic+precursors+to+the+L-kynurenine+and+quinolinic+acid+pools+in+brain.&rft.au=Kita%2C+Tomoyuki%3BMorrison%2C+Paul+F%3BHeyes%2C+Melvyn+P%3BMarkey%2C+S+P&rft.aulast=Kita&rft.aufirst=Tomoyuki&rft.date=2002-07-01&rft.volume=82&rft.issue=2&rft.spage=258&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 - 2002-08-06 N1 - Date created - 2002-07-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The 1.1 A crystal structure of human TGF-beta type II receptor ligand binding domain. AN - 71914372; 12121646 AB - Transforming growth factor beta (TGF-beta) is involved in a wide range of biological functions including development, carcinogenesis, and immune regulation. Here we report the 1.1 A resolution crystal structure of human TGF-beta type II receptor ectodomain (TBRII). The overall structure of TBRII is similar to that of activin type II receptor ectodomain (ActRII) and bone morphogenic protein receptor type IA (BRIA). It displays a three-finger toxin fold with fingers formed by the beta strand pairs beta1-beta2, beta3-beta4, and beta5-beta6. The first finger in the TBRII is significantly longer than in ActRII and BRIA and folds tightly between the second finger and the C terminus. Surface charge distributions and hydrophobic patches predict potential TBRII binding sites. JF - Structure (London, England : 1993) AU - Boesen, Christian C AU - Radaev, Sergei AU - Motyka, Shawn A AU - Patamawenu, Apisit AU - Sun, Peter D AD - Structural Biology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA. Y1 - 2002/07// PY - 2002 DA - July 2002 SP - 913 EP - 919 VL - 10 IS - 7 SN - 0969-2126, 0969-2126 KW - Ligands KW - 0 KW - Receptors, Growth Factor KW - Receptors, Transforming Growth Factor beta KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Activin Receptors, Type I KW - EC 2.7.11.30 KW - BMPR1A protein, human KW - Bone Morphogenetic Protein Receptors, Type I KW - transforming growth factor-beta type II receptor KW - Index Medicus KW - Activin Receptors, Type I -- chemistry KW - Models, Molecular KW - Humans KW - Molecular Sequence Data KW - Crystallography, X-Ray KW - Amino Acid Sequence KW - Protein Structure, Tertiary KW - Binding Sites KW - Receptors, Transforming Growth Factor beta -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71914372?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Structure+%28London%2C+England+%3A+1993%29&rft.atitle=The+1.1+A+crystal+structure+of+human+TGF-beta+type+II+receptor+ligand+binding+domain.&rft.au=Boesen%2C+Christian+C%3BRadaev%2C+Sergei%3BMotyka%2C+Shawn+A%3BPatamawenu%2C+Apisit%3BSun%2C+Peter+D&rft.aulast=Boesen&rft.aufirst=Christian&rft.date=2002-07-01&rft.volume=10&rft.issue=7&rft.spage=913&rft.isbn=&rft.btitle=&rft.title=Structure+%28London%2C+England+%3A+1993%29&rft.issn=09692126&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-05 N1 - Date created - 2002-07-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modifications in synthesis strategy improve the yield and efficacy of geldanamycin-herceptin immunoconjugates. AN - 71910392; 12121134 AB - Geldanamycin (GA) was modified with N-tert-butyloxycarbonyl-1,3-diaminopropane to introduce a latent primary amine. After deprotection, this primary amine provided a site for introduction of a maleimide group that enabled linkage to proteins. This maleimido derivative of geldanamycin (GMB-APA-GA) was linked to the monoclonal antibody Herceptin after the antibody had been modified with Traut's reagent to introduce thiol groups. By this sequence, a new immunoconjugate (H:APA-GA) was generated that showed greater antiproliferative activity than the previously reported analogous immunoconjugate created with a 1,4-diaminobutane spacer derivative of geldanamycin to form an immunoconjugate, H:ABA-GA. Both immunoconjugates inhibited in vitro the growth of MDA-361/DYT2 cells, a cell line overexpressing the HER2 antigen, while Herceptin alone was ineffective. However, H:APA-GA showed better efficacy than H:ABA-GA (IC(50) = 0.2 vs 0.58 mg/mL and cell doubling time >12 vs 6 days, respectively). Results of the in vivo therapy experiments in a xenograft model were consistent with the in vitro findings. Treatment with Herceptin prolonged the survival of the tumor-bearing mice when compared with the control group, but H:ABA-GA and H:APA-GA were each more efficacious than unmodified Herceptin. However, unlike H:ABA-GA, the immunoconjugate H:APA-GA caused stable tumor regression (in 25% of the recipients), showing a qualitative improvement with potential clinical relevance. JF - Bioconjugate chemistry AU - Mandler, Raya AU - Kobayashi, Hisataka AU - Davis, Marie Y AU - Waldmann, Thomas A AU - Brechbiel, Martin W AD - Metabolism Branch, National Cancer Institute, NIH, Bethesda, Maryland 20982-1002, USA. PY - 2002 SP - 786 EP - 791 VL - 13 IS - 4 SN - 1043-1802, 1043-1802 KW - Antibiotics, Antineoplastic KW - 0 KW - Antibodies, Monoclonal KW - Antibodies, Monoclonal, Humanized KW - Benzoquinones KW - Diamines KW - Immunoconjugates KW - Lactams, Macrocyclic KW - Quinones KW - Trastuzumab KW - P188ANX8CK KW - geldanamycin KW - Z3K3VJ16KU KW - Index Medicus KW - Animals KW - Humans KW - Cell Division -- drug effects KW - Mice KW - Diamines -- chemistry KW - Therapeutic Equivalency KW - Tumor Cells, Cultured KW - Survival Rate KW - Treatment Outcome KW - Transplantation, Heterologous KW - Inhibitory Concentration 50 KW - Neoplasms, Experimental -- drug therapy KW - Female KW - Quinones -- administration & dosage KW - Quinones -- chemistry KW - Immunoconjugates -- chemistry KW - Antibiotics, Antineoplastic -- chemistry KW - Antibiotics, Antineoplastic -- administration & dosage KW - Immunoconjugates -- administration & dosage KW - Antibiotics, Antineoplastic -- pharmacology KW - Quinones -- pharmacology KW - Antibodies, Monoclonal -- chemistry KW - Immunoconjugates -- pharmacology KW - Antibodies, Monoclonal -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71910392?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioconjugate+chemistry&rft.atitle=Modifications+in+synthesis+strategy+improve+the+yield+and+efficacy+of+geldanamycin-herceptin+immunoconjugates.&rft.au=Mandler%2C+Raya%3BKobayashi%2C+Hisataka%3BDavis%2C+Marie+Y%3BWaldmann%2C+Thomas+A%3BBrechbiel%2C+Martin+W&rft.aulast=Mandler&rft.aufirst=Raya&rft.date=2002-07-01&rft.volume=13&rft.issue=4&rft.spage=786&rft.isbn=&rft.btitle=&rft.title=Bioconjugate+chemistry&rft.issn=10431802&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-05 N1 - Date created - 2002-07-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Altered expression of G1/S regulatory genes occurs early and frequently in lung carcinogenesis in transforming growth factor-beta1 heterozygous mice. AN - 71905229; 12117781 AB - We developed the AJBL6 transforming growth factor-beta 1 (TGF-beta1) heterozygous (HT) mouse by mating A/J mice with C57BL/6 TGF-beta1 HT mice that shows increased carcinogen-induced lung lesions with decreased latency to examine progressive events in lung tumorigenesis. Mouse cDNA macroarrays were used to identify cell cycle genes that are differentially regulated in ethyl carbamate-induced lung adenocarcinomas compared with normal lung tissue in AJBL6 TGF-beta1 HT mice using probes that were generated from tissues isolated using laser capture microdissection. While expression of the genes for cyclin D1, CDK4, and E2F1 increased in lung adenocarcinomas relative to normal lung, expression of p15(Ink4b), p16(Ink4a), p21(Cip1), p27(Kip1), p57(Kip2), and pRb genes decreased in comparison. Competitive RT-PCR showed that the levels of cyclin D1 and CDK4 mRNAs were 2- and 3-fold higher, respectively, in lung adenocarcinomas than in normal lung, while the mRNAs for p15(Ink4b), p16(Ink4a), p21(Cip1), p27(Kip1), and pRb were 3- to 4-fold lower in adenocarcinomas than in normal lung, thus validating the macroarray findings. Competitive RT-PCR of microdissected lesions also showed that the levels of cyclin D1 and CDK4 mRNAs increased significantly, while the mRNAs for p15(Ink4b) and p27(Kip1) decreased significantly as lung tumorigenesis progressed. Immunohistochemical staining for cyclin D1 and CDK4 showed staining in >80% of nuclei in adenocarcinomas compared with fewer than 20% of nuclei staining positively in normal lung. In contrast, while >60% of normal lung cells showed immunostaining for p15(Ink4b), p16(Ink4a), p21(Cip1), p27(Kip1), and pRb, staining for these proteins decreased in hyperplasias, adenomas, and adenocarcinomas. These data show that multiple components of the cyclin D1/CDK4/p16(Ink4a)/pRb signaling pathway are frequently altered early in lung lesions of AJBL6 TGF-beta1 HT mice that are induced by ethyl carbamate as a function of progressive lung carcinogenesis, suggesting that components of this pathway may be potential targets for gene therapy. JF - Carcinogenesis AU - Kang, Yang AU - Ozbun, Laurent L AU - Angdisen, Jerry AU - Moody, Terry W AU - Prentice, Margaret AU - Diwan, Bhalchandra A AU - Jakowlew, Sonia B AD - Cell and Cancer Biology Branch, National Cancer Institute/NIH, Rockville, MD 20850, USA. Y1 - 2002/07// PY - 2002 DA - July 2002 SP - 1217 EP - 1227 VL - 23 IS - 7 SN - 0143-3334, 0143-3334 KW - Cell Cycle Proteins KW - 0 KW - DNA Primers KW - RNA, Messenger KW - Tgfb1 protein, mouse KW - Transforming Growth Factor beta KW - Transforming Growth Factor beta1 KW - Urethane KW - 3IN71E75Z5 KW - Index Medicus KW - Animals KW - Oligonucleotide Array Sequence Analysis KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - RNA, Messenger -- genetics KW - Mice, Knockout KW - Gene Expression Profiling KW - RNA, Messenger -- metabolism KW - Signal Transduction -- genetics KW - Mice, Inbred C57BL KW - Urethane -- toxicity KW - Female KW - Immunoenzyme Techniques KW - Male KW - Cell Division KW - DNA Primers -- chemistry KW - Genes, Regulator KW - Adenocarcinoma -- metabolism KW - G1 Phase -- genetics KW - Cell Cycle Proteins -- genetics KW - Adenocarcinoma -- chemically induced KW - Lung Neoplasms -- genetics KW - S Phase -- genetics KW - Adenocarcinoma -- genetics KW - Lung Neoplasms -- chemically induced KW - Transforming Growth Factor beta -- genetics KW - Transforming Growth Factor beta -- metabolism KW - Lung Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71905229?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Altered+expression+of+G1%2FS+regulatory+genes+occurs+early+and+frequently+in+lung+carcinogenesis+in+transforming+growth+factor-beta1+heterozygous+mice.&rft.au=Kang%2C+Yang%3BOzbun%2C+Laurent+L%3BAngdisen%2C+Jerry%3BMoody%2C+Terry+W%3BPrentice%2C+Margaret%3BDiwan%2C+Bhalchandra+A%3BJakowlew%2C+Sonia+B&rft.aulast=Kang&rft.aufirst=Yang&rft.date=2002-07-01&rft.volume=23&rft.issue=7&rft.spage=1217&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-08-30 N1 - Date created - 2002-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Novel anti-CD30 recombinant immunotoxins containing disulfide-stabilized Fv fragments. AN - 71896498; 12114439 AB - To develop a novel targeting reagent to CD30 expressed on Hodgkin'sdisease and anaplastic large cell lymphoma, we made a panel of recombinant immunotoxins specific for CD30 using Fvs of newly produced anti-CD30 monoclonal antibodies (MAbs) and a M(r) 38,000 truncated mutant of Pseudomonas exotoxin. A group of MAbs against CD30 was produced and characterized for their reactivity and epitopes. Recombinant immunotoxins were made using the Fv genes cloned from the hybridomas. Their cytotoxic activities were examined on various CD30-positive cell lines. Six MAbs were produced. All reacted with recombinant soluble CD30 and to a CD30-Fc fusion protein, and bound to native CD30 expressed on Hodgkin's lymphoma-derived cell lines. The epitopes of the six MAbs were classified into two groups by a mutual competition assay for the binding to CD30 on cells. Sequencing the cDNAs revealed that all of the variable chains are unique except one valiable light that is shared by two MAbs. We made four disulfide stabilized Fv-based recombinant immunotoxins, in which the valiable heavy, which is genetically fused with truncated mutant of Pseudomonas exotoxin, forms a disulfide bond with the valiable light. The purified immunotoxins bound to recombinant soluble CD30 immobilized on a biosensor chip with K(d)s of 4-400 nM. Fluorescence-activated cell sorter analysis confirmed their specific binding. In vitro cytotoxicity tests showed that the immunotoxins specifically kill a variety of CD30-positive lymphoma cell lines as well as CD30-transfected A431 cells. The IC(50) ranged from 0.3 to 100 ng/ml. Four anti-CD30 disulfide stabilized Fv immunotoxins were successfully produced. Two of these showed good cytotoxic activity to various CD30-positive cell lines. These newly produced immunotoxins should be additionally evaluated for the treatment of CD30-positive lymphomas. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Nagata, Satoshi AU - Onda, Masanori AU - Numata, Yoshito AU - Santora, Kenneth AU - Beers, Richard AU - Kreitman, Robert J AU - Pastan, Ira AD - Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-4264, USA. Y1 - 2002/07// PY - 2002 DA - July 2002 SP - 2345 EP - 2355 VL - 8 IS - 7 SN - 1078-0432, 1078-0432 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, CD30 KW - Bacterial Toxins KW - Disulfides KW - Exotoxins KW - Immunoglobulin Fragments KW - Immunoglobulin Light Chains KW - Immunoglobulin Variable Region KW - Immunotoxins KW - Recombinant Fusion Proteins 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 Variable Region -- genetics KW - Immunoglobulin Light Chains -- immunology KW - Animals KW - Antibodies, Monoclonal -- genetics KW - Humans KW - Immunoglobulin Variable Region -- immunology KW - Antigens, CD30 -- genetics KW - Immunoglobulin Fragments -- genetics KW - Mice KW - Amino Acid Sequence KW - Antibodies, Monoclonal -- immunology KW - Cloning, Molecular KW - In Vitro Techniques KW - Molecular Sequence Data KW - Immunoglobulin Light Chains -- genetics KW - Sequence Homology, Amino Acid KW - Pseudomonas aeruginosa KW - Immunoglobulin Fragments -- immunology KW - Antigens, CD30 -- immunology KW - Virulence Factors -- pharmacology KW - Exotoxins -- pharmacology KW - Tumor Cells, Cultured -- immunology KW - Tumor Cells, Cultured -- drug effects KW - Recombinant Fusion Proteins -- pharmacology KW - Bacterial Toxins -- pharmacology KW - Immunotoxins -- pharmacology KW - ADP Ribose Transferases -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71896498?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Novel+anti-CD30+recombinant+immunotoxins+containing+disulfide-stabilized+Fv+fragments.&rft.au=Nagata%2C+Satoshi%3BOnda%2C+Masanori%3BNumata%2C+Yoshito%3BSantora%2C+Kenneth%3BBeers%2C+Richard%3BKreitman%2C+Robert+J%3BPastan%2C+Ira&rft.aulast=Nagata&rft.aufirst=Satoshi&rft.date=2002-07-01&rft.volume=8&rft.issue=7&rft.spage=2345&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 - 2003-01-21 N1 - Date created - 2002-07-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Three-month tolerability of orlistat in adolescents with obesity-related comorbid conditions. AN - 71889525; 12105286 AB - To study the safety, tolerability, and potential efficacy of orlistat in adolescents with obesity and its comorbid conditions. We studied 20 adolescents (age, 14.6 +/- 2.0 years; body mass index, 44.1 +/- 12.6 kg/m(2)). Subjects were evaluated before and after taking orlistat (120 mg three times daily) and a multivitamin for 3 months. Subjects were simultaneously enrolled in a 12-week program emphasizing diet, exercise, and strategies for behavior change. Participants who completed treatment (85%) reported taking 80% of prescribed medication. Adverse effects were generally mild, limited to gastrointestinal effects observed in adults, and decreased with time. Three subjects required additional vitamin D supplementation despite the prescription of a daily multivitamin containing vitamin D. Weight decreased significantly (-4.4 +/- 4.6 kg, p < 0.001; -3.8 +/- 4.1% of initial weight), as did body mass index (-1.9 +/- 2.5 kg/m(2); p < 0.0002). Total cholesterol (-21.3 +/- 24.7 mg/dL; p < 0.001), low-density lipoprotein-cholesterol (-17.3 +/- 15.8 mg/dL; p < 0.0001), fasting insulin (-13.7 +/- 19.0 microU/mL; p < 0.02), and fasting glucose (-15.4 +/- 7.4 mg/dL; p < 0.003) were also significantly lower after orlistat. Insulin sensitivity, assessed by a frequently sampled intravenous glucose-tolerance test, improved significantly (p < 0.02). We conclude that, in adolescents, short-term treatment with orlistat, in the context of a behavioral program, is well-tolerated and has a side-effect profile similar to that observed in adults, but its true benefit versus conventional therapy remains to be determined in placebo-controlled trials. JF - Obesity research AU - McDuffie, Jennifer R AU - Calis, Karim A AU - Uwaifo, Gabriel I AU - Sebring, Nancy G AU - Fallon, Erica M AU - Hubbard, Van S AU - Yanovski, Jack A AD - Unit on Growth and Obesity, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, NIH, Bethesda, Maryland 20892, USA. Mcduffj@mail.nih.gov Y1 - 2002/07// PY - 2002 DA - July 2002 SP - 642 EP - 650 VL - 10 IS - 7 SN - 1071-7323, 1071-7323 KW - Blood Glucose KW - 0 KW - Cholesterol, LDL KW - Insulin KW - Lactones KW - Vitamins KW - Vitamin D KW - 1406-16-2 KW - orlistat KW - 95M8R751W8 KW - Cholesterol KW - 97C5T2UQ7J KW - Index Medicus KW - Cholesterol, LDL -- blood KW - Glucose Tolerance Test KW - Humans KW - Insulin -- blood KW - Pilot Projects KW - Vitamin D -- administration & dosage KW - Blood Glucose -- analysis KW - Body Mass Index KW - Fasting KW - Cholesterol -- blood KW - Weight Loss KW - Vitamins -- administration & dosage KW - Treatment Outcome KW - Dietary Supplements KW - Adolescent KW - Female KW - Male KW - Obesity -- drug therapy KW - Lactones -- adverse effects KW - Lactones -- therapeutic use KW - Obesity -- complications KW - Obesity -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71889525?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+research&rft.atitle=Three-month+tolerability+of+orlistat+in+adolescents+with+obesity-related+comorbid+conditions.&rft.au=McDuffie%2C+Jennifer+R%3BCalis%2C+Karim+A%3BUwaifo%2C+Gabriel+I%3BSebring%2C+Nancy+G%3BFallon%2C+Erica+M%3BHubbard%2C+Van+S%3BYanovski%2C+Jack+A&rft.aulast=McDuffie&rft.aufirst=Jennifer&rft.date=2002-07-01&rft.volume=10&rft.issue=7&rft.spage=642&rft.isbn=&rft.btitle=&rft.title=Obesity+research&rft.issn=10717323&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-01-07 N1 - Date created - 2002-07-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A randomized controlled trial of octreotide pamoate long-acting release and carboplatin versus carboplatin alone in dogs with naturally occurring osteosarcoma: evaluation of insulin-like growth factor suppression and chemotherapy. AN - 71887048; 12114446 AB - The purpose of this research was to determine whether insulin-like growth factor (IGF) suppression, using a long-acting analogue of somatostatin (OncoLAR, octreotide pamoate long-acting release), will decrease chemotherapy resistance by eliminating an important survival signal to osteosarcoma (OSA) cells in a relevant naturally occurring cancer model. EXPERIMNETAL DESIGN: We conducted a randomized, blinded, placebo-controlled preclinical study in pet dogs with naturally occurring OSA. The study compared primary tumor necrosis and apoptosis, and survival of pet dogs receiving OncoLAR and carboplatin chemotherapy compared with dogs receiving placebo and carboplatin. Dogs receiving OncoLAR had suppression of serum IGF levels by approximately 43% without toxicity. No differences in primary tumor necrosis, apoptosis, tumor IGF mRNA expression, or survival were seen between the dogs receiving OncoLAR plus chemotherapy compared with OncoLAR alone. The suppression of IGF levels by the extent and/or duration achieved in the trial was not sufficient to improve chemotherapy-related antitumor effects in pet dogs with OSA. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Khanna, Chand AU - Prehn, Jennifer AU - Hayden, David AU - Cassaday, Ryan D AU - Caylor, Jana AU - Jacob, Shevin AU - Bose, Seuli M AU - Hong, Sung-Hyeok AU - Hewitt, Stephen M AU - Helman, Lee J AD - Pediatric Oncology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. khannac@mail.nih.gov Y1 - 2002/07// PY - 2002 DA - July 2002 SP - 2406 EP - 2412 VL - 8 IS - 7 SN - 1078-0432, 1078-0432 KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Carboplatin KW - BG3F62OND5 KW - Octreotide KW - RWM8CCW8GP KW - Index Medicus KW - Animals KW - Disease-Free Survival KW - Random Allocation KW - Cell Division -- drug effects KW - Disease Models, Animal KW - Carboplatin -- administration & dosage KW - Survival Rate KW - Apoptosis -- drug effects KW - Treatment Outcome KW - Dogs KW - Octreotide -- administration & dosage KW - Follow-Up Studies KW - Maximum Tolerated Dose KW - Drug Evaluation, Preclinical KW - Female KW - Male KW - Insulin-Like Growth Factor I -- genetics KW - Osteosarcoma -- drug therapy KW - Bone Neoplasms -- blood KW - Bone Neoplasms -- drug therapy KW - Insulin-Like Growth Factor I -- metabolism KW - Osteosarcoma -- blood KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71887048?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=A+randomized+controlled+trial+of+octreotide+pamoate+long-acting+release+and+carboplatin+versus+carboplatin+alone+in+dogs+with+naturally+occurring+osteosarcoma%3A+evaluation+of+insulin-like+growth+factor+suppression+and+chemotherapy.&rft.au=Khanna%2C+Chand%3BPrehn%2C+Jennifer%3BHayden%2C+David%3BCassaday%2C+Ryan+D%3BCaylor%2C+Jana%3BJacob%2C+Shevin%3BBose%2C+Seuli+M%3BHong%2C+Sung-Hyeok%3BHewitt%2C+Stephen+M%3BHelman%2C+Lee+J&rft.aulast=Khanna&rft.aufirst=Chand&rft.date=2002-07-01&rft.volume=8&rft.issue=7&rft.spage=2406&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 - 2003-01-21 N1 - Date created - 2002-07-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I pharmacologic and pharmacodynamic study of pyrazoloacridine given as a weekly 24-hour continuous intravenous infusion in adult cancer patients. AN - 71886467; 12114415 AB - Pyrazoloacridine (PZA) is an investigational nucleic acid binding agent that inhibits the activity of topoisomerases I and II through a mechanism distinct from other topoisomerase poisons. PZA shows schedule-independent cytotoxicity against tumor cells, whereas host toxicity is greater with shorter infusions. We assessed the clinical toxicities and pharmacologic effects of PZA given as a 24-h i.v. infusion weekly for 3 of 4 weeks. Thirty-two adult patients with solid tumors received PZA at five dose levels (100-351 mg/m(2)). Plasma samples were obtained at the end of the PZA infusion at all of the dose levels, with extended sampling in a cohort treated at the recommended dose. Dose-limiting granulocytopenia and mucositis occurred in 2 of 6 patients at 351 mg/m(2), but lower doses were well tolerated. No responses were seen, but 28% had stable disease for > or =3 months. Plasma levels strongly correlated with the degree of granulocytopenia. Extended pharmacokinetics in 7 patients treated with 281 mg/m(2) indicated the following averages: maximum plasma level, 1.6 microM; area under the plasma concentration-time curve, 56 microM.h; terminal half-life, 27 h; urinary recovery, 17% over 72 h. DNA fragmentation in post-PZA bone marrow mononuclear cells was seen in 9 of 28 samples (all at > or =281 mg/m(2)). Unlike other schedules of PZA, neurotoxicity and thrombocytopenia were not problematic with a weekly 24-h infusion of PZA. The recommended Phase II dose is 281 mg/m(2), which was well tolerated. Both end of infusion plasma levels and presence of DNA damage correlated with granulocyte toxicity. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Grem, Jean L AU - Harold, Nancy AU - Keith, Bruce AU - Chen, Alice P AU - Kao, Viven AU - Takimoto, Chris H AU - Hamilton, J Michael AU - Pang, Janet AU - Pace, Marie AU - Jasser, Gada B AU - Quinn, Mary G AU - Monahan, Brian P AD - National Cancer Institute-Navy Hematology/Oncology, National Naval Medical Center, Bethesda, Maryland 20889, USA. gremj@mail.nih.gov Y1 - 2002/07// PY - 2002 DA - July 2002 SP - 2149 EP - 2156 VL - 8 IS - 7 SN - 1078-0432, 1078-0432 KW - Acridines KW - 0 KW - Antineoplastic Agents KW - Pyrazoles KW - NSC 366140 KW - 99009-20-8 KW - Index Medicus KW - Drug Administration Schedule KW - Apoptosis KW - Infusions, Intravenous KW - Aged, 80 and over KW - Humans KW - Adult KW - Gastrointestinal Diseases -- chemically induced KW - Aged KW - Middle Aged KW - Male KW - Female KW - Agranulocytosis -- chemically induced KW - Pyrazoles -- administration & dosage KW - Neoplasms -- drug therapy KW - Acridines -- administration & dosage KW - Antineoplastic Agents -- administration & dosage KW - Acridines -- adverse effects KW - Antineoplastic Agents -- pharmacokinetics KW - Acridines -- pharmacokinetics KW - Pyrazoles -- adverse effects KW - Pyrazoles -- pharmacokinetics KW - Neoplasms -- metabolism KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71886467?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=A+phase+I+pharmacologic+and+pharmacodynamic+study+of+pyrazoloacridine+given+as+a+weekly+24-hour+continuous+intravenous+infusion+in+adult+cancer+patients.&rft.au=Grem%2C+Jean+L%3BHarold%2C+Nancy%3BKeith%2C+Bruce%3BChen%2C+Alice+P%3BKao%2C+Viven%3BTakimoto%2C+Chris+H%3BHamilton%2C+J+Michael%3BPang%2C+Janet%3BPace%2C+Marie%3BJasser%2C+Gada+B%3BQuinn%2C+Mary+G%3BMonahan%2C+Brian+P&rft.aulast=Grem&rft.aufirst=Jean&rft.date=2002-07-01&rft.volume=8&rft.issue=7&rft.spage=2149&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 - 2003-01-21 N1 - Date created - 2002-07-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Abstinence reinforcement maintenance contingency and one-year follow-up. AN - 71878500; 12095662 AB - Relapse to drug use is often seen when contingencies designed to reduce drug use are discontinued. This paper reports on a stepdown maintenance contingency and 1-year follow-up in 110 patients who were maintained on methadone (50 or 70 mg/day) and who had completed a contingency management trial targeted to decreasing their opiate use. In the prior study (induction phase, 8 weeks) participants received vouchers for each opiate-negative urine screen or noncontingently. In this study (maintenance phase, 12 weeks), participants were rerandomized to receive vouchers and take-home methadone doses contingent on providing opiate-negative urine specimens (N=55) or noncontingently (N=55). Since participants had been rerandomized from induction-phase contingencies, most study data were analyzed as if from a 2 x 2 (inductionxmaintenance) design. Follow-up interviews were conducted at 3, 6, and 12 months after study participation. Patients who received the maintenance contingency following an 8-week induction contingency had better outcomes than those who received noncontingent incentives in either the maintenance or induction phases of the trial. Good outcome at follow-up was predicted by enrollment in methadone maintenance after the study. Significantly more participants in the maintenance contingency group transferred directly to another methadone program. These findings support the therapeutic value of extending the duration of contingency management and long-term methadone maintenance. JF - Drug and alcohol dependence AU - Preston, Kenzie L AU - Umbricht, Annie AU - Epstein, David H AD - National Institute on Drug Abuse (NIDA) Intramural Research Program, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. kpreston@intra.nida.nih.gov Y1 - 2002/07/01/ PY - 2002 DA - 2002 Jul 01 SP - 125 EP - 137 VL - 67 IS - 2 SN - 0376-8716, 0376-8716 KW - Methadone KW - UC6VBE7V1Z KW - Index Medicus KW - Analysis of Variance KW - Methadone -- therapeutic use KW - Humans KW - Chi-Square Distribution KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Follow-Up Studies KW - Statistics, Nonparametric KW - Male KW - Female KW - Opioid-Related Disorders -- epidemiology KW - Reinforcement (Psychology) KW - Opioid-Related Disorders -- rehabilitation KW - Opioid-Related Disorders -- urine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71878500?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Abstinence+reinforcement+maintenance+contingency+and+one-year+follow-up.&rft.au=Preston%2C+Kenzie+L%3BUmbricht%2C+Annie%3BEpstein%2C+David+H&rft.aulast=Preston&rft.aufirst=Kenzie&rft.date=2002-07-01&rft.volume=67&rft.issue=2&rft.spage=125&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 - 2002-10-22 N1 - Date created - 2002-07-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DDT metabolite and androgens in African-American farmers. AN - 71878475; 12094101 AB - The ubiquitous dichlorodiphenyltrichloroethane (DDT) metabolite 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) is an androgen receptor antagonist. Data on potential antiandrogenic activity of DDE in humans are limited. The relations between concentrations of plasma DDE and several serum androgens (total testosterone, bioavailable testosterone, 5alpha-dihydrotestosterone, and free androgen index) were examined in 137 North Carolina black male farmers, using multiple linear regression. Participants ranged in age from 30 to 88 years (mean = 62 years). Most had farmed for about 30 years and 27% reported having used DDT. The median DDE level was 7.7 microg per liter (1213 microg per kg lipid), slightly higher than in other recent studies. Overall, concentrations of DDE and androgens were unrelated. Total testosterone decreased 2% (95% confidence limits [CL] = -9%, 5%) per increase in interquartile distance of lipid-adjusted DDE. The percentage change in other hormones was similarly negligible. However, among those whose DDE level was in the top tenth percentile, compared with all others, total testosterone and free androgen index were lower by 23% (CL= -40%, 1%) and 22% (CL =-41%, 4%) respectively. Plasma androgen levels decreased with age, a relation that has previously been studied only in whites. Studies of more highly exposed populations may be needed to evaluate effects, if any, of DDE. JF - Epidemiology (Cambridge, Mass.) AU - Martin, Stephen A AU - Harlow, Siobán D AU - Sowers, Mary Fran AU - Longnecker, Matthew P AU - Garabrant, David AU - Shore, David L AU - Sandler, Dale P AD - National Institute of Environmental Health Sciences, Epidemiology Branch, MD A3-05, Research Triangle Park, NC 27709, USA. Y1 - 2002/07// PY - 2002 DA - July 2002 SP - 454 EP - 458 VL - 13 IS - 4 SN - 1044-3983, 1044-3983 KW - Androgen Antagonists KW - 0 KW - Androgens KW - Insecticides KW - Lipids KW - Dichlorodiphenyl Dichloroethylene KW - 4M7FS82U08 KW - Index Medicus KW - Lipids -- blood KW - Agriculture KW - Regression Analysis KW - Hypogonadism -- epidemiology KW - Aged, 80 and over KW - Humans KW - Adult KW - Surveys and Questionnaires KW - Aged KW - Middle Aged KW - North Carolina -- epidemiology KW - Male KW - Androgens -- blood KW - Androgen Antagonists -- blood KW - African Americans -- statistics & numerical data KW - Dichlorodiphenyl Dichloroethylene -- blood KW - Insecticides -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71878475?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=DDT+metabolite+and+androgens+in+African-American+farmers.&rft.au=Martin%2C+Stephen+A%3BHarlow%2C+Siob%C3%A1n+D%3BSowers%2C+Mary+Fran%3BLongnecker%2C+Matthew+P%3BGarabrant%2C+David%3BShore%2C+David+L%3BSandler%2C+Dale+P&rft.aulast=Martin&rft.aufirst=Stephen&rft.date=2002-07-01&rft.volume=13&rft.issue=4&rft.spage=454&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 - 2002-08-16 N1 - Date created - 2002-07-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of carcinogen-activating enzymes by 16alpha-fluoro-5-androsten-17-one. AN - 71876157; 12097275 AB - In the present study, we examined the effect of a synthetic analogue of the chemopreventive hormone dehydroepiandrosterone, 16alpha-fluoro-5-androsten-17-one, also known as fluasterone, on the activity and expression of carcinogen-activating enzymes in MCF-7 cells. The increase in cytochrome P450 (CYP) 1A1 and 1B1 activity, as measured by ethoxyresorufin-O-deethylase activity, in cells treated with the carcinogens dimethylbenzanthracene (DMBA) or 2,3,5,7-tetrachlorodibenzo-p-dioxin (TCDD), was inhibited by cotreatment with fluasterone. However, treatment of the cells with fluasterone after induction with DMBA or TCDD failed to decrease enzyme activity, indicating that inhibition was not the result of direct enzyme inhibition. Therefore, we examined the effect of fluasterone on gene expression at the mRNA level. Both DMBA and TCDD caused a dramatic increase in the amount of CYP1A1 and CYP1B1 mRNA, the two major isoforms involved in carcinogen activation in these cells. In cells cotreated with fluasterone, however, there was a dose-dependent decrease in CYP1A1 and CYP1B1 mRNA. Fluasterone also inhibited the basal level of CYP1A1 mRNA but not CYP1B1. Fluasterone inhibited the rate of CYP1A1 promoter-controlled transcription, indicating that it affects the transcriptional regulation of the gene. Actinomycin D chase experiments showed that fluasterone also caused an increase in the degradation of CYP1A1 mRNA, while leaving CYP1B1 mRNA unaffected. These results indicate that fluasterone inhibits the increase in the expression of CYP1A1 normally caused by exposure to carcinogens by both transcriptional and post-transcriptional mechanisms and that CYP1B1 expression is not susceptible to the same post-transcriptional mechanism. JF - Cancer research AU - Ciolino, Henry P AU - MacDonald, Christopher J AU - Yeh, Grace Chao AD - Cellular Defense and Carcinogenesis Section, Basic Research Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, NIH, Frederick, Maryland 21702-1201, USA. hciolino@ncifcrf.gov Y1 - 2002/07/01/ PY - 2002 DA - 2002 Jul 01 SP - 3685 EP - 3690 VL - 62 IS - 13 SN - 0008-5472, 0008-5472 KW - Antineoplastic Agents KW - 0 KW - Carcinogens KW - Cytochrome P-450 Enzyme Inhibitors KW - Enzyme Inhibitors KW - Polychlorinated Dibenzodioxins KW - RNA, Messenger KW - Dehydroepiandrosterone KW - 459AG36T1B KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - CYP1B1 protein, human KW - Cytochrome P-450 CYP1A1 KW - Cytochrome P-450 CYP1B1 KW - 5-androstene-16-fluoro-17-one KW - R7M5UGD04G KW - Index Medicus KW - Drug Interactions KW - Cytochrome P-450 Enzyme System -- genetics KW - Humans KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Cytochrome P-450 Enzyme System -- metabolism KW - RNA, Messenger -- genetics KW - Biotransformation -- drug effects KW - RNA, Messenger -- biosynthesis KW - 9,10-Dimethyl-1,2-benzanthracene -- pharmacokinetics KW - Polychlorinated Dibenzodioxins -- pharmacokinetics KW - Tumor Cells, Cultured KW - RNA, Messenger -- metabolism KW - 9,10-Dimethyl-1,2-benzanthracene -- toxicity KW - Polychlorinated Dibenzodioxins -- toxicity KW - Breast Neoplasms -- drug therapy KW - Cytochrome P-450 CYP1A1 -- genetics KW - Liver Neoplasms -- enzymology KW - Carcinogens -- pharmacokinetics KW - Carcinogens -- toxicity KW - Cytochrome P-450 CYP1A1 -- metabolism KW - Dehydroepiandrosterone -- analogs & derivatives KW - Cytochrome P-450 CYP1A1 -- antagonists & inhibitors KW - Cytochrome P-450 CYP1A1 -- biosynthesis KW - Liver Neoplasms -- drug therapy KW - Enzyme Inhibitors -- pharmacology KW - Breast Neoplasms -- enzymology KW - Dehydroepiandrosterone -- pharmacology KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71876157?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Inhibition+of+carcinogen-activating+enzymes+by+16alpha-fluoro-5-androsten-17-one.&rft.au=Ciolino%2C+Henry+P%3BMacDonald%2C+Christopher+J%3BYeh%2C+Grace+Chao&rft.aulast=Ciolino&rft.aufirst=Henry&rft.date=2002-07-01&rft.volume=62&rft.issue=13&rft.spage=3685&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 - 2002-08-08 N1 - Date created - 2002-07-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Coincident elevation of cAMP and calcium influx by PACAP-27 synergistically regulates vasoactive intestinal polypeptide gene transcription through a novel PKA-independent signaling pathway. AN - 71875441; 12097482 AB - Pituitary adenylate cyclase-activating polypeptide (PACAP) causes calcium influx, intracellular calcium release, and elevation of cAMP in chromaffin cells. Calcium influx is required for PACAP-stimulated secretion of catecholamines and neuropeptides. The role of cAMP elevation in the action of PACAP at either sympathetic or adrenomedullary synapses, however, is unknown. Here, we show that PACAP-27-induced calcium influx through voltage-sensitive calcium channels (VSCCs), together with elevation of intracellular cAMP, was sufficient to stimulate vasoactive intestinal polypeptide (VIP) biosynthesis at least 40-fold. Combined treatment of chromaffin cells with 40 mm KCl, which elevates intracellular calcium, and 25 micrometer forskolin, which elevates intracellular cAMP, caused an increase in VIP peptide and mRNA much greater than that elicited by either agent alone, and comparable to the increase caused by 10-100 nm PACAP-27. Elevation of VIP mRNA by either KCl plus forskolin, or PACAP, (1) was independent of new protein synthesis, (2) was blocked by inhibition of calcium influx through voltage-sensitive calcium channels, (3) was calcineurin dependent, and (4) was dependent on MAP kinase activation but not activation of protein kinase A. The degree of activation of two different second-messenger pathways, calcium influx and cAMP elevation, appears to determine the magnitude of transcriptional activation of the VIP gene in chromaffin cells. Maximal stimulation of VIP biosynthesis by PACAP appears to require the coincident activation of both of these pathways. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Hamelink, Carol AU - Lee, Hyeon-Woo AU - Chen, Yun AU - Grimaldi, Maurizio AU - Eiden, Lee E AD - Section on Molecular Neuroscience, Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/07/01/ PY - 2002 DA - 2002 Jul 01 SP - 5310 EP - 5320 VL - 22 IS - 13 KW - ADCYAP1 protein, human KW - 0 KW - Calcium Channel Blockers KW - Neuropeptides KW - Pituitary Adenylate Cyclase-Activating Polypeptide KW - RNA, Messenger KW - Colforsin KW - 1F7A44V6OU KW - Vasoactive Intestinal Peptide KW - 37221-79-7 KW - Cyclic AMP KW - E0399OZS9N KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Potassium KW - RWP5GA015D KW - Index Medicus KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Animals KW - Second Messenger Systems KW - Mitogen-Activated Protein Kinases -- metabolism KW - Humans KW - RNA, Messenger -- biosynthesis KW - Cattle KW - Colforsin -- pharmacology KW - MAP Kinase Signaling System KW - Tumor Cells, Cultured KW - Calcium Channel Blockers -- pharmacology KW - Cells, Cultured KW - Potassium -- pharmacology KW - Drug Synergism KW - Cyclic AMP -- biosynthesis KW - Neuropeptides -- pharmacology KW - Vasoactive Intestinal Peptide -- metabolism KW - Chromaffin Cells -- metabolism KW - Chromaffin Cells -- drug effects KW - Transcriptional Activation KW - Calcium Signaling UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71875441?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Coincident+elevation+of+cAMP+and+calcium+influx+by+PACAP-27+synergistically+regulates+vasoactive+intestinal+polypeptide+gene+transcription+through+a+novel+PKA-independent+signaling+pathway.&rft.au=Hamelink%2C+Carol%3BLee%2C+Hyeon-Woo%3BChen%2C+Yun%3BGrimaldi%2C+Maurizio%3BEiden%2C+Lee+E&rft.aulast=Hamelink&rft.aufirst=Carol&rft.date=2002-07-01&rft.volume=22&rft.issue=13&rft.spage=5310&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=1529-2401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-29 N1 - Date created - 2002-07-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Raloxifene, a selective estrogen receptor modulator, induces apoptosis in androgen-responsive human prostate cancer cell line LNCaP through an androgen-independent pathway. AN - 71874735; 12097269 AB - Raloxifene, a selective estrogen receptor (ER) modulator, is a mixed estrogen agonist/antagonist that has been shown to prevent osteoporosis and breast cancer in women. Because the prostate contains a high level of ER-beta, the present study investigated the effect of raloxifene in the androgen-sensitive human prostate cancer cell line LNCaP. Previously, it has been demonstrated that LNCaP cells express ER-beta but not ER-alpha and that tamoxifene induces apoptosis in these cells. After treatment with raloxifene, a dramatic increase in cell death occurred in a dose-dependent manner (10(-9) to 10(-6) M range). Using the terminal deoxynucleotidyl transferase-mediated nick end labeling apoptotic assay, we demonstrated that the nuclear fragmentation was due to apoptosis. The dramatic change in cellular morphology after treatment with raloxifene was no longer observed when cells were pretreated with a pan-caspase inhibitor, Z-VAD-FMK, and a specific caspase-9 inhibitor, Z-LEHD-FMK. Furthermore, immunoblot demonstrated an activation of caspase-9 in LNCaP cells. Because LNCaP cells contain a mutated androgen receptor that allows cellular proliferation in the presence of antiandrogens, prostate-specific antigen assay and transfection with a reporter construct containing luciferase gene under the control of androgen response element (pARE) were carried out. The results demonstrated that raloxifene does not significantly alter androgen receptor activity in LNCaP cells. Taken together, these results demonstrate that raloxifene, a selective ER modulator, induces apoptosis in the androgen-sensitive human prostate cancer cell line LNCaP through an androgen-independent pathway. JF - Cancer research AU - Kim, Isaac Yi AU - Seong, Do Hwan AU - Kim, Byung-Chul AU - Lee, Dug Keun AU - Remaley, Alan T AU - Leach, Fredrick AU - Morton, Ronald A AU - Kim, Seong-Jin AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2002/07/01/ PY - 2002 DA - 2002 Jul 01 SP - 3649 EP - 3653 VL - 62 IS - 13 SN - 0008-5472, 0008-5472 KW - Androgens KW - 0 KW - Receptors, Androgen KW - Selective Estrogen Receptor Modulators KW - Raloxifene Hydrochloride KW - 4F86W47BR6 KW - Index Medicus KW - Tumor Cells, Cultured KW - Dose-Response Relationship, Drug KW - Humans KW - Receptors, Androgen -- physiology KW - Male KW - Prostatic Neoplasms -- pathology KW - Raloxifene Hydrochloride -- pharmacology KW - Apoptosis -- physiology KW - Apoptosis -- drug effects KW - Androgens -- physiology KW - Neoplasms, Hormone-Dependent -- drug therapy KW - Selective Estrogen Receptor Modulators -- pharmacology KW - Neoplasms, Hormone-Dependent -- pathology KW - Prostatic Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71874735?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Raloxifene%2C+a+selective+estrogen+receptor+modulator%2C+induces+apoptosis+in+androgen-responsive+human+prostate+cancer+cell+line+LNCaP+through+an+androgen-independent+pathway.&rft.au=Kim%2C+Isaac+Yi%3BSeong%2C+Do+Hwan%3BKim%2C+Byung-Chul%3BLee%2C+Dug+Keun%3BRemaley%2C+Alan+T%3BLeach%2C+Fredrick%3BMorton%2C+Ronald+A%3BKim%2C+Seong-Jin&rft.aulast=Kim&rft.aufirst=Isaac&rft.date=2002-07-01&rft.volume=62&rft.issue=13&rft.spage=3649&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 - 2002-08-08 N1 - Date created - 2002-07-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Olfactory bulbectomy protects hippocampal pyramidal neurons against excitotoxic death. AN - 71873666; 12093105 AB - The olfactory system is functionally linked to the hippocampus, and odors can modify the activity of hippocampal neurons. Because hippocampal neurons are selectively vulnerable to death in several prominent neurodegenerative conditions, we tested the hypothesis that activity in olfactory pathways can modify the sensitivity of hippocampal neurons to excitotoxic damage. We report that rats subjected to olfactory bulbectomy exhibit a decrease in the vulnerability of hippocampal pyramidal neurons to excitotoxic injury. Four-month-old male Sprague-Dawley rats were subjected to bilateral olfactory bulbectomy or a sham operation. Three months later the rats were given a unilateral infusion of kainic acid in the dorsal hippocampus and were euthanized 24 h later. There was a threefold increase in the number of CA3 neurons that survived kainic acid administration in the bulbectomized rats compared to sham-operated rats. These findings provide the first evidence that olfactory input affects the vulnerability of neurons to excitotoxic death. JF - Experimental neurology AU - Gary, Devin S AU - Getchell, Thomas V AU - Getchell, Marilyn L AU - Mattson, Mark P AD - Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, 5600 Nathan Shock Drive, Baltimore, Maryland 21224, USA. Y1 - 2002/07// PY - 2002 DA - July 2002 SP - 266 EP - 268 VL - 176 IS - 1 SN - 0014-4886, 0014-4886 KW - Neurotoxins KW - 0 KW - Kainic Acid KW - SIV03811UC KW - Index Medicus KW - Rats KW - Drug Resistance -- physiology KW - Animals KW - Rats, Sprague-Dawley KW - Kainic Acid -- pharmacology KW - Cell Survival -- drug effects KW - Cell Count KW - Male KW - Pyramidal Cells -- drug effects KW - Pyramidal Cells -- physiology KW - Hippocampus -- physiology KW - Olfactory Bulb -- physiology KW - Hippocampus -- cytology KW - Neurotoxins -- pharmacology KW - Pyramidal Cells -- cytology KW - Olfactory Bulb -- surgery KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71873666?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Olfactory+bulbectomy+protects+hippocampal+pyramidal+neurons+against+excitotoxic+death.&rft.au=Gary%2C+Devin+S%3BGetchell%2C+Thomas+V%3BGetchell%2C+Marilyn+L%3BMattson%2C+Mark+P&rft.aulast=Gary&rft.aufirst=Devin&rft.date=2002-07-01&rft.volume=176&rft.issue=1&rft.spage=266&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 - 2002-08-16 N1 - Date created - 2002-07-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - RPE65 is highly uveitogenic in rats. AN - 71865637; 12091425 AB - To examine the hypothesis that RPE65, a protein specific to the retinal pigment epithelium, is uveitogenic in rats. Rats of four inbred strains (Lewis, Brown Norway, Fischer, and SHR) were immunized with native or recombinant bovine RPE65, or with S-antigen (S-Ag), emulsified with complete Freund adjuvant, and treated simultaneously with killed Bordetella pertussis bacteria, as indicated. Development of ocular changes was examined and scored both clinically and histologically. Lewis rats immunized with RPE65 showed development of acute and severe inflammatory eye disease that affected most ocular tissues. The minimum uveitogenic dose of RPE65 was similar to that of S-Ag (1 microg per rat), but the changes induced by RPE65 at higher dose ranges were less severe than those induced by S-Ag. Concurrent treatment of the RPE65-immunized rats with B. pertussis bacteria was not critical for disease induction, but enhanced dramatically the pathogenic reaction. Unlike the results with several other retinal proteins, no pinealitis was detected in rats immunized with RPE65. Fischer (F344) rats resembled Lewis rats in being similarly affected by RPE65 or S-Ag. In contrast, Brown Norway (BN) rats developed severe disease when immunized with RPE65, but showed minimal changes in response to S-Ag. SHR rats responded poorly to disease induced by RPE65, and S-Ag-induced disease failed to develop. RPE65 is highly uveitogenic in rats, thus suggesting that this molecule could be involved in pathogenic autoimmunity in the human eye. JF - Investigative ophthalmology & visual science AU - Ham, Don-Il AU - Gentleman, Susan AU - Chan, Chi-Chao AU - McDowell, J Hugh AU - Redmond, T Michael AU - Gery, Igal AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, 10 Center Drive, Building 10, Room 10N112, Bethesda, MD 20892-1857, USA. Y1 - 2002/07// PY - 2002 DA - July 2002 SP - 2258 EP - 2263 VL - 43 IS - 7 SN - 0146-0404, 0146-0404 KW - Carrier Proteins KW - 0 KW - Eye Proteins KW - Proteins KW - Recombinant Proteins KW - retinoid isomerohydrolase KW - EC 3.1.1.64 KW - cis-trans-Isomerases KW - EC 5.2.- KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred Lew KW - Rats, Inbred F344 KW - Rats, Inbred SHR KW - Electrophoresis, Polyacrylamide Gel KW - Rats, Inbred BN KW - Male KW - Immunization KW - Eye Proteins -- isolation & purification KW - Eye Proteins -- toxicity KW - Uveitis -- pathology KW - Proteins -- isolation & purification KW - Pigment Epithelium of Eye -- chemistry KW - Autoimmune Diseases -- pathology KW - Autoimmune Diseases -- chemically induced KW - Uveitis -- chemically induced KW - Proteins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71865637?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Investigative+ophthalmology+%26+visual+science&rft.atitle=RPE65+is+highly+uveitogenic+in+rats.&rft.au=Ham%2C+Don-Il%3BGentleman%2C+Susan%3BChan%2C+Chi-Chao%3BMcDowell%2C+J+Hugh%3BRedmond%2C+T+Michael%3BGery%2C+Igal&rft.aulast=Ham&rft.aufirst=Don-Il&rft.date=2002-07-01&rft.volume=43&rft.issue=7&rft.spage=2258&rft.isbn=&rft.btitle=&rft.title=Investigative+ophthalmology+%26+visual+science&rft.issn=01460404&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-15 N1 - Date created - 2002-07-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of [76Br]FBAU 3',5'-dibenzoate as a lipophilic prodrug for brain imaging. AN - 71863219; 12088722 AB - [76Br]FBAU is a potential PET tracer for assessing proliferation. This study proposes that [76Br]FBAU 3',5'-dibenzoate has higher blood-brain-barrier permeability than [76Br]FBAU itself and thus might be better suited for applications in the brain. The brain uptake indexes of the two compounds measured after carotid injection (29.6 +/- 13.9 for [76Br]FBAU 3',5'-dibenzoate, versus 10.0 +/- 8.7 for [76Br]FBAU) support this claim. Biodistribution study also showed that the brain accumulation of activity was higher in rats injected with [76Br]FBAU 3',5'-dibenzoate than with [76Br]FBAU (0.119+/-0.023 DUR at 1 h, versus 0.061 +/- 0.006). [76Br]FBAU 3',5'-dibenzoate was relatively stable in rat plasma, gradually being hydrolyzed to [76Br]FBAU exponentially with a calculated half-life of 0.8 h. DNA incorporation of [76Br]FBAU was also confirmed. The results presented support the hypothesis that the 3',5'-dibenzoate can act as a prodrug for FBAU and deliver more radiolabeled nucleoside to the brain. JF - Nuclear medicine and biology AU - Kao, Chih-Hao K AU - Waki, Atsuo AU - Sassaman, Mark B AU - Jagoda, Elaine M AU - Szajek, Lawrence P AU - Ravasi, Laura AU - Shimoji, Kazuaki AU - Eckelman, William C AD - Positron Emission Tomography Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA. ck123j@nih.gov Y1 - 2002/07// PY - 2002 DA - July 2002 SP - 527 EP - 535 VL - 29 IS - 5 SN - 0969-8051, 0969-8051 KW - 1-(2-fluoro-2-deoxy-3,5-O-dibenzoylarabinofuranosyl)-5-bromouracil KW - 0 KW - 1-(2-fluoro-2-deoxyarabinofuranosyl)-5-bromouracil KW - Prodrugs KW - Radiopharmaceuticals KW - Bromouracil KW - 4HK400G5UO KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Sensitivity and Specificity KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Reproducibility of Results KW - Models, Molecular KW - DNA -- metabolism KW - Models, Chemical KW - Tissue Distribution KW - Hydrolysis KW - Male KW - Female KW - Radiopharmaceuticals -- pharmacokinetics KW - Radiopharmaceuticals -- chemical synthesis KW - Prodrugs -- pharmacokinetics KW - Brain -- metabolism KW - Bromouracil -- chemical synthesis KW - Bromouracil -- analogs & derivatives KW - Bromouracil -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71863219?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nuclear+medicine+and+biology&rft.atitle=Evaluation+of+%5B76Br%5DFBAU+3%27%2C5%27-dibenzoate+as+a+lipophilic+prodrug+for+brain+imaging.&rft.au=Kao%2C+Chih-Hao+K%3BWaki%2C+Atsuo%3BSassaman%2C+Mark+B%3BJagoda%2C+Elaine+M%3BSzajek%2C+Lawrence+P%3BRavasi%2C+Laura%3BShimoji%2C+Kazuaki%3BEckelman%2C+William+C&rft.aulast=Kao&rft.aufirst=Chih-Hao&rft.date=2002-07-01&rft.volume=29&rft.issue=5&rft.spage=527&rft.isbn=&rft.btitle=&rft.title=Nuclear+medicine+and+biology&rft.issn=09698051&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-02-10 N1 - Date created - 2002-06-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effects of the corset. AN - 71855200; 12084685 JF - American journal of public health AU - Fee, Elizabeth AU - Brown, Theodore M AU - Lazarus, Jan AU - Theerman, Paul AD - History of Medicine Division, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA. elizabeth_fee@nlm.nih.gov Y1 - 2002/07// PY - 2002 DA - July 2002 SP - 1085 VL - 92 IS - 7 SN - 0090-0036, 0090-0036 KW - Abridged Index Medicus KW - Index Medicus KW - Feminism -- history KW - Women's Health KW - Humans KW - History, 18th Century KW - Constriction, Pathologic -- etiology KW - History, 19th Century KW - Medical Illustration -- history KW - Female KW - Constriction, Pathologic -- history KW - Clothing -- history KW - Clothing -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71855200?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+effects+of+the+corset.&rft.au=Fee%2C+Elizabeth%3BBrown%2C+Theodore+M%3BLazarus%2C+Jan%3BTheerman%2C+Paul&rft.aulast=Fee&rft.aufirst=Elizabeth&rft.date=2002-07-01&rft.volume=92&rft.issue=7&rft.spage=1085&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 - 2002-07-12 N1 - Date created - 2002-06-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Bull N Y Acad Med. 1979 Jun;55(6):551-90 [380699] N Engl J Med. 1973 Sep 27;289(13):698 [4580475] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Acrylonitrile is a multisite carcinogen in male and female B6C3F1 mice. AN - 71839316; 12075111 AB - Acrylonitrile is a heavily produced unsaturated nitrile, which is used in the production of synthetic fibers, plastics, resins, and rubber. Acrylonitrile is a multisite carcinogen in rats after exposure via gavage, drinking water, or inhalation. No carcinogenicity studies of acrylonitrile in a second animal species were available. The current studies were designed to assess the carcinogenicity of acrylonitrile in B6C3F1 mice of both sexes. Acrylonitrile was administered by gavage at 0, 2.5, 10, or 20 mg/kg/day, 5 days per week, for 2 years. Urinary thiocyanate and N-acetyl-S-(2-cyanoethyl)-L-cysteine were measured as markers of exposure to acrylonitrile. In general, there were dose-related increases in urinary thiocyanate and N-acetyl-S-(2-cyanoethyl)-L-cysteine concentrations in all dosed groups of mice and at all time points. Survival was significantly (p < 0.001) reduced in the top dose (20 mg/kg) group of male and female mice relative to controls. The incidence of forestomach papillomas and carcinomas was increased in mice of both sexes in association with an increase in forestomach epithelial hyperplasia. The incidence of Harderian gland adenomas and carcinomas was also markedly increased in the acrylonitrile-dosed groups. In female mice, the incidence of benign or malignant granulosa cell tumors (combined) in the ovary in the 10 mg/kg dose group was greater than that in the vehicle control group, but because of a lack of dose response, this was considered an equivocal finding. In addition, the incidences of atrophy and cysts in the ovary of the 10 and 20 mg/kg dose groups were significantly increased. The incidences of alveolar/bronchiolar adenoma or carcinoma (combined) were significantly increased in female mice treated with acrylonitrile at 10 mg/kg/day for 2 years. This was also considered an equivocal result. In conclusion, these studies demonstrated that acrylonitrile causes multiple carcinogenic effects after gavage administration to male and female B6C3F1 mice for 2 years. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Ghanayem, Burhan I AU - Nyska, Abraham AU - Haseman, Joseph K AU - Bucher, John R AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. ghanayem@niehs.nih.gov Y1 - 2002/07// PY - 2002 DA - July 2002 SP - 59 EP - 68 VL - 68 IS - 1 SN - 1096-6080, 1096-6080 KW - Carcinogens KW - 0 KW - Acrylonitrile KW - MP1U0D42PE KW - Index Medicus KW - Mice, Inbred Strains KW - Animals KW - Dose-Response Relationship, Drug KW - Longevity -- drug effects KW - Mice KW - Male KW - Female KW - Neoplasms, Multiple Primary -- pathology KW - Neoplasms, Experimental -- chemically induced KW - Carcinogens -- pharmacokinetics KW - Acrylonitrile -- toxicity KW - Carcinogens -- toxicity KW - Carcinogenicity Tests -- methods KW - Neoplasms, Multiple Primary -- chemically induced KW - Neoplasms, Experimental -- pathology KW - Acrylonitrile -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71839316?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Acrylonitrile+is+a+multisite+carcinogen+in+male+and+female+B6C3F1+mice.&rft.au=Ghanayem%2C+Burhan+I%3BNyska%2C+Abraham%3BHaseman%2C+Joseph+K%3BBucher%2C+John+R&rft.aulast=Ghanayem&rft.aufirst=Burhan&rft.date=2002-07-01&rft.volume=68&rft.issue=1&rft.spage=59&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-11-21 N1 - Date created - 2002-06-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Processing map and essential cleavage sites of the nonstructural polyprotein encoded by ORF1 of the feline calicivirus genome. AN - 71831572; 12072506 AB - Feline calicivirus (FCV) nonstructural proteins are translated as part of a large polyprotein that undergoes autocatalytic processing by the virus-encoded 3C-like proteinase. In this study, we mapped three new cleavage sites (E(46)/A(47), E(331)/D(332), and E(685)/N(686)) recognized by the virus proteinase in the N-terminal part of the open reading frame 1 (ORF1) polyprotein to complete the processing map. Taken together with two sites we identified previously (E(960)/A(961) and E(1071)/S(1072)), the FCV ORF1 polyprotein contains five cleavage sites that define the borders of six proteins with calculated molecular masses of 5.6, 32, 38.9, 30.1, 12.7, and 75.7 kDa, which we designated p5.6, p32, p39 (NTPase), p30, p13 (VPg), and p76 (Pro-Pol), respectively. Mutagenesis of the E to A in each of these cleavage sites in an infectious FCV cDNA clone was lethal for the virus, indicating that these cleavages are essential in a productive virus infection. Mutagenesis of two cleavage sites (E(1345)/T(1346) and E(1419)/G(1420)) within the 75.7-kDa Pro-Pol protein previously mapped in bacterial expression studies was not lethal. JF - Journal of virology AU - Sosnovtsev, Stanislav V AU - Garfield, Mark AU - Green, Kim Y AD - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-8007, USA. ss216m@nih.gov Y1 - 2002/07// PY - 2002 DA - July 2002 SP - 7060 EP - 7072 VL - 76 IS - 14 SN - 0022-538X, 0022-538X KW - Polyproteins KW - 0 KW - Proteins KW - Viral Nonstructural Proteins KW - Viral Proteins KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - 3C proteases KW - EC 3.4.22.28 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Protein Biosynthesis KW - Animals KW - Cysteine Endopeptidases -- metabolism KW - Cats KW - Molecular Sequence Data KW - Viral Proteins -- metabolism KW - Transcription, Genetic KW - Amino Acid Sequence KW - Proteins -- genetics KW - Cell Line KW - Polyproteins -- chemistry KW - Calicivirus, Feline -- enzymology KW - Viral Nonstructural Proteins -- genetics KW - Calicivirus, Feline -- metabolism KW - Viral Nonstructural Proteins -- chemistry KW - Calicivirus, Feline -- growth & development KW - Polyproteins -- genetics KW - Polyproteins -- metabolism KW - Viral Nonstructural Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71831572?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Processing+map+and+essential+cleavage+sites+of+the+nonstructural+polyprotein+encoded+by+ORF1+of+the+feline+calicivirus+genome.&rft.au=Sosnovtsev%2C+Stanislav+V%3BGarfield%2C+Mark%3BGreen%2C+Kim+Y&rft.aulast=Sosnovtsev&rft.aufirst=Stanislav&rft.date=2002-07-01&rft.volume=76&rft.issue=14&rft.spage=7060&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 - 2002-07-25 N1 - Date created - 2002-06-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Gen Virol. 2000 Jan;81(Pt 1):195-9 [10640558] Proc Int Conf Intell Syst Mol Biol. 1998;6:175-82 [9783223] Virology. 2000 Oct 25;276(2):349-63 [11040126] J Virol. 2000 Nov;74(22):10846-51 [11044135] Virology. 2000 Nov 10;277(1):193-203 [11062050] J Virol. 2001 Feb;75(3):1211-9 [11152494] J Virol. 2001 Feb;75(4):1611-9 [11160659] Virus Genes. 2001;23(1):5-16 [11556401] Vet Clin North Am. 1976 Aug;6(3):399-413 [183336] Nature. 1977 Jul 21;268(5617):208-13 [196204] Virology. 1983 Jul 15;128(1):33-47 [6308897] Nucleic Acids Res. 1988 Nov 25;16(22):10881-90 [2849754] FEBS Lett. 1990 Mar 12;262(1):145-8 [2156730] Virus Res. 1990 Nov;17(3):145-60 [2077782] Virology. 1991 Oct;184(2):664-76 [1840711] J Gen Virol. 1991 Sep;72 ( Pt 9):2197-206 [1895057] J Virol. 1991 Oct;65(10):5440-7 [1716692] Arch Virol. 1992;122(3-4):223-35 [1731695] J Mol Biol. 1993 Jul 20;232(2):584-99 [8345525] Virology. 1994 Feb 15;199(1):188-99 [8116242] Virology. 1994 Jul;202(1):129-45 [8009827] Virology. 1995 Apr 20;208(2):540-53 [7747426] J Gen Virol. 1995 Sep;76 ( Pt 9):2349-55 [7561776] J Virol. 1995 Nov;69(11):7159-68 [7474137] J Gen Virol. 1996 Jan;77 ( Pt 1):123-7 [8558120] J Virol. 1996 Apr;70(4):2605-10 [8642693] J Biol Chem. 1996 Sep 20;271(38):23134-7 [8798506] Virology. 1998 Dec 5;252(1):218-27 [9875331] J Gen Virol. 1999 Feb;80 ( Pt 2):291-6 [10073687] Arch Virol. 1999;144(1):199-208 [10076521] J Virol. 1999 Aug;73(8):6626-33 [10400760] Vet Microbiol. 1999 Jun 30;67(3):175-93 [10418872] Arch Virol. 1989;108(1-2):69-79 [2596975] Virology. 1995 Jul 10;210(2):383-90 [7618275] J Virol. 1996 Nov;70(11):7974-83 [8892921] J Virol. 1997 Jun;71(6):4679-93 [9151862] Virology. 1997 Oct 13;237(1):66-77 [9344908] J Virol. 1998 Apr;72(4):3051-9 [9525628] J Infect Dis. 2000 May;181 Suppl 2:S322-30 [10804145] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pretargeting radioimmunotherapy of a murine model of adult T-cell leukemia with the alpha-emitting radionuclide, bismuth 213. AN - 71829868; 12070029 AB - We used a pretargeting technique to treat a nonobese diabetic/severe combined immunodeficient murine model of human adult T-cell leukemia with an anti-Tac antibody-streptavidin (HAT-SA) conjugate, which recognizes CD25, followed by bismuth 213 ((213)Bi)-1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA)- biotin. In the 3-step pretargeting radioimmunotherapy protocol, HAT-SA (140 or 400 microg) was administered intravenously (i.v.) to bind to the interleukin 2 receptor alpha (IL-2R alpha; CD25)-expressing tumor cells. After 24 hours, 100 microg of a synthetic clearing agent was administered i.v. to remove unbound circulating HAT-SA conjugate from the circulation. Four hours later, (213)Bi-DOTA-biotin was administered i.v. for therapy. Tumor growth was significantly inhibited in 3 trials by using 250 microCi (9.25 MBq) of (213)Bi-DOTA-biotin with a pretargeting technique as monitored by serum levels of soluble IL-2R alpha and/or human beta-2-microglobulin (P <.05, t test) and by survival of tumor-bearing mice in the treatment groups (P <.02, log rank test) as compared with the control groups. No prolongation of survival was observed with a nonspecific antibody-SA conjugate or in the absence of the radionuclide. Additionally, no prolongation of survival resulted from administration of (213)Bi directly linked to intact HAT. Furthermore, there was no prolongation of survival when the beta-emitting radionuclide yttrium 90 instead of the alpha-emitting radionuclide (213)Bi was used. The pretargeting approach with (213)Bi inhibited tumor growth more effectively than did immunotherapy with unmodified HAT. The best results were obtained with combination therapy that involved (213)Bi-DOTA-biotin with a pretargeting technique supplemented by 4 weekly doses of HAT. The findings of this study support the use of this combination approach in a clinical trial in patients with IL-2R alpha-expressing leukemias. JF - Blood AU - Zhang, Meili AU - Yao, Zhengsheng AU - Garmestani, Kayhan AU - Axworthy, Donald B AU - Zhang, Zhuo AU - Mallett, Robert W AU - Theodore, Louis J AU - Goldman, Carolyn K AU - Brechbiel, Martin W AU - Carrasquillo, Jorge A AU - Waldmann, Thomas A AD - Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2002/07/01/ PY - 2002 DA - 2002 Jul 01 SP - 208 EP - 216 VL - 100 IS - 1 SN - 0006-4971, 0006-4971 KW - Antigens, Neoplasm KW - 0 KW - Heterocyclic Compounds, 1-Ring KW - Radioisotopes KW - Radiopharmaceuticals KW - Receptors, Interleukin-2 KW - 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid KW - 1HTE449DGZ KW - Biotin KW - 6SO6U10H04 KW - Streptavidin KW - 9013-20-1 KW - Bismuth KW - U015TT5I8H KW - Abridged Index Medicus KW - Index Medicus KW - Radiopharmaceuticals -- pharmacokinetics KW - Animals KW - Radiopharmaceuticals -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacokinetics KW - Mice, Inbred NOD KW - Neoplasms, Experimental -- therapy KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Mice KW - Antineoplastic Combined Chemotherapy Protocols -- toxicity KW - Receptors, Interleukin-2 -- immunology KW - Survival Rate KW - Radiopharmaceuticals -- toxicity KW - Treatment Outcome KW - Alpha Particles KW - Antigens, Neoplasm -- immunology KW - Bismuth -- administration & dosage KW - Leukemia-Lymphoma, Adult T-Cell -- radiotherapy KW - Bismuth -- toxicity KW - Bismuth -- pharmacokinetics KW - Radioisotopes -- pharmacokinetics KW - Radioimmunotherapy -- methods KW - Radioisotopes -- toxicity KW - Radioisotopes -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71829868?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Pretargeting+radioimmunotherapy+of+a+murine+model+of+adult+T-cell+leukemia+with+the+alpha-emitting+radionuclide%2C+bismuth+213.&rft.au=Zhang%2C+Meili%3BYao%2C+Zhengsheng%3BGarmestani%2C+Kayhan%3BAxworthy%2C+Donald+B%3BZhang%2C+Zhuo%3BMallett%2C+Robert+W%3BTheodore%2C+Louis+J%3BGoldman%2C+Carolyn+K%3BBrechbiel%2C+Martin+W%3BCarrasquillo%2C+Jorge+A%3BWaldmann%2C+Thomas+A&rft.aulast=Zhang&rft.aufirst=Meili&rft.date=2002-07-01&rft.volume=100&rft.issue=1&rft.spage=208&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-26 N1 - Date created - 2002-06-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Testing the Intraclass Version of Kappa Coeffcient of Agreement with Binary Scale and Sample Size Determination AN - 21095487; 11132248 AB - The intraclass version of kappa coefficient has been commonly applied as a measure of agreement for two ratings per subject with binary outcome in reliability studies. We present an efficient statistic for testing the strength of kappa agreement using likelihood scores, and derive asymptotic power and sample size formula. Exact evaluation shows that the score test is generally conservative and more powerful than a method based on a chi-square goodness-of-fit statistic (Donner and Eliasziw, 1992, Statistics in Medicine 11, 1511-1519). In particular, when the research question is one directional, the one-sided score test is substantially more powerful and the reduction in sample size is appreciable. JF - Biometrical Journal AU - Nam, Jun-mo Y1 - 2002/07// PY - 2002 DA - Jul 2002 SP - 558 EP - 570 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 USA VL - 44 IS - 5 SN - 0323-3847, 0323-3847 KW - Biotechnology and Bioengineering Abstracts KW - Biometrics KW - Statistics KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21095487?accountid=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=Biometrical+Journal&rft.atitle=Testing+the+Intraclass+Version+of+Kappa+Coeffcient+of+Agreement+with+Binary+Scale+and+Sample+Size+Determination&rft.au=Nam%2C+Jun-mo&rft.aulast=Nam&rft.aufirst=Jun-mo&rft.date=2002-07-01&rft.volume=44&rft.issue=5&rft.spage=558&rft.isbn=&rft.btitle=&rft.title=Biometrical+Journal&rft.issn=03233847&rft_id=info:doi/10.1002%2F1521-4036%28200207%2944%3A53.0.CO%3B2-5 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-11-01 N1 - Last updated - 2013-02-22 N1 - SubjectsTermNotLitGenreText - Statistics; Biometrics DO - http://dx.doi.org/10.1002/1521-4036(200207)44:5<558::AID-BIMJ558>3.0.CO;2-5 ER - TY - JOUR T1 - Mutational Consequences on Replication of M13 Constructs Containing Isomeric Diol Epoxide Adducts in E. coli AN - 19648307; 7394780 AB - Eight isomeric dGuo and eight dAdo adducts resulting from cis and trans opening of each of the four optically active diol epoxides (DEs) derived from benzo[a]pyrene (BaP) and benzo[c]phenanthrene (BcPh) were placed in each of two 16-mer DNA sequences to give 32 modified oligonucleotides, which were ligated into M13mp7L2 and allowed to replicate in SOS-induced Escherichia coli. The effects of parent hydrocarbon, adduct stereochemistry, and sequence context on mutagenic response are highly interdependent. BaP de adducts are generally more mutagenic than the corresponding BcPh adducts. The mutational frequency is generally larger for cis- relative to trans-opened de adducts of both dGuo and dAdo. In a simTAGsim context, BcPh de dAdo adducts (A) with R configuration at the site of attachment to the adenine base produced very few substitution mutations when compared with adducts having S configuration. This configurational effect is not observed for BaP de dAdo adducts, nor for BaP or BcPh dGuo adducts. JF - Polycyclic Aromatic Compounds AU - Sayer, J M AU - Kroth, H AU - Yagi, H AU - Kalena, G AU - Jerina, D M AU - Ramos, L A AU - Dipple, A AU - Ponten, I AU - Goodman, M F AD - Laboratory of Bioorganic Chemistry, NIDDK, The National Institutes of Health, Bethesda, Maryland, USA Y1 - 2002/07// PY - 2002 DA - Jul 2002 SP - 871 EP - 879 PB - Taylor & Francis Ltd., 11 New Fetter Lane London EC4P 4EE UK, [mailto:info@tandf.co.uk], [URL:http://www.tandf.co.uk] VL - 22 IS - 3 SN - 1040-6638, 1040-6638 KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - benzo[a]pyrene KW - benzo[c]phenanthrene KW - DNA adducts KW - Escherichia coli KW - M13 KW - mutagenesis KW - Epoxides KW - Amino acid substitution KW - Replication KW - Hydrocarbons KW - Adducts KW - Nucleotide sequence KW - Oligonucleotides KW - Stereochemistry KW - Aromatic compounds KW - Adenine KW - Benzo(a)pyrene KW - J 02310:Genetics & Taxonomy KW - N 14820:DNA Metabolism & Structure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19648307?accountid=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=Polycyclic+Aromatic+Compounds&rft.atitle=Mutational+Consequences+on+Replication+of+M13+Constructs+Containing+Isomeric+Diol+Epoxide+Adducts+in+E.+coli&rft.au=Sayer%2C+J+M%3BKroth%2C+H%3BYagi%2C+H%3BKalena%2C+G%3BJerina%2C+D+M%3BRamos%2C+L+A%3BDipple%2C+A%3BPonten%2C+I%3BGoodman%2C+M+F&rft.aulast=Sayer&rft.aufirst=J&rft.date=2002-07-01&rft.volume=22&rft.issue=3&rft.spage=871&rft.isbn=&rft.btitle=&rft.title=Polycyclic+Aromatic+Compounds&rft.issn=10406638&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-06-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Epoxides; Aromatic compounds; Amino acid substitution; Hydrocarbons; Replication; Nucleotide sequence; Adducts; Adenine; Benzo(a)pyrene; Oligonucleotides; Stereochemistry; Escherichia coli ER - TY - JOUR T1 - Feasibility and assessment of non-invasive in vivo redox status using electron paramagnetic resonance imaging AN - 19614814; 7331227 AB - Purpose: To test the feasibility of electron paramagnetic resonance imaging (EPRI) to provide non-invasive images of tissue redox status using redox- sensitive paramagnetic contrast agents. Material and Methods: Nitroxide free radicals were used as paramagnetic agents and a custom-built 300 MHz EPR spectrometer/imager was used for all studies. A phantom was constructed consisting of four tubes containing equal concentrations of a nitroxide. Varying concentrations of hypoxanthine/xanthine oxidase were added to each tube and reduction of the nitroxide was monitored by EPR as a function of time. Tumor- bearing mice were intravenously infused with a nitroxide and the corresponding reduction rate was monitored on a pixel-by-pixel basis using 2D EPR of the tumor- bearing leg and normal leg serving as control. For animal studies, nitroxides were injected intravenously (1.25 mmol/kg) and EPR projections were collected every 3 min after injection using a magnetic field gradient of 2.5 G/cm. The reduction rates of signal intensity on a pixel-by-pixel basis were calculated and plotted as a redox map. Redox maps were also collected from the mice treated with diethylmaleate (DEM), which depletes tissue thiols and alters the global redox status. Results: Redox maps obtained from the phantoms were in agreement with the intensity change in each of the tubes where the signals were decreasing as a function of the enzymatic activity, validating the ability of EPRI to accurately access changes in nitroxide reduction. Redox imaging capability of EPR was next evaluated in vivo. EPR images of the nitroxide distribution and reduction rates in tumor-bearing leg of mice exhibited more heterogeneity than in the normal tissue. Reduction rates were found to be significantly decreased in tumors of mice treated with DEM, consistent with the depletion of thiols and the consequent alteration of the redox status. Conclusion: Using redox- sensitive paramagnetic contrast agents, EPRI can non-invasively discriminate redox status differences between normal tissue and tumors. JF - Acta Radiologica AU - K.-I. Yamada AU - Kuppusamy, P AU - English, S AU - Yoo, J AU - Irie, A AU - Subramanian, S AU - Mitchell, J B AU - Krishna, M C AD - Radiation Biology Branch, National Cancer Institute, NIH, Bethesda, MD Y1 - 2002/07// PY - 2002 DA - Jul 2002 SP - 433 EP - 440 PB - Blackwell Publishing Ltd., 9600 Garsington Road Oxford OX4 2DQ UK, [URL:http://www.blackwellpublishing.com] VL - 43 IS - 4 SN - 0284-1851, 0284-1851 KW - Biotechnology and Bioengineering Abstracts KW - Tumor KW - redox status KW - thiols KW - nitroxides KW - electron paramagnetic resonance imaging KW - experimental KW - E.S.R. KW - Free radicals KW - Magnetic resonance imaging KW - Tumors KW - Leg KW - Magnetic fields KW - Xanthine oxidase KW - Computed tomography KW - Thiols KW - Hypoxanthine KW - Contrast media KW - Enzymatic activity KW - Nitroxide KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19614814?accountid=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=Acta+Radiologica&rft.atitle=Feasibility+and+assessment+of+non-invasive+in+vivo+redox+status+using+electron+paramagnetic+resonance+imaging&rft.au=K.-I.+Yamada%3BKuppusamy%2C+P%3BEnglish%2C+S%3BYoo%2C+J%3BIrie%2C+A%3BSubramanian%2C+S%3BMitchell%2C+J+B%3BKrishna%2C+M+C&rft.aulast=K.-I.+Yamada&rft.aufirst=&rft.date=2002-07-01&rft.volume=43&rft.issue=4&rft.spage=433&rft.isbn=&rft.btitle=&rft.title=Acta+Radiologica&rft.issn=02841851&rft_id=info:doi/10.1034%2Fj.1600-0455.2002.430418.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-07-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - E.S.R.; Free radicals; Magnetic resonance imaging; Tumors; Leg; Magnetic fields; Thiols; Computed tomography; Xanthine oxidase; Contrast media; Hypoxanthine; Enzymatic activity; Nitroxide DO - http://dx.doi.org/10.1034/j.1600-0455.2002.430418.x ER - TY - JOUR T1 - Generation of NY-ESO-1-specific CD4+ and CD8+ T Cells by a Single Peptide with Dual MHC Class I and Class II Specificities: A New Strategy for Vaccine Design AN - 18754333; 5624578 AB - The existence of overlapping CD8+ and CD4+ T-cell epitopes within certain tumor antigens provides an opportunity to test the hypothesis that relatively short peptides could be used to generate both CD8+ and CD4+ T cells against tumor. In this report, T-cell responses to a fragment of the tumor antigen NY-ESO-1 that contained an HLA-DP4-restricted helper T cell epitope as well as an HLA-A2-restricted cytotoxic T cell epitope were analyzed. One peptide, ESO: 157-170 (SLLMWITQCFLPVF) was recognized by both NY-ESO-1-reactive CD8+ and CD4+ T-cell clones. Both CD4+ and CD8+ T cells were efficiently generated from the peripheral blood of multiple melanoma patients after in vitro stimulations using ESO: 157-170. Dual-specific peptides containing both cytotoxic T-cell and helper T-cell epitopes may represent an attractive strategy of vaccine design aimed at generating tumor-reactive CD4+ and CD8+ T cells. JF - Cancer Research AU - Zeng, G AU - Li, Y AU - El-Gamil, M AU - Sidney, J AU - Sette, A AU - Wang, R-F AU - Rosenberg, SA AU - Robbins, P F AD - Surgery Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA Y1 - 2002/07/01/ PY - 2002 DA - 2002 Jul 01 SP - 3630 EP - 3635 VL - 62 IS - 13 SN - 0008-5472, 0008-5472 KW - A2 determinant KW - CD4 antigen KW - CD8 antigen KW - DP4 determinant KW - NY-ESO-1 antigen KW - histocompatibility antigen HLA KW - man KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33350:Cancer vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18754333?accountid=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=Generation+of+NY-ESO-1-specific+CD4%2B+and+CD8%2B+T+Cells+by+a+Single+Peptide+with+Dual+MHC+Class+I+and+Class+II+Specificities%3A+A+New+Strategy+for+Vaccine+Design&rft.au=Zeng%2C+G%3BLi%2C+Y%3BEl-Gamil%2C+M%3BSidney%2C+J%3BSette%2C+A%3BWang%2C+R-F%3BRosenberg%2C+SA%3BRobbins%2C+P+F&rft.aulast=Zeng&rft.aufirst=G&rft.date=2002-07-01&rft.volume=62&rft.issue=13&rft.spage=3630&rft.isbn=&rft.btitle=&rft.title=Cancer+Research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Body Composition in Studies of Aging: New Opportunities to Better Understand Health Risks Associated with Weight AN - 18705335; 5594728 AB - The expected increase in the proportion of older persons over the next century underscores the need to identify modifiable risk factors for disease and disability in this population. One such risk factor is weight, which plays a role in many of the diseases common in old age and contributes to risk of disability and death. However, there is confusion and controversy regarding health risks associated with weight in old age. The emergence of new technologies to assess body composition should allow opportunities to better understand health risks associated with weight in old age, as suggested by the new report in this issue of the Journal. While application of these technologies to population studies will still require careful attention to methodological caveats important in studies of weight, the ability to separately examine lean mass, bone, and fat should shed light on the underlying biologic processes pertinent to risk. JF - American Journal of Epidemiology AU - Harris, T B AD - Geriatric Epidemiology Section, Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA Y1 - 2002/07// PY - 2002 DA - Jul 2002 SP - 122 EP - 124 VL - 156 IS - 2 SN - 0002-9262, 0002-9262 KW - Physical Education Index KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18705335?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Epidemiology&rft.atitle=Body+Composition+in+Studies+of+Aging%3A+New+Opportunities+to+Better+Understand+Health+Risks+Associated+with+Weight&rft.au=Harris%2C+T+B&rft.aulast=Harris&rft.aufirst=T&rft.date=2002-07-01&rft.volume=156&rft.issue=2&rft.spage=122&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Epidemiology&rft.issn=00029262&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - An integrative theory of the phasic and tonic modes of dopamine modulation in the prefrontal cortex AN - 18609358; 5469745 AB - This paper presents a model of both tonic and phasic dopamine (DA) effects on maintenance of working memory representations in the prefrontal cortex (PFC). The central hypothesis is that DA modulates the efficacy of inputs to prefrontal pyramidal neurons to prevent interferences for active maintenance. Phasic DA release, due to DA neurons discharges, acts at a short time-scale (a few seconds), while the tonic mode of DA release, independent of DA neurons firing, acts at a long time-scale (a few minutes). The overall effect of DA modulation is modeled as a threshold restricting incoming inputs arriving on PFC neurons. Phasic DA release temporary increases this threshold while tonic DA release progressively increases the basal level of this threshold. Thus, unlike the previous gating theory of phasic DA release, proposing that it facilitates incoming inputs at the time of their arrival, the effect of phasic DA release is supposed to restrict incoming inputs during a period of time after DA neuron discharges. The model links the cellular and behavioral levels during performance of a working memory task. It allows us to understand why a critical range of DA D1 receptors stimulation is required for optimal working memory performance and how D1 receptor agonists (respectively antagonists) increase perseverations (respectively distractability). Finally, the model leads to several testable predictions, including that the PFC regulates DA neurons firing rate to adapt to the delay of the task and that increase in tonic DA release may either improve or decrease performance, depending on the level of DA receptors stimulation at the beginning of the task. JF - Neural Networks AU - Dreher, J-C AU - Burnod, Y AD - Clinical Brain Disorder Branch, National Institute of Mental Health, Room 4C/108, MSC 1440, Bethesda, MD 20892-1440, USA, dreherj@intra.nimh.nih.gov Y1 - 2002/07// PY - 2002 DA - Jul 2002 SP - 583 EP - 602 VL - 15 IS - 4-6 SN - 0893-6080, 0893-6080 KW - firing rate KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; CSA Neurosciences Abstracts KW - N3 11046:Memory and learning KW - W4 340:Neurocomputing & Neural Networks KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18609358?accountid=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=Neural+Networks&rft.atitle=An+integrative+theory+of+the+phasic+and+tonic+modes+of+dopamine+modulation+in+the+prefrontal+cortex&rft.au=Dreher%2C+J-C%3BBurnod%2C+Y&rft.aulast=Dreher&rft.aufirst=J-C&rft.date=2002-07-01&rft.volume=15&rft.issue=4-6&rft.spage=583&rft.isbn=&rft.btitle=&rft.title=Neural+Networks&rft.issn=08936080&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 - Ecteinascidin 743: a novel anticancer drug with a unique mechanism of action AN - 18588849; 5445628 AB - Ecteinascidin 743 (Et743) is an interesting compound in phase II/III clinical trials. Its chemistry is complex, its mechanism of action is original and it is active in human cancers, such as sarcomas refractory to conventional chemotherapy. The present review describes the discovery of the drug, its specific interactions with DNA and its reversible alkylation mechanism with guanine N super(2) in the DNA minor groove. Et743 is a selective transcription inhibitor, which has the unique characteristic of poisoning transcription-coupled nucleotide excision repair. Understanding the molecular pharmacology of Et743 should help in deciding which patients should receive Et743 treatments and which agents should be most useful in association. JF - Anti-Cancer Drugs AU - Aune, G J AU - Furuta, T AU - Pommier, Y AD - Laboratory of Molecular Pharmacology, Center for Cancer Research, Bldg 37, Rm 5068, National Cancer Institute, Bethesda, MD 20892-4255, USA, pommier@nih.gov Y1 - 2002/07// PY - 2002 DA - Jul 2002 SP - 545 EP - 555 VL - 13 IS - 6 SN - 0959-4973, 0959-4973 KW - clinical trials KW - ecteinascidin 743 KW - man KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33374:Antitumor agents KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18588849?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anti-Cancer+Drugs&rft.atitle=Ecteinascidin+743%3A+a+novel+anticancer+drug+with+a+unique+mechanism+of+action&rft.au=Aune%2C+G+J%3BFuruta%2C+T%3BPommier%2C+Y&rft.aulast=Aune&rft.aufirst=G&rft.date=2002-07-01&rft.volume=13&rft.issue=6&rft.spage=545&rft.isbn=&rft.btitle=&rft.title=Anti-Cancer+Drugs&rft.issn=09594973&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Occupation and risk of esophageal and gastric cardia adenocarcinoma AN - 18506993; 5472542 AB - Adenocarcinomas of the esophagus and gastric cardia have risen dramatically in incidence over the past few decades, however, little research has been conducted on the occupational risk factors for these cancers. In this population-based case-control study, lifetime job histories were compared between cases of esophageal adenocarcinoma (n = 283), gastric cardia adenocarcinoma (n = 259), and population controls (n = 689). Odds ratios (OR) and 95% confidence intervals (CI) for ever employment and by duration in various occupational and industrial categories were calculated using unconditional logistic regression. The risk of esophageal adenocarcinoma was elevated for persons ever employed in administrative support (OR = 1.5; 95% CI = 1.0-2.1); financial, insurance, and real estate (OR = 1.6; 95% CI = 1.0-2.4); and health services (OR = 2.2; 95% CI = 1.2-3.9). The risk of gastric cardia adenocarcinoma was increased among transportation workers (OR = 1.7; 95% CI = 1.1-2.6), as well as among carpenters (OR = 1.8; 95% CI = 0.9-3.9) and workers in the furniture manufacturing industry (OR = 2.4; 95% CI = 0.9-6.3). However, we observed few duration-response relations between length of employment in any category and cancer risk. This study revealed associations of esophageal adenocarcinoma with employment in administrative support, health services, and a category of financial, insurance, and real estate industries, and of gastric cardia adenocarcinoma with transportation and certain woodworking occupations. Some of these findings may be due to the play of chance associated with the multiple comparisons made in this study. Our results suggest that, overall, workplace exposures play a minor role in the etiology and upward trend of esophageal and gastric cardia adenocarcinomas. JF - American Journal of Industrial Medicine AU - Engel, L S AU - Vaughan, T L AU - Gammon, MD AU - Chow, Wong-Ho AU - Risch, HA AU - Dubrow, R AU - Mayne, ST AU - Rotterdam, H AU - Schoenberg, J B AU - Stanford, J L AU - West, AB AU - Blot, W J AU - Fraumeni, JF Jr AD - Occupational Epidemiology Branch, National Cancer Institute, 6120 Executive Blvd., Room 8113, Bethesda, MD 20892-7240, USA, engell@mail.nih.gov Y1 - 2002/07// PY - 2002 DA - Jul 2002 SP - 11 EP - 22 VL - 42 IS - 1 SN - 0271-3586, 0271-3586 KW - adenocarcinoma KW - Health & Safety Science Abstracts KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18506993?accountid=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+Industrial+Medicine&rft.atitle=Occupation+and+risk+of+esophageal+and+gastric+cardia+adenocarcinoma&rft.au=Engel%2C+L+S%3BVaughan%2C+T+L%3BGammon%2C+MD%3BChow%2C+Wong-Ho%3BRisch%2C+HA%3BDubrow%2C+R%3BMayne%2C+ST%3BRotterdam%2C+H%3BSchoenberg%2C+J+B%3BStanford%2C+J+L%3BWest%2C+AB%3BBlot%2C+W+J%3BFraumeni%2C+JF+Jr&rft.aulast=Engel&rft.aufirst=L&rft.date=2002-07-01&rft.volume=42&rft.issue=1&rft.spage=11&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Industrial+Medicine&rft.issn=02713586&rft_id=info:doi/10.1002%2Fajim.10077 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1002/ajim.10077 ER - TY - JOUR T1 - Amine-modified random primers to label probes for DNA microarrays AN - 18484299; 5452482 AB - DNA microarrays have been used to study the expression of thousands of genes at the same time in a variety of cells and tissues. The methods most commonly used to label probes for microarray studies require a minimum of 20 mu g of total RNA or 2 mu g of poly (A) RNA. This has made it difficult to study small and rare tissue samples. RNA amplification techniques and improved labeling methods have recently been described. These new procedures and reagents allow the use of less input RNA, but they are relatively time-consuming and expensive. Here we introduce a technique for preparing fluorescent probes that can be used to label as little as 1 mu g of total RNA. The method is based on priming cDNA synthesis with random hexamer oligonucleotides, on the 5' ends of which are bases with free amino groups. These amine-modified primers are incorporated into the cDNA along with aminoallyl nucleotides, and fluorescent dyes are then chemically added to the free amines. The method is simple to execute, and amine-reactive dyes are considerably less expensive than dye-labeled bases or dendrimers. JF - Nature Biotechnology AU - Xiang, C C AU - Kozhich, O A AU - Chen, M AU - Inman, J M AU - Phan, Q N AU - Chen, Y AU - Brownstein, MJ AD - Laboratory of Genetics, National Institute of Mental Health, Bethesda, MD 20892, USA, mike@codon.nih.gov Y1 - 2002/07// PY - 2002 DA - Jul 2002 SP - 738 EP - 742 PB - Nature Publishing Group VL - 20 IS - 7 SN - 1087-0156, 1087-0156 KW - DNA microarrays KW - RNA amplification KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33385:DNA/RNA KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18484299?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Biotechnology&rft.atitle=Amine-modified+random+primers+to+label+probes+for+DNA+microarrays&rft.au=Xiang%2C+C+C%3BKozhich%2C+O+A%3BChen%2C+M%3BInman%2C+J+M%3BPhan%2C+Q+N%3BChen%2C+Y%3BBrownstein%2C+MJ&rft.aulast=Xiang&rft.aufirst=C&rft.date=2002-07-01&rft.volume=20&rft.issue=7&rft.spage=738&rft.isbn=&rft.btitle=&rft.title=Nature+Biotechnology&rft.issn=10870156&rft_id=info:doi/00.1038%2Fnb0702-738 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/00.1038/nb0702-738 ER - TY - JOUR T1 - Acute administration of cocaine regulates the phosphorylation of serine-19, -31 and -40 in tyrosine hydroxylase AN - 18469246; 5434130 AB - Acute cocaine can inhibit catecholamine biosynthesis by regulating the enzymatic activity of tyrosine hydroxylase via alterations in the phosphorylation state of the enzyme. The mechanisms underlying acute cocaine-dependent regulation of tyrosine hydroxylase phosphorylation have not been determined. In this study, 0, 15 or 30 mg/kg cocaine was administered intraperitoneally to rats and the phosphorylation state of tyrosine hydroxylase in the brain was examined using antibodies specific for the phosphorylated forms of serine-19, -31 and -40 in tyrosine hydroxylase. In the caudate and nucleus accumbens, cocaine dose-dependently decreased the levels of phosphorylated serine-19, -31 and -40. In the ventral tegmental area, the levels of phosphorylated serine-19, but not serine-31 and -40, were decreased by 15 and 30 mg/kg cocaine. In the amygdala, the levels of phosphorylated serine-19, but not serine-31 or -40, were decreased. The functional effects of these alterations in phosphorylation state were assessed by measuring tyrosine hydroxylase activity in vivo (accumulation of DOPA after administration of the decarboxylase inhibitor NSD-1015). Acute administration of 30 mg/kg cocaine significantly decreased 1-DOPA production in caudate and accumbens but not in amygdala. These data suggest that the phosphorylation of serine-31 or -40, but not serine-19, is involved in the regulation of tyrosine hydroxylase activity by acute cocaine. JF - Journal of Neurochemistry AU - Jedynak, J P AU - Ali, S F AU - Haycock, J W AU - Hope, B T AD - Behavioral Neuroscience Branch, The National Institute of Drug Abuse, Intramural Research Program, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA, bhope@intra.nida.nih.gov Y1 - 2002/07// PY - 2002 DA - Jul 2002 SP - 382 EP - 388 VL - 82 IS - 2 SN - 0022-3042, 0022-3042 KW - rats KW - CSA Neurosciences Abstracts; Toxicology Abstracts KW - N3 11106:Neurobiology of drug abuse KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18469246?accountid=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+Neurochemistry&rft.atitle=Acute+administration+of+cocaine+regulates+the+phosphorylation+of+serine-19%2C+-31+and+-40+in+tyrosine+hydroxylase&rft.au=Jedynak%2C+J+P%3BAli%2C+S+F%3BHaycock%2C+J+W%3BHope%2C+B+T&rft.aulast=Jedynak&rft.aufirst=J&rft.date=2002-07-01&rft.volume=82&rft.issue=2&rft.spage=382&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Evaluation of the C6 Peptide Enzyme-Linked Immunosorbent Assay for Individuals Vaccinated with the Recombinant OspA Vaccine AN - 18466466; 5430999 AB - The C6 enzyme-linked immunosorbent assay (ELISA), based on a peptide (C6) that reproduces the sequence of invariable region 6 of VlsE, the antigenic variation protein of Borrelia burgdorferi, has been shown to be a sensitive and specific test for the serologic diagnosis of Lyme disease. We now report that none of 29 uninfected individuals vaccinated with the recombinant OspA vaccine had an antibody response to the C6 peptide. The C6 peptide ELISA can be used to diagnose Lyme disease in patients who have received the OspA vaccine. JF - Journal of Clinical Microbiology AU - Marques, A R AU - Martin, D S AU - Philipp, M T AD - Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, Bldg. 10, Room 11N228, 10 Center Dr., Bethesda, MD 20892- 1888., amarques@niaid.nih.gov Y1 - 2002/07// PY - 2002 DA - Jul 2002 SP - 2591 EP - 2593 VL - 40 IS - 7 SN - 0095-1137, 0095-1137 KW - OspA protein KW - VlsE protein KW - double prime C6 peptide KW - antigenic variants KW - invariable region 6 KW - Microbiology Abstracts B: Bacteriology KW - J 02834:Vaccination and immunization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18466466?accountid=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=Evaluation+of+the+C6+Peptide+Enzyme-Linked+Immunosorbent+Assay+for+Individuals+Vaccinated+with+the+Recombinant+OspA+Vaccine&rft.au=Marques%2C+A+R%3BMartin%2C+D+S%3BPhilipp%2C+M+T&rft.aulast=Marques&rft.aufirst=A&rft.date=2002-07-01&rft.volume=40&rft.issue=7&rft.spage=2591&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Microbiology&rft.issn=00951137&rft_id=info:doi/10.1128%2FJCM.40.7.2591-2593.2002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/JCM.40.7.2591-2593.2002 ER - TY - JOUR T1 - The Bacteriophage T4 Transcription Activator MotA Interacts with the Far-C- Terminal Region of the sigma super(70) Subunit of Escherichia coli RNA Polymerase AN - 18455512; 5434937 AB - Transcription from bacteriophage T4 middle promoters uses Escherichia coli RNA polymerase together with the T4 transcriptional activator MotA and the T4 coactivator AsiA. AsiA binds tightly within the C-terminal portion of the sigma super(70) subunit of RNA polymerase, while MotA binds to the 9-bp MotA box motif, which is centered at -30, and also interacts with sigma super(70). We show here that the N-terminal half of MotA (MotA super(NTD)), which is thought to include the activation domain, interacts with the C-terminal region of sigma super(70) in an E. coli two-hybrid assay. Replacement of the C-terminal 17 residues of sigma super(70) with comparable sigma super(38) residues abolishes the interaction with MotA super(NTD) in this assay, as does the introduction of the amino acid substitution R608C. Furthermore, in vitro transcription experiments indicate that a polymerase reconstituted with a sigma super(70) that lacks C-terminal amino acids 604 to 613 or 608 to 613 is defective for MotA-dependent activation. We also show that a proteolyzed fragment of MotA that contains the C-terminal half (MotA super(CTD)) binds DNA with a K sub(D(app)) that is similar to that of full-length MotA. Our results support a model for MotA-dependent activation in which protein- protein contact between DNA-bound MotA and the far-C-terminal region of sigma super(70) helps to substitute functionally for an interaction between sigma super(70) and a promoter -35 element. JF - Journal of Bacteriology AU - Pande, S AU - Makela, A AU - Dove, S L AU - Nickels, B E AU - Hochschild, A AU - Hinton, D M AD - Hochschild, A ; Building 8, Room 2A-13, National Institutes of Health, Bethesda, MD 20892- 0830., dhinton@helix.nih.gov Y1 - 2002/07// PY - 2002 DA - Jul 2002 SP - 3957 EP - 3964 VL - 184 IS - 14 SN - 0021-9193, 0021-9193 KW - AsiA protein KW - MotA protein KW - Biochemistry Abstracts 2: Nucleic Acids; Virology & AIDS Abstracts; Microbiology Abstracts B: Bacteriology KW - N 14721:RNA polymerases KW - J 02750:Phage-host interactions KW - V 22070:Phage-host interactions including lysogeny & transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18455512?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=The+Bacteriophage+T4+Transcription+Activator+MotA+Interacts+with+the+Far-C-+Terminal+Region+of+the+sigma+super%2870%29+Subunit+of+Escherichia+coli+RNA+Polymerase&rft.au=Pande%2C+S%3BMakela%2C+A%3BDove%2C+S+L%3BNickels%2C+B+E%3BHochschild%2C+A%3BHinton%2C+D+M&rft.aulast=Pande&rft.aufirst=S&rft.date=2002-07-01&rft.volume=184&rft.issue=14&rft.spage=3957&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.184.14.3957-3964.2002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/JB.184.14.3957-3964.2002 ER - TY - JOUR T1 - Scalable Purification of Adeno-Associated Virus Type 2, 4, or 5 Using Ion-Exchange Chromatography AN - 18442831; 5419051 AB - The availability of high-titer, high-purity, adeno-associated virus type 2 (AAV2) stocks has dramatically increased our understanding of this virus and its utility as a gene transfer vector. Current methods of purification take advantage of the stable interaction of AAV2 with heparin sulfate. This affinity chromatography, however, is not useful for purifying AAV4 and AAV5, because these serotypes lack heparin-binding activity. We have developed simple ion exchange high-performance liquid chromatography (HPLC) method for purifying different AAV serotypes that does not rely on the affinity of the viruses for heparin. The protocol is fast, efficient, and yields highly infectious material. Analysis of the highly purified virus indicated that more than 90% of the particles contained genomes and were more active than virus purified by cesium chloride (CsCl) gradient purification. This procedure is scalable and can easily be streamlined for large-scale production of recombinant adeno-associated virus (rAAV), regardless of the serotype. Ultimately, the new purification method will further the characterization of rAAV of different serotypes as vectors for gene therapy applications. JF - Human Gene Therapy AU - Kaludov, N AU - Handelman, B AU - Chiorini, JA AD - National Institutes of Health 10/1N113, 10 Center Drive MSC 1190, Bethesda, MD 20902-1190, USA, Jchiorini@dir.nidcr.nih.gov Y1 - 2002/07/01/ PY - 2002 DA - 2002 Jul 01 SP - 1235 EP - 1243 VL - 13 IS - 10 SN - 1043-0342, 1043-0342 KW - cesium chloride KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews KW - W4 120:Genetic Engineering in Medicine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18442831?accountid=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=Scalable+Purification+of+Adeno-Associated+Virus+Type+2%2C+4%2C+or+5+Using+Ion-Exchange+Chromatography&rft.au=Kaludov%2C+N%3BHandelman%2C+B%3BChiorini%2C+JA&rft.aulast=Kaludov&rft.aufirst=N&rft.date=2002-07-01&rft.volume=13&rft.issue=10&rft.spage=1235&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Inhibition of Fusion of Chlamydia trachomatis Inclusions at 32 degree C Correlates with Restricted Export of IncA AN - 18409240; 5393755 AB - Chlamydia trachomatis is an obligate intracellular bacterium that develops within a parasitophorous vacuole termed an inclusion. The inclusion is nonfusogenic with lysosomes but intercepts lipids from a host cell exocytic pathway. Initiation of chlamydial development is concurrent with modification of the inclusion membrane by a set of C. trachomatis-encoded proteins collectively designated Incs. One of these Incs, IncA, is functionally associated with the homotypic fusion of inclusions. Inclusions also do not fuse when cultures are multiply infected with C. trachomatis and cultivated at 32 degree C. We obtained evidence linking these experimental observations by characterizing IncA localization in 32 degree C cultures. Analysis of inclusions by light and transmission electron microscopy confirmed that HeLa cells infected with multiple C. trachomatis elementary bodies and cultivated at 32 degree C for 24 h contained multiple, independent inclusions. Reverse transcriptase PCR and immunoblot analyses of C. trachomatis-infected HeLa cells demonstrated the presence of IncA at 24 h in 32 degree C cultures. When parallel cultures were probed with IncA-specific antibodies in indirect immunofluorescence assays, IncA was detectable in intracellular chlamydiae but not within the inclusion membrane. In addition, analysis of purified reticulate bodies from 37 and 32 degree C cultures showed that bacterium-associated pools of IncA are enriched in cultures grown at 32 degree C. Microscopic observation of infected cells revealed that some vacuoles had fused by 48 h postinfection, and this finding was correlated with the detection of IncA in inclusion membranes by immunofluorescence microscopy. The data are consistent with a requirement for IncA in fusions of C. trachomatis inclusions and suggest that the effect of incubation at 32 degree C is manifested by restricted export of IncA to the inclusion membrane. JF - Infection and Immunity AU - Fields, KA AU - Fischer, E AU - Hackstadt, T AD - Host-Parasite Interactions Section, Laboratory of Intracellular Parasites, National Institute of Allergy and Infectious Diseases, Rocky Mountain Laboratories, Hamilton, MT 59840., Ted_Hackstadt@NIH.GOV Y1 - 2002/07// PY - 2002 DA - Jul 2002 SP - 3816 EP - 3823 VL - 70 IS - 7 SN - 0019-9567, 0019-9567 KW - IncA protein KW - Microbiology Abstracts B: Bacteriology KW - J 02849:Sexually-transmitted diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18409240?accountid=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=Inhibition+of+Fusion+of+Chlamydia+trachomatis+Inclusions+at+32+degree+C+Correlates+with+Restricted+Export+of+IncA&rft.au=Fields%2C+KA%3BFischer%2C+E%3BHackstadt%2C+T&rft.aulast=Fields&rft.aufirst=KA&rft.date=2002-07-01&rft.volume=70&rft.issue=7&rft.spage=3816&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.70.7.3816-3823.2002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/IAI.70.7.3816-3823.2002 ER - TY - JOUR T1 - Chlamydia trachomatis Induces Remodeling of the Actin Cytoskeleton during Attachment and Entry into HeLa Cells AN - 18407097; 5393754 AB - To elucidate the host cell machinery utilized by Chlamydia trachomatis to invade epithelial cells, we examined the role of the actin cytoskeleton in the internalization of chlamydial elementary bodies (EBs). Treatment of HeLa cells with cytochalasin D markedly inhibited the internalization of C. trachomatis serovar L2 and D EBs. Association of EBs with HeLa cells induced localized actin polymerization at the site of attachment, as visualized by either phalloidin staining of fixed cells or the active recruitment of GFP-actin in viable infected cells. The recruitment of actin to the specific site of attachment was accompanied by dramatic changes in the morphology of cell surface microvilli. Ultrastructural studies revealed a transient microvillar hypertrophy that was dependent upon C. trachomatis attachment, mediated by structural components on the EBs, and cytochalasin D sensitive. In addition, a mutant CHO cell line that does not support entry of C. trachomatis serovar L2 did not display such microvillar hypertrophy following exposure to L2 EBs, which is in contrast to infection with serovar D, to which it is susceptible. We propose that C. trachomatis entry is facilitated by an active actin remodeling process that is induced by the attachment of this pathogen, resulting in distinct microvillar reorganization throughout the cell surface and the formation of a pedestal-like structure at the immediate site of attachment and entry. JF - Infection and Immunity AU - Carabeo, R A AU - Grieshaber, S S AU - Fischer, E AU - Hackstadt, T AD - Host-Parasite Interactions Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT 59840., Ted_Hackstadt@NIH.gov Y1 - 2002/07// PY - 2002 DA - Jul 2002 SP - 3793 EP - 3803 VL - 70 IS - 7 SN - 0019-9567, 0019-9567 KW - cytochalasin D KW - Microbiology Abstracts B: Bacteriology KW - J 02849:Sexually-transmitted diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18407097?accountid=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=Chlamydia+trachomatis+Induces+Remodeling+of+the+Actin+Cytoskeleton+during+Attachment+and+Entry+into+HeLa+Cells&rft.au=Carabeo%2C+R+A%3BGrieshaber%2C+S+S%3BFischer%2C+E%3BHackstadt%2C+T&rft.aulast=Carabeo&rft.aufirst=R&rft.date=2002-07-01&rft.volume=70&rft.issue=7&rft.spage=3793&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.70.7.3793-3803.2002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/IAI.70.7.3793-3803.2002 ER - TY - JOUR T1 - Effect of O Acetylation of Neisseria meningitidis Serogroup A Capsular Polysaccharide on Development of Functional Immune Responses AN - 18405069; 5393805 AB - The importance of O-acetyl groups to the immunogenicity of Neisseria meningitidis serogroup A polysaccharide (PS) was examined in studies using human sera and mouse immunization. In 17 of 18 postimmunization human sera, inhibition enzyme-linked immunosorbent assay indicated that the majority of antibodies binding to serogroup A PS were specific for epitopes involving O- acetyl groups. Studies with mice also showed an essential role for O-acetyl groups, where serum bactericidal titers following immunization with de-O- acetylated (de-O-Ac) conjugate vaccine were at least 32-fold lower than those following immunization with O-Ac PS-conjugate vaccine and 4-fold lower than those following immunization with native capsular PS. Inhibition studies using native and de-O-Ac PS confirmed the specificity of murine antibodies to native PS. The dramatic reduction in immunogenicity associated with removal of O-acetyl groups indicates that O acetylation is essential to the immunogenic epitopes of serogroup A PS. Since levels of bactericidal antibodies are correlated with protection against disease, O-acetyl groups appear to be important in protection. JF - Infection and Immunity AU - Berry, D S AU - Lynn, F AU - Lee, C AU - Frasch, CE AU - Bash, M C AD - Division of Bacterial, Parasitic and Allergenic Products, HFM-428, Center for Biologics Evaluation and Research, 1401 Rockville Pike, Rockville, MD 20852., mbash@helix.nih.gov Y1 - 2002/07// PY - 2002 DA - Jul 2002 SP - 3707 EP - 3713 VL - 70 IS - 7 SN - 0019-9567, 0019-9567 KW - mice KW - polysaccharides KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - J 02833:Immune response and immune mechanisms KW - F 06008:Bacteria UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18405069?accountid=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=Effect+of+O+Acetylation+of+Neisseria+meningitidis+Serogroup+A+Capsular+Polysaccharide+on+Development+of+Functional+Immune+Responses&rft.au=Berry%2C+D+S%3BLynn%2C+F%3BLee%2C+C%3BFrasch%2C+CE%3BBash%2C+M+C&rft.aulast=Berry&rft.aufirst=D&rft.date=2002-07-01&rft.volume=70&rft.issue=7&rft.spage=3707&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.70.7.3707-3713.2002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/IAI.70.7.3707-3713.2002 ER - TY - JOUR T1 - Microengineering neocartilage scaffolds AN - 18592397; 5404318 AB - Advances in micropatterning methodologies have made it possible to create structures with precise architecture on the surface of cell culture substrata. We applied these techniques to fabricate microfeatures (15-65 mu m wide; 40 mu m deep) on the surface of a flexible, biocompatible polysaccharide gel. The micropatterned polymer gels were subsequently applied as scaffolds for chondrocyte culture and proved effective in maintaining key aspects of the chondrogenic phenotype. These were rounded cell morphology and a positive and statistically significant (p < 0.0001) immunofluorescence assay for the production of type II collagen throughout the maximum culture time of 10 days after cell seeding. Further, cells housed within individual surface features were observed to proliferate, while serial application of chondrocytes resulted in the formation of cellular aggregates. These methods represent a novel approach to the problem of engineering reparative cartilage in vitro. JF - Biotechnology and Bioengineering AU - Petersen, E F AU - Spencer, RGS AU - McFarland, E W AD - NMR Unit, National Institute on Aging, National Institutes of Health, Gerontology Research Center, Room 4D-06, 5600 Nathan Shock Drive, Baltimore, Maryland 21224, USA, spencer@helix.nih.gov Y1 - 2002/06/30/ PY - 2002 DA - 2002 Jun 30 SP - 802 EP - 805 VL - 78 IS - 7 SN - 0006-3592, 0006-3592 KW - micropatterning KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Bioengineering Abstracts KW - Cartilage KW - Cell culture KW - Immunofluorescence KW - Tissue engineering KW - Collagen KW - Gels KW - Chondrogenesis KW - W 30965:Miscellaneous, Reviews KW - W3 33220:Cell culture KW - W4 110:Biomedical Materials & Tissue Engineering UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18592397?accountid=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=Microengineering+neocartilage+scaffolds&rft.au=Petersen%2C+E+F%3BSpencer%2C+RGS%3BMcFarland%2C+E+W&rft.aulast=Petersen&rft.aufirst=E&rft.date=2002-06-30&rft.volume=78&rft.issue=7&rft.spage=802&rft.isbn=&rft.btitle=&rft.title=Biotechnology+and+Bioengineering&rft.issn=00063592&rft_id=info:doi/10.1002%2Fbit.10256 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cartilage; Tissue engineering; Gels; Chondrogenesis; Cell culture; Immunofluorescence; Collagen DO - http://dx.doi.org/10.1002/bit.10256 ER - TY - JOUR T1 - Relationship between the native-state hydrogen exchange and folding pathways of a four-helix bundle protein. AN - 71821929; 12069590 AB - The hydrogen exchange behavior of a four-helix bundle protein in low concentrations of denaturant reveals some partially unfolded forms that are significantly more stable than the fully unfolded state. Kinetic folding of the protein, however, is apparently two-state in the absence of the accumulation of early folding intermediates. The partially unfolded forms are either as folded as or more folded than the rate-limiting transition state and appear to represent the major intermediates in a folding and unfolding reaction. These results are consistent with the suggestion that partially unfolded intermediates may form after the rate-limiting step for small proteins with apparent two-state folding kinetics. JF - Biochemistry AU - Chu, Ruiai AU - Pei, Wuhong AU - Takei, Jiro AU - Bai, Yawen AD - Laboratory of Biochemistry, Building 37, Room 6114E, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2002/06/25/ PY - 2002 DA - 2002 Jun 25 SP - 7998 EP - 8003 VL - 41 IS - 25 SN - 0006-2960, 0006-2960 KW - Amides KW - 0 KW - Apoproteins KW - Cytochrome b Group KW - Protons KW - Hydrogen KW - 7YNJ3PO35Z KW - Deuterium KW - AR09D82C7G KW - Guanidine KW - JU58VJ6Y3B KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Guanidine -- chemistry KW - Thermodynamics KW - Protein Denaturation -- genetics KW - Kinetics KW - Protein Engineering -- methods KW - Models, Chemical KW - Protein Structure, Secondary -- genetics KW - Hydrogen Bonding KW - Cytochrome b Group -- genetics KW - Apoproteins -- chemistry KW - Hydrogen -- chemistry KW - Protein Folding KW - Apoproteins -- genetics KW - Cytochrome b Group -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71821929?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Relationship+between+the+native-state+hydrogen+exchange+and+folding+pathways+of+a+four-helix+bundle+protein.&rft.au=Chu%2C+Ruiai%3BPei%2C+Wuhong%3BTakei%2C+Jiro%3BBai%2C+Yawen&rft.aulast=Chu&rft.aufirst=Ruiai&rft.date=2002-06-25&rft.volume=41&rft.issue=25&rft.spage=7998&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-12 N1 - Date created - 2002-06-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase is essential for viability in Drosophila melanogaster. AN - 71824800; 11925446 AB - We report the first demonstration that the activity of a member of the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase gene family is necessary for viability in Drosophila melanogaster. Expression of the wild-type recombinant pgant35A gene in COS7 cells resulted in in vitro activity against peptide and glycopeptide substrates, demonstrating that this gene encodes a biochemically active transferase. Previous mutagenesis studies identified recessive lethal mutations that were rescued by a genomic fragment containing the pgant35A gene; however, the presence of additional open reading frames within this fragment left open the possibility that another gene was responsible for rescue of the observed lethality. Here, we have determined the molecular nature of the mutations in three independent mutant alleles. Two of the mutant alleles contain premature stop codons within the coding region of pgant35A. The third mutant contains an arginine to tryptophan amino acid change, which, when expressed in COS7 cells, resulted in a dramatic reduction of transferase activity in vitro. PCR amplification of this gene from Drosophila cDNA panels and Northern analysis revealed that it is expressed throughout embryonic, larval, and pupal stages as well as in adult males and females. This study provides the first direct evidence for the involvement of a member of this conserved multigene family in eukaryotic development and viability. JF - The Journal of biological chemistry AU - Ten Hagen, Kelly G AU - Tran, Duy T AD - Section of Biological Chemistry, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Kelly.Tenhagen@nih.gov Y1 - 2002/06/21/ PY - 2002 DA - 2002 Jun 21 SP - 22616 EP - 22622 VL - 277 IS - 25 SN - 0021-9258, 0021-9258 KW - Codon KW - 0 KW - DNA, Complementary KW - Luminescent Proteins KW - Protein Isoforms KW - Recombinant Fusion Proteins KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Tryptophan KW - 8DUH1N11BX KW - Arginine KW - 94ZLA3W45F KW - N-Acetylgalactosaminyltransferases KW - EC 2.4.1.- KW - polypeptide N-acetylgalactosaminyltransferase KW - EC 2.4.1.41 KW - Index Medicus KW - Animals KW - Blotting, Northern KW - COS Cells KW - Electrophoresis, Polyacrylamide Gel KW - Open Reading Frames KW - Cell Survival KW - Phenotype KW - Recombinant Fusion Proteins -- metabolism KW - Alleles KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Male KW - Homozygote KW - Arginine -- chemistry KW - Amino Acid Sequence KW - Luminescent Proteins -- metabolism KW - Tryptophan -- chemistry KW - Base Sequence KW - DNA, Complementary -- metabolism KW - Drosophila melanogaster KW - Mutation KW - Female KW - N-Acetylgalactosaminyltransferases -- metabolism KW - N-Acetylgalactosaminyltransferases -- chemistry KW - N-Acetylgalactosaminyltransferases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71824800?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+UDP-GalNAc%3Apolypeptide+N-acetylgalactosaminyltransferase+is+essential+for+viability+in+Drosophila+melanogaster.&rft.au=Ten+Hagen%2C+Kelly+G%3BTran%2C+Duy+T&rft.aulast=Ten+Hagen&rft.aufirst=Kelly&rft.date=2002-06-21&rft.volume=277&rft.issue=25&rft.spage=22616&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 - 2002-07-19 N1 - Date created - 2002-06-17 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF478700; GENBANK; AF478699; AF478698; AF478697 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Breast cancer mortality among female radiologic technologists in the United States. AN - 71830873; 12072548 AB - We evaluated breast cancer mortality through 1997 among 69 525 female radiologic technologists who were certified in the United States from 1926 through 1982 and who responded to our questionnaire. Risk of breast cancer mortality was examined according to work history and practices and was adjusted for known risk factors. Breast cancer mortality risk was highest among women who were first employed as radiologic technologists prior to 1940 (relative risk [RR] = 2.92, 95% confidence interval [CI] = 1.22 to 7.00) compared with risk of those first employed in 1960 or later and declined with more recent calendar year of first employment (P for trend =.002). Breast cancer mortality risk increased with increasing number of years of employment as a technologist prior to 1950 (P for trend =.018). However, risk was not associated with the total number of years a woman worked as a technologist. Technologists who first performed fluoroscopy (RR = 1.69, 95% CI = 1.02 to 3.11) and multifilm procedures (RR = 1.87, 95% CI = 1.04 to 3.34) before 1950 had statistically significantly elevated risks compared with technologists who first performed these procedures in 1960 or later. The high risks of breast cancer mortality for women exposed to occupational radiation prior to 1950 and the subsequent decline in risk are consistent with the dramatic reduction in recommended radiation exposure limits over time. JF - Journal of the National Cancer Institute AU - Mohan, Aparna K AU - Hauptmann, Michael AU - Linet, Martha S AU - Ron, Elaine AU - Lubin, Jay H AU - Freedman, D Michal AU - Alexander, Bruce H AU - Boice, John D AU - Doody, Michele Morin AU - Matanoski, Genevieve M AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7244, USA. mohan@cber.fda.gov Y1 - 2002/06/19/ PY - 2002 DA - 2002 Jun 19 SP - 943 EP - 948 VL - 94 IS - 12 SN - 0027-8874, 0027-8874 KW - Index Medicus KW - Risk KW - Risk Factors KW - Humans KW - United States -- epidemiology KW - Female KW - Occupational Exposure KW - Allied Health Personnel KW - Breast Neoplasms -- mortality KW - Radiography UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71830873?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Breast+cancer+mortality+among+female+radiologic+technologists+in+the+United+States.&rft.au=Mohan%2C+Aparna+K%3BHauptmann%2C+Michael%3BLinet%2C+Martha+S%3BRon%2C+Elaine%3BLubin%2C+Jay+H%3BFreedman%2C+D+Michal%3BAlexander%2C+Bruce+H%3BBoice%2C+John+D%3BDoody%2C+Michele+Morin%3BMatanoski%2C+Genevieve+M&rft.aulast=Mohan&rft.aufirst=Aparna&rft.date=2002-06-19&rft.volume=94&rft.issue=12&rft.spage=943&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 - 2002-07-24 N1 - Date created - 2002-06-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Minimum number of 2'-O-(2-aminoethyl) residues required for gene knockout activity by triple helix forming oligonucleotides. AN - 71808029; 12056903 AB - Triple helix forming oligonucleotides (TFOs) that bind chromosomal targets in living cells may become tools for genome manipulation, including gene knockout, conversion, or recombination. However, triplex formation by DNA third strands, particularly those in the pyrimidine motif, requires nonphysiological pH and Mg(2+) concentration, and this limits their development as gene-targeting reagents. Recent advances in oligonucleotide chemistry promise to solve these problems. For this study TFOs containing 2'-O-methoxy (2'-OMe) and 2'-O-(2-aminoethyl) (2'-AE) ribose substitutions in varying proportion have been constructed. The TFOs were linked to psoralen and designed to target and mutagenize a site in the hamster HPRT gene. T(m) analyses showed that triplexes formed by these TFOs were more stable than the underlying duplex, regardless of 2'-OMe/2'-AE ratio. However, TFOs with 2'-AE residues were more stable in physiological pH than those with only 2'-OMe sugars, as a simple function of 2'-AE content. In contrast, gene knockout assays revealed a threshold requirement--TFOs with three or four 2'-AE residues were at least 10-fold more active than the TFO with two 2'-AE residues. The HPRT knockout frequencies with the most active TFOs were 300-400-fold above the background, whereas there was no activity against the APRT gene, a monitor of nonspecific mutagenesis. JF - Biochemistry AU - Puri, Nitin AU - Majumdar, Alokes AU - Cuenoud, Bernard AU - Natt, Francois AU - Martin, Pierre AU - Boyd, Andre AU - Miller, Paul S AU - Seidman, Michael M AD - Laboratory of Molecular Gerontology, National Institutes on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 2002/06/18/ PY - 2002 DA - 2002 Jun 18 SP - 7716 EP - 7724 VL - 41 IS - 24 SN - 0006-2960, 0006-2960 KW - Oligonucleotides KW - 0 KW - triplex DNA KW - Ribose KW - 681HV46001 KW - Cytosine KW - 8J337D1HZY KW - DNA KW - 9007-49-2 KW - Hypoxanthine Phosphoribosyltransferase KW - EC 2.4.2.8 KW - Thymidine KW - VC2W18DGKR KW - Index Medicus KW - Ribose -- analogs & derivatives KW - Hot Temperature KW - Animals KW - Electroporation KW - Cytosine -- chemistry KW - Cricetulus KW - Thymidine -- chemistry KW - Ribose -- chemistry KW - CHO Cells KW - Cytosine -- analogs & derivatives KW - Thymidine -- analogs & derivatives KW - Cricetinae KW - Hypoxanthine Phosphoribosyltransferase -- genetics KW - Gene Targeting -- methods KW - Oligonucleotides -- chemistry KW - DNA -- chemistry KW - Nucleic Acid Conformation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71808029?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Minimum+number+of+2%27-O-%282-aminoethyl%29+residues+required+for+gene+knockout+activity+by+triple+helix+forming+oligonucleotides.&rft.au=Puri%2C+Nitin%3BMajumdar%2C+Alokes%3BCuenoud%2C+Bernard%3BNatt%2C+Francois%3BMartin%2C+Pierre%3BBoyd%2C+Andre%3BMiller%2C+Paul+S%3BSeidman%2C+Michael+M&rft.aulast=Puri&rft.aufirst=Nitin&rft.date=2002-06-18&rft.volume=41&rft.issue=24&rft.spage=7716&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-26 N1 - Date created - 2002-06-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of an in situ disulfide cross-linking strategy to map proximities between amino acid residues in transmembrane domains I and VII of the M3 muscarinic acetylcholine receptor. AN - 71795801; 12056896 AB - In this study, we employed an in situ disulfide cross-linking strategy to gain insight into the structure of the inactive and active state of the M(3) muscarinic acetylcholine receptor. Specifically, this study was designed to identify residues in TM I that are located in close to Cys532 (position 7.42), an endogenous cysteine residue present in the central portion of TM VII. Cysteine residues were substituted, one at a time, into 10 consecutive positions of TM I (Ala71-Val80) of a modified version of the M(3) muscarinic receptor that lacked most endogenous cysteine residues and contained a factor Xa cleavage site within the third intracellular loop. Following their expression in COS-7 cells, the 10 resulting cysteine mutant receptors were oxidized in their native membrane environment, either in the absence or in the presence of muscarinic ligands. Disulfide cross-link formation was monitored by examining changes in the electrophoretic mobility of oxidized and factor Xa-digested receptors on SDS gels. When molecular iodine was used as the oxidizing agent, the L77C receptor (position 1.42) was the only mutant receptor that displayed significant disulfide cross-linking, either in the absence or in the presence of muscarinic agonists or antagonists. On the other hand, when the Cu(II)-(1,10-phenanthroline)(3) complex served as the redox catalyst, muscarinic ligands inhibited disulfide cross-linking of the L77C receptor, probably because of impaired access of this relatively bulky oxidizing agent to the ligand binding crevice. The iodine cross-linking data suggest that M(3) muscarinic receptor activation is not associated with significant changes in the relative orientations of the outer and/or central segments of TM I and VII. In bovine rhodopsin, the residues present at the positions corresponding to Cys532 and Leu77 in the rat M(3) muscarinic receptor are not located directly adjacent to each other, raising the possibility that the relative orientations of TM I and VII are not identical among different class I GPCRs. Alternatively, dynamic protein backbone fluctuation may occur, enabling Cys532 to move within cross-linking distance of Leu77 (Cys77). JF - Biochemistry AU - Hamdan, Fadi F AU - Ward, Stuart D C AU - Siddiqui, Nasir A AU - Bloodworth, Lanh M AU - Wess, Jürgen AD - Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 8 Center Drive, Bethesda, Maryland 20892, USA. Y1 - 2002/06/18/ PY - 2002 DA - 2002 Jun 18 SP - 7647 EP - 7658 VL - 41 IS - 24 SN - 0006-2960, 0006-2960 KW - Cross-Linking Reagents KW - 0 KW - Disulfides KW - Ligands KW - Muscarinic Agonists KW - Muscarinic Antagonists KW - Peptide Fragments KW - Phosphatidylinositols KW - Receptor, Muscarinic M3 KW - Receptors, Muscarinic KW - Sulfhydryl Compounds KW - methanethiosulfonate ethylammonium KW - Tritium KW - 10028-17-8 KW - Ethyl Methanesulfonate KW - 9H154DI0UP KW - Cysteine KW - K848JZ4886 KW - Alanine KW - OF5P57N2ZX KW - N-Methylscopolamine KW - VDR09VTQ8U KW - Index Medicus KW - Phosphatidylinositols -- metabolism KW - Animals KW - COS Cells KW - Cysteine -- genetics KW - Protein Structure, Tertiary -- drug effects KW - Amino Acid Sequence KW - Rats KW - Mutagenesis, Site-Directed KW - Protein Structure, Tertiary -- genetics KW - Transfection KW - Sulfhydryl Compounds -- chemistry KW - Binding Sites -- drug effects KW - Muscarinic Agonists -- pharmacology KW - Muscarinic Antagonists -- pharmacology KW - Molecular Sequence Data KW - Alanine -- genetics KW - Hydrolysis -- drug effects KW - N-Methylscopolamine -- metabolism KW - Ethyl Methanesulfonate -- analogs & derivatives KW - Peptide Mapping -- methods KW - Receptors, Muscarinic -- genetics KW - Peptide Fragments -- genetics KW - Receptors, Muscarinic -- chemistry KW - Peptide Fragments -- physiology KW - Peptide Fragments -- biosynthesis KW - Cross-Linking Reagents -- chemistry KW - Disulfides -- chemistry KW - Peptide Fragments -- chemistry KW - Ethyl Methanesulfonate -- pharmacology KW - Receptors, Muscarinic -- physiology KW - Receptors, Muscarinic -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71795801?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Use+of+an+in+situ+disulfide+cross-linking+strategy+to+map+proximities+between+amino+acid+residues+in+transmembrane+domains+I+and+VII+of+the+M3+muscarinic+acetylcholine+receptor.&rft.au=Hamdan%2C+Fadi+F%3BWard%2C+Stuart+D+C%3BSiddiqui%2C+Nasir+A%3BBloodworth%2C+Lanh+M%3BWess%2C+J%C3%BCrgen&rft.aulast=Hamdan&rft.aufirst=Fadi&rft.date=2002-06-18&rft.volume=41&rft.issue=24&rft.spage=7647&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-26 N1 - Date created - 2002-06-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 2001 anthrax crisis in Washington, D.C.: pharmacists' role in screening patients and selecting prophylaxis. AN - 71829260; 12073861 AB - Pharmacists' development and use of a worksheet facilitating their rapid selection of patient-appropriate prophylactic antimicrobials in an anthrax clinic is described. A clinic housed at D.C. General Hospital, in Washington, D.C., treated most of the people--many of them postal workers--who may have been exposed to anthrax in that city during the 2001 anthrax crisis. A form was needed to assist pharmacists in the rapid selection of prophylactic antimicrobials and in patient education and counseling. A team of pharmacists collaborated on the development of a form tailored to the clinical and logistical needs of the operation. The questions on the form were based largely on the two antianthrax agents most likely to be used, ciprofloxacin and doxycycline, and were designed to identify the circumstances that would most frequently require a medication change or a modification of patient education. Yes-or-no check boxes allowed pertinent data to be captured most efficiently. A positive response to any question triggered a personal interview and assessment by a pharmacist. A treatment algorithm was also developed to ensure consistent pharmacist selection of agents in the face of potentially changing policies and staff. The worksheet questions sought to establish treatment objectives, document allergies and concomitant therapies, and identify patients who were pregnant or lactating. Pharmacists developed a patient-screening worksheet that helped determine their choice of treatment for people who may have been exposed to anthrax in Washington, D.C., during the 2001 anthrax crisis. JF - American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists AU - Montello, Michael J AU - Ostroff, Craig AU - Frank, Ellen C AU - Haffer, Andrew S T AU - Rogers, James R AD - PHS-1 Disaster Medical Assistance Team, U.S. Public Health Service (USPHS), Protocol and Information Office, Cancer Therapeutics Evaluation Program, National Cancer Institute, Rockville, MD, USA. montellom@ctep.nci.nih.gov Y1 - 2002/06/15/ PY - 2002 DA - 2002 Jun 15 SP - 1193 EP - 1199 VL - 59 IS - 12 SN - 1079-2082, 1079-2082 KW - Anti-Infective Agents KW - 0 KW - Index Medicus KW - Humans KW - Algorithms KW - Ambulatory Care Facilities KW - Pregnancy KW - Lactation KW - Anti-Infective Agents -- therapeutic use KW - District of Columbia KW - Mass Screening KW - Anti-Infective Agents -- adverse effects KW - Adult KW - Drug Hypersensitivity KW - Female KW - Male KW - Terrorism KW - Anthrax -- transmission KW - Anthrax -- prevention & control KW - Anthrax -- drug therapy KW - Pharmacists UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71829260?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+health-system+pharmacy+%3A+AJHP+%3A+official+journal+of+the+American+Society+of+Health-System+Pharmacists&rft.atitle=2001+anthrax+crisis+in+Washington%2C+D.C.%3A+pharmacists%27+role+in+screening+patients+and+selecting+prophylaxis.&rft.au=Montello%2C+Michael+J%3BOstroff%2C+Craig%3BFrank%2C+Ellen+C%3BHaffer%2C+Andrew+S+T%3BRogers%2C+James+R&rft.aulast=Montello&rft.aufirst=Michael&rft.date=2002-06-15&rft.volume=59&rft.issue=12&rft.spage=1193&rft.isbn=&rft.btitle=&rft.title=American+journal+of+health-system+pharmacy+%3A+AJHP+%3A+official+journal+of+the+American+Society+of+Health-System+Pharmacists&rft.issn=10792082&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-12-03 N1 - Date created - 2002-06-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Am J Health Syst Pharm. 2004 Jun 1;61(11):1167-75 [15237570] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Deficiency of either cyclooxygenase (COX)-1 or COX-2 alters epidermal differentiation and reduces mouse skin tumorigenesis. AN - 71827162; 12067981 AB - Nonsteroidal anti-inflammatory drugs are widely reported to inhibit carcinogenesis in humans and in rodents. These drugs are believed to act by inhibiting one or both of the known isoforms of cyclooxygenase (COX). However, COX-2, and not COX-1, is the isoform most frequently reported to have a key role in tumor development. Here we report that homozygous deficiency of either COX-1 or COX-2 reduces skin tumorigenesis by 75% in a multistage mouse skin model. Reduced tumorigenesis was observed even though the levels of stable 7,12-dimethylbenz(a)anthracene-DNA adducts were increased about 2-fold in the COX-deficient mice compared with wild-type mice. The premature onset of keratinocyte terminal differentiation appeared to be the cellular event leading to the reduced tumorigenesis because keratin 1 and keratin 10, two keratins that indicate the commitment of keratinocytes to differentiate, were expressed 8-13-fold and 10-20-fold more frequently in epidermal basal cells of the COX-1-deficient and COX-2-deficient mice, respectively, than in wild-type mice. Papillomas on the COX-deficient mice also displayed the premature onset of keratinocyte terminal differentiation. However, loricrin, a late marker of epidermal differentiation, was not significantly altered, suggesting that it was the early stages of keratinocyte differentiation that were primarily affected by COX deficiency. Because keratin 5, a keratin associated with basal cells, was detected differently in papillomas of COX-1-deficient as compared with COX-2-deficient mice, it appears that the isoforms do not have identical roles in papilloma development. Interestingly, apoptosis, a cellular process associated with nonsteroidal anti-inflammatory drug-induced inhibition of tumorigenesis, was not significantly altered in the epidermis or in papillomas of the COX-deficient mice. Thus, both COX-1 and COX-2 have roles in keratinocyte differentiation, and we propose that the absence of either isoform causes premature terminal differentiation of initiated keratinocytes and reduced tumor formation. JF - Cancer research AU - Tiano, Howard F AU - Loftin, Charles D AU - Akunda, Jackie AU - Lee, Christopher A AU - Spalding, Judson AU - Sessoms, Alisha AU - Dunson, David B AU - Rogan, Eleanor G AU - Morham, Scott G AU - Smart, Robert C AU - Langenbach, Robert AD - Laboratory of Experimental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2002/06/15/ PY - 2002 DA - 2002 Jun 15 SP - 3395 EP - 3401 VL - 62 IS - 12 SN - 0008-5472, 0008-5472 KW - 7,12-dimethylbenz(a)anthracene-DNA adduct KW - 0 KW - Carcinogens KW - DNA Adducts KW - Isoenzymes KW - Membrane Proteins KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Cyclooxygenase 1 KW - EC 1.14.99.1 KW - Cyclooxygenase 2 KW - Prostaglandin-Endoperoxide Synthases KW - Ptgs1 protein, mouse KW - Dinoprostone KW - K7Q1JQR04M KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Tetradecanoylphorbol Acetate -- toxicity KW - Animals KW - Cell Death -- physiology KW - Papilloma -- pathology KW - Keratinocytes -- drug effects KW - Apoptosis -- physiology KW - Carcinogens -- toxicity KW - Cell Division -- physiology KW - Mice KW - Papilloma -- genetics KW - Papilloma -- enzymology KW - Carcinogens -- metabolism KW - Cell Differentiation -- physiology KW - Keratinocytes -- enzymology KW - Dinoprostone -- metabolism KW - Mice, Inbred C57BL KW - Keratinocytes -- cytology KW - Immunohistochemistry KW - Female KW - Skin -- enzymology KW - Skin Neoplasms -- pathology KW - Skin Neoplasms -- prevention & control KW - Isoenzymes -- genetics KW - Skin Neoplasms -- genetics KW - Prostaglandin-Endoperoxide Synthases -- deficiency KW - Skin Neoplasms -- enzymology KW - 9,10-Dimethyl-1,2-benzanthracene -- analogs & derivatives KW - Isoenzymes -- deficiency KW - Skin -- drug effects KW - 9,10-Dimethyl-1,2-benzanthracene -- toxicity KW - Isoenzymes -- biosynthesis KW - Skin -- cytology KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - 9,10-Dimethyl-1,2-benzanthracene -- metabolism KW - Prostaglandin-Endoperoxide Synthases -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71827162?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Deficiency+of+either+cyclooxygenase+%28COX%29-1+or+COX-2+alters+epidermal+differentiation+and+reduces+mouse+skin+tumorigenesis.&rft.au=Tiano%2C+Howard+F%3BLoftin%2C+Charles+D%3BAkunda%2C+Jackie%3BLee%2C+Christopher+A%3BSpalding%2C+Judson%3BSessoms%2C+Alisha%3BDunson%2C+David+B%3BRogan%2C+Eleanor+G%3BMorham%2C+Scott+G%3BSmart%2C+Robert+C%3BLangenbach%2C+Robert&rft.aulast=Tiano&rft.aufirst=Howard&rft.date=2002-06-15&rft.volume=62&rft.issue=12&rft.spage=3395&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 - 2002-07-19 N1 - Date created - 2002-06-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - KIR2DL4 (CD158d), an NK cell-activating receptor with inhibitory potential. AN - 71799275; 12055234 AB - KIR2DL4 (CD158d) is an unusual member of the killer cell Ig-like receptor family expressed in all NK cells and some T cells. KIR2DL4 activates the cytotoxicity of NK cells, despite the presence of an immunoreceptor tyrosine-based inhibition motif (ITIM) in its cytoplasmic tail. The role of this ITIM on the activating function of KIR2DL4, and whether it can provide inhibitory signals, is not known. Mutated forms of KIR2DL4 were engineered that lacked either the tyrosine in the ITIM or an arginine-tyrosine motif in the transmembrane region that is required for the activation signal. The activity of the mutated KIR2DL4 molecules was tested in a redirected lysis assay. The ITIM was not necessary for activation of lysis by KIR2DL4. The activation signal of KIR2DL4 was sensitive to inhibition by another ITIM-containing receptor. The activation-deficient mutant of KIR2DL4 inhibited the signal delivered by the activating receptor CD16. In pull-down experiments with GST fusion proteins, the tyrosine-phosphorylated cytoplasmic tail of KIR2DL4 bound the Src homology 2-containing phosphatases 1 and 2, as did the tail of the inhibitory receptor KIR2DL1. Therefore, KIR2DL4 has inhibitory potential in addition to its activating function. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Faure, Mathias AU - Long, Eric O AD - Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA. Y1 - 2002/06/15/ PY - 2002 DA - 2002 Jun 15 SP - 6208 EP - 6214 VL - 168 IS - 12 SN - 0022-1767, 0022-1767 KW - Intracellular Signaling Peptides and Proteins KW - 0 KW - KIR2DL4 protein, human KW - Peptide Fragments KW - Receptors, Immunologic KW - Receptors, KIR KW - Receptors, KIR2DL1 KW - Receptors, KIR2DL4 KW - Recombinant Fusion Proteins KW - PTPN11 protein, human KW - EC 3.1.3.48 KW - PTPN6 protein, human KW - Protein Tyrosine Phosphatase, Non-Receptor Type 11 KW - Protein Tyrosine Phosphatase, Non-Receptor Type 6 KW - Protein Tyrosine Phosphatases KW - SH2 Domain-Containing Protein Tyrosine Phosphatases KW - Abridged Index Medicus KW - Index Medicus KW - Vaccinia virus -- immunology KW - Amino Acid Motifs -- immunology KW - Protein Tyrosine Phosphatases -- metabolism KW - Humans KW - Mutagenesis, Site-Directed KW - src Homology Domains -- genetics KW - Cytoplasm -- genetics KW - Cytoplasm -- immunology KW - Genetic Vectors KW - Recombination, Genetic KW - Signal Transduction -- immunology KW - Antibody-Dependent Cell Cytotoxicity -- genetics KW - Vaccinia virus -- genetics KW - Peptide Fragments -- genetics KW - Amino Acid Motifs -- genetics KW - Recombinant Fusion Proteins -- immunology KW - Peptide Fragments -- immunology KW - Protein Binding -- immunology KW - Signal Transduction -- genetics KW - Protein Binding -- genetics KW - src Homology Domains -- immunology KW - Receptors, Immunologic -- genetics KW - Lymphocyte Activation -- genetics KW - Receptors, Immunologic -- physiology KW - Cytotoxicity, Immunologic -- genetics KW - Killer Cells, Natural -- metabolism KW - Receptors, Immunologic -- antagonists & inhibitors KW - Killer Cells, Natural -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71799275?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=KIR2DL4+%28CD158d%29%2C+an+NK+cell-activating+receptor+with+inhibitory+potential.&rft.au=Faure%2C+Mathias%3BLong%2C+Eric+O&rft.aulast=Faure&rft.aufirst=Mathias&rft.date=2002-06-15&rft.volume=168&rft.issue=12&rft.spage=6208&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 - 2002-07-16 N1 - Date created - 2002-06-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Distinct gene expression signatures in the striata of wild-type and heterozygous c-fos knockout mice following methamphetamine administration: evidence from cDNA array analyses. AN - 71716268; 11984857 AB - Methamphetamine (METH) is a drug of abuse which can cause apoptosis and degeneration of monoaminergic terminals in the mammalian brain. c-fos appears to play a protective role against METH-induced damage because METH toxicity is exacerbated in c-fos heterozygous knockout mice. In the present study, we used the comprehensive technique of cDNA array to test the idea that heterozygous c-fos knockout mice might show differential METH-induced molecular responses in comparison to wild-type (WT) animals. Of 1,176 genes examined, the expression of 195 genes in either of the two groups of mice was affected by at least 2-fold at 2 or 12 h after METH treatment. More genes were either up- or downregulated in the WT mice. Moreover, there were substantial differences in the pattern of responses between the two genotypes, with more genes involved in DNA repair and protective processes being upregulated in WT mice after METH administration. These results support the idea that the c-fos knockout genotype may render the animals unable to trigger multicomponent responses in order to protect against the multifaceted toxic effects of this illicit neurotoxin. Copyright 2002 Wiley-Liss, Inc. JF - Synapse (New York, N.Y.) AU - Cadet, Jean Lud AU - McCoy, Michael T AU - Ladenheim, Bruce AD - Molecular Neuropsychiatry Section, Intramural Research Program, NIH/NIDA, PO Box 5180, Baltimore, MD 21224, USA. jcadet@intra.nida.nih.gov Y1 - 2002/06/15/ PY - 2002 DA - 2002 Jun 15 SP - 211 EP - 226 VL - 44 IS - 4 SN - 0887-4476, 0887-4476 KW - DNA Probes KW - 0 KW - Dopamine Uptake Inhibitors KW - Methamphetamine KW - 44RAL3456C KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Phenotype KW - Animals KW - In Situ Hybridization KW - Up-Regulation -- drug effects KW - Mice KW - Down-Regulation -- drug effects KW - Cluster Analysis KW - Male KW - DNA Repair -- drug effects KW - Mice, Knockout KW - Dopamine Uptake Inhibitors -- toxicity KW - Neostriatum -- metabolism KW - Oligonucleotide Array Sequence Analysis KW - Neostriatum -- drug effects KW - DNA -- genetics KW - DNA -- chemistry KW - Genes, fos -- genetics KW - Gene Expression Regulation -- drug effects KW - Methamphetamine -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71716268?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Distinct+gene+expression+signatures+in+the+striata+of+wild-type+and+heterozygous+c-fos+knockout+mice+following+methamphetamine+administration%3A+evidence+from+cDNA+array+analyses.&rft.au=Cadet%2C+Jean+Lud%3BMcCoy%2C+Michael+T%3BLadenheim%2C+Bruce&rft.aulast=Cadet&rft.aufirst=Jean&rft.date=2002-06-15&rft.volume=44&rft.issue=4&rft.spage=211&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 - 2002-06-24 N1 - Date created - 2002-05-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A Physiologically Based Pharmacokinetic Model of p , p '-Dichlorodiphenylsulfone AN - 18417142; 5407691 AB - A physiologically based pharmacokinetic model of the absorption, distribution, metabolism, and elimination of p,p'-dichlorodiphenylsulfone (DDS) in male and female rats and mice is presented. Data used in constructing the model come from single-dose intravenous administration of DDS to male Fischer 344 rats (10 mg/kg, with data taken up to 504 h after administration), from single-dose gavage administration to male rats (10, 100, or 1000 mg/kg, with data up to 72 h after administration), and from chronic feed studies in male and female rats and male and female B6C3F sub(1) mice (studies of duration from 2 weeks up to 18 months, with feed concentrations of DDS up to 300 ppm). The model uses diffusion-limited kinetic for the distribution of the parent compound. Because fewer data are available for the metabolites of DDS (at least five of which are known to exist in the data), the model groups the metabolites into one metabolic pathway and uses simpler flow-limited kinetics for the metabolites. The data show that the kinetics of DDS are nonlinear. Possible sources of nonlinearity considered in the model were nonlinear (Michaelis-Menten) metabolism, nonlinear absorption of DDS from the gut, and induction by DDS of its own metabolism. A model using Michaelis-Menten metabolism was not found to give a significantly better fit than one using first-order linear metabolism, but omitting either of the other nonlinear effects was found to give a significantly poorer fit to the data. Because the data from mice are limited compared to those from rats, there is more confidence in the model's description of DDS kinetics in rats than in its description of kinetics in mice. JF - Toxicology and Applied Pharmacology AU - Parham, F M AU - Matthews, H B AU - Portier, C J AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709, parham@niehs.nih.gov Y1 - 2002/06/15/ PY - 2002 DA - 2002 Jun 15 SP - 153 EP - 163 PB - Academic Press VL - 181 IS - 3 SN - 0041-008X, 0041-008X KW - dichlorodiphenylsulfone KW - mice KW - pharmacokinetics KW - rats KW - Toxicology Abstracts KW - X 24153:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18417142?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+Applied+Pharmacology&rft.atitle=A+Physiologically+Based+Pharmacokinetic+Model+of+p+%2C+p+%27-Dichlorodiphenylsulfone&rft.au=Parham%2C+F+M%3BMatthews%2C+H+B%3BPortier%2C+C+J&rft.aulast=Parham&rft.aufirst=F&rft.date=2002-06-15&rft.volume=181&rft.issue=3&rft.spage=153&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+Applied+Pharmacology&rft.issn=0041008X&rft_id=info:doi/10.1006%2Ftaap.2002.9410 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1006/taap.2002.9410 ER - TY - JOUR T1 - Toxic proteins in neurodegenerative disease. AN - 71821518; 12065827 AB - A broad range of neurodegenerative disorders is characterized by neuronal damage that may be caused by toxic, aggregation-prone proteins. As genes are identified for these disorders and cell culture and animal models are developed, it has become clear that a major effect of mutations in these genes is the abnormal processing and accumulation of misfolded protein in neuronal inclusions and plaques. Increased understanding of the cellular mechanisms for disposal of abnormal proteins and of the effects of toxic protein accumulation on neuronal survival may allow the development of rational, effective treatment for these disorders. JF - Science (New York, N.Y.) AU - Taylor, J Paul AU - Hardy, John AU - Fischbeck, Kenneth H AD - Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA. taylorjp@ninds.nih.gov Y1 - 2002/06/14/ PY - 2002 DA - 2002 Jun 14 SP - 1991 EP - 1995 VL - 296 IS - 5575 KW - Peptides KW - 0 KW - Proteins KW - polyglutamine KW - 26700-71-0 KW - Index Medicus KW - Animals KW - Prion Diseases -- metabolism KW - Alzheimer Disease -- genetics KW - Prion Diseases -- therapy KW - Parkinson Disease -- therapy KW - Amyotrophic Lateral Sclerosis -- genetics KW - Amyotrophic Lateral Sclerosis -- metabolism KW - Humans KW - Parkinson Disease -- metabolism KW - Peptides -- metabolism KW - Trinucleotide Repeat Expansion KW - Parkinson Disease -- pathology KW - Parkinson Disease -- genetics KW - Amyotrophic Lateral Sclerosis -- pathology KW - Tauopathies -- pathology KW - Prion Diseases -- genetics KW - Inclusion Bodies -- metabolism KW - Alzheimer Disease -- therapy KW - Amyotrophic Lateral Sclerosis -- therapy KW - Protein Folding KW - Prion Diseases -- pathology KW - Peptides -- genetics KW - Alzheimer Disease -- metabolism KW - Tauopathies -- metabolism KW - Mutation KW - Tauopathies -- therapy KW - Alzheimer Disease -- pathology KW - Neurodegenerative Diseases -- genetics KW - Proteins -- chemistry KW - Neurons -- metabolism KW - Neurodegenerative Diseases -- metabolism KW - Neurodegenerative Diseases -- pathology KW - Proteins -- metabolism KW - Proteins -- genetics KW - Neurodegenerative Diseases -- therapy KW - Neurons -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71821518?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Toxic+proteins+in+neurodegenerative+disease.&rft.au=Taylor%2C+J+Paul%3BHardy%2C+John%3BFischbeck%2C+Kenneth+H&rft.aulast=Taylor&rft.aufirst=J&rft.date=2002-06-14&rft.volume=296&rft.issue=5575&rft.spage=1991&rft.isbn=&rft.btitle=&rft.title=Science+%28New+York%2C+N.Y.%29&rft.issn=1095-9203&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-15 N1 - Date created - 2002-06-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of low doses of aged and freshly fractured silica on pulmonary inflammation and damage in the rat. AN - 71786255; 12049836 AB - Most previous studies of silica toxicity have used relatively high exposure doses of silica. In this study, male rats received by intratracheal instillation either vehicle, aged or freshly fractured silica at a dose of either 5 microg/rat once a week for 12 weeks (total dose=60 microg) or 20 microg/rat once a week for 12 weeks (total dose=240 microg). One week after the last exposure, bronchoalveolar lavage (BAL) was conducted and markers of pulmonary inflammation, alveolar macrophage (AM) activation and pulmonary damage were examined. For rats exposed to a total of 60 microg silica, both aged and freshly fractured silica increased polymorphonuclear leukocytes (PMN) yield and AM activation above control to a similar degree, but no evidence of pulmonary damage, as measured by BAL fluid lactate dehydrogenase activity or albumin concentration, was detected. For rats exposed to 240 microg silica, aged or freshly fractured silica increased PMN yield and AM activation above control. However, zymosan-stimulated and L-NAME sensitive AM chemiluminescence was greater for rats exposed to freshly fractured silica compared to aged silica. Exposure to 240 microg aged or freshly fractured silica also resulted in pulmonary damage, but the extent of this damage did not differ between the two types of silica. The results suggest that exposure of rats to silica levels far lower than those previously examined can cause pulmonary inflammation. In addition, exposure to freshly fractured silica causes greater generation of reactive oxygen species from AM, measured as AM chemiluminescence, in comparison to aged silica, but there is an apparent threshold below which this difference does not occur. JF - Toxicology AU - Porter, Dale W AU - Barger, Mark AU - Robinson, Victor A AU - Leonard, Stephen S AU - Landsittel, Douglas AU - Castranova, Vincent AD - Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, National Institutes of Health, 1095 Willowdale Road, M/S 2015, Morgantown, WV 26505, USA. dporter@cdc.gov Y1 - 2002/06/14/ PY - 2002 DA - 2002 Jun 14 SP - 63 EP - 71 VL - 175 IS - 1-3 SN - 0300-483X, 0300-483X KW - Albumins KW - 0 KW - Silicon Dioxide KW - 7631-86-9 KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Index Medicus KW - Specific Pathogen-Free Organisms KW - Albumins -- metabolism KW - Animals KW - Neutrophils -- cytology KW - Cell Count KW - Dose-Response Relationship, Drug KW - Rats KW - Rats, Sprague-Dawley KW - Bronchoalveolar Lavage Fluid -- chemistry KW - Bronchoalveolar Lavage Fluid -- cytology KW - L-Lactate Dehydrogenase -- metabolism KW - Macrophages, Alveolar -- cytology KW - Male KW - Pneumonia -- chemically induced KW - Pneumonia -- enzymology KW - Silicon Dioxide -- toxicity KW - Pneumonia -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71786255?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Comparison+of+low+doses+of+aged+and+freshly+fractured+silica+on+pulmonary+inflammation+and+damage+in+the+rat.&rft.au=Porter%2C+Dale+W%3BBarger%2C+Mark%3BRobinson%2C+Victor+A%3BLeonard%2C+Stephen+S%3BLandsittel%2C+Douglas%3BCastranova%2C+Vincent&rft.aulast=Porter&rft.aufirst=Dale&rft.date=2002-06-14&rft.volume=175&rft.issue=1-3&rft.spage=63&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-30 N1 - Date created - 2002-06-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Acute ethanol administration downregulates human immunodeficiency virus-1 glycoprotein 120-induced KC and RANTES production by murine Kupffer cells and splenocytes. AN - 71776254; 12044837 AB - Glycoprotein 120 from HIV-1, HIV-2 and SIV is known to stimulate secretion of chemokines by mononuclear cells. Thus, this work tests the hypothesis that acute ethanol intoxication suppresses HIV-1 gp120-induced chemokine production by murine Kupffer cells and splenocytes. Male Balb/c mice were given ethanol (1.70 g/Kg) by intragastric gavage in 0.1 ml volume of saline. Five minutes after ethanol administration, mice received an intravenous injection of HIV-1 gp120 (5 microg/Kg). After 24 hr, serum samples, splenocytes and Kupffer cells were obtained. Isolated cells were cultured in DMEM for 24 hr to determine production of chemokines and cytokines in vitro. Chemokines (MIP-2, KC, RANTES, MIP-1 alpha and MCP-1) and cytokines (IL-1 beta, TNF alpha, IL-10, gamma-IFN) were measured by ELISA. M-RNA abundance of these mediators was determined by RT-PCR. Results show that HIV-1 gp120 treatment was associated with significant elevations in serum KC and RANTES. No changes were observed with regard to other chemokines and cytokines. Oral administration of ethanol significantly suppressed HIV-1gp120-induced KC and RANTES release. KC and RANTES-mRNA expression and protein release by splenocytes and Kupffer cells were up-regulated by HIV-1 gp120. Such up-regulation was attenuated by ethanol treatment. These data show that acute ethanol administration attenuates HIV-1 gp120-induced chemokine release in vivo by isolated splenocytes and Kupffer cells. Through this mechanism, previous in vivo ethanol use may compromise the ability of HIV-1 gp120 to induce chemokine-mediated inhibition of HIV-1 entry into target cells. JF - Life sciences AU - Bautista, Abraham P AU - Wang, Enze AD - Department of Physiology and NIAAA-Sponsored Alcohol Research Center, Louisiana State University Health Sciences Center in New Orleans, 1901 Perdido Street, Box P7-3, New Orleans, LA 70112-1393, USA. abauti123@cs.com Y1 - 2002/06/14/ PY - 2002 DA - 2002 Jun 14 SP - 371 EP - 382 VL - 71 IS - 4 SN - 0024-3205, 0024-3205 KW - CXCL1 protein, human KW - 0 KW - Chemokine CCL5 KW - Chemokine CXCL1 KW - Chemokines, CXC KW - Chemotactic Factors KW - Cxcl1 protein, mouse KW - Cytokines KW - Growth Substances KW - HIV Envelope Protein gp120 KW - Intercellular Signaling Peptides and Proteins KW - RNA, Messenger KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Animals KW - Drug Interactions KW - Analysis of Variance KW - RNA, Messenger -- metabolism KW - Down-Regulation KW - RNA, Messenger -- drug effects KW - Mice KW - Cytokines -- metabolism KW - Mice, Inbred BALB C KW - Male KW - Growth Substances -- genetics KW - Spleen -- cytology KW - Ethanol -- pharmacology KW - Kupffer Cells -- drug effects KW - Chemotactic Factors -- metabolism KW - Chemokine CCL5 -- metabolism KW - Growth Substances -- metabolism KW - Chemokine CCL5 -- genetics KW - Chemotactic Factors -- genetics KW - HIV Envelope Protein gp120 -- pharmacology KW - Kupffer Cells -- metabolism KW - Spleen -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71776254?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Acute+ethanol+administration+downregulates+human+immunodeficiency+virus-1+glycoprotein+120-induced+KC+and+RANTES+production+by+murine+Kupffer+cells+and+splenocytes.&rft.au=Bautista%2C+Abraham+P%3BWang%2C+Enze&rft.aulast=Bautista&rft.aufirst=Abraham&rft.date=2002-06-14&rft.volume=71&rft.issue=4&rft.spage=371&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 - 2002-07-30 N1 - Date created - 2002-06-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Site-specific cross-linking of human and bovine hemoglobins differentially alters oxygen binding and redox side reactions producing rhombic heme and heme degradation. AN - 71785280; 12044174 AB - Chemically modified human or bovine hemoglobins (Hb) have been developed as oxygen-carrying therapeutics and are currently under clinical evaluation. Oxidative processes, which are in many cases enhanced when modifications are introduced that lower the oxygen affinity, can limit the safety of these proteins. We have carried out a systematic evaluation of two modified human Hbs (O-R-polyHbA(0) and DBBF-Hb) and one bovine Hb (polyHbBv). We have both measured the oxidative products present in the Hb preparations and followed the oxidative reactions during 37 degrees C incubations. Autoxidation, the primary oxidative reaction which initiates the oxidative cascade, is highly correlated with P(50) (R = 0.987; p < 0.002). However, when the results for the other oxidative processes are compared, two different classes of oxidative reactions are identified. The formation of oxyferrylHb, like the rate of autoxidation, increases for all modified Hbs. However, the subsequent reactions, which lead to heme damage and eventually heme degradation, are enhanced for the modified human Hbs but are actually suppressed for bovine-modified Hbs. The rhombic heme measured by electron paramagnetic resonance, which is the initial step that causes irreversible damage to the heme, is found to be a reliable measure of the stability of ferrylHb and has the tendency to produce degradation products. DBBF-Hb, a Hb-based oxygen carrier (HBOC) for which toxic side effects have been well documented, has the highest level of rhombic heme (41-fold greater than for HbA(0)), even though its rate of autoxidation is relatively low. These findings establish the importance of these secondary oxidative reactions over autoxidation in evaluating the toxicity of HBOCs. JF - Biochemistry AU - Nagababu, Enika AU - Ramasamy, Somasundaram AU - Rifkind, Joseph Moses AU - Jia, Yiping AU - Alayash, Abdu I AD - Molecular Dynamics Section, National Institute on Aging/NIH, 5600 Nathan Shock Drive, Baltimore, MD 21224-6823, USA. Y1 - 2002/06/11/ PY - 2002 DA - 2002 Jun 11 SP - 7407 EP - 7415 VL - 41 IS - 23 SN - 0006-2960, 0006-2960 KW - Benzofurans KW - 0 KW - Blood Substitutes KW - Cross-Linking Reagents KW - Dicarboxylic Acids KW - Hemoglobins KW - dibenzofuran-4,6-dicarboxylic acid KW - polyhemoglobin KW - Heme KW - 42VZT0U6YR KW - Methemoglobin KW - 9008-37-1 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Animals KW - Methemoglobin -- chemistry KW - Blood Substitutes -- chemistry KW - Spectrometry, Fluorescence KW - Dicarboxylic Acids -- chemistry KW - Humans KW - Hydrogen Peroxide -- metabolism KW - Binding Sites KW - Oxidation-Reduction KW - Cattle KW - Methemoglobin -- metabolism KW - Blood Substitutes -- metabolism KW - Benzofurans -- metabolism KW - Benzofurans -- chemistry KW - Dicarboxylic Acids -- metabolism KW - Hydrogen Peroxide -- chemistry KW - Cross-Linking Reagents -- chemistry KW - Hemoglobins -- metabolism KW - Oxygen -- metabolism KW - Heme -- chemistry KW - Oxygen -- chemistry KW - Cross-Linking Reagents -- metabolism KW - Hemoglobins -- chemistry KW - Heme -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71785280?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Site-specific+cross-linking+of+human+and+bovine+hemoglobins+differentially+alters+oxygen+binding+and+redox+side+reactions+producing+rhombic+heme+and+heme+degradation.&rft.au=Nagababu%2C+Enika%3BRamasamy%2C+Somasundaram%3BRifkind%2C+Joseph+Moses%3BJia%2C+Yiping%3BAlayash%2C+Abdu+I&rft.aulast=Nagababu&rft.aufirst=Enika&rft.date=2002-06-11&rft.volume=41&rft.issue=23&rft.spage=7407&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-19 N1 - Date created - 2002-06-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retrovirus-Mediated WASP Gene Transfer Corrects Wiskott-Aldrich Syndrome T-Cell Dysfunction AN - 18427691; 5404499 AB - The Wiskott-Aldrich syndrome (WAS) is an X-linked disorder characterized by thrombocytopenia, eczema, and immunodeficiency. At present, the only definitive therapy for the disease is allogeneic bone marrow transplantation (BMT). Because of the frequent lack of suitable donors and the potential severe complications associated with BMT, the development of gene-based therapeutic strategies for WAS is highly desirable. To study whether corrective gene transfer into WAS T cells can lead to restoration of the immunologic defects of WAS, a retroviral vector expressing the WAS protein (WASP) gene was used to transduce human T-lymphotropic virus type 1-transformed T-cell lines and primary T lymphocytes from patients with WAS. After transduction, WAS T cells showed levels of WASP expression similar to those found in cells from normal individuals. In addition, the reconstituted WASP interacted in vitro with proteins containing SH3 domain such as Grb2, PLC- gamma 1, and Fyn, each of which are connected to signaling pathways linked to the actin cytoskeleton. Furthermore, after CD3 cross-linking, transduced WAS T lines showed improvement of actin polymerization and T-cell receptor/CD3 down-regulation. More importantly, primary WAS T lymphocytes transduced with WASP acquired the ability to proliferate in response to anti-CD3 stimulation. These findings suggest that biologic defects of WAS T cells can be corrected in vitro by retrovirus-mediated gene transfer and pose the basis for future investigation of gene therapy as treatment for WAS. JF - Human Gene Therapy AU - Wada, T AU - Jagadeesh, G J AU - Nelson, D L AU - Candotti, F AD - Disorders of Immunity Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, 10 Center Drive, MSC 1851, Building 10, Room 10C103, Bethesda, MD 20852-1851, USA, fabio@nhgri.nih.gov Y1 - 2002/06/10/ PY - 2002 DA - 2002 Jun 10 SP - 1039 EP - 1046 VL - 13 IS - 9 SN - 1043-0342, 1043-0342 KW - WASP protein KW - dysfunction KW - man KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W 30965:Miscellaneous, Reviews KW - W4 120:Genetic Engineering in Medicine KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18427691?accountid=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:dissertation&rft.genre=dissertations+%26+theses&rft.jtitle=&rft.atitle=&rft.au=Duron%2C+Kelly+M.&rft.aulast=Duron&rft.aufirst=Kelly&rft.date=2016-01-01&rft.volume=&rft.issue=&rft.spage=&rft.isbn=978-1321637250&rft.btitle=&rft.title=A+multi-method+approach+to+examining+stress+and+anxiety+among+Mexican+American+college+students&rft.issn=&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 - Crystal structure of shikimate kinase from Mycobacterium tuberculosis reveals the dynamic role of the LID domain in catalysis. AN - 71803952; 12054870 AB - Shikimate kinase (SK) and other enzymes in the shikimate pathway are potential targets for developing non-toxic antimicrobial agents, herbicides, and anti-parasite drugs, because the pathway is essential in the above species but is absent from mammals. The crystal structure of Mycobacterium tuberculosis SK (MtSK) in complex with MgADP has been determined at 1.8 A resolution, revealing critical information for the structure-based design of novel anti-M. tuberculosis agents. MtSK, with a five-stranded parallel beta-sheet flanked by eight alpha-helices, has three domains: the CORE domain, the shikimate-binding domain (SB), and the LID domain. The ADP molecule is bound with its adenine moiety sandwiched between the side-chains of Arg110 and Pro155, its beta-phosphate group in the P-loop, and the alpha and beta-phosphate groups hydrogen bonded to the guanidinium group of Arg117. Arg117 is located in the LID domain, is strictly conserved in SK sequences, is observed for the first time to interact with any bound nucleotide, and appears to be important in both substrate binding and catalysis. The crystal structure of MtSK (this work) and that of Erwinia chrysanthemi SK suggest a concerted conformational change of the LID and SB domains upon nucleotide binding. (c) 2002 Elsevier Science Ltd. JF - Journal of molecular biology AU - Gu, Yijun AU - Reshetnikova, Ludmila AU - Li, Yue AU - Wu, Yan AU - Yan, Honggao AU - Singh, Shivendra AU - Ji, Xinhua AD - Macromolecular Crystallography Laboratory, National Cancer Institute, Frederick, MD 21702, USA. Y1 - 2002/06/07/ PY - 2002 DA - 2002 Jun 07 SP - 779 EP - 789 VL - 319 IS - 3 SN - 0022-2836, 0022-2836 KW - Ligands KW - 0 KW - Aspartic Acid KW - 30KYC7MIAI KW - Platinum KW - 49DFR088MY KW - Adenosine Diphosphate KW - 61D2G4IYVH KW - Arginine KW - 94ZLA3W45F KW - Phosphotransferases (Alcohol Group Acceptor) KW - EC 2.7.1.- KW - shikimate kinase KW - EC 2.7.1.71 KW - Magnesium KW - I38ZP9992A KW - HEPES KW - RWW266YE9I KW - Index Medicus KW - Aspartic Acid -- metabolism KW - Platinum -- metabolism KW - Protein Structure, Secondary KW - Arginine -- metabolism KW - Models, Molecular KW - Amino Acid Sequence KW - Escherichia coli -- enzymology KW - Protein Binding KW - Drug Design KW - Binding Sites KW - Magnesium -- metabolism KW - Sequence Alignment KW - Amino Acid Motifs KW - Kinetics KW - HEPES -- metabolism KW - Molecular Sequence Data KW - Crystallography, X-Ray KW - Protein Structure, Tertiary KW - Hydrogen Bonding KW - Adenosine Diphosphate -- metabolism KW - Catalysis KW - Phosphotransferases (Alcohol Group Acceptor) -- chemistry KW - Mycobacterium tuberculosis -- enzymology KW - Phosphotransferases (Alcohol Group Acceptor) -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71803952?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Crystal+structure+of+shikimate+kinase+from+Mycobacterium+tuberculosis+reveals+the+dynamic+role+of+the+LID+domain+in+catalysis.&rft.au=Gu%2C+Yijun%3BReshetnikova%2C+Ludmila%3BLi%2C+Yue%3BWu%2C+Yan%3BYan%2C+Honggao%3BSingh%2C+Shivendra%3BJi%2C+Xinhua&rft.aulast=Gu&rft.aufirst=Yijun&rft.date=2002-06-07&rft.volume=319&rft.issue=3&rft.spage=779&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 - 2002-07-10 N1 - Date created - 2002-06-10 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 1L4Y; PDB; 1L4U N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A role for mitochondria as potential regulators of cellular life span. AN - 71795090; 12051701 AB - We demonstrate that by simply raising extracellular pyruvate levels, and hence increasing metabolic supply, human diploid fibroblasts undergo a concentration-dependent induction of cellular senescence. Fibroblasts treated with pyruvate undergo a rapid growth arrest accompanied by elevated levels of the cell-cycle regulatory molecules p53, p21, and p16. These cells also exhibit a rise in mitochondrial oxidant production and a fall in intracellular glutathione levels. Exposure of pyruvate treated cells to the antioxidant and glutathione precursor N-acetylcysteine restores cell growth and reverses the increase in senescence-associated beta-galactosidase activity. Similarly, we demonstrate that by increasing mitochondrial number via retroviral-mediated expression of the mitochondrial biogenesis regulator PGC-1 there is also a reduction in cell growth and the more rapid induction of senescence. These results suggest that mitochondria appear to play a central role in regulating cellular life span. (c) 2002 Elsevier Science (USA). JF - Biochemical and biophysical research communications AU - Xu, Dong AU - Finkel, Toren AD - Cardiovascular Branch, NHLBI, NIH, Building 10/6N-240, 10 Center Drive, Bethesda, MD 20892-1622, USA. Y1 - 2002/06/07/ PY - 2002 DA - 2002 Jun 07 SP - 245 EP - 248 VL - 294 IS - 2 SN - 0006-291X, 0006-291X KW - Antioxidants KW - 0 KW - CDKN1A protein, human KW - Cyclin-Dependent Kinase Inhibitor p16 KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - Oxidants KW - Tumor Suppressor Protein p53 KW - Pyruvic Acid KW - 8558G7RUTR KW - beta-Galactosidase KW - EC 3.2.1.23 KW - Acetylcysteine KW - WYQ7N0BPYC KW - Index Medicus KW - Dose-Response Relationship, Drug KW - Humans KW - Cell Division -- drug effects KW - Acetylcysteine -- pharmacology KW - Cyclin-Dependent Kinase Inhibitor p16 -- metabolism KW - Energy Metabolism KW - Tumor Suppressor Protein p53 -- metabolism KW - beta-Galactosidase -- metabolism KW - Antioxidants -- pharmacology KW - Enzyme Activation -- drug effects KW - Cyclins -- metabolism KW - Oxidants -- metabolism KW - Cell Line KW - Fibroblasts -- drug effects KW - Pyruvic Acid -- pharmacology KW - Cell Aging -- physiology KW - Mitochondria -- metabolism KW - Pyruvic Acid -- metabolism KW - Fibroblasts -- cytology KW - Fibroblasts -- metabolism KW - Cell Aging -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71795090?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+role+for+mitochondria+as+potential+regulators+of+cellular+life+span.&rft.au=Xu%2C+Dong%3BFinkel%2C+Toren&rft.aulast=Xu&rft.aufirst=Dong&rft.date=2002-06-07&rft.volume=19&rft.issue=9&rft.spage=799&rft.isbn=&rft.btitle=&rft.title=Aging+%26+Mental+Health&rft.issn=13607863&rft_id=info:doi/10.1080%2F13607863.2014.967659 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-07-16 N1 - Date created - 2002-06-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Macrophage migration inhibitory factor in drug-induced liver injury: a role in susceptibility and stress responsiveness. AN - 71787105; 12051698 AB - Idiosyncratic drug-induced hepatitis may depend upon many factors including a balance between pro- and anti-inflammatory mediator production levels. Using a guinea pig model of liver injury induced by bioactivation of the anesthetic drug, halothane, we found that toxicity was commensurate with an increase in serum macrophage migration inhibitory factor (MIF), a pro-inflammatory signal and counter-regulator of glucocorticoids, but only in susceptible animals. The pathogenic role of MIF was further investigated using a murine model in which liver injury was induced by the reactive metabolite of another drug, acetaminophen (APAP). MIF leakage from the liver into the sera preceded peak increases in toxicity following APAP administration. MIF null (-/-) mice were significantly less susceptible to this toxicity at 8 h. At 48 h following a 300 mg/kg dose, complete lethality was observed in wild-type mice, while 46% survival was noted in MIF-/- mice. The decreased hepatic injury in MIF-/- mice correlated with a reduction in mRNA levels of interferon-gamma and a significant increase in heat shock protein expression, but was unrelated to the APAP-protein adduct formation in the liver. These findings support MIF as a critical pro-toxicant signal in drug-induced liver injury with potentially important and novel effects on heat shock protein responsiveness. (c) 2002 Published by Elsevier Science (USA). JF - Biochemical and biophysical research communications AU - Bourdi, Mohammed AU - Reilly, Timothy P AU - Elkahloun, Abdel G AU - George, John W AU - Pohl, Lance R AD - Molecular and Cellular Toxicology Section, Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, 9000 Rockville Pike, Bldg. 10, Rm. 8N110 Bethesda, MD 20892-1760, USA. bourdim@nih.gov Y1 - 2002/06/07/ PY - 2002 DA - 2002 Jun 07 SP - 225 EP - 230 VL - 294 IS - 2 SN - 0006-291X, 0006-291X KW - Biomarkers KW - 0 KW - Heat-Shock Proteins KW - Inflammation Mediators KW - Macrophage Migration-Inhibitory Factors KW - RNA, Messenger KW - Acetaminophen KW - 362O9ITL9D KW - Interferon-gamma KW - 82115-62-6 KW - Alanine Transaminase KW - EC 2.6.1.2 KW - Halothane KW - UQT9G45D1P KW - Index Medicus KW - Animals KW - Guinea Pigs KW - Disease Progression KW - Disease Models, Animal KW - Liver -- metabolism KW - Liver -- chemistry KW - Mice, Knockout KW - Heat-Shock Proteins -- analysis KW - Biotransformation KW - Liver -- drug effects KW - Interferon-gamma -- metabolism KW - Biomarkers -- blood KW - Male KW - Heat-Shock Proteins -- metabolism KW - Interferon-gamma -- genetics KW - Liver -- pathology KW - Dose-Response Relationship, Drug KW - Mice KW - Inflammation Mediators -- metabolism KW - Alanine Transaminase -- blood KW - Survival Rate KW - RNA, Messenger -- metabolism KW - Biomarkers -- analysis KW - Macrophage Migration-Inhibitory Factors -- deficiency KW - Chemical and Drug Induced Liver Injury -- pathology KW - Macrophage Migration-Inhibitory Factors -- genetics KW - Chemical and Drug Induced Liver Injury -- genetics KW - Genetic Predisposition to Disease KW - Chemical and Drug Induced Liver Injury -- metabolism KW - Macrophage Migration-Inhibitory Factors -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71787105?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Macrophage+migration+inhibitory+factor+in+drug-induced+liver+injury%3A+a+role+in+susceptibility+and+stress+responsiveness.&rft.au=Bourdi%2C+Mohammed%3BReilly%2C+Timothy+P%3BElkahloun%2C+Abdel+G%3BGeorge%2C+John+W%3BPohl%2C+Lance+R&rft.aulast=Bourdi&rft.aufirst=Mohammed&rft.date=2002-06-07&rft.volume=294&rft.issue=2&rft.spage=225&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 - 2002-07-16 N1 - Date created - 2002-06-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Metastable macromolecular complexes containing high mobility group nucleosome-binding chromosomal proteins in HeLa nuclei. AN - 71772718; 11909857 AB - High mobility group nucleosome-binding (HMGN) proteins belong to a family of nuclear proteins that bind to nucleosomes and enhance transcription from chromatin templates by altering the structure of the chromatin fiber. The intranuclear organization of these proteins is dynamic and related to the metabolic state of the cell. Here we report that approximately 50% of the HMGN proteins are organized into macromolecular complexes in a fashion that is similar to that of other nuclear activities that modify the structure of the chromatin fiber. We identify several distinct HMGN-containing complexes that are relatively unstable and find that the inclusion of HMGN in the complexes varies according to the metabolic state of the cell. The nucleosome binding ability of HMGN in the complex is stronger than that of the free HMGN. We suggest that the inclusion of HMGN proteins into metastable multiprotein complexes serves to target the HMGN proteins to specific sites in chromatin and enhances their interaction with nucleosomes. JF - The Journal of biological chemistry AU - Lim, Jae-Hwan AU - Bustin, Michael AU - Ogryzko, Vasily V AU - Postnikov, Yuri V AD - Protein Section, CCR, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2002/06/07/ PY - 2002 DA - 2002 Jun 07 SP - 20774 EP - 20782 VL - 277 IS - 23 SN - 0021-9258, 0021-9258 KW - Amanitins KW - 0 KW - High Mobility Group Proteins KW - Nucleosomes KW - Index Medicus KW - Microscopy, Confocal KW - Chromatography, Affinity KW - HeLa Cells KW - Electrophoresis, Polyacrylamide Gel KW - Amanitins -- pharmacology KW - Humans KW - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization KW - Cell Nucleus -- metabolism KW - Nucleosomes -- metabolism KW - High Mobility Group Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71772718?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Metastable+macromolecular+complexes+containing+high+mobility+group+nucleosome-binding+chromosomal+proteins+in+HeLa+nuclei.&rft.au=Lim%2C+Jae-Hwan%3BBustin%2C+Michael%3BOgryzko%2C+Vasily+V%3BPostnikov%2C+Yuri+V&rft.aulast=Lim&rft.aufirst=Jae-Hwan&rft.date=2002-06-07&rft.volume=277&rft.issue=23&rft.spage=20774&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 - 2002-07-12 N1 - Date created - 2002-06-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structure-based design of beta 1,4-galactosyltransferase I (beta 4Gal-T1) with equally efficient N-acetylgalactosaminyltransferase activity: point mutation broadens beta 4Gal-T1 donor specificity. AN - 71770553; 11916963 AB - beta1,4-Galactosyltransferase I (Gal-T1) normally transfers Gal from UDP-Gal to GlcNAc in the presence of Mn(2+) ion. In the presence of alpha-lactalbumin (LA), the Gal acceptor specificity is altered from GlcNAc to Glc. Gal-T1 also transfers GalNAc from UDP-GalNAc to GlcNAc, but with only approximately 0.1% of Gal-T activity. To understand this low GalNAc-transferase activity, we have carried out the crystal structure analysis of the Gal-T1.LA complex with UDP-GalNAc at 2.1-A resolution. The crystal structure reveals that the UDP-GalNAc binding to Gal-T1 is similar to the binding of UDP-Gal to Gal-T1, except for an additional hydrogen bond formed between the N-acetyl group of GalNAc moiety with the Tyr-289 side chain hydroxyl group. Elimination of this additional hydrogen bond by mutating Tyr-289 residue to Leu, Ile, or Asn enhances the GalNAc-transferase activity. Although all three mutants exhibit enhanced GalNAc-transferase activity, the mutant Y289L exhibits GalNAc-transferase activity that is nearly 100% of its Gal-T activity, even while completely retaining its Gal-T activity. The steady state kinetic analyses on the Leu-289 mutant indicate that the K(m) for GlcNAc has increased compared to the wild type. On the other hand, the catalytic constant (k(cat)) in the Gal-T reaction is comparable with the wild type, whereas it is 3-5-fold higher in the GalNAc-T reaction. Interestingly, in the presence of LA, these mutants also transfer GalNAc to Glc instead of to GlcNAc. The present study demonstrates that, in the Gal-T family, the Tyr-289/Phe-289 residue largely determines the sugar donor specificity. JF - The Journal of biological chemistry AU - Ramakrishnan, Boopathy AU - Qasba, Pradman K AD - Structural Glycobiology Section and Intramural Research Support Program-SAIC, Laboratory of Experimental and Computational Biology, Center for Cancer Research, NCI-Frederick, National Institutes of Health, Frederick, Maryland 21702, USA. Y1 - 2002/06/07/ PY - 2002 DA - 2002 Jun 07 SP - 20833 EP - 20839 VL - 277 IS - 23 SN - 0021-9258, 0021-9258 KW - DNA Primers KW - 0 KW - Galactosyltransferases KW - EC 2.4.1.- KW - N-Acetylgalactosaminyltransferases KW - beta-1,4-galactosyltransferase I KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Cattle KW - Base Sequence KW - Models, Molecular KW - Humans KW - Substrate Specificity KW - Magnetic Resonance Spectroscopy KW - Catalysis KW - Galactosyltransferases -- metabolism KW - N-Acetylgalactosaminyltransferases -- metabolism KW - Galactosyltransferases -- genetics KW - Point Mutation KW - Galactosyltransferases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71770553?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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-based+design+of+beta+1%2C4-galactosyltransferase+I+%28beta+4Gal-T1%29+with+equally+efficient+N-acetylgalactosaminyltransferase+activity%3A+point+mutation+broadens+beta+4Gal-T1+donor+specificity.&rft.au=Ramakrishnan%2C+Boopathy%3BQasba%2C+Pradman+K&rft.aulast=Ramakrishnan&rft.aufirst=Boopathy&rft.date=2002-06-07&rft.volume=277&rft.issue=23&rft.spage=20833&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 - 2002-07-12 N1 - Date created - 2002-06-03 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 1L7W; PDB N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Manganese(II) Induces Apoptotic Cell Death in NIH3T3 Cells via a Caspase-12-dependent Pathway AN - 18395522; 5383424 AB - Under physiological conditions, manganese(II) exhibits catalase-like activity. However, at elevated concentrations, it induces apoptosis via a non-mitochondria-mediated mechanism (Oubrahim, H., Stadtman, E. R., and Chock, P. B. (2001) Proc. Natl. Acad. Sci. U. S. A. 98, 9505-9510). In this study, we show that the Mn(II)-induced apoptosis, as monitored by caspase-3-like activity, in NIH3T3 cells was inhibited by calpain inhibitors I and II or the p38 MAP kinase inhibitor, SB202190. The control experiments showed that each of these inhibitors in the concentration ranges used exerted no effect on activated caspase-3-like activity. Furthermore, caspase-12 was cleaved in Mn(II)-treated cells, suggesting that the Mn(II)-induced apoptosis is mediated by caspase-12. This notion is confirmed by the observations that pretreatment of NIH3T3 cells with either caspase-12 antisense RNA or dsRNA corresponding to the full-length caspase-12 led to a dramatic decrease in caspase-3-like activity induced by Mn(II). The precise mechanism by which Mn(II) induced the apoptosis is not clear. Nevertheless, Mn(II), in part, exerts its effect via its ability to replace Ca(II) in the activation of m-calpain, which in turn activates caspase-12 and degrades Bcl-xL. In addition, the dsRNA sub(i) method serves as an effective technique for knocking out caspase-12 in NIH3T3 cells without causing apoptosis. JF - Journal of Biological Chemistry AU - Oubrahim, H AU - Chock, P B AU - Stadtman, E R AD - Laboratory of Biochemistry, NHLBI, National Institutes of Health, Bethesda, Maryland 20892-8012, USA, erstadtman@nih.gov Y1 - 2002/06/07/ PY - 2002 DA - 2002 Jun 07 SP - 20135 EP - 20138 VL - 277 IS - 23 SN - 0021-9258, 0021-9258 KW - NIH3T3 cells KW - Biochemistry Abstracts 2: Nucleic Acids; Toxicology Abstracts KW - X 24165:Biochemistry KW - N 14560:Antisense research UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18395522?accountid=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=Manganese%28II%29+Induces+Apoptotic+Cell+Death+in+NIH3T3+Cells+via+a+Caspase-12-dependent+Pathway&rft.au=Oubrahim%2C+H%3BChock%2C+P+B%3BStadtman%2C+E+R&rft.aulast=Oubrahim&rft.aufirst=H&rft.date=2002-06-07&rft.volume=277&rft.issue=23&rft.spage=20135&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 - STAT3 activation is required for interleukin-6 induced transformation in tumor-promotion sensitive mouse skin epithelial cells. AN - 71764874; 12037677 AB - STAT3, a member of signal transducers and activators of transcription (STATs) originally discovered as mediators in cytokine signaling pathways, plays an active role in oncogenesis. However, the function of STAT3 in signaling multistage carcinogenesis, especially in transformation of tumor-promotion sensitive epithelial cells has not been elucidated. The present study demonstrates that STAT3 is activated in interleukin-6 induced transformation in mouse skin epithelial cells. DNA binding and transcriptional activities of STAT3 were significantly increased by interleukin-6. This induced anchorage-independent transformation in tumor-promotion sensitive JB6 mouse skin P+ cells but not in the resistant variant P- cells. Two forms of dominant negative STAT3 (mutant of transcriptional domain, mF, or DNA-binding domain, mD) were stably transfected into P+ cells. Activation of STAT3 was abolished and importantly, interleukin-6 induced anchorage-independent growth was absent in both mutant STAT3 transfectants. To determine the genes targeted by STAT3, three matrix metalloproteinase proteins linked with carcinogenesis of epithelial cells were analysed. Both basal and interleukin-6 induced expression of collagenase I and stromelysin I, but not gelatinase A, were inhibited in the mutant STAT3 transfectants. Furthermore, transfection of a wild type STAT3 restored STAT3 transactivation and response to interleukin-6 induced transformation in mutant STAT3 transfectants, which up-regulated collagenase I and stromelysin I as well. Together, these results provide the first evidence that STAT3 activation is required in the progression of multistage carcinogenesis of mouse skin epithelial cells, and matrix metalloproteinases are actively involved in STAT3-mediated cell transformation. JF - Oncogene AU - Yu, Cheng-Yong AU - Wang, Lihua AU - Khaletskiy, Alexander AU - Farrar, William L AU - Larner, Andrew AU - Colburn, Nancy H AU - Li, Jian Jian AD - Laboratory of Experimental Immunology, National Cancer Institute, National Institutes of Health, Frederick, Maryland, MD 21702, USA. Y1 - 2002/06/06/ PY - 2002 DA - 2002 Jun 06 SP - 3949 EP - 3960 VL - 21 IS - 25 SN - 0950-9232, 0950-9232 KW - DNA-Binding Proteins KW - 0 KW - Interleukin-6 KW - RNA, Messenger KW - STAT1 Transcription Factor KW - STAT1 protein, human KW - STAT3 Transcription Factor KW - STAT3 protein, human KW - Stat1 protein, mouse KW - Stat3 protein, mouse KW - Trans-Activators KW - Transcription Factor AP-1 KW - DNA KW - 9007-49-2 KW - Luciferases KW - EC 1.13.12.- KW - Matrix Metalloproteinases KW - EC 3.4.24.- KW - Index Medicus KW - Animals KW - Transcription Factor AP-1 -- metabolism KW - DNA -- metabolism KW - Humans KW - Luciferases -- metabolism KW - Mice KW - Precipitin Tests KW - Reverse Transcriptase Polymerase Chain Reaction KW - Promoter Regions, Genetic KW - RNA, Messenger -- metabolism KW - Transfection KW - Cells, Cultured KW - Molecular Sequence Data KW - Skin -- cytology KW - Matrix Metalloproteinases -- metabolism KW - Signal Transduction KW - Epithelial Cells -- metabolism KW - Trans-Activators -- metabolism KW - Epithelial Cells -- drug effects KW - Trans-Activators -- genetics KW - Cell Transformation, Neoplastic -- metabolism KW - DNA-Binding Proteins -- genetics KW - Cell Transformation, Neoplastic -- drug effects KW - Interleukin-6 -- pharmacology KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71764874?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=STAT3+activation+is+required+for+interleukin-6+induced+transformation+in+tumor-promotion+sensitive+mouse+skin+epithelial+cells.&rft.au=Yu%2C+Cheng-Yong%3BWang%2C+Lihua%3BKhaletskiy%2C+Alexander%3BFarrar%2C+William+L%3BLarner%2C+Andrew%3BColburn%2C+Nancy+H%3BLi%2C+Jian+Jian&rft.aulast=Yu&rft.aufirst=Cheng-Yong&rft.date=2002-06-06&rft.volume=21&rft.issue=25&rft.spage=3949&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-06-21 N1 - Date created - 2002-05-30 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - NM_008607; RefSeq N1 - Last updated - 2017-01-18 ER - TY - CPAPER T1 - Innate immune defense mechanisms involved in the control of HIV replication: Inverse correlation of HIV viremia with NK cell function AN - 39522467; 3672497 AU - Kottilil, S AU - Chun, T W AU - Moir, S AU - Liu, S AU - McLaughlin, M AU - Maldarelli, F AU - Fauci, A S Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39522467?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Innate+immune+defense+mechanisms+involved+in+the+control+of+HIV+replication%3A+Inverse+correlation+of+HIV+viremia+with+NK+cell+function&rft.au=Kottilil%2C+S%3BChun%2C+T+W%3BMoir%2C+S%3BLiu%2C+S%3BMcLaughlin%2C+M%3BMaldarelli%2C+F%3BFauci%2C+A+S&rft.aulast=Kottilil&rft.aufirst=S&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: 9th Conference on Retroviruses and Opportunistic Infections, 115 South Saint Asaph St., Alexandria, VA 22314, USA; phone: 703-535-6862; fax: 703-535-6899; email: info@retroconference.org; URL: 63.126.3.84/2002/default.htm. Paper No. 25 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Poly(ADP-ribose) polymerase role in the repair of topoisomerase L - Induced DNA damage AN - 39508542; 3673928 AU - Barcelo, J M AU - Kholhagen, G AU - Van Hattum, A AU - Simbulan-Rosenthal, C M AU - Smulson, ME AU - Pommier, Y Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39508542?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Poly%28ADP-ribose%29+polymerase+role+in+the+repair+of+topoisomerase+L+-+Induced+DNA+damage&rft.au=Barcelo%2C+J+M%3BKholhagen%2C+G%3BVan+Hattum%2C+A%3BSimbulan-Rosenthal%2C+C+M%3BSmulson%2C+ME%3BPommier%2C+Y&rft.aulast=Barcelo&rft.aufirst=J&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Biological Therapy, 611 East Wells Street, Milwaukee, Wisconsin, USA; phone: 414-271-2456; fax: 414-276-3349; email: info@socbiother.com; URL: www.socbiother.com. Poster Paper No. 3 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Replicative senescence of HIV-specific CD8+ T cells defined by CD57 AN - 39450144; 3672461 AU - Brenchley, J AU - Ambrozak, D AU - Karandikar, N AU - Betts, M AU - Kuruppu, J AU - Douek, D AU - Koup, R Y1 - 2002/06/03/ PY - 2002 DA - 2002 Jun 03 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39450144?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Replicative+senescence+of+HIV-specific+CD8%2B+T+cells+defined+by+CD57&rft.au=Brenchley%2C+J%3BAmbrozak%2C+D%3BKarandikar%2C+N%3BBetts%2C+M%3BKuruppu%2C+J%3BDouek%2C+D%3BKoup%2C+R&rft.aulast=Brenchley&rft.aufirst=J&rft.date=2002-06-03&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: 9th Conference on Retroviruses and Opportunistic Infections, 115 South Saint Asaph St., Alexandria, VA 22314, USA; phone: 703-535-6862; fax: 703-535-6899; email: info@retroconference.org; URL: 63.126.3.84/2002/default.htm. Paper No. 217-T N1 - Last updated - 2010-05-03 ER -