TY - JOUR T1 - Early onset and rapid progression of dominant nonsyndromic DFNA36 hearing loss. AN - 85376474; pmid-15354000 AB - To characterize the auditory and vestibular phenotype of autosomal dominant nonsyndromic DFNA36 hearing loss.Clinical evaluation of individuals with DFNA36 hearing loss linked to the D572N mutation of transmembrane channel-like gene 1 (TMC1). Medical history interviews, physical examinations, and pure-tone air conduction audiometry were performed in the field. Audiology and radiology reports were available and retrospectively reviewed for a subset of subjects.Primary, secondary, and tertiary referral centers (retrospectively reviewed studies); subjects' homes (prospective clinical evaluations).Thirteen affected members of a North American Caucasian family segregating DFNA36 hearing loss.Pure-tone audiometric thresholds and their rates of progression.Subjects had bilateral, symmetric, sensorineural hearing loss with a postlingual onset in the first decade of life. High frequencies were initially affected, followed by rapid progression (5.9 dB/yr for the 0.5/1/2/4-kHz pure-tone average) to profound deafness across all frequencies by the second decade of life. Two individuals had excellent auditory-verbal communication after rehabilitation with cochlear implants placed over two decades after total deafening.DFNA36 has one of the earliest onsets and most rapid rates of progression among the autosomal dominant non-syndromic hearing loss phenotypes. These distinctive features should facilitate its clinical detection and the development of clinical-molecular genetic diagnostic algorithms for dominant nonsyndromic hearing loss. JF - Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology AU - Makishima, Tomoko AU - Kurima, Kiyoto AU - Brewer, Carmen C AU - Griffith, Andrew J AD - Section on Gene Structure and Function, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, Maryland 20850, USA. Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 714 EP - 719 VL - 25 IS - 5 SN - 1531-7129, 1531-7129 KW - Index Medicus KW - National Library of Medicine KW - Adult KW - Age of Onset KW - Aged KW - Audiometry, Pure-Tone KW - *Auditory Threshold: physiology KW - Child KW - Child, Preschool KW - Cross-Sectional Studies KW - Disease Progression KW - Female KW - *Hearing Loss, Sensorineural: genetics KW - Humans KW - Male KW - Middle Aged KW - Pedigree KW - Phenotype KW - Regression Analysis KW - Retrospective Studies UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85376474?accountid=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=Otology+%26+neurotology+%3A+official+publication+of+the+American+Otological+Society%2C+American+Neurotology+Society+%5Band%5D+European+Academy+of+Otology+and+Neurotology&rft.atitle=Early+onset+and+rapid+progression+of+dominant+nonsyndromic+DFNA36+hearing+loss.&rft.au=Makishima%2C+Tomoko%3BKurima%2C+Kiyoto%3BBrewer%2C+Carmen+C%3BGriffith%2C+Andrew+J&rft.aulast=Makishima&rft.aufirst=Tomoko&rft.date=2004-09-01&rft.volume=25&rft.issue=5&rft.spage=714&rft.isbn=&rft.btitle=&rft.title=Otology+%26+neurotology+%3A+official+publication+of+the+American+Otological+Society%2C+American+Neurotology+Society+%5Band%5D+European+Academy+of+Otology+and+Neurotology&rft.issn=15317129&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 - HIV and the kidney: a status report after 20 years. AN - 67291924; 16091230 AB - The first association between HIV-1 infection and kidney disease was made in 1984 and much has been learned over the past 20 years. In recent years, more effective therapies for HIV-1 infection and its associated opportunistic infections have led to improved patient survival. However, with prolonged survival, morbidity associated with renal disease has also increased. Among the multiple glomerulopathies that can affect patients with HIV, focal segmental glomerulosclerosis (FSGS) is most common and frequently leads to end-stage renal disease. Although the precise mechanisms of HIV-associated FSGS remain to be elucidated, it appears that host genetic susceptibility, direct infection of the renal epithelium, and toxicity of one or more viral accessory protein contribute. Therapy for HIV-associated FSGS includes control of blood pressure and the use of angiotensin antagonist therapy. A randomized trial of angiotensin receptor blocker will be initiated shortly. Drug-related nephropathies are also common, manifesting as acute renal failure, nephrolithiasis, and interstitial nephritis. Tenofovir, a newer nucleoside analogue, has recently been implicated in causing tubular toxicity, although the incidence is low. Appropriate screening for renal dysfunction can minimize the likelihood of progressive renal injury in all patients with HIV-1 infection. JF - Current HIV/AIDS reports AU - Cho, Monique E AU - Kopp, Jeffrey B AD - Kidney Disease Section, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health/DHHS, 9000 Rockville Pike, Bethesda, MD 20892, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 109 EP - 115 VL - 1 IS - 3 SN - 1548-3568, 1548-3568 KW - Angiotensin-Converting Enzyme Inhibitors KW - 0 KW - Anti-HIV Agents KW - Antihypertensive Agents KW - Index Medicus KW - Kidney Failure, Chronic -- diagnosis KW - Hypertension, Renal -- etiology KW - Anti-HIV Agents -- therapeutic use KW - Angiotensin-Converting Enzyme Inhibitors -- therapeutic use KW - Kidney Failure, Chronic -- drug therapy KW - HIV Long-Term Survivors KW - Humans KW - Hypertension, Renal -- drug therapy KW - Prognosis KW - Anti-HIV Agents -- adverse effects KW - Kidney Failure, Chronic -- etiology KW - Glomerulosclerosis, Focal Segmental -- drug therapy KW - Glomerulosclerosis, Focal Segmental -- diagnosis KW - AIDS-Associated Nephropathy -- etiology KW - AIDS-Associated Nephropathy -- diagnosis KW - AIDS-Associated Nephropathy -- drug therapy KW - Glomerulosclerosis, Focal Segmental -- etiology KW - HIV-1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67291924?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+HIV%2FAIDS+reports&rft.atitle=HIV+and+the+kidney%3A+a+status+report+after+20+years.&rft.au=Cho%2C+Monique+E%3BKopp%2C+Jeffrey+B&rft.aulast=Cho&rft.aufirst=Monique&rft.date=2004-09-01&rft.volume=1&rft.issue=3&rft.spage=109&rft.isbn=&rft.btitle=&rft.title=Current+HIV%2FAIDS+reports&rft.issn=15483568&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-11-25 N1 - Date created - 2005-08-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Early changes in Huntington's disease patient brains involve alterations in cytoskeletal and synaptic elements. AN - 67286609; 15906159 AB - Huntington's disease (HD) is caused by a polyglutamine repeat expansion in the N-terminus of the huntingtin protein. Huntingtin is normally present in the cytoplasm where it may interact with structural and synaptic elements. The mechanism of HD pathogenesis remains unknown but studies indicate a toxic gain-of-function possibly through aberrant protein interactions. To investigate whether early degenerative changes in HD involve alterations of cytoskeletal and vesicular components, we examined early cellular changes in the frontal cortex of HD presymptomatic (PS), early pathological grade (grade 1) and late-stage (grade 3 and 4) patients as compared to age-matched controls. Morphologic analysis using silver impregnation revealed a progressive decrease in neuronal fiber density and organization in pyramidal cell layers beginning in presymptomatic HD cases. Immunocytochemical analyses for the cytoskeletal markers alpha -tubulin, microtubule-associated protein 2, and phosphorylated neurofilament demonstrated a concomitant loss of staining in early grade cases. Immunoblotting for synaptic proteins revealed a reduction in complexin 2, which was marked in some grade 1 HD cases and significantly reduced in all late stage cases. Interestingly, we demonstrate that two synaptic proteins, dynamin and PACSIN 1, which were unchanged by immunoblotting, showed a striking loss by immunocytochemistry beginning in early stage HD tissue suggesting abnormal distribution of these proteins. We propose that mutant huntingtin affects proteins involved in synaptic function and cytoskeletal integrity before symptoms develop which may influence early disease onset and/or progression. JF - Journal of neurocytology AU - DiProspero, Nicholas A AU - Chen, Er-Yun AU - Charles, Vinod AU - Plomann, Markus AU - Kordower, Jeffrey H AU - Tagle, Danilo A AD - Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA. diprospern@ninds.nih.gov Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 517 EP - 533 VL - 33 IS - 5 SN - 0300-4864, 0300-4864 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - Adaptor Proteins, Vesicular Transport KW - Carrier Proteins KW - HTT protein, human KW - Huntingtin Protein KW - MAP2 protein, human KW - Microtubule-Associated Proteins KW - Nerve Tissue Proteins KW - Neurofilament Proteins KW - Nuclear Proteins KW - PACSIN1 protein, human KW - Tubulin KW - complexin II KW - Dynamins KW - EC 3.6.5.5 KW - Index Medicus KW - Microtubule-Associated Proteins -- metabolism KW - Carrier Proteins -- metabolism KW - Age of Onset KW - Humans KW - Pyramidal Cells -- metabolism KW - Tubulin -- metabolism KW - Neurofilament Proteins -- metabolism KW - Aged KW - Pyramidal Cells -- pathology KW - Dynamins -- metabolism KW - Aged, 80 and over KW - Adult KW - Nerve Tissue Proteins -- metabolism KW - Middle Aged KW - Nuclear Proteins -- metabolism KW - Immunohistochemistry KW - Male KW - Female KW - Huntington Disease -- physiopathology KW - Frontal Lobe -- physiopathology KW - Frontal Lobe -- pathology KW - Cytoskeleton -- metabolism KW - Presynaptic Terminals -- pathology KW - Cytoskeleton -- pathology KW - Huntington Disease -- pathology KW - Presynaptic Terminals -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67286609?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurocytology&rft.atitle=Early+changes+in+Huntington%27s+disease+patient+brains+involve+alterations+in+cytoskeletal+and+synaptic+elements.&rft.au=DiProspero%2C+Nicholas+A%3BChen%2C+Er-Yun%3BCharles%2C+Vinod%3BPlomann%2C+Markus%3BKordower%2C+Jeffrey+H%3BTagle%2C+Danilo+A&rft.aulast=DiProspero&rft.aufirst=Nicholas&rft.date=2004-09-01&rft.volume=33&rft.issue=5&rft.spage=517&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurocytology&rft.issn=03004864&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-08-30 N1 - Date created - 2005-05-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Therapy for unresectable hepatocellular carcinoma: time for XRT? AN - 67047480; 15530257 JF - Cancer journal (Sudbury, Mass.) AU - Pingpank, James F AD - Surgery Branch, Center for Cancer Research, National CancerInstitute, National Institutes of Health, Bethesda, Maryland 20892, USA. james_pingpank@nih.gov PY - 2004 SP - 291 EP - 293 VL - 10 IS - 5 SN - 1528-9117, 1528-9117 KW - Mitomycin KW - 50SG953SK6 KW - Cisplatin KW - Q20Q21Q62J KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Fluorouracil -- administration & dosage KW - Fluorouracil -- adverse effects KW - Radiotherapy, Adjuvant KW - Mitomycin -- adverse effects KW - Humans KW - Radiography KW - Cisplatin -- adverse effects KW - Mitomycin -- administration & dosage KW - Liver Failure -- epidemiology KW - Survival Analysis KW - Cisplatin -- administration & dosage KW - Chemoembolization, Therapeutic -- adverse effects KW - Carcinoma, Hepatocellular -- diagnostic imaging KW - Liver Neoplasms -- therapy KW - Chemoembolization, Therapeutic -- methods KW - Liver Neoplasms -- mortality KW - Carcinoma, Hepatocellular -- therapy KW - Liver Neoplasms -- diagnostic imaging KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Carcinoma, Hepatocellular -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67047480?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+journal+%28Sudbury%2C+Mass.%29&rft.atitle=Therapy+for+unresectable+hepatocellular+carcinoma%3A+time+for+XRT%3F&rft.au=Pingpank%2C+James+F&rft.aulast=Pingpank&rft.aufirst=James&rft.date=2004-09-01&rft.volume=10&rft.issue=5&rft.spage=291&rft.isbn=&rft.btitle=&rft.title=Cancer+journal+%28Sudbury%2C+Mass.%29&rft.issn=15289117&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-17 N1 - Date created - 2004-11-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Cancer J. 2004 Sep-Oct;10(5):307-16 [15530260] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Insights into amyloid structural formation and assembly through computational approaches. AN - 67036428; 15523917 AB - Amyloids are long, insoluble ordered fibers. Due to their insolubility, to date the determination of an amyloid structure with an atomic scale resolution has proven to be a difficult task. Under such circumstances, computational approaches are a preferred option, providing the means to build likely models, test their stabilities and figure out the chemistry of their prevailing interactions. Computational models can be validated by targeted experiments, such as introducing mutations and testing for amyloid formation. Computations further provide vehicles for the comprehension of the mechanisms of amyloid seed formation and oligomer toxicity. Nevertheless, computations face an immense hurdle, the outcome of the time scales involved in amyloid formation and the immense sizes of the systems. In an attempt to overcome these, we adopt a strategy that encompasses (1) bioinformatics studies of native proteins containing beta-sheet structures; (2) simulations of shorter peptides; and finally (3) construction of potential oligomeric models and tests of their stabilities. The results are correlated with experimental data where available. Here, we describe the computational methods in simple terms and present an overview of the results. The systems derive from amyloidogenic, disease-related proteins, including gelsolin, beta2-microglobulin, and peptides derived from the prion, Alzheimer's Abeta, IAPP and human calcitonin. Ultimately, obtaining molecular structures should facilitate efforts to therapy and drug design. JF - Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis AU - Zanuy, David AU - Gunasekaran, K AU - Ma, Buyong AU - Tsai, Hui-Hsu Gavin AU - Tsai, Chung-Jung AU - Nussinov, Ruth AD - Laboratory of Experimental and Computational Biology, NCI-Frederick, Bldg 469, Rm 151, Frederick, MD 21702, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 143 EP - 161 VL - 11 IS - 3 SN - 1350-6129, 1350-6129 KW - Amyloid KW - 0 KW - Index Medicus KW - Animals KW - Protein Structure, Secondary KW - Humans KW - Protein Folding KW - Computational Biology KW - Protein Structure, Tertiary KW - Models, Molecular KW - Amyloid -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67036428?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Amyloid+%3A+the+international+journal+of+experimental+and+clinical+investigation+%3A+the+official+journal+of+the+International+Society+of+Amyloidosis&rft.atitle=Insights+into+amyloid+structural+formation+and+assembly+through+computational+approaches.&rft.au=Zanuy%2C+David%3BGunasekaran%2C+K%3BMa%2C+Buyong%3BTsai%2C+Hui-Hsu+Gavin%3BTsai%2C+Chung-Jung%3BNussinov%2C+Ruth&rft.aulast=Zanuy&rft.aufirst=David&rft.date=2004-09-01&rft.volume=11&rft.issue=3&rft.spage=143&rft.isbn=&rft.btitle=&rft.title=Amyloid+%3A+the+international+journal+of+experimental+and+clinical+investigation+%3A+the+official+journal+of+the+International+Society+of+Amyloidosis&rft.issn=13506129&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-03 N1 - Date created - 2004-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Does the sequence of gemcitabine and vinorelbine affect their efficacy in non-small cell lung cancer in vitro? AN - 67026159; 15517905 AB - We have recently completed a large phase III trial in advanced non-small cell lung cancer (NSCLC) in the elderly which showed that the combination of gemcitabine (GEM) plus vinorelbine (VNR), with GEM administered first, did not improve any outcome as compared with each single drug. The anti-tumor efficacy of different sequences of administration of GEM and VNR was investigated in a small panel of NSCLC cell lines, by using an in vitro cytotoxic assay and isobologram analysis. Treatment of lung cancer cells with GEM followed by VNR resulted in moderate synergism in one cell line (A549), and in antagonism in two cell lines (H838 and H1355). However, treatment of NSCLC cells with VNR followed by GEM resulted in antagonism in all cell lines. The results of this study show that the GEM/VNR combination is not superior to both single agents against NSCLC cells, independently of the schedule of administration of the drugs. JF - Anticancer research AU - De Luca, Antonella AU - Grassii, Michele AU - Maiello, Monica R AU - Di Maio, Massimo AU - Mancino, Mario AU - De Maio, Ermelinda AU - Gridelli, Cesare AU - Perrone, Francesco AU - Normanno, Nicola AD - Department of Experimental Oncology, National Cancer Institute, Fondazione Pascale, Naples, Italy. PY - 2004 SP - 2985 EP - 2989 VL - 24 IS - 5A SN - 0250-7005, 0250-7005 KW - Deoxycytidine KW - 0W860991D6 KW - Vinblastine KW - 5V9KLZ54CY KW - gemcitabine KW - B76N6SBZ8R KW - vinorelbine KW - Q6C979R91Y KW - Index Medicus KW - Drug Administration Schedule KW - Dose-Response Relationship, Drug KW - Humans KW - Cell Line, Tumor KW - Inhibitory Concentration 50 KW - Vinblastine -- analogs & derivatives KW - Deoxycytidine -- analogs & derivatives KW - Lung Neoplasms -- drug therapy KW - Vinblastine -- administration & dosage KW - Deoxycytidine -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Carcinoma, Non-Small-Cell Lung -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67026159?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Does+the+sequence+of+gemcitabine+and+vinorelbine+affect+their+efficacy+in+non-small+cell+lung+cancer+in+vitro%3F&rft.au=De+Luca%2C+Antonella%3BGrassii%2C+Michele%3BMaiello%2C+Monica+R%3BDi+Maio%2C+Massimo%3BMancino%2C+Mario%3BDe+Maio%2C+Ermelinda%3BGridelli%2C+Cesare%3BPerrone%2C+Francesco%3BNormanno%2C+Nicola&rft.aulast=De+Luca&rft.aufirst=Antonella&rft.date=2004-09-01&rft.volume=24&rft.issue=5A&rft.spage=2985&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 - 2004-12-10 N1 - Date created - 2004-11-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High throughput drug screening. AN - 67014172; 15512863 JF - Amyotrophic lateral sclerosis and other motor neuron disorders : official publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases AU - Heemskerk, Jill AD - National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 19 EP - 21 VL - 5 Suppl 1 SN - 1466-0822, 1466-0822 KW - Neurotoxins KW - 0 KW - SOD1 protein, human KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Superoxide Dismutase-1 KW - Index Medicus KW - United States KW - Animals KW - Computer Simulation KW - Drug Therapy KW - Humans KW - National Institutes of Health (U.S.) KW - Apoptosis -- drug effects KW - Superoxide Dismutase -- genetics KW - Neurotoxins -- pharmacology KW - Drug Design KW - Combinatorial Chemistry Techniques -- methods KW - Drug Evaluation, Preclinical -- methods KW - Amyotrophic Lateral Sclerosis -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67014172?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Amyotrophic+lateral+sclerosis+and+other+motor+neuron+disorders+%3A+official+publication+of+the+World+Federation+of+Neurology%2C+Research+Group+on+Motor+Neuron+Diseases&rft.atitle=High+throughput+drug+screening.&rft.au=Heemskerk%2C+Jill&rft.aulast=Heemskerk&rft.aufirst=Jill&rft.date=2004-09-01&rft.volume=5+Suppl+1&rft.issue=&rft.spage=19&rft.isbn=&rft.btitle=&rft.title=Amyotrophic+lateral+sclerosis+and+other+motor+neuron+disorders+%3A+official+publication+of+the+World+Federation+of+Neurology%2C+Research+Group+on+Motor+Neuron+Diseases&rft.issn=14660822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-11 N1 - Date created - 2004-10-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Targeted point mutagenesis of mouse Kcnq1: phenotypic analysis of mice with point mutations that cause Romano-Ward syndrome in humans. AN - 67010192; 15498462 AB - Inherited long QT syndrome is most frequently associated with mutations in KCNQ1, which encodes the primary subunit of a potassium channel. Patients with mutations in KCNQ1 may show only the cardiac defect (Romano-Ward syndrome or RWS) or may also have severe deafness (Jervell and Lange-Nielsen syndrome or JLNS). Targeted disruption of mouse Kcnq1 models JLNS in that mice are deaf and show abnormal ECGs. However, the phenotype is broader than that seen in patients. Most dramatically, the inner ear defects result in a severe hyperactivity/circling behavior, which may influence cardiac function. To understand the etiology of the cardiac phenotype in these mice and to generate a potentially more useful model system, we generated new mouse lines by introducing point mutations associated with RWS. The A340E line phenocopies RWS: the repolarization phenotype is inherited in a dominant manner and is observed independent of any inner ear defect. The T311I line phenocopies JLNS, with deafness associated with inner hair cell malfunction. JF - Genomics AU - Casimiro, Mathew C AU - Knollmann, Bjoern C AU - Yamoah, Ebenezer N AU - Nie, Liping AU - Vary, Jay C AU - Sirenko, Syevda G AU - Greene, Anne E AU - Grinberg, Alexander AU - Huang, Sing Ping AU - Ebert, Steven N AU - Pfeifer, Karl AD - Laboratory of Mammalian Genes and Development, NICHD/National Institutes of Health, Building 6B Room 2B-206, Bethesda, MD 20892, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 555 EP - 564 VL - 84 IS - 3 SN - 0888-7543, 0888-7543 KW - DNA Primers KW - 0 KW - KCNQ Potassium Channels KW - KCNQ1 Potassium Channel KW - Kcnq1 protein, mouse KW - Potassium Channels, Voltage-Gated KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Blotting, Northern KW - Evoked Potentials, Auditory, Brain Stem KW - Electrocardiography KW - Hair Cells, Auditory, Inner -- pathology KW - Deafness -- genetics KW - Phenotype KW - Potassium Channels, Voltage-Gated -- genetics KW - Romano-Ward Syndrome -- genetics KW - Mice -- genetics KW - Disease Models, Animal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67010192?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genomics&rft.atitle=Targeted+point+mutagenesis+of+mouse+Kcnq1%3A+phenotypic+analysis+of+mice+with+point+mutations+that+cause+Romano-Ward+syndrome+in+humans.&rft.au=Casimiro%2C+Mathew+C%3BKnollmann%2C+Bjoern+C%3BYamoah%2C+Ebenezer+N%3BNie%2C+Liping%3BVary%2C+Jay+C%3BSirenko%2C+Syevda+G%3BGreene%2C+Anne+E%3BGrinberg%2C+Alexander%3BHuang%2C+Sing+Ping%3BEbert%2C+Steven+N%3BPfeifer%2C+Karl&rft.aulast=Casimiro&rft.aufirst=Mathew&rft.date=2004-09-01&rft.volume=84&rft.issue=3&rft.spage=555&rft.isbn=&rft.btitle=&rft.title=Genomics&rft.issn=08887543&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-24 N1 - Date created - 2004-10-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemoradiation with gemcitabine for cervical cancer in patients with renal failure. AN - 66987126; 15494637 AB - The prognosis of cervical cancer patients with renal failure secondary to obstructive uropathy is poor. Our objective was to analyze our experience in the management with chemoradiation of untreated cervical cancer patients complicated by obstructive nephropathy and kidney dysfunction. Untreated patients with cervical cancer and renal failure as manifested by raised serum creatinine were treated with pelvic radiotherapy concurrently with weekly gemcitabine at 300 mg/m2. Response, toxicity and renal function pre- and post-therapy were evaluated. Eight FIGO stage IIIB and one IVB patients were treated. Pre-treatment serum creatinine ranged from 1.6 to 18.5 mg/100 ml (median 3.3, mean 6.8) and creatinine clearance varied from 4 to 57 mg/ml/min (median 17, mean 22.1). Four patients had a percutaneous nephrostomy placed and four patients had symptoms from kidney failure. All patient completed chemoradiation. Most patients had grade 3 leukopenia and neutropenia. Dermatitis, colitis and proctitis were common. All patients had improvement in creatinine clearance (pre-therapy 22.78, post-therapy 54.3 mg/ml/min) (p=0.0058) and all but one normalized serum creatinine. Eight (89%) of nine patients achieved complete response and one patient had persistence. At a median follow-up of 11 months (range 6-14), all patients are alive, one with pelvic and another with systemic disease. Ureteral obstruction causing any degree of renal insufficiency should not be a contraindication to receive chemoradiation to attempt cure. In this setting where cisplatin-based therapy is contraindicated, the use of gemcitabine may be considered. JF - Anti-cancer drugs AU - Cetina, Lucely AU - Rivera, Lesbia AU - Candelaria, Myrna AU - de la Garza, Jaime AU - Dueñas-González, Alfonso AD - Division of Clinical Research, National Cancer Institute/Institute of Biomedical Research, National Autonomous University of México. Mexico City, Mexico. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 761 EP - 766 VL - 15 IS - 8 SN - 0959-4973, 0959-4973 KW - Radiation-Sensitizing Agents KW - 0 KW - Deoxycytidine KW - 0W860991D6 KW - Creatinine KW - AYI8EX34EU KW - gemcitabine KW - B76N6SBZ8R KW - Index Medicus KW - Drug Administration Schedule KW - Neoplasm Staging KW - Injections, Intravenous KW - Humans KW - Carcinoma, Squamous Cell -- complications KW - Urethral Obstruction -- complications KW - Radiation-Sensitizing Agents -- therapeutic use KW - Creatinine -- blood KW - Kidney Function Tests -- methods KW - Mexico KW - Drug Evaluation -- methods KW - Treatment Outcome KW - Brachytherapy -- methods KW - Middle Aged KW - Follow-Up Studies KW - Time Factors KW - Radiation-Sensitizing Agents -- adverse effects KW - Carcinoma, Squamous Cell -- drug therapy KW - Carcinoma, Squamous Cell -- radiotherapy KW - Radiation-Sensitizing Agents -- administration & dosage KW - Female KW - Uterine Cervical Neoplasms -- complications KW - Deoxycytidine -- toxicity KW - Uterine Cervical Neoplasms -- drug therapy KW - Renal Insufficiency -- drug therapy KW - Deoxycytidine -- analogs & derivatives KW - Chemotherapy, Adjuvant -- methods KW - Deoxycytidine -- therapeutic use KW - Deoxycytidine -- administration & dosage KW - Radiotherapy, Adjuvant -- methods KW - Uterine Cervical Neoplasms -- radiotherapy KW - Renal Insufficiency -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66987126?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chemoradiation+with+gemcitabine+for+cervical+cancer+in+patients+with+renal+failure.&rft.au=Cetina%2C+Lucely%3BRivera%2C+Lesbia%3BCandelaria%2C+Myrna%3Bde+la+Garza%2C+Jaime%3BDue%C3%B1as-Gonz%C3%A1lez%2C+Alfonso&rft.aulast=Cetina&rft.aufirst=Lucely&rft.date=2004-09-01&rft.volume=15&rft.issue=8&rft.spage=761&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 - 2004-12-16 N1 - Date created - 2004-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cellular cholesterol enrichment impairs T cell activation and chemotaxis. AN - 66986829; 15491683 AB - Human aging is associated with an increase in immune cell cholesterol levels, independent of circulating cholesterol levels. The effects of such an increase in membrane cholesterol on lipid raft-associated immune cell function have not been investigated. We sought to examine the effects of in vitro cholesterol loading on two known lipid raft-associated pathways of T cells, namely T cell activation and chemokine stimulation. Using beta-cyclodextrin (BCD) as a vehicle, we were able to rapidly load cholesterol onto human T cell lines and primary peripheral blood T cells without inducing significant cell toxicity. Loading of cholesterol to four-fold that of normal levels induced significant inhibition of intracellular calcium mobilization by both alphaCD3 and SDF-1alpha. Cholesterol-loaded peripheral T cells were completely unresponsive to alphaCD3/alphaCD28 stimulation, demonstrating no increase in IL-2, GM1 expression or cell size. T cell polarization of lipid rafts to alphaCD3/alphaCD28 beads was also impaired. In addition, cholesterol loading potently inhibited SDF-1alpha-induced chemotaxis. We propose that excess membrane cholesterol could potentially disrupt raft-related cell functions downstream of receptor triggering and that the loss of cholesterol regulation of aging immune cells could contribute to immune cell senescence. JF - Mechanisms of ageing and development AU - Nguyen, Dzung H AU - Espinoza, Juan C AU - Taub, Dennis D AD - Laboratory of Immunology, National Institute on Aging, NIH, Intramural Research Program, 5600 Nathan Shock Drive, Baltimore, MD 21224-6825, USA. taubd@grc.nia.nih.gov Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 641 EP - 650 VL - 125 IS - 9 SN - 0047-6374, 0047-6374 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, CD3 KW - CXCL12 protein, human KW - Chemokine CXCL12 KW - Chemokines, CXC KW - Protein Isoforms KW - Cholesterol KW - 97C5T2UQ7J KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Humans KW - Membrane Microdomains -- physiology KW - Jurkat Cells KW - Protein Isoforms -- physiology KW - Antibodies, Monoclonal -- pharmacology KW - Chemotaxis, Leukocyte KW - Microspheres KW - Protein Isoforms -- immunology KW - Antigens, CD3 -- immunology KW - Calcium -- metabolism KW - Chemokines, CXC -- physiology KW - Cell Polarity KW - Biological Transport -- physiology KW - Intracellular Membranes -- metabolism KW - Cell Line KW - Antigens, CD3 -- physiology KW - Lymphocyte Activation -- drug effects KW - T-Lymphocytes -- metabolism KW - Cholesterol -- metabolism KW - Cholesterol -- pharmacology KW - T-Lymphocytes -- drug effects KW - T-Lymphocytes -- immunology KW - Lymphocyte Activation -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66986829?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+ageing+and+development&rft.atitle=Cellular+cholesterol+enrichment+impairs+T+cell+activation+and+chemotaxis.&rft.au=Nguyen%2C+Dzung+H%3BEspinoza%2C+Juan+C%3BTaub%2C+Dennis+D&rft.aulast=Nguyen&rft.aufirst=Dzung&rft.date=2004-09-01&rft.volume=125&rft.issue=9&rft.spage=641&rft.isbn=&rft.btitle=&rft.title=Mechanisms+of+ageing+and+development&rft.issn=00476374&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-04-26 N1 - Date created - 2004-10-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Endogenous estrogen receptor beta is transcriptionally active in primary ovarian cells from estrogen receptor knockout mice. AN - 66944648; 15465114 AB - The estrogen receptor (ER) alpha is a hormone-inducible transcription factor that has a pivotal physiological role. Intriguingly, a clear and undisputed physiological function of the recently described ERbeta remains elusive, with the exception of the ovary where a cooperative role of ERalpha and ERbeta has been demonstrated. We have, therefore, investigated whether endogenous ERs, in particular ERbeta, act as ligand-inducible transcription factors in primary ovarian cells derived from wild-type, ERalpha or ERbeta knockout mice. Granulosa-enriched cell fractions naturally expressing ERbeta and thecal cell fractions that express ERalpha were analyzed in transactivation assays using the vitellogenin A2 consensus estrogen response element and potent ER agonists diethylstilbestrol and S-indenestrol A. We studied also the potency-selective ERbeta agonist R-indenestrol A, the pure ERalpha agonist and ERbeta antagonist R,R-diethyl-tetrahydrochrysene and the pure ERalpha agonist propylpyrazole-triol. Using ER subtype-specific physiological cell models and these ER subtype-specific structural probes, we analyzed trans-activation of ERalpha and ERbeta. This analysis revealed that endogenously expressed ERbeta is indeed functional as a transcription factor, that it responds to estrogens appropriately, and that the ligands used are true ER subtype-specific probes in primary ovarian cells. In conclusion, this study demonstrates that endogenously expressed ERbeta is capable of regulating gene transcription independent of ERalpha. JF - Steroids AU - Mueller, Stefan O AU - Katzenellenbogen, John A AU - Korach, Kenneth S AD - Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 681 EP - 686 VL - 69 IS - 10 SN - 0039-128X, 0039-128X KW - 5,11-diethyl-5,6,11,12-tetrahydrochrysene-2,8-diol KW - 0 KW - Chrysenes KW - Estrogen Receptor alpha KW - Estrogen Receptor beta KW - Estrogens KW - Indenes KW - Phenols KW - Pyrazoles KW - Receptors, Estrogen KW - Recombinant Fusion Proteins KW - Vitellogenins KW - 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole KW - 0T83Y6JZPF KW - fulvestrant KW - 22X328QOC4 KW - indenestrol KW - 4A464K3BSI KW - Estradiol KW - 4TI98Z838E KW - Diethylstilbestrol KW - 731DCA35BT KW - Luciferases KW - EC 1.13.12.- KW - Index Medicus KW - Animals KW - Chrysenes -- pharmacology KW - Vitellogenins -- genetics KW - Receptors, Estrogen -- physiology KW - Mice, Knockout KW - Recombinant Fusion Proteins -- metabolism KW - Indenes -- pharmacology KW - Recombinant Fusion Proteins -- genetics KW - Gene Expression Regulation -- drug effects KW - Response Elements -- genetics KW - Luciferases -- genetics KW - Estrogen Receptor alpha -- agonists KW - Receptors, Estrogen -- agonists KW - Luciferases -- metabolism KW - Mice KW - Transcriptional Activation KW - Pyrazoles -- pharmacology KW - Estrogen Receptor alpha -- genetics KW - Receptors, Estrogen -- genetics KW - Estrogens -- pharmacology KW - Ovary -- cytology KW - Transfection KW - Cells, Cultured KW - Diethylstilbestrol -- pharmacology KW - Mice, Inbred C57BL KW - Female KW - Estrogen Receptor beta -- agonists KW - Estradiol -- analogs & derivatives KW - Estradiol -- pharmacology KW - Estrogen Receptor beta -- physiology KW - Theca Cells -- metabolism KW - Granulosa Cells -- metabolism KW - Estrogen Receptor beta -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66944648?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Steroids&rft.atitle=Endogenous+estrogen+receptor+beta+is+transcriptionally+active+in+primary+ovarian+cells+from+estrogen+receptor+knockout+mice.&rft.au=Mueller%2C+Stefan+O%3BKatzenellenbogen%2C+John+A%3BKorach%2C+Kenneth+S&rft.aulast=Mueller&rft.aufirst=Stefan&rft.date=2004-09-01&rft.volume=69&rft.issue=10&rft.spage=681&rft.isbn=&rft.btitle=&rft.title=Steroids&rft.issn=0039128X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-15 N1 - Date created - 2004-10-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Euthanasia of mouse fetuses and neonates. AN - 66933151; 15461437 AB - We sought to determine whether any of the common methods of euthanasia for adult rodents would lead to an acceptable death for fetuses or neonates. We wanted to identify a method that was rapid, free of signs of pain or distress, reliable, and minimally distressful to the person performing the procedure and that minimized the amount of handling required to perform the procedure. We evaluated six methods of euthanasia, with and without anesthesia, in three age groups of mice: gravid mice (E14-20) and neonatal pups (P1-P7 and P8-P14). Euthanasia methods included: halothane inhalation, carbon dioxide inhalation, intraperitoneal sodium pentobarbital, intravenous potassium chloride, and cervical dislocation with and without anesthesia. Noninvasive echocardiography was used to assess heartbeat during euthanasia. With cardiac arrest as the definition of death, no method of euthanasia killed fetal mice. Halothane inhalation (5% by vaporizer) was not an acceptable method of euthanasia for mice of the age groups tested. Intraperitoneal administration of sodium pentobarbital for euthanasia required a higher dose than the previously established dose, and there is a risk of reduced efficacy in pregnant animals due to potential intrauterine injection. Carbon dioxide asphyxiation was the most efficient method of euthanasia for neonatal mouse pups P1-14. For pregnant adult mice, intravenous potassium chloride under anesthesia, carbon dioxide asphyxiation, and cervical dislocation alone or under anesthesia were excellent methods of euthanasia. Copyright 2004 American Association for Laboratory Animal Science JF - Contemporary topics in laboratory animal science AU - Klaunberg, Brenda A AU - O'malley, James AU - Clark, Terri AU - Davis, Judith A AD - 10 Center Drive, Bldg 10, Room B1D69, NMRF, DIR, NINDS, NIH, DHHS, Bethesda, Maryland 20892, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 29 EP - 34 VL - 43 IS - 5 SN - 1060-0558, 1060-0558 KW - Carbon Dioxide KW - 142M471B3J KW - Potassium Chloride KW - 660YQ98I10 KW - Pentobarbital KW - I4744080IR KW - Halothane KW - UQT9G45D1P KW - Index Medicus KW - Carbon Dioxide -- poisoning KW - Fetus KW - Animals, Newborn KW - Animals KW - Heart Arrest -- chemically induced KW - Spinal Injuries -- veterinary KW - Pentobarbital -- poisoning KW - Potassium Chloride -- poisoning KW - Halothane -- poisoning KW - Echocardiography -- veterinary KW - Laboratory Animal Science -- methods KW - Euthanasia, Animal -- methods KW - Animals, Laboratory -- physiology KW - Mice -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66933151?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Contemporary+topics+in+laboratory+animal+science&rft.atitle=Euthanasia+of+mouse+fetuses+and+neonates.&rft.au=Klaunberg%2C+Brenda+A%3BO%27malley%2C+James%3BClark%2C+Terri%3BDavis%2C+Judith+A&rft.aulast=Klaunberg&rft.aufirst=Brenda&rft.date=2004-09-01&rft.volume=43&rft.issue=5&rft.spage=29&rft.isbn=&rft.btitle=&rft.title=Contemporary+topics+in+laboratory+animal+science&rft.issn=10600558&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-21 N1 - Date created - 2004-10-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Assessing the risk of birth defects associated with antiretroviral exposure during pregnancy. AN - 66932320; 15467577 AB - The purpose of this study was to examine teratogenic risk of antiretroviral (ARV) drugs. The Antiretroviral Pregnancy Registry (APR) monitors prenatal exposures to ARV drugs and pregnancy outcome through a prospective exposure-registration cohort. Statistical inference uses exact methods for binomial proportions. Through July 2003, APR has monitored 3583 live births exposed to ARV. Among 1391 first trimester exposures, there were 38 birth defects, prevalence of 2.7% (95% CI 1.9-3.7), not significantly higher than the CDC's population surveillance rate, 3.1 per 100 live births (95% CI 3.1-3.2). For lamivudine, nelfinavir, nevirapine, stavudine, and zidovudine, sufficient numbers of live births (>200) following first-trimester exposures have been monitored to allow detection of a 2-fold increase in risk of birth defects overall; no increases have been detected. APR data demonstrate no increase in prevalence of birth defects overall or among women exposed to lamivudine, nelfinavir, nevirapine, stavudine, and zidovudine. JF - American journal of obstetrics and gynecology AU - Watts, D Heather AU - Covington, Deborah L AU - Beckerman, Karen AU - Garcia, Patricia AU - Scheuerle, Angela AU - Dominguez, Kenneth AU - Ross, Brenda AU - Sacks, Susan AU - Chavers, Scott AU - Tilson, Hugh AD - Pediatric, Adolescent, and Maternal AIDS Branch, National Institute of Child Health and Human Development, NIH, Bethesda, Md 20892, USA. hw59i@nih.gov Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 985 EP - 992 VL - 191 IS - 3 SN - 0002-9378, 0002-9378 KW - Anti-Retroviral Agents KW - 0 KW - Lamivudine KW - 2T8Q726O95 KW - Zidovudine KW - 4B9XT59T7S KW - Nevirapine KW - 99DK7FVK1H KW - Stavudine KW - BO9LE4QFZF KW - Nelfinavir KW - HO3OGH5D7I KW - Abridged Index Medicus KW - Index Medicus KW - Nevirapine -- adverse effects KW - Nelfinavir -- adverse effects KW - Prospective Studies KW - Zidovudine -- adverse effects KW - Risk Factors KW - Humans KW - Lamivudine -- adverse effects KW - Gestational Age KW - Stavudine -- adverse effects KW - Female KW - Pregnancy KW - Maternal-Fetal Exchange KW - Abnormalities, Drug-Induced -- epidemiology KW - Anti-Retroviral Agents -- adverse effects KW - Pregnancy Outcome UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66932320?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+obstetrics+and+gynecology&rft.atitle=Assessing+the+risk+of+birth+defects+associated+with+antiretroviral+exposure+during+pregnancy.&rft.au=Watts%2C+D+Heather%3BCovington%2C+Deborah+L%3BBeckerman%2C+Karen%3BGarcia%2C+Patricia%3BScheuerle%2C+Angela%3BDominguez%2C+Kenneth%3BRoss%2C+Brenda%3BSacks%2C+Susan%3BChavers%2C+Scott%3BTilson%2C+Hugh&rft.aulast=Watts&rft.aufirst=D&rft.date=2004-09-01&rft.volume=191&rft.issue=3&rft.spage=985&rft.isbn=&rft.btitle=&rft.title=American+journal+of+obstetrics+and+gynecology&rft.issn=00029378&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-06 N1 - Date created - 2004-10-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Picosecond time-resolved X-ray crystallography: probing protein function in real time. AN - 66920596; 15450293 AB - A detailed mechanistic understanding of how a protein functions requires knowledge not only of its static structure, but also how its conformation evolves as it executes its function. The recent development of picosecond time-resolved X-ray crystallography has allowed us to visualize in real time and with atomic detail the conformational evolution of a protein. Here, we report the photolysis-induced structural evolution of wild-type and L29F myoglobin over times ranging from 100 ps to 3 micros. The sub-ns structural rearrangements that accompany ligand dissociation in wild-type and the mutant form differ dramatically, and lead to vastly different ligand migration dynamics. The correlated protein displacements provide a structural explanation for the kinetic differences. Our observation of functionally important protein motion on the sub-ns time scale was made possible by the 150-ps time resolution of the measurement, and demonstrates that picosecond dynamics are relevant to protein function. To visualize subtle structural changes without modeling, we developed a novel method for rendering time-resolved electron density that depicts motion as a color gradient across the atom or group of atoms that move. A sequence of these time-resolved images have been stitched together into a movie, which allows one to literally "watch" the protein as it executes its function. JF - Journal of structural biology AU - Schotte, Friedrich AU - Soman, Jayashree AU - Olson, John S AU - Wulff, Michael AU - Anfinrud, Philip A AD - Laboratory of Chemical Physics, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 235 EP - 246 VL - 147 IS - 3 SN - 1047-8477, 1047-8477 KW - Myoglobin KW - 0 KW - Proteins KW - carboxymyoglobin KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Protein Structure, Secondary KW - Myoglobin -- chemistry KW - Models, Molecular KW - Kinetics KW - Myoglobin -- metabolism KW - Lasers KW - Amino Acid Substitution KW - Protein Conformation KW - Computer Systems KW - Proteins -- chemistry KW - Crystallography, X-Ray -- instrumentation KW - Crystallography, X-Ray -- methods KW - Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66920596?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+structural+biology&rft.atitle=Picosecond+time-resolved+X-ray+crystallography%3A+probing+protein+function+in+real+time.&rft.au=Schotte%2C+Friedrich%3BSoman%2C+Jayashree%3BOlson%2C+John+S%3BWulff%2C+Michael%3BAnfinrud%2C+Philip+A&rft.aulast=Schotte&rft.aufirst=Friedrich&rft.date=2004-09-01&rft.volume=147&rft.issue=3&rft.spage=235&rft.isbn=&rft.btitle=&rft.title=Journal+of+structural+biology&rft.issn=10478477&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-17 N1 - Date created - 2004-09-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential oblique angle spectroscopy of the oral epithelium. AN - 66914293; 15447016 AB - Increasing evidence suggests that inflammation may contribute to the process of carcinogenesis. This is the basis of several clinical trials evaluating potential chemopreventive drugs. These trials require quantitative assessments of inflammation, which, for the oral epithelium, are traditionally provided by histopathological evaluation. To reduce patient discomfort and morbidity of tissue biopsy procedures, we develop a noninvasive alternative using diffuse reflectance spectroscopy to measure epithelial thickness as an index of tissue inflammation. Although any optical system has the potential for probing near-surface structures, traditional methods of accounting for scattering of photons are generally invalid for typical epithelial thicknesses. We develop a single-scattering theory that is valid for typical epithelial thicknesses. The theory accurately predicts a distinctive feature that can be used to quantify epithelial thickness given intensity measurements with sources at two different angles relative to the tissue surface. This differential measure approach has acute sensitivity to small, layer-related changes in scattering coefficients. To assess the capability of our method to quantify epithelial thickness, detailed Monte Carlo simulations and measurements on phantom models of a two-layered structure are performed. The results show that the intensity ratio maximum feature can be used to quantify epithelial thickness with an error less than 30% despite fourfold changes in scattering coefficients and 10-fold changes in absorption coefficients. An initial study using a simple two-source, four-detector probe on patients shows that the technique has promise. We believe that this new method will perform well on patients with diverse tissue optical characteristics and therefore be of practical clinical value for quantifying epithelial thickness in vivo. (c) 2004 Society of Photo-Optical Instrumentation Engineers. JF - Journal of biomedical optics AU - Hattery, David AU - Hattery, Brenda AU - Chernomordik, Victor AU - Smith, Paul AU - Loew, Murray AU - Mulshine, James AU - Gandjbakhche, Amir AD - National Institutes of Health, National Institute of Child Health and Human Development, Laboratory of Integrative and Medical Biophysics, Building 9, Room B1E11, Bethesda, Maryland 20892-0924, USA. hattery@ieee.org PY - 2004 SP - 951 EP - 960 VL - 9 IS - 5 SN - 1083-3668, 1083-3668 KW - Index Medicus KW - Sensitivity and Specificity KW - Scattering, Radiation KW - Computer Simulation KW - Reproducibility of Results KW - Humans KW - Monte Carlo Method KW - Models, Biological KW - Image Interpretation, Computer-Assisted -- methods KW - Mouth Neoplasms -- diagnosis KW - Precancerous Conditions -- physiopathology KW - Mouth Mucosa -- pathology KW - Algorithms KW - Spectrum Analysis -- methods KW - Mouth Mucosa -- physiopathology KW - Precancerous Conditions -- diagnosis KW - Spectrum Analysis -- instrumentation KW - Mouth Neoplasms -- pathology KW - Precancerous Conditions -- pathology KW - Mouth Neoplasms -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66914293?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+biomedical+optics&rft.atitle=Differential+oblique+angle+spectroscopy+of+the+oral+epithelium.&rft.au=Hattery%2C+David%3BHattery%2C+Brenda%3BChernomordik%2C+Victor%3BSmith%2C+Paul%3BLoew%2C+Murray%3BMulshine%2C+James%3BGandjbakhche%2C+Amir&rft.aulast=Hattery&rft.aufirst=David&rft.date=2004-09-01&rft.volume=9&rft.issue=5&rft.spage=951&rft.isbn=&rft.btitle=&rft.title=Journal+of+biomedical+optics&rft.issn=10833668&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-21 N1 - Date created - 2004-09-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulatory roles for the homeodomain and C2H2 zinc finger regions of Cryptococcus neoformans Ste12alphap. AN - 66903910; 15387817 AB - The STE12alpha gene of Cryptococcus neoformans encodes a protein containing both homeodomain and zinc finger regions. As homeodomains and zinc finger regions are important domains for the function of many transcription factors, we used site-specific mutagenesis to delineate the roles of these two domains. The homeodomain and zinc finger regions are each important for the function of Ste12alphap. DNA binding ability, mating frequency, and haploid fruiting capability were reduced in strains with mutations in the homeodomain, whereas virulence and capsule size in the mouse brain were increased. In contrast, mutations in the zinc fingers region resulted in decreased virulence, reduced capsule size in the mouse brain and decreased gene expression of capsule associated genes. In addition, phospholipase activity was increased in the zinc finger mutants. Taken together, most of the phenotypes previously observed in the ste12alpha deletion strains were reproduced in these two types of mutants. However, unlike mutations in the homeodomain/zinc finger region, complete deletion of STE12alpha caused a severe reduction in virulence and a decrease in phospholipase activity. These data suggest that region(s) other than the homeodomain and zinc finger regions of Ste12alphap contribute to the variable influences on the different phenotypes observed in C. neoformans. Copyright 2004 Blackwell Publishing Ltd JF - Molecular microbiology AU - Chang, Yun C AU - Wright, L C AU - Tscharke, R L AU - Sorrell, T C AU - Wilson, C F AU - Kwon-Chung, K J AD - Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 1385 EP - 1396 VL - 53 IS - 5 SN - 0950-382X, 0950-382X KW - Fungal Proteins KW - 0 KW - Homeodomain Proteins KW - Transcription Factors KW - Index Medicus KW - Phenotype KW - Mutagenesis, Site-Directed KW - Gene Expression Regulation, Fungal KW - Animals KW - Survival Rate KW - Humans KW - Two-Hybrid System Techniques KW - Mice KW - Brain -- metabolism KW - Mice, Inbred BALB C KW - Female KW - Transcription Factors -- metabolism KW - Cryptococcus neoformans -- genetics KW - Cryptococcus neoformans -- metabolism KW - Fungal Proteins -- genetics KW - Cryptococcus neoformans -- growth & development KW - Transcription Factors -- genetics KW - Homeodomain Proteins -- chemistry KW - Fungal Proteins -- chemistry KW - Fungal Proteins -- metabolism KW - Homeodomain Proteins -- genetics KW - Homeodomain Proteins -- metabolism KW - Transcription Factors -- chemistry KW - Zinc Fingers KW - Cryptococcus neoformans -- pathogenicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66903910?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+microbiology&rft.atitle=Regulatory+roles+for+the+homeodomain+and+C2H2+zinc+finger+regions+of+Cryptococcus+neoformans+Ste12alphap.&rft.au=Chang%2C+Yun+C%3BWright%2C+L+C%3BTscharke%2C+R+L%3BSorrell%2C+T+C%3BWilson%2C+C+F%3BKwon-Chung%2C+K+J&rft.aulast=Chang&rft.aufirst=Yun&rft.date=2004-09-01&rft.volume=53&rft.issue=5&rft.spage=1385&rft.isbn=&rft.btitle=&rft.title=Molecular+microbiology&rft.issn=0950382X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-24 N1 - Date created - 2004-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intraocular lymphoma: update on diagnosis and management. AN - 66896529; 15377987 AB - Primary intraocular lymphoma (PIOL) is a subset of primary central nervous system lymphoma (PCNSL) in which lymphoma cells initially invade the retina, vitreous, or optic nerve head, with or without concomitant CNS involvement. The incidence of this previously rare condition has increased dramatically. Given its nonspecific presentation and aggressive course, PIOL provides a diagnostic and therapeutic challenge. We review the current strategies for diagnosis and treatment of PIOL and present our own experience with PIOL. Recent developments in the diagnosis of PIOL include immunohistochemistry, flow cytometry, cytokine evaluation, and molecular analysis. However, definitive diagnosis still requires harvesting of tissue for histopathology. Optimal treatment for PIOL remains unclear. Initial therapeutic regimens should include methotrexate-based chemotherapy and radiotherapy to the brain and eye. In addition, promising results have been seen with intravitreal methotrexate and autologous stem cell transplantation for recurrent and refractory disease. Efforts to further determine the immunophenotype and molecular characteristics of PIOL will continue to assist in the diagnosis of PIOL. Future studies are required to determine the role of radiotherapy and optimal local and systemic chemotherapeutic regimens. JF - Cancer control : journal of the Moffitt Cancer Center AU - Chan, Chi-Chao AU - Wallace, Dana J AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA. chanc@nei.nih.gov PY - 2004 SP - 285 EP - 295 VL - 11 IS - 5 KW - Antimetabolites, Antineoplastic KW - 0 KW - Antineoplastic Agents KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Stem Cell Transplantation -- methods KW - Injections, Intralymphatic KW - Antimetabolites, Antineoplastic -- administration & dosage KW - Vitrectomy -- methods KW - Humans KW - Diagnostic Techniques, Neurological KW - Treatment Outcome KW - Radiotherapy -- methods KW - Diagnostic Techniques, Ophthalmological KW - Antineoplastic Agents -- therapeutic use KW - Methotrexate -- administration & dosage KW - Lymphoma -- therapy KW - Eye Neoplasms -- therapy KW - Eye Neoplasms -- diagnosis KW - Lymphoma -- diagnosis KW - Central Nervous System Neoplasms -- therapy KW - Central Nervous System Neoplasms -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66896529?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+control+%3A+journal+of+the+Moffitt+Cancer+Center&rft.atitle=Intraocular+lymphoma%3A+update+on+diagnosis+and+management.&rft.au=Chan%2C+Chi-Chao%3BWallace%2C+Dana+J&rft.aulast=Chan&rft.aufirst=Chi-Chao&rft.date=2004-09-01&rft.volume=11&rft.issue=5&rft.spage=285&rft.isbn=&rft.btitle=&rft.title=Cancer+control+%3A+journal+of+the+Moffitt+Cancer+Center&rft.issn=1526-2359&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2007-09-28 N1 - Date created - 2004-09-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: N Engl J Med. 2001 Jan 11;344(2):114-23 [11150363] J Clin Oncol. 2001 Feb 1;19(3):742-9 [11157026] Ophthalmology. 2001 Feb;108(2):386-99 [11158819] Ophthalmology. 2001 Mar;108(3):426-7 [11237883] Curr Opin Oncol. 2001 May;13(3):137-42 [11307054] Retina. 2001;21(3):281-4 [11421029] Surv Ophthalmol. 2001 May-Jun;45(6):463-71 [11425352] Onkologie. 2001 Oct;24(5):491-4 [11694778] Hematology Am Soc Hematol Educ Program. 2001;:194-220 [11722985] Blood. 2002 Feb 15;99(4):1136-43 [11830458] Retina. 2002 Feb;22(1):37-43 [11884876] Curr Mol Med. 2001 May;1(2):259-72 [11899075] Surv Ophthalmol. 2002 Mar-Apr;47(2):81-124 [11918892] Ann Oncol. 2002 Apr;13(4):531-8 [12056702] Eur J Cancer. 2002 Jul;38(10):1298-312 [12091059] J Neurooncol. 2002 Jun;58(2):175-8 [12164690] Leukemia. 2002 Sep;16(9):1852-6 [12200703] Ophthalmology. 2002 Sep;109(9):1709-16 [12208721] Curr Opin Ophthalmol. 2002 Dec;13(6):411-8 [12441846] J Clin Oncol. 2002 Dec 15;20(24):4643-8 [12488408] Blood. 2003 Jan 15;101(2):466-8 [12393404] J Neurol. 2002 Dec;249(12):1713-6 [12529795] Clin Cancer Res. 2003 Feb;9(2):711-5 [12576439] Ophthalmology. 2003 Feb;110(2):421-6 [12578791] Ophthalmology. 2003 Mar;110(3):595-9 [12623828] J Clin Oncol. 2003 Mar 15;21(6):1044-9 [12637469] Clin Cancer Res. 2003 Jun;9(6):2133-9 [12796378] Ophthalmology. 2003 Jun;110(6):1241-4 [12799254] Eye (Lond). 2003 May;17(4):513-21 [12802353] J Clin Oncol. 2003 Jun 15;21(12):2407-14 [12805341] Clin Lymphoma. 2003 Jun;4(1):22-9 [12837150] Curr Hematol Rep. 2003 Jan;2(1):13-22 [12901150] Ophthalmology. 2003 Aug;110(8):1671-2 [12917196] Onkologie. 2003 Aug;26(4):351-4 [12972702] Br J Cancer. 2003 Oct 20;89(8):1389-94 [14562003] Graefes Arch Clin Exp Ophthalmol. 2003 Oct;241(10):860-70 [14605902] J Clin Oncol. 2003 Nov 15;21(22):4151-6 [14615443] Invest Ophthalmol Vis Sci. 2003 Dec;44(12):5235-41 [14638722] Ann Oncol. 2004 Jan;15(1):129-33 [14679132] Trans Am Ophthalmol Soc. 2003;101:275-92 [14971583] Arch Ophthalmol. 1975 Feb;93(2):123-4 [1090291] Surv Ophthalmol. 1979 Mar-Apr;23(5):279-96 [380030] Cancer. 1980 Feb 15;45(4):688-92 [6766795] Dev Ophthalmol. 1981;2:114-20 [7021249] N Engl J Med. 1982 Nov 11;307(20):1231-6 [7133054] Cancer. 1983 Sep 1;52(5):878-86 [6347357] Cancer. 1986 Apr 1;57(7):1273-5 [2418934] J Exp Med. 1986 Jul 1;164(1):315-20 [3014037] N Engl J Med. 1987 Nov 5;317(19):1185-9 [3657890] Br J Ophthalmol. 1987 Oct;71(10):748-52 [3314978] Ophthalmology. 1987 Dec;94(12):1631-9 [3323986] J Neurosurg. 1988 Jun;68(6):835-53 [3286832] N Engl J Med. 1988 Jun 23;318(25):1638-44 [3287162] Ophthalmology. 1988 May;95(5):625-30 [3050698] Br J Ophthalmol. 1988 Dec;72(12):905-11 [3067746] Cancer. 1989 May 15;63(10):1918-21 [2702565] Br J Ophthalmol. 1989 May;73(5):342-6 [2659067] Blood. 1990 Jul 1;76(1):131-5 [2194586] Nature. 1990 Nov 22;348(6299):334-6 [2250705] Am J Ophthalmol. 1991 Oct 15;112(4):472-4 [1928262] J Clin Oncol. 1992 Apr;10(4):635-43 [1548527] Ophthalmology. 1992 Feb;99(2):250-6 [1553217] Int J Radiat Oncol Biol Phys. 1992;23(1):9-17 [1572835] Retina. 1992;12(3 Suppl):S64-70 [1455086] Cancer. 1993 Aug 1;72(3):843-9 [8334638] Ophthalmology. 1993 Sep;100(9):1399-406 [8371930] Ophthalmology. 1994 May;101(5):850-5 [8190470] Mod Pathol. 1994 May;7(4):429-34 [8066071] Retina. 1995;15(2):125-9 [7624599] Int J Radiat Oncol Biol Phys. 1995 Oct 15;33(3):663-73 [7558957] Am J Ophthalmol. 1995 Nov;120(5):671-3 [7485372] Am J Ophthalmol. 1996 Apr;121(4):442-4 [8604740] Arch Pathol Lab Med. 1996 Apr;120(4):357-63 [8619747] Retina. 1996;16(1):47-56 [8927810] Leuk Lymphoma. 1996 Oct;23(3-4):339-45 [9031115] Retina. 1997;17(2):118-23 [9143039] Arch Ophthalmol. 1997 Sep;115(9):1152-6 [9298056] Arch Ophthalmol. 1997 Sep;115(9):1157-60 [9298057] Am J Ophthalmol. 1997 Sep;124(3):362-72 [9439362] J Clin Oncol. 1998 Mar;16(3):859-63 [9508166] J Clin Oncol. 1998 Sep;16(9):3000-6 [9738568] Ophthalmology. 1998 Sep;105(9):1664-9 [9754175] Blood. 1998 Nov 1;92(9):3152-62 [9787151] Blood. 1999 May 1;93(9):3081-7 [10216105] Br J Ophthalmol. 1999 Apr;83(4):448-51 [10434868] Ophthalmology. 1999 Sep;106(9):1805-10 [10485554] Arch Ophthalmol. 1999 Sep;117(9):1239-42 [10496399] Ocul Immunol Inflamm. 2000 Dec;8(4):243-50 [11262654] J Neurooncol. 1999 Jul;43(3):199-201 [10563423] J Neurooncol. 1999 Jul;43(3):203-8 [10563424] J Neurooncol. 1999 Jul;43(3):219-26 [10563426] J Neurooncol. 1999 Jul;43(3):249-57 [10563431] J Clin Oncol. 1999 Apr;17(4):1329 [10561199] Ophthalmology. 1999 Dec;106(12):2291-5 [10599659] J Neurosurg. 2000 Feb;92(2):261-6 [10659013] Curr Opin Neurol. 1999 Dec;12(6):687-91 [10676749] Blood. 2000 Mar 15;95(6):2084-92 [10706878] Oncology (Williston Park). 2000 Feb;14(2):228-34; discussion 237-42, 244 [10736810] Surv Ophthalmol. 2000 May-Jun;44(6):518-26 [10906383] Cytopathology. 2000 Aug;11(4):276-8 [10983729] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Breast cancer incidence in postmenopausal women using testosterone in addition to usual hormone therapy. AN - 66866452; 15356405 AB - There is now convincing evidence that usual hormone therapy for ovarian failure increases the risk for breast cancer. We have previously shown that ovarian androgens normally protect mammary epithelial cells from excessive estrogenic stimulation, and therefore we hypothesized that the addition of testosterone to usual hormone therapy might protect women from breast cancer. This was a retrospective, observational study that followed 508 postmenopausal women receiving testosterone in addition to usual hormone therapy in South Australia. Breast cancer status was ascertained by mammography at the initiation of testosterone treatment and biannually thereafter. The average age at the start of follow-up was 56.4 years, and the mean duration of follow-up was 5.8 years. Breast cancer incidence in this group was compared with that of untreated women and women using usual hormone therapy reported in the medical literature and to age-specific local population rates. There were seven cases of invasive breast cancer in this population of testosterone users, for an incidence of 238 per 100,000 woman-years. The rate for estrogen/progestin and testosterone users was 293 per 100,000 woman-years--substantially less than women receiving estrogen/pro-gestin in the Women's Health Initiative study (380 per 100,000 woman-years) or in the "Million Women" Study (521 per 100,000 woman-years). The breast cancer rate in our testosterone users was closest to that reported for hormone therapy never-users in the latter study (283 per 100,000 woman-years), and their age-standardized rate was the same as for the general population in South Australia. These observations suggest that the addition of testosterone to conventional hormone therapy for postmenopausal women does not increase and may indeed reduce the hormone therapy-associated breast cancer risk-thereby returning the incidence to the normal rates observed in the general, untreated population. JF - Menopause (New York, N.Y.) AU - Dimitrakakis, Constantine AU - Jones, Robert A AU - Liu, Aiyi AU - Bondy, Carolyn A AD - Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. PY - 2004 SP - 531 EP - 535 VL - 11 IS - 5 SN - 1072-3714, 1072-3714 KW - Testosterone KW - 3XMK78S47O KW - Index Medicus KW - Australia -- epidemiology KW - Humans KW - Retrospective Studies KW - Aged KW - Risk Assessment KW - Age Distribution KW - Drug Therapy, Combination KW - Aged, 80 and over KW - Adult KW - Cohort Studies KW - Incidence KW - Middle Aged KW - Female KW - Testosterone -- therapeutic use KW - Estrogen Replacement Therapy -- adverse effects KW - Estrogen Replacement Therapy -- methods KW - Testosterone -- adverse effects KW - Breast Neoplasms -- epidemiology KW - Breast Neoplasms -- chemically induced KW - Postmenopause -- physiology KW - Postmenopause -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66866452?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Menopause+%28New+York%2C+N.Y.%29&rft.atitle=Breast+cancer+incidence+in+postmenopausal+women+using+testosterone+in+addition+to+usual+hormone+therapy.&rft.au=Dimitrakakis%2C+Constantine%3BJones%2C+Robert+A%3BLiu%2C+Aiyi%3BBondy%2C+Carolyn+A&rft.aulast=Dimitrakakis&rft.aufirst=Constantine&rft.date=2004-09-01&rft.volume=11&rft.issue=5&rft.spage=531&rft.isbn=&rft.btitle=&rft.title=Menopause+%28New+York%2C+N.Y.%29&rft.issn=10723714&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-18 N1 - Date created - 2004-09-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Menopause. 2004 Sep-Oct;11(5):505-7 [15356402] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of cerebellar granule cell neurons with the neurotrophic factor pigment epithelium-derived factor in vitro enhances expression of other neurotrophic factors as well as cytokines and chemokines. AN - 66853470; 15352210 AB - Microarray analyses demonstrated that a variety of genes was affected by treatment of cerebellar granule cell neurons with the neurotrophic factor pigment epithelium-derived factor (PEDF). The genes for neurotrophins, glial cell-derived neurotrophic factor (GDNF), and their receptors were regulated differentially in immature versus mature neurons; however, nerve growth factor (NGF), neurotrophin (NT)-3, and GDNF did not contribute to the protective effect of PEDF. Brain-derived neurotrophic factor (BDNF) seemed capable of inducing apoptosis, because a blocking antibody enhanced the protective effect of PEDF. In addition, PEDF exposure also stimulated expression of several cytokine and chemokine genes. Removal of the less than 1% of microglia in the cultures by treatment with L-leucine methyl ester, combined with enzyme-linked immunosorbent assays (ELISAs), demonstrated that the cerebellar granule cells constitutively produce three chemokines, macrophage inflammatory protein (MIP)-1alpha, MIP-2, and MIP-3alpha, whose production is enhanced further by treatment with PEDF. Blocking antibodies to each of the chemokines was protective under control conditions, suggesting that they may contribute to the "natural" apoptosis occurring in the cultures, and enhanced the effects of PEDF. Although PEDF enhanced production of all three chemokines, the blocking antibodies did not increase its protective effect against induced apoptosis. These results suggest that although PEDF enhances expression of other neurotrophic factors or chemokines, it does not exert its neuroprotective effect on cerebellar granule cells through their production. JF - Journal of neuroscience research AU - Yabe, Takeshi AU - Herbert, J Taylor AU - Takanohashi, Asako AU - Schwartz, Joan P AD - Neurotrophic Factors Section, NINDS, NIH, Bethesda, Maryland 20892, USA. Y1 - 2004/09/01/ PY - 2004 DA - 2004 Sep 01 SP - 642 EP - 652 VL - 77 IS - 5 SN - 0360-4012, 0360-4012 KW - Antibodies KW - 0 KW - Chemokines KW - Cytokines KW - Eye Proteins KW - Nerve Growth Factors KW - RNA, Messenger KW - Serpins KW - pigment epithelium-derived factor KW - Index Medicus KW - Animals KW - Drug Interactions KW - Oligonucleotide Array Sequence Analysis -- methods KW - Reverse Transcriptase Polymerase Chain Reaction -- methods KW - RNA, Messenger -- biosynthesis KW - Rats KW - Animals, Newborn KW - Enzyme-Linked Immunosorbent Assay -- methods KW - Rats, Sprague-Dawley KW - Cells, Cultured KW - Antibodies -- pharmacology KW - Apoptosis -- drug effects KW - Time Factors KW - Microglia -- drug effects KW - Microglia -- metabolism KW - Nerve Growth Factors -- metabolism KW - Neurons -- metabolism KW - Nerve Growth Factors -- pharmacology KW - Neurons -- drug effects KW - Cytokines -- immunology KW - Chemokines -- immunology KW - Cytokines -- metabolism KW - Eye Proteins -- pharmacology KW - Cerebellum -- cytology KW - Chemokines -- metabolism KW - Serpins -- pharmacology KW - Nerve Growth Factors -- genetics KW - Gene Expression Regulation -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66853470?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Treatment+of+cerebellar+granule+cell+neurons+with+the+neurotrophic+factor+pigment+epithelium-derived+factor+in+vitro+enhances+expression+of+other+neurotrophic+factors+as+well+as+cytokines+and+chemokines.&rft.au=Yabe%2C+Takeshi%3BHerbert%2C+J+Taylor%3BTakanohashi%2C+Asako%3BSchwartz%2C+Joan+P&rft.aulast=Yabe&rft.aufirst=Takeshi&rft.date=2004-09-01&rft.volume=77&rft.issue=5&rft.spage=642&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 - 2004-12-22 N1 - Date created - 2004-09-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Indoor allergens, asthma, and asthma-related symptoms among adolescents in Wuhan, China. AN - 66847804; 15350953 AB - Information on indoor allergen exposures among non-Western populations, which have lower prevalence of atopic illness, is scant. We examined whether exposures to common indoor allergens were associated with doctor-diagnosed asthma and asthma-related symptoms among Chinese adolescents. A cross-sectional study of 4,185 ninth grade students was conducted at 22 randomly selected schools in Wuhan, China. Information on respiratory health and exposures to indoor allergens was obtained by a self-administered questionnaire completed in class. Having animals currently was associated with persistent cough [prevalence odds ratio (POR)=1.54, 95% confidence interval (CI ): 1.21-2.11] and wheeze (POR=1.41, 95% CI: 1.03-1.94). Early-life exposure to animals was also associated with doctor-diagnosed asthma (POR=1.95, 95% CI: 1.35-2.82). Associations with respiratory symptoms strengthened with higher levels of exposure and for exposure in both early childhood and in adolescence. Exposure to cockroaches and having mold/water damage in the home contributed especially to wheezing (POR=2.03, 95% CI: 1.41-2.90 for cockroaches; POR=2.49, 95% CI: 1.82-3.40 for mold/water damage). Indoor allergen exposures were positively associated with asthma diagnosis and persistent respiratory symptoms among Chinese adolescents. Neither early-life nor current exposure to animals was protective for asthma or asthma-related symptoms. JF - Annals of epidemiology AU - Salo, Päivi M AU - Xia, Jiang AU - Johnson, C Anderson AU - Li, Yan AU - Avol, Edward L AU - Gong, Jie AU - London, Stephanie J AD - National Institute of Environmental Health Sciences, Epidemiology Branch, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 543 EP - 550 VL - 14 IS - 8 SN - 1047-2797, 1047-2797 KW - Allergens KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Cross-Sectional Studies KW - China -- epidemiology KW - Cats KW - Surveys and Questionnaires KW - Dogs KW - Population KW - Adolescent KW - Female KW - Male KW - Animals, Domestic -- immunology KW - Prevalence KW - Allergens -- immunology KW - Asthma -- epidemiology KW - Air Pollution, Indoor -- adverse effects KW - Asthma -- etiology KW - Allergens -- classification KW - Allergens -- poisoning UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66847804?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Analysis+of+the+role+of+ubiquitin-interacting+motifs+in+ubiquitin+binding+and+ubiquitylation.&rft.au=Miller%2C+Stephanie+L+H%3BMalotky%2C+Erica%3BO%27Bryan%2C+John+P&rft.aulast=Miller&rft.aufirst=Stephanie+L&rft.date=2004-08-06&rft.volume=279&rft.issue=32&rft.spage=33528&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 - 2005-04-21 N1 - Date created - 2004-09-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Epidemiol. 1990 Dec;132(6):1176-84 [2260550] Clin Exp Allergy. 1994 Apr;24(4):353-8 [8039021] Curr Opin Allergy Clin Immunol. 2003 Feb;3(1):7-14 [12582308] Am J Epidemiol. 2002 Nov 15;156(10):977-83 [12419771] Lancet. 2002 Sep 7;360(9335):781-2 [12241839] Environ Health Perspect. 2002 Sep;110(9):961-7 [12204833] JAMA. 2002 Aug 28;288(8):963-72 [12190366] Clin Exp Allergy. 2002 Aug;32(8):1155-9 [12190651] Thorax. 1994 Dec;49(12):1205-10 [7878553] Clin Exp Allergy. 1997 May;27(5):540-5 [9179428] Ann Allergy Asthma Immunol. 1997 Jun;78(6):544-54; quiz 555-6 [9207717] J Allergy Clin Immunol. 1997 Dec;100(6 Pt 1):S2-24 [9438476] Allergy. 1998 Feb;53(2):120-8 [9534909] Int J Epidemiol. 1998 Feb;27(1):41-8 [9563692] Am J Respir Crit Care Med. 1998 May;157(5 Pt 1):1536-41 [9603135] Clin Exp Allergy. 1998 Apr;28 Suppl 1:2-7; discussion 32-6 [9641582] Eur Respir J. 1998 Aug;12(2):315-35 [9727780] Clin Exp Allergy. 1998 Oct;28(10):1178-81 [9824383] Clin Exp Allergy. 1998 Oct;28(10):1191-200 [9824385] Clin Exp Allergy. 1999 Jan;29(1):28-34 [10051699] Thorax. 1999 Mar;54(3):268-72 [10325905] Thorax. 1999 Jan;54(1):27-32 [10343627] Environ Health Perspect. 1999 Jun;107 Suppl 3:473-80 [10423390] Environ Health Perspect. 1999 Jun;107 Suppl 3:481-3 [10423391] Lancet. 1999 Sep;354 Suppl 2:SII12-5 [10507253] Clin Exp Allergy. 2000 Feb;30(2):187-93 [10651770] Clin Exp Allergy. 2000 Feb;30(2):194-200 [10651771] J Allergy Clin Immunol. 2000 Feb;105(2 Pt 2):S503-8 [10669532] Thorax. 2000 May;55(5):424-31 [10770825] Am J Respir Crit Care Med. 2000 May;161(5):1563-6 [10806155] Am J Respir Crit Care Med. 2000 Sep;162(3 Pt 1):930-5 [10988108] Am J Respir Crit Care Med. 2000 Sep;162(3 Pt 2):S128-33 [10988167] Clin Exp Allergy. 2000 Nov;30(11):1536-9 [11069560] Toxicology. 2000 Nov 2;152(1-3):47-52 [11090939] Environ Health Perspect. 2000 Nov;108(11):1023-8 [11102291] J Allergy Clin Immunol. 2001 Mar;107(3):455-60 [11240945] Lancet. 2001 Mar 10;357(9258):752-6 [11253969] Thorax. 2001 May;56(5):406-11 [11312411] Am J Respir Crit Care Med. 2001 Apr;163(5):1108-12 [11316644] Prev Med. 2001 May;32(5):437-45 [11330994] J Allergy Clin Immunol. 2001 May;107(5):790-6 [11344344] Clin Exp Allergy. 2001 Apr;31(4):570-5 [11359424] Pediatrics. 2001 Jun;107(6):E98 [11389296] Thorax. 2001 Sep;56 Suppl 2:ii58-63 [11514708] Clin Exp Allergy. 2001 Aug;31(8):1225-31 [11529892] J Allergy Clin Immunol. 2001 Oct;108(4):509-15 [11590373] Lancet. 2001 Oct 6;358(9288):1129-33 [11597666] Ann Allergy Asthma Immunol. 2001 Oct;87(4):296-302 [11686421] Clin Exp Allergy. 2001 Dec;31(12):1839-45 [11737034] Chest. 2002 Jan;121(1):6-8 [11796423] Clin Exp Allergy. 2002 Mar;32(3):361-6 [11940064] Curr Opin Allergy Clin Immunol. 2001 Oct;1(5):407-12 [11964720] Curr Opin Allergy Clin Immunol. 2002 Apr;2(2):133-9 [11964762] Epidemiology. 2002 May;13(3):288-95 [11964930] Clin Exp Allergy. 2002 May;32(5):714-20 [11994095] J Allergy Clin Immunol. 2002 May;109(5):784-8 [11994700] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Classification and prediction of survival in hepatocellular carcinoma by gene expression profiling. AN - 66846645; 15349906 AB - We analyzed global gene expression patterns of 91 human hepatocellular carcinomas (HCCs) to define the molecular characteristics of the tumors and to test the prognostic value of the expression profiles. Unsupervised classification methods revealed two distinctive subclasses of HCC that are highly associated with patient survival. This association was validated via 5 independent supervised learning methods. We also identified the genes most strongly associated with survival by using the Cox proportional hazards survival analysis. This approach identified a limited number of genes that accurately predicted the length of survival and provides new molecular insight into the pathogenesis of HCC. Tumors from the low survival subclass have strong cell proliferation and antiapoptosis gene expression signatures. In addition, the low survival subclass displayed higher expression of genes involved in ubiquitination and histone modification, suggesting an etiological involvement of these processes in accelerating the progression of HCC. In conclusion, the biological differences identified in the HCC subclasses should provide an attractive source for the development of therapeutic targets (e.g., HIF1a) for selective treatment of HCC patients. Supplementary material for this article can be found on the HEPATOLOGY Web site (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html) Copyright 2004 American Association for the Study of Liver Diseases JF - Hepatology (Baltimore, Md.) AU - Lee, Ju-Seog AU - Chu, In-Sun AU - Heo, Jeonghoon AU - Calvisi, Diego F AU - Sun, Zongtang AU - Roskams, Tania AU - Durnez, Anne AU - Demetris, Anthony J AU - Thorgeirsson, Snorri S AD - Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 667 EP - 676 VL - 40 IS - 3 SN - 0270-9139, 0270-9139 KW - Index Medicus KW - Humans KW - Liver -- metabolism KW - Gene Expression Profiling KW - Carcinoma, Hepatocellular -- genetics KW - Liver Neoplasms -- mortality KW - Carcinoma, Hepatocellular -- classification KW - Liver Neoplasms -- classification KW - Carcinoma, Hepatocellular -- mortality KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66846645?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Classification+and+prediction+of+survival+in+hepatocellular+carcinoma+by+gene+expression+profiling.&rft.au=Lee%2C+Ju-Seog%3BChu%2C+In-Sun%3BHeo%2C+Jeonghoon%3BCalvisi%2C+Diego+F%3BSun%2C+Zongtang%3BRoskams%2C+Tania%3BDurnez%2C+Anne%3BDemetris%2C+Anthony+J%3BThorgeirsson%2C+Snorri+S&rft.aulast=Lee&rft.aufirst=Ju-Seog&rft.date=2004-09-01&rft.volume=40&rft.issue=3&rft.spage=667&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 - 2004-09-23 N1 - Date created - 2004-09-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Liver Transpl. 2005 Apr;11(4):469-72 [15776402] Hepatology. 2004 Sep;40(3):521-3 [15349888] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vitro differentiation of rat liver derived stem cells results in sensitization to TNFalpha-mediated apoptosis. AN - 66846517; 15349897 AB - Hepatic stem cells are activated after liver damage and have a critical role in tissue homeostasis and repair. Characterization of molecular and cellular events accompanying the expansion and differentiation of liver stem cells is essential for understanding the basic biology of stem cells and for facilitating clinical application of the stem cells. We assessed whether in vitro differentiation of putative hepatic progenitor (rat liver epithelial [RLE]) cells toward hepatocytic lineage affects the response to TNFalpha-mediated cytotoxicity, a common determinant of liver injury. The data show that 50% of differentiated cells underwent apoptosis after 6 hours of TNFalpha treatment whereas control RLE cells were resistant. Both cell types displayed mitochondrial depolarization and release of cytochrome c but the TNFalpha treatment resulted in activation of caspases 9 and 3 and the execution of apoptosis only in differentiated RLE cells. Apoptotic death was associated with increased ROS production and depletion of glutathione. Antioxidants completely prevented both glutathione depletion and apoptosis induced by TNFalpha in differentiated RLE cells. Conversely, glutathione-depleting agents sensitized control RLE cells to TNFalpha induced apoptosis. In conclusion, efficient antioxidant defense system involving glutathione renders hepatic progenitor cells resistant to TNFalpha-mediated apoptosis and acquisition of sensitivity to death stimuli is an implicit feature of the differentiation process. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html). Copyright 2004 American Association for the Study of Liver Diseases JF - Hepatology (Baltimore, Md.) AU - Sánchez, Aránzazu AU - Factor, Valentina M AU - Espinoza, Luis A AU - Schroeder, Insa S AU - Thorgeirsson, Snorri S AD - Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute/National Institutes of Health, Bethesda, MD 20892-4258, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 590 EP - 599 VL - 40 IS - 3 SN - 0270-9139, 0270-9139 KW - Reactive Oxygen Species KW - 0 KW - Tumor Necrosis Factor-alpha KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - Rats KW - Animals KW - Cell Lineage KW - Oxidative Stress KW - Glutathione -- physiology KW - Cell Differentiation KW - Mitochondria, Liver -- drug effects KW - Cell Line KW - Liver -- cytology KW - Stem Cells -- cytology KW - Liver -- drug effects KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Apoptosis -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66846517?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=In+vitro+differentiation+of+rat+liver+derived+stem+cells+results+in+sensitization+to+TNFalpha-mediated+apoptosis.&rft.au=S%C3%A1nchez%2C+Ar%C3%A1nzazu%3BFactor%2C+Valentina+M%3BEspinoza%2C+Luis+A%3BSchroeder%2C+Insa+S%3BThorgeirsson%2C+Snorri+S&rft.aulast=S%C3%A1nchez&rft.aufirst=Ar%C3%A1nzazu&rft.date=2004-09-01&rft.volume=40&rft.issue=3&rft.spage=590&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 - 2004-09-23 N1 - Date created - 2004-09-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hepatitis C infection and injection drug use: the role of hepatologists in evolving treatment efforts. AN - 66845810; 15349886 AB - Treatment regimens for both substance abuse and hepatitis C infection are complex and evolving. New pharmacotherapy for opioid addiction allows for office-based treatment and, thus, an opportunity for expanded treatment in the context of hepatitis C infection. The current article addresses the newly evolving, complex issues in the medical management of hepatitis C and injection drug use. Copyright 2004 American Association for the Study of Liver Diseases JF - Hepatology (Baltimore, Md.) AU - Kresina, Thomas F AU - Seeff, Leonard B AU - Francis, Henry AD - Center on AIDS and other Medical Consequences of Drug Abuse, National Institute on Drug Abuse, Department of Health and Human Services, Bethesda, MD 20892, USA. tk13v@nih.gov Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 516 EP - 519 VL - 40 IS - 3 SN - 0270-9139, 0270-9139 KW - Index Medicus KW - Humans KW - Hepatitis C -- drug therapy KW - Hepatitis C -- etiology KW - Substance Abuse, Intravenous -- therapy KW - Substance Abuse, Intravenous -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66845810?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Hepatitis+C+infection+and+injection+drug+use%3A+the+role+of+hepatologists+in+evolving+treatment+efforts.&rft.au=Kresina%2C+Thomas+F%3BSeeff%2C+Leonard+B%3BFrancis%2C+Henry&rft.aulast=Kresina&rft.aufirst=Thomas&rft.date=2004-09-01&rft.volume=40&rft.issue=3&rft.spage=516&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 - 2004-09-23 N1 - Date created - 2004-09-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biodistribution and radiation dosimetry of the serotonin transporter ligand 11C-DASB determined from human whole-body PET. AN - 66845262; 15347724 AB - 11C-Labeled 3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile (DASB) is a selective radioligand for the in vivo quantitation of serotonin transporters (SERTs) using PET. The goal of this study was to provide dosimetry estimates for 11C-DASB based on human whole-body PET. Dynamic whole-body PET scans were acquired for 7 subjects after the injection of 669 +/- 97 MBq (18.1 +/- 2.6 mCi) of 11C-DASB. The acquisition for each subject was obtained at 14 time points for a total of 115 min after injection of the radioligand. Regions of interest were placed over compressed planar images of source organs that could be visually identified to generate time-activity curves. Radiation burden to the body was calculated from residence times of these source organs using the MIRDOSE3.1 program. The organs with high radiation burden included the lungs, urinary bladder wall, kidneys, gallbladder wall, heart wall, spleen, and liver. The activity peaked within 10 min after the injection of 11C-DASB for all these organs except two--the excretory organs gallbladder and urinary bladder wall, which had peak activities at 32 and 22 min, respectively. Monoexponential fitting of activity overlying the urinary bladder suggested that approximately 12% of activity was excreted via the urine. Simulations in which the urinary voiding interval was decreased from 4.8 to 0.6 h produced only modest effects on the dose to the urinary bladder wall. With a 2.4-h voiding interval, the calculated effective dose was 6.98 microGy/MBq (25.8 mrem/mCi). The estimated radiation burden of 11C-DASB is relatively modest and would allow multiple PET examinations of the same research subject per year. JF - Journal of nuclear medicine : official publication, Society of Nuclear Medicine AU - Lu, Jian-Qiang AU - Ichise, Masanori AU - Liow, Jeih-San AU - Ghose, Subroto AU - Vines, Doug AU - Innis, Robert B AD - Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-0135, USA. lujq@intra.nih.gov Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 1555 EP - 1559 VL - 45 IS - 9 SN - 0161-5505, 0161-5505 KW - 3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile KW - 0 KW - Aniline Compounds KW - Carbon Radioisotopes KW - Carrier Proteins KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Radiopharmaceuticals KW - SLC6A4 protein, human KW - Serotonin Plasma Membrane Transport Proteins KW - Sulfides KW - Index Medicus KW - Carbon Radioisotopes -- pharmacokinetics KW - Radiopharmaceuticals -- pharmacokinetics KW - Radiation Dosage KW - Humans KW - Body Burden KW - Metabolic Clearance Rate KW - Organ Specificity KW - Brain -- metabolism KW - Tissue Distribution KW - Brain -- diagnostic imaging KW - Carrier Proteins -- metabolism KW - Sulfides -- pharmacokinetics KW - Aniline Compounds -- pharmacokinetics KW - Whole-Body Counting -- methods KW - Nerve Tissue Proteins -- metabolism KW - Risk Assessment -- methods KW - Radiometry -- methods KW - Tomography, Emission-Computed -- methods KW - Membrane Glycoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66845262?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+nuclear+medicine+%3A+official+publication%2C+Society+of+Nuclear+Medicine&rft.atitle=Biodistribution+and+radiation+dosimetry+of+the+serotonin+transporter+ligand+11C-DASB+determined+from+human+whole-body+PET.&rft.au=Lu%2C+Jian-Qiang%3BIchise%2C+Masanori%3BLiow%2C+Jeih-San%3BGhose%2C+Subroto%3BVines%2C+Doug%3BInnis%2C+Robert+B&rft.aulast=Lu&rft.aufirst=Jian-Qiang&rft.date=2004-09-01&rft.volume=45&rft.issue=9&rft.spage=1555&rft.isbn=&rft.btitle=&rft.title=Journal+of+nuclear+medicine+%3A+official+publication%2C+Society+of+Nuclear+Medicine&rft.issn=01615505&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-01 N1 - Date created - 2004-09-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Global expression profiling identifies signatures of tumor virulence in MMTV-PyMT-transgenic mice: correlation to human disease. AN - 66836784; 15342376 AB - FVB/N-Tg (MMTV-PyMT)(634Mul)-transgenic mice develop multifocal mammary tumors with a high incidence of pulmonary metastasis. We have demonstrated previously that mammary tumors derived from transgene-positive F1 progeny in particular inbred strains display altered latency, tumor growth rates, and metastatic rates when compared with the FVB/NJ homozygous parent. To identify genes with expression that might be critical in modifying the biological behavior of MMTV-PyMT tumors, we performed a detailed comparative analysis of expression profiles from mammary tumors arising in the parental FVB/NJ background and F1 progeny from crosses with I/LnJ, LP/J, MOLF/Ei, and NZB/B1NJ mice. Compared with normal mammary glands, gene expression profiles of tumors from all five strains exhibited up-regulation of genes involved in cell growth (e.g., Cks1 and CDC25C) and down-regulation of cell adhesion molecules, with many genes associated previously with human breast cancer such as STAT2, CD24 antigen, gelsolin, and lipocalin2. To identify genes with significant variation in expression between the five different genotypes, significance analysis of microarrays (SAM) and one-way ANOVA were used. Three definable groupings of tumors were identified: (a) tumors derived in the LP/J F1 and MOLF/Ei F1 strains in which tumor growth and dissemination are suppressed and latency prolonged; (b) the most aggressive tumors from the FVB/NJ parental strain and I/LnJ F1 genomic backgrounds; and (c) an intermediate virulence phenotype with tumors from NZB/B1NJ-F1 crosses. These array based assessments correlated well with a composite phenotype ranking using a "virulence" index. The gene expression signature that is associated with a high metastatic rate in the mouse contains the same 17 genes described recently as the signature gene set predictive of metastasis in human tumors (1) with 16 of the 17 genes exhibiting the same directional change in expression associated with human metastases. These results demonstrate that the genetic analysis of mouse models of tumorigenesis may be highly relevant to human cancer and that the metastatic phenotype of a tumor may be affected by the germline genetic configuration of the host. JF - Cancer research AU - Qiu, Ting Hu AU - Chandramouli, Gadisetti V R AU - Hunter, Kent W AU - Alkharouf, Nawal W AU - Green, Jeffrey E AU - Liu, Edison T AD - Laboratory of Cell Regulation and Carcinogenesis, Cancer Research Center, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2004/09/01/ PY - 2004 DA - 2004 Sep 01 SP - 5973 EP - 5981 VL - 64 IS - 17 SN - 0008-5472, 0008-5472 KW - Antigens, Polyomavirus Transforming KW - 0 KW - Index Medicus KW - Gene Expression Profiling KW - Animals KW - Cell Transformation, Neoplastic -- pathology KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - Disease Models, Animal KW - Mice KW - Mice, Transgenic KW - Cell Transformation, Neoplastic -- genetics KW - Gene Expression Regulation, Neoplastic -- genetics KW - Mammary Neoplasms, Experimental -- genetics KW - Mammary Neoplasms, Experimental -- virology KW - Mammary Neoplasms, Experimental -- metabolism KW - Antigens, Polyomavirus Transforming -- genetics KW - Mammary Tumor Virus, Mouse -- genetics KW - Mammary Neoplasms, Experimental -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66836784?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Global+expression+profiling+identifies+signatures+of+tumor+virulence+in+MMTV-PyMT-transgenic+mice%3A+correlation+to+human+disease.&rft.au=Qiu%2C+Ting+Hu%3BChandramouli%2C+Gadisetti+V+R%3BHunter%2C+Kent+W%3BAlkharouf%2C+Nawal+W%3BGreen%2C+Jeffrey+E%3BLiu%2C+Edison+T&rft.aulast=Qiu&rft.aufirst=Ting&rft.date=2004-09-01&rft.volume=64&rft.issue=17&rft.spage=5973&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 - 2004-10-05 N1 - Date created - 2004-09-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bayesian multivariate logistic regression. AN - 66834007; 15339297 AB - Bayesian analyses of multivariate binary or categorical outcomes typically rely on probit or mixed effects logistic regression models that do not have a marginal logistic structure for the individual outcomes. In addition, difficulties arise when simple noninformative priors are chosen for the covariance parameters. Motivated by these problems, we propose a new type of multivariate logistic distribution that can be used to construct a likelihood for multivariate logistic regression analysis of binary and categorical data. The model for individual outcomes has a marginal logistic structure, simplifying interpretation. We follow a Bayesian approach to estimation and inference, developing an efficient data augmentation algorithm for posterior computation. The method is illustrated with application to a neurotoxicology study. JF - Biometrics AU - O'Brien, Sean M AU - Dunson, David B AD - Biostatistics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. obrien4@niehs.nih.gov Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 739 EP - 746 VL - 60 IS - 3 SN - 0006-341X, 0006-341X KW - Insecticides KW - 0 KW - Methoxychlor KW - RIA79UD69L KW - Index Medicus KW - Insecticides -- toxicity KW - Animals KW - Biometry KW - Methoxychlor -- administration & dosage KW - Insecticides -- administration & dosage KW - Algorithms KW - Monte Carlo Method KW - Pregnancy KW - Multivariate Analysis KW - Methoxychlor -- toxicity KW - Rats KW - Markov Chains KW - Motor Activity -- drug effects KW - Female KW - Male KW - Logistic Models KW - Bayes Theorem UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66834007?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+multivariate+logistic+regression.&rft.au=O%27Brien%2C+Sean+M%3BDunson%2C+David+B&rft.aulast=O%27Brien&rft.aufirst=Sean&rft.date=2004-09-01&rft.volume=60&rft.issue=3&rft.spage=739&rft.isbn=&rft.btitle=&rft.title=Biometrics&rft.issn=0006341X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-01 N1 - Date created - 2004-09-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacogenomics and stomach cancer. AN - 66830646; 15335285 AB - In subgroups of gastric cancer patients, chemotherapy treatments carry a high risk of toxicity without any clear evidence of antitumor activity. Individualization of therapy is required to treat each patient with the optimal drug and dose. Genetic polymorphisms are the hereditary determinants for interindividual variations of drug effect and the genetic approach represents a new tool to design a tailored therapy. This review focuses on the relevance of the host polymorphisms involved in metabolism, cellular transport and interaction with molecular targets of the drugs used in gastric cancer in conventional or innovative chemotherapy regimens. Pharmacogenetic studies based on a single gene or multi-gene approach (pharmacogenomics) are promising to identify gastric cancer patients at risk for adverse toxicity, but larger and controlled studies are needed to justify changes in the chemotherapeutic strategies. JF - Pharmacogenomics AU - Toffoli, Giuseppe AU - Cecchin, Erika AD - Experimental and Clinical Pharmacology, CRO--National Cancer Institute, via Pedemontana Occidentale, 12, 33081 Aviano, Italy. gtoffoli@cro.it Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 627 EP - 641 VL - 5 IS - 6 SN - 1462-2416, 1462-2416 KW - Anthracyclines KW - 0 KW - Taxoids KW - irinotecan KW - 0H43101T0J KW - Cisplatin KW - Q20Q21Q62J KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Taxoids -- pharmacokinetics KW - Cisplatin -- pharmacokinetics KW - Anthracyclines -- pharmacology KW - Anthracyclines -- pharmacokinetics KW - Humans KW - Clinical Trials as Topic KW - Cisplatin -- pharmacology KW - Anthracyclines -- administration & dosage KW - Taxoids -- pharmacology KW - Taxoids -- administration & dosage KW - Cisplatin -- administration & dosage KW - Stomach Neoplasms -- drug therapy KW - Camptothecin -- pharmacology KW - Camptothecin -- pharmacokinetics KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacokinetics KW - Stomach Neoplasms -- genetics KW - Camptothecin -- analogs & derivatives KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacology KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Pharmacogenetics KW - Camptothecin -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66830646?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacogenomics&rft.atitle=Pharmacogenomics+and+stomach+cancer.&rft.au=Toffoli%2C+Giuseppe%3BCecchin%2C+Erika&rft.aulast=Toffoli&rft.aufirst=Giuseppe&rft.date=2004-09-01&rft.volume=5&rft.issue=6&rft.spage=627&rft.isbn=&rft.btitle=&rft.title=Pharmacogenomics&rft.issn=14622416&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-08 N1 - Date created - 2004-08-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of painful temporomandibular joints with a cyclooxygenase-2 inhibitor: a randomized placebo-controlled comparison of celecoxib to naproxen. AN - 66815929; 15327804 AB - To compare the efficacy and adverse effects of celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, with naproxen, a non-steroidal anti-inflammatory drug, and placebo in the treatment of painful temporomandibular joints (TMJs). In this randomized, double-blind, placebo-controlled trial, 68 subjects with painful TMJs secondary to disc-displacement with reduction, received celecoxib 100 mg twice a day; naproxen, 500 mg twice a day; or placebo for 6 weeks. Subjects were evaluated with standard measures of efficacy: pain intensity measured by visual analogue scale, maximal comfortable mandibular opening, and quality of life (SF-36), at baseline (1 week after discontinuing previous analgesic therapy) and again after 6 weeks of drug treatment. Naproxen significantly reduced the symptoms of painful temporomandibular joint disc-displacement (TMJ DD) with reduction as determined by most efficacy measures. Significant improvement in pain intensity occurred within 3 weeks of treatment, and was sustained throughout the 6-week study. Clinically significant improvement in mandibular range of motion was observed for naproxen compared to celecoxib and placebo. Celecoxib showed slightly better pain reduction than placebo, but was not significantly effective for temporomandibular disorder pain. Celecoxib and naproxen were well tolerated, with similar number of reported adverse effects. Dual COX-1 and COX-2 inhibition with naproxen was demonstrated to be effective for the treatment of painful TMJs, as seen by significant improvement in clinical signs and symptoms of TMJ DD with reduction compared to celecoxib and placebo. Inhibition of both COX isozymes is needed to achieve effective analgesia for this type of musculoskeletal pain. JF - Pain AU - Ta, Lauren E AU - Dionne, Raymond A AD - Pain and Neurosensory Mechanisms Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 10 Center Drive, Room 1N-103, Bethesda, MD 20892, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 13 EP - 21 VL - 111 IS - 1-2 SN - 0304-3959, 0304-3959 KW - Cyclooxygenase 2 Inhibitors KW - 0 KW - Cyclooxygenase Inhibitors KW - Isoenzymes KW - Membrane Proteins KW - Placebos KW - Pyrazoles KW - Sulfonamides KW - Naproxen KW - 57Y76R9ATQ KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - PTGS2 protein, human KW - Prostaglandin-Endoperoxide Synthases KW - Celecoxib KW - JCX84Q7J1L KW - Index Medicus KW - Range of Motion, Articular KW - Humans KW - Quality of Life KW - Isoenzymes -- antagonists & inhibitors KW - Adult KW - Treatment Outcome KW - Chronic Disease KW - Middle Aged KW - Female KW - Male KW - Cyclooxygenase Inhibitors -- adverse effects KW - Facial Pain -- etiology KW - Sulfonamides -- adverse effects KW - Temporomandibular Joint Disorders -- complications KW - Cyclooxygenase Inhibitors -- administration & dosage KW - Naproxen -- administration & dosage KW - Facial Pain -- drug therapy KW - Sulfonamides -- administration & dosage KW - Naproxen -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66815929?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pain&rft.atitle=Treatment+of+painful+temporomandibular+joints+with+a+cyclooxygenase-2+inhibitor%3A+a+randomized+placebo-controlled+comparison+of+celecoxib+to+naproxen.&rft.au=Ta%2C+Lauren+E%3BDionne%2C+Raymond+A&rft.aulast=Ta&rft.aufirst=Lauren&rft.date=2004-09-01&rft.volume=111&rft.issue=1-2&rft.spage=13&rft.isbn=&rft.btitle=&rft.title=Pain&rft.issn=03043959&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-09 N1 - Date created - 2004-08-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Breast cancer risk associated with ovulation-stimulating drugs. AN - 66809233; 15217997 AB - Despite the recognized role of hormones in the aetiology of breast cancer, there has been little evaluation of hormonal preparations used to treat infertility. A retrospective cohort study of 12,193 women evaluated for infertility between 1965 and 1988 at five clinical sites identified 292 in situ and invasive breast cancers in follow-up through 1999. Standardized incidence ratios (SIRs) compared breast cancer risks with those of the general population. Analyses within the cohort estimated rate ratios (RRs) associated with medications after adjustment for other breast cancer predictors. Infertile patients had a significantly higher breast cancer risk than the general population [SIR = 1.29, 95% confidence interval (CI) 1.1-1.4]. Analyses within the cohort showed adjusted RRs of 1.02 for clomiphene citrate and 1.07 for gonadotrophins, and no substantial relationships to dosage or cycles of use. Slight and non-significant elevations in risk were seen for both drugs after > or = 20 years of follow-up (RRs = 1.39 for clomiphene and 1.54 for gonadotrophins). However, the risk associated with clomiphene for invasive breast cancers was statistically significant (RR = 1.60, 95% CI 1.0-2.5). Although there was no overall increase in breast cancer risk associated with use of ovulation-stimulating drugs, long-term effects should continue to be monitored. JF - Human reproduction (Oxford, England) AU - Brinton, Louise A AU - Scoccia, Bert AU - Moghissi, Kamran S AU - Westhoff, Carolyn L AU - Althuis, Michelle D AU - Mabie, Jerome E AU - Lamb, Emmet J AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. brinton@nih.gov Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 2005 EP - 2013 VL - 19 IS - 9 SN - 0268-1161, 0268-1161 KW - Gonadotropins KW - 0 KW - Clomiphene KW - 1HRS458QU2 KW - Index Medicus KW - Neoplasm Invasiveness KW - Odds Ratio KW - Humans KW - Cohort Studies KW - Adult KW - Retrospective Studies KW - Female KW - Infertility, Female -- drug therapy KW - Gonadotropins -- adverse effects KW - Breast Neoplasms -- pathology KW - Breast Neoplasms -- chemically induced KW - Ovulation Induction -- adverse effects KW - Clomiphene -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66809233?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+reproduction+%28Oxford%2C+England%29&rft.atitle=Breast+cancer+risk+associated+with+ovulation-stimulating+drugs.&rft.au=Brinton%2C+Louise+A%3BScoccia%2C+Bert%3BMoghissi%2C+Kamran+S%3BWesthoff%2C+Carolyn+L%3BAlthuis%2C+Michelle+D%3BMabie%2C+Jerome+E%3BLamb%2C+Emmet+J&rft.aulast=Brinton&rft.aufirst=Louise&rft.date=2004-09-01&rft.volume=19&rft.issue=9&rft.spage=2005&rft.isbn=&rft.btitle=&rft.title=Human+reproduction+%28Oxford%2C+England%29&rft.issn=02681161&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-09 N1 - Date created - 2004-08-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Hum Reprod. 2005 Apr;20(4):1112; author reply 1112-3 [15788697] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p21Cip1 and p27Kip1 act in synergy to alter the sensitivity of naive T cells to TGF-beta-mediated G1 arrest through modulation of IL-2 responsiveness. AN - 66805094; 15322169 AB - Induction of G(1) arrest by TGF-beta correlates with the regulation of p21(Cip1) and p27(Kip1), members of the Cip/Kip family of cyclin-dependent kinase inhibitors (cki). However, no definitive evidence exists that these proteins play a causal role in TGF-beta(1)-induced growth arrest in lymphocytes. In this report we show the suppression of cell cycle progression by TGF-beta is diminished in T cells from mice deficient for both p21(Cip1) and p27(Kip1) (double-knockout (DKO)) only when activated under conditions of optimal costimulation. Although there is an IL-2-dependent enhanced proliferation of CD8(+) T cells from DKO mice, TGF-beta is able to maximally suppress the proliferation of DKO T cells when activated under conditions of low costimulatory strength. We also show that the induction of p15(Ink4b) in T cells stimulated in the presence of TGF-beta is not essential, as TGF-beta also efficiently suppressed proliferation of T cells from p15(Ink4b-/-) mice. Finally, although these cki are dispensable for the suppression of T cell proliferation by TGF-beta, we now describe a Smad3-dependent down-regulation of cdk4, suggesting a potential mechanism underlying to resistance of Smad3(-/-) T cells to the induction of growth arrest by TGF-beta. In summary, the growth suppressive effects of TGF-beta in naive T cells are a function of the strength of costimulation, and alterations in the expression of cki modify the sensitivity to TGF-beta by lowering thresholds for a maximal mitogenic response. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Wolfraim, Lawrence A AU - Walz, Thomas M AU - James, Zakiya AU - Fernandez, Tania AU - Letterio, John J AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. wolfraim@tolergenics.com Y1 - 2004/09/01/ PY - 2004 DA - 2004 Sep 01 SP - 3093 EP - 3102 VL - 173 IS - 5 SN - 0022-1767, 0022-1767 KW - Cdkn1a protein, mouse KW - 0 KW - Cdkn1b protein, mouse KW - Cdkn2b protein, mouse KW - Cell Cycle Proteins KW - Cyclin-Dependent Kinase Inhibitor p15 KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - Interleukin-2 KW - Proto-Oncogene Proteins KW - Transforming Growth Factor beta KW - Tumor Suppressor Proteins KW - Cyclin-Dependent Kinase Inhibitor p27 KW - 147604-94-2 KW - Cdk4 protein, mouse KW - EC 2.7.11.22 KW - Cyclin-Dependent Kinase 4 KW - Cyclin-Dependent Kinases KW - Abridged Index Medicus KW - Index Medicus KW - Cyclin-Dependent Kinases -- metabolism KW - Animals KW - Cyclin-Dependent Kinases -- immunology KW - Immunologic Memory -- physiology KW - Mice KW - Lymphoid Tissue -- immunology KW - Mice, Knockout KW - Down-Regulation KW - Immunologic Memory -- immunology KW - Lymphoid Tissue -- cytology KW - Up-Regulation KW - Interleukin-2 -- metabolism KW - Cell Cycle Proteins -- immunology KW - Transforming Growth Factor beta -- immunology KW - Cell Cycle Proteins -- metabolism KW - G1 Phase -- immunology KW - Tumor Suppressor Proteins -- immunology KW - T-Lymphocytes -- metabolism KW - Tumor Suppressor Proteins -- metabolism KW - Cyclins -- metabolism KW - Cyclins -- immunology KW - Interleukin-2 -- immunology KW - Transforming Growth Factor beta -- metabolism KW - T-Lymphocytes -- immunology KW - G1 Phase -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66805094?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=p21Cip1+and+p27Kip1+act+in+synergy+to+alter+the+sensitivity+of+naive+T+cells+to+TGF-beta-mediated+G1+arrest+through+modulation+of+IL-2+responsiveness.&rft.au=Wolfraim%2C+Lawrence+A%3BWalz%2C+Thomas+M%3BJames%2C+Zakiya%3BFernandez%2C+Tania%3BLetterio%2C+John+J&rft.aulast=Wolfraim&rft.aufirst=Lawrence&rft.date=2004-09-01&rft.volume=173&rft.issue=5&rft.spage=3093&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 - 2004-09-21 N1 - Date created - 2004-08-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pregnane X receptor up-regulation of P-glycoprotein expression and transport function at the blood-brain barrier. AN - 66801541; 15322232 AB - P-glycoprotein, an ATP-driven drug export pump, is a critical, selective component of the blood-brain barrier responsible for the poor penetration of many therapeutic drugs. In liver, ligand-activated, nuclear receptors are transcriptional regulators of drug metabolizing enzymes and drug export pumps, but only one, the pregnane X receptor (PXR in rodents, SXR in humans), regulates p-glycoprotein expression. We report for the first time that PXR is expressed in rat brain capillaries. Moreover, exposing isolated capillaries to the PXR ligands pregnenolone-16alpha-carbonitrile (PCN) and dexamethasone increased p-glycoprotein expression and p-glycoprotein-specific transport of a fluorescent cyclosporine A derivative into capillary lumens. Dosing rats with PCN and dexamethasone increased p-glycoprotein expression in liver plasma membranes and in brain capillaries and up-regulated specific transport in capillaries. This is the first evidence for PXR expression in brain and for regulation by nuclear receptors of a xenobiotic export pump at the blood-brain barrier. These results imply selective tightening of the barrier in patients exposed to the wide range of xenobiotics that are PXR/SXR ligands, including drugs, dietary constituents, and toxicants. JF - Molecular pharmacology AU - Bauer, Björn AU - Hartz, Anika M S AU - Fricker, Gert AU - Miller, David S AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 413 EP - 419 VL - 66 IS - 3 SN - 0026-895X, 0026-895X KW - P-Glycoprotein KW - 0 KW - Receptors, Cytoplasmic and Nuclear KW - Receptors, Steroid KW - Xenobiotics KW - pregnane X receptor KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Blotting, Western KW - Xenobiotics -- pharmacology KW - Gene Expression KW - Biological Transport KW - Up-Regulation KW - Immunohistochemistry KW - Male KW - Receptors, Cytoplasmic and Nuclear -- physiology KW - Blood-Brain Barrier -- drug effects KW - P-Glycoprotein -- physiology KW - P-Glycoprotein -- genetics KW - Receptors, Steroid -- physiology KW - P-Glycoprotein -- metabolism KW - Blood-Brain Barrier -- metabolism KW - Receptors, Cytoplasmic and Nuclear -- genetics KW - Receptors, Steroid -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66801541?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmacology&rft.atitle=Pregnane+X+receptor+up-regulation+of+P-glycoprotein+expression+and+transport+function+at+the+blood-brain+barrier.&rft.au=Bauer%2C+Bj%C3%B6rn%3BHartz%2C+Anika+M+S%3BFricker%2C+Gert%3BMiller%2C+David+S&rft.aulast=Bauer&rft.aufirst=Bj%C3%B6rn&rft.date=2004-09-01&rft.volume=66&rft.issue=3&rft.spage=413&rft.isbn=&rft.btitle=&rft.title=Molecular+pharmacology&rft.issn=0026895X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-03 N1 - Date created - 2004-08-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Catecholamine metabolism: a contemporary view with implications for physiology and medicine. AN - 66799563; 15317907 AB - This article provides an update about catecholamine metabolism, with emphasis on correcting common misconceptions relevant to catecholamine systems in health and disease. Importantly, most metabolism of catecholamines takes place within the same cells where the amines are synthesized. This mainly occurs secondary to leakage of catecholamines from vesicular stores into the cytoplasm. These stores exist in a highly dynamic equilibrium, with passive outward leakage counterbalanced by inward active transport controlled by vesicular monoamine transporters. In catecholaminergic neurons, the presence of monoamine oxidase leads to formation of reactive catecholaldehydes. Production of these toxic aldehydes depends on the dynamics of vesicular-axoplasmic monoamine exchange and enzyme-catalyzed conversion to nontoxic acids or alcohols. In sympathetic nerves, the aldehyde produced from norepinephrine is converted to 3,4-dihydroxyphenylglycol, not 3,4-dihydroxymandelic acid. Subsequent extraneuronal O-methylation consequently leads to production of 3-methoxy-4-hydroxyphenylglycol, not vanillylmandelic acid. Vanillylmandelic acid is instead formed in the liver by oxidation of 3-methoxy-4-hydroxyphenylglycol catalyzed by alcohol and aldehyde dehydrogenases. Compared to intraneuronal deamination, extraneuronal O-methylation of norepinephrine and epinephrine to metanephrines represent minor pathways of metabolism. The single largest source of metanephrines is the adrenal medulla. Similarly, pheochromocytoma tumor cells produce large amounts of metanephrines from catecholamines leaking from stores. Thus, these metabolites are particularly useful for detecting pheochromocytomas. The large contribution of intraneuronal deamination to catecholamine turnover, and dependence of this on the vesicular-axoplasmic monoamine exchange process, helps explain how synthesis, release, metabolism, turnover, and stores of catecholamines are regulated in a coordinated fashion during stress and in disease states. JF - Pharmacological reviews AU - Eisenhofer, Graeme AU - Kopin, Irwin J AU - Goldstein, David S AD - Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Dr., MSC-1620, Bethesda, MD 20892-1620, USA. ge@box-g.nih.gov Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 331 EP - 349 VL - 56 IS - 3 SN - 0031-6997, 0031-6997 KW - Catecholamines KW - 0 KW - Index Medicus KW - Molecular Structure KW - Animals KW - Biological Transport, Active -- physiology KW - Humans KW - Models, Biological KW - Catecholamines -- pharmacokinetics KW - Catecholamines -- metabolism KW - Catecholamines -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66799563?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacological+reviews&rft.atitle=Catecholamine+metabolism%3A+a+contemporary+view+with+implications+for+physiology+and+medicine.&rft.au=Eisenhofer%2C+Graeme%3BKopin%2C+Irwin+J%3BGoldstein%2C+David+S&rft.aulast=Eisenhofer&rft.aufirst=Graeme&rft.date=2004-09-01&rft.volume=56&rft.issue=3&rft.spage=331&rft.isbn=&rft.btitle=&rft.title=Pharmacological+reviews&rft.issn=00316997&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-09 N1 - Date created - 2004-08-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In utero exposure to polychlorinated biphenyls and sensorineural hearing loss in 8-year-old children. AN - 66797540; 15315812 AB - Early-life exposure to polychlorinated biphenyls (PCBs), a ubiquitous environmental contaminant, increases the hearing threshold at selected frequencies in rats. Among humans from the Faroe Islands with unusually high early-life PCB exposure, exposure was directly associated with increased hearing thresholds at two frequencies, although the deficits were present in the left ear but not the right. We examined PCB levels in maternal pregnancy serum in relation with audiometrically determined hearing thresholds among offspring when they were of school age. Complete data were available for 195 children with sensorineural hearing loss (SNHL) and 615 children selected at random, all of whom were born in 1959-1966 in the Collaborative Perinatal Project (CPP) U.S. cohort. The median exposure among those selected at random, as reflected by the mother's third trimester serum total PCB concentration, was 2.8 microg/l, about twofold higher than recent background levels in the United States. Based on the average hearing threshold across the frequencies essential for speech recognition in the "worst ear," the maternal serum PCB level was unrelated to the adjusted odds of SNHL or to adjusted mean hearing threshold. Overall, an adverse effect of early-life, background-level PCB exposure on SNHL was not supported by these data. JF - Neurotoxicology and teratology AU - Longnecker, Matthew P AU - Hoffman, Howard J AU - Klebanoff, Mark A AU - Brock, John W AU - Zhou, Haibo AU - Needham, Larry AU - Adera, Tilahun AU - Guo, Xuguang AU - Gray, Kimberly A AD - Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, P.O. Box 12233, MD A3-05, Research Triangle Park, NC 27709, USA. longnecker@niehs.nih.gov PY - 2004 SP - 629 EP - 637 VL - 26 IS - 5 SN - 0892-0362, 0892-0362 KW - Environmental Pollutants KW - 0 KW - Polychlorinated Biphenyls KW - DFC2HB4I0K KW - Index Medicus KW - Audiometry -- methods KW - Humans KW - Adult KW - Retrospective Studies KW - Follow-Up Studies KW - Child KW - Birth Weight -- drug effects KW - Male KW - Female KW - Body Height -- drug effects KW - Pregnancy KW - Hearing Loss, Sensorineural -- chemically induced KW - Polychlorinated Biphenyls -- blood KW - Environmental Pollutants -- poisoning KW - Polychlorinated Biphenyls -- poisoning KW - Environmental Pollutants -- blood KW - Maternal Exposure KW - Prenatal Exposure Delayed Effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66797540?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+and+teratology&rft.atitle=In+utero+exposure+to+polychlorinated+biphenyls+and+sensorineural+hearing+loss+in+8-year-old+children.&rft.au=Longnecker%2C+Matthew+P%3BHoffman%2C+Howard+J%3BKlebanoff%2C+Mark+A%3BBrock%2C+John+W%3BZhou%2C+Haibo%3BNeedham%2C+Larry%3BAdera%2C+Tilahun%3BGuo%2C+Xuguang%3BGray%2C+Kimberly+A&rft.aulast=Longnecker&rft.aufirst=Matthew&rft.date=2004-09-01&rft.volume=26&rft.issue=5&rft.spage=629&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 completed - 2004-11-09 N1 - Date created - 2004-08-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dietary supplementation with 2-deoxy-D-glucose improves cardiovascular and neuroendocrine stress adaptation in rats. AN - 66796579; 15317676 AB - Dietary restriction and physical exercise can enhance stress resistance and reduce the risk of cardiovascular disease. We investigated the effects of dietary supplementation with 2-deoxy-d-glucose (2-DG), a glucose analog that limits glucose availability at the cellular level, on cardiovascular and neuroendocrine responses to stress in rats. Young adult male Sprague-Dawley rats were implanted with telemetry probes to monitor blood pressure (BP), heart rate, body temperature, and body movements. These variables were measured at designated times during a 6-mo period in rats fed control and 2-DG-supplemented (0.4% 2-DG, fed ad libitum on a schedule of 2 days on the diet and 1 day off the diet) diets during unperturbed conditions and during and after immobilization stress or cold-water swim stress. Rats fed the 2-DG diet exhibited significant reductions in resting BP, attenuated BP responses during stress, and accelerated recovery to baseline after stress. Plasma concentrations of ACTH and corticosterone were elevated under nonstress conditions in rats fed the 2-DG diet and exhibited differential responses to single (enhanced response) and multiple (reduced response) stress sessions compared with rats fed control rat chow ad libitum. The 2-DG diet improved glucose metabolism, as indicated by decreased concentrations of blood glucose and insulin under nonstress conditions, but glucose and insulin responses to stress were maintained. We conclude that improvements in some cardiovascular risk factors and stress adaptation in rats maintained on a 2-DG-supplemented diet are associated with reduced neuroendocrine responses to the stressors. JF - American journal of physiology. Heart and circulatory physiology AU - Wan, Ruiqian AU - Camandola, Simonetta AU - Mattson, Mark P AD - Laboratory of Neurosciences, National Institute on Aging, Baltimore, Maryland 21224, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - H1186 EP - H1193 VL - 287 IS - 3 SN - 0363-6135, 0363-6135 KW - Antimetabolites KW - 0 KW - Blood Glucose KW - Insulin KW - Deoxyglucose KW - 9G2MP84A8W KW - Glucose KW - IY9XDZ35W2 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Heart Rate -- drug effects KW - Insulin -- blood KW - Glucose -- metabolism KW - Rest KW - Blood Pressure -- drug effects KW - Blood Glucose -- analysis KW - Male KW - Antimetabolites -- pharmacology KW - Cardiovascular System -- physiopathology KW - Dietary Supplements KW - Adaptation, Physiological KW - Deoxyglucose -- pharmacology KW - Stress, Physiological -- physiopathology KW - Neurosecretory Systems -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66796579?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+physiology.+Heart+and+circulatory+physiology&rft.atitle=Dietary+supplementation+with+2-deoxy-D-glucose+improves+cardiovascular+and+neuroendocrine+stress+adaptation+in+rats.&rft.au=Wan%2C+Ruiqian%3BCamandola%2C+Simonetta%3BMattson%2C+Mark+P&rft.aulast=Wan&rft.aufirst=Ruiqian&rft.date=2004-09-01&rft.volume=287&rft.issue=3&rft.spage=H1186&rft.isbn=&rft.btitle=&rft.title=American+journal+of+physiology.+Heart+and+circulatory+physiology&rft.issn=03636135&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-10 N1 - Date created - 2004-08-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Disregulation of E-cadherin in transgenic mouse models of liver cancer. AN - 66790523; 15220935 AB - E-cadherin is a cell-cell adhesion molecule that plays a pivotal role in the development and maintenance of cell polarity. Disruption of E-cadherin-mediated adhesion represents a key step toward the invasive phenotype in a variety of solid tumors, including hepatocellular carcinoma (HCC). Here, we investigate whether deregulation of E-cadherin occurs along the multistep process of hepatocarcinogenesis in transgenic mouse models, including c-Myc, E2F1, c-Myc/TGF-alpha and c-Myc/E2F1 mice. Liver tumors from the transgenic mouse lines could be divided into two categories based on E-cadherin levels. Of 28, 20 (71.4%) c-Myc HCCs showed marked reduction of E-cadherin expression when compared with wild-type livers. In contrast, all of c-Myc/TGF-alpha and the majority of E2F1 and c-myc/E2F1 preneoplastic and neoplastic lesions exhibited overexpression of E-cadherin. Downregulation of E-cadherin was associated with promoter hypermethylation in seven of 20 c-Myc HCCs (35%), while no loss of heterozygosity at the E-cadherin locus was detected. Nuclear accumulation of beta-catenin did not correlate with E-cadherin downregulation. Furthermore, c-Myc HCCs with reduced E-cadherin displayed upregulation of hypoxia-inducible factor-1alpha and vascular endothelial growth factor proteins. Importantly, loss of E-cadherin was associated with increased cell proliferation and higher microvessel density in c-Myc tumors. Taken together, these data suggest that loss of E-cadherin might favor tumor progression in relatively more benign HCC from c-Myc transgenic mice by stimulating neoplastic proliferation and angiogenesis under hypoxic conditions. JF - Laboratory investigation; a journal of technical methods and pathology AU - Calvisi, Diego F AU - Ladu, Sara AU - Conner, Elizabeth A AU - Factor, Valentina M AU - Thorgeirsson, Snorri S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 1137 EP - 1147 VL - 84 IS - 9 SN - 0023-6837, 0023-6837 KW - Cadherins KW - 0 KW - DNA, Neoplasm KW - Index Medicus KW - Polymerase Chain Reaction KW - Microsatellite Repeats KW - Mice, Inbred Strains KW - Animals KW - Blotting, Western KW - Microcirculation -- pathology KW - Apoptosis KW - Disease Models, Animal KW - Mice KW - DNA, Neoplasm -- analysis KW - Neovascularization, Pathologic KW - Immunohistochemistry KW - Gene Expression Regulation, Neoplastic KW - Liver Neoplasms -- pathology KW - Liver Neoplasms -- metabolism KW - Carcinoma, Hepatocellular -- metabolism KW - Cadherins -- metabolism KW - Carcinoma, Hepatocellular -- genetics KW - Carcinoma, Hepatocellular -- pathology KW - Mice, Transgenic KW - Cadherins -- genetics KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66790523?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Laboratory+investigation%3B+a+journal+of+technical+methods+and+pathology&rft.atitle=Disregulation+of+E-cadherin+in+transgenic+mouse+models+of+liver+cancer.&rft.au=Calvisi%2C+Diego+F%3BLadu%2C+Sara%3BConner%2C+Elizabeth+A%3BFactor%2C+Valentina+M%3BThorgeirsson%2C+Snorri+S&rft.aulast=Calvisi&rft.aufirst=Diego&rft.date=2004-09-01&rft.volume=84&rft.issue=9&rft.spage=1137&rft.isbn=&rft.btitle=&rft.title=Laboratory+investigation%3B+a+journal+of+technical+methods+and+pathology&rft.issn=00236837&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-28 N1 - Date created - 2004-08-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Long-term exposure to elevated levels of circulating TIMP-1 but not mammary TIMP-1 suppresses growth of mammary carcinomas in transgenic mice. AN - 66789572; 15166086 AB - Tissue inhibitor of metalloproteinases-1 (TIMP-1) regulates matrix metalloproteinase activity, acts as a growth stimulator and inhibits apoptosis. We developed transgenic mice to evaluate the relevance of circulating versus mammary TIMP-1 in mammary carcinogenesis. The transgene was placed under the control of the albumin (Alb) promoter for the production of large amounts of TIMP-1 in the liver and release into the systemic circulation to achieve chronically elevated blood levels. The initial 7,12-dimethylbenz[a]anthracene (DMBA) mammary carcinogenesis study showed greatly decreased tumor incidence in heterozygous Alb-TIMP-1 mice (25%), compared with their wild-type (wt) littermates (83.3%). Metastatic mammary carcinomas were induced in the Alb-TIMP-1 mice through breeding with mice expressing the polyomavirus Middle T antigen (MT) under the control of the mouse mammary tumor virus-long terminal repeat (MMTV-LTR). Both the mammary tumor burden and the incidence of lung metastases were lower in the Alb-TIMP-1/MMTV-MT mice than their MMTV-MT littermates. Analysis of the Alb-TIMP-1/MMTV-MT tumors showed evidence of decreased proliferative activity and inhibition of apoptosis, whereas microvascular density was not affected. Transgenic expression of TIMP-1 in mammary epithelial cells was accomplished by using MMTV-LTR. In contrast to the Alb-TIMP-1 mice, there was insignificant difference in the growth of both DMBA- and MT-induced mammary tumors between heterozygous MMTV-TIMP-1 mice and their wt littermates. The MT-induced mammary tumors of the MMTV-TIMP-1 mice were separated into 'low' and 'high' TIMP-1 expressing groups. The 'high' TIMP-1 expressing tumors exhibited significantly higher proliferative activity than the tumors of the MMTV-MT only mice, whereas the number of apoptotic cells and microvascular density were not different. The findings of this study show that circulating TIMP-1, but not mammary-derived TIMP-1, has growth suppressive effects on DMBA and MT-induced mammary carcinomas. JF - Carcinogenesis AU - Yamazaki, Masaharu AU - Akahane, Takemi AU - Buck, Todd AU - Yoshiji, Hitoshi AU - Gomez, Daniel E AU - Schoeffner, Daniel J AU - Okajima, Eijiro AU - Harris, Steven R AU - Bunce, Opal R AU - Thorgeirsson, Snorri S AU - Thorgeirsson, Unnur P AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 1735 EP - 1746 VL - 25 IS - 9 SN - 0143-3334, 0143-3334 KW - Albumins KW - 0 KW - Antigens, Polyomavirus Transforming KW - Tissue Inhibitor of Metalloproteinase-1 KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Index Medicus KW - Animals KW - Mice, Inbred CBA KW - Terminal Repeat Sequences -- genetics KW - Apoptosis KW - 9,10-Dimethyl-1,2-benzanthracene -- toxicity KW - Transgenes KW - Mice, Inbred C57BL KW - Mice KW - Mice, Transgenic KW - Antigens, Polyomavirus Transforming -- genetics KW - Female KW - Mammary Neoplasms, Experimental -- chemically induced KW - Lung Neoplasms -- prevention & control KW - Lung Neoplasms -- blood KW - Tissue Inhibitor of Metalloproteinase-1 -- metabolism KW - Lung Neoplasms -- secondary KW - Albumins -- genetics KW - Mammary Neoplasms, Experimental -- prevention & control KW - Mammary Neoplasms, Experimental -- metabolism KW - Tissue Inhibitor of Metalloproteinase-1 -- genetics KW - Mammary Tumor Virus, Mouse -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66789572?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Long-term+exposure+to+elevated+levels+of+circulating+TIMP-1+but+not+mammary+TIMP-1+suppresses+growth+of+mammary+carcinomas+in+transgenic+mice.&rft.au=Yamazaki%2C+Masaharu%3BAkahane%2C+Takemi%3BBuck%2C+Todd%3BYoshiji%2C+Hitoshi%3BGomez%2C+Daniel+E%3BSchoeffner%2C+Daniel+J%3BOkajima%2C+Eijiro%3BHarris%2C+Steven+R%3BBunce%2C+Opal+R%3BThorgeirsson%2C+Snorri+S%3BThorgeirsson%2C+Unnur+P&rft.aulast=Yamazaki&rft.aufirst=Masaharu&rft.date=2004-09-01&rft.volume=25&rft.issue=9&rft.spage=1735&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-10-05 N1 - Date created - 2004-08-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo analysis of the 3' untranslated region of GB virus B after in vitro mutagenesis of an infectious cDNA clone: persistent infection in a transfected tamarin. AN - 66785127; 15308733 AB - GB virus B (GBV-B), the virus most closely related to hepatitis C virus (HCV), infects tamarins and causes acute hepatitis. The 3' untranslated region (UTR) of an infectious GBV-B clone (pGBB) has a proximal short sequence followed by a poly(U) tract and a 3' terminal sequence. Our investigators previously demonstrated that the 3' terminal sequence was critical for in vivo infectivity. Here, we tested the effect of deleting the short sequence and/or the poly(U) tract from pGBB; infectivity of each mutant was tested by intrahepatic transfection of two tamarins with transcribed RNA. A mutant lacking both regions was not viable. However, mutants lacking either the short sequence or the poly(U) tract were viable. All four tamarins had a wild-type-like acute infection and developed acute hepatitis. Whereas we found that five tamarins transfected with the wild-type clone pGBB had acute resolving infection, one tamarin transfected with the poly(U) deletion mutant became persistently infected. This animal had viremia and hepatitis until its death at week 90. The genomes recovered at weeks 2, 7, 15, 20, 60, and 90 lacked the poly(U) stretch. Eight amino acid changes were identified at week 90. One change, in the putative p7 protein, was dominant at week 15. Thus, persistence of GBV-B, like persistence of HCV, was associated with the emergence of virus variants. Four tamarins inoculated with serum collected at weeks 2 and 90 from the tamarin with persistent infection had an acute resolving infection. Nonetheless, the demonstration that GBV-B can persist in tamarins strengthens its relevance as a surrogate model for the study of HCV. JF - Journal of virology AU - Nam, Jae-Hwan AU - Faulk, Kristina AU - Engle, Ronald E AU - Govindarajan, Sugantha AU - St Claire, Marisa AU - Bukh, Jens AD - Hepatitis Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-8009, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 9389 EP - 9399 VL - 78 IS - 17 SN - 0022-538X, 0022-538X KW - 3' Untranslated Regions KW - 0 KW - DNA, Complementary KW - Luminescent Proteins KW - Polyproteins KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Poly U KW - 27416-86-0 KW - Index Medicus KW - Virus Replication KW - Animals KW - DNA, Complementary -- genetics KW - Genome, Viral KW - Cloning, Molecular KW - Hepatitis, Viral, Animal -- virology KW - Poly U -- genetics KW - Base Sequence KW - Transfection KW - Sequence Deletion -- genetics KW - Molecular Sequence Data KW - Polyproteins -- genetics KW - Time Factors KW - Luminescent Proteins -- genetics KW - Flaviviridae Infections -- virology KW - GB virus B -- genetics KW - Saguinus -- virology KW - Genetic Engineering KW - GB virus B -- physiology KW - GB virus B -- pathogenicity KW - Mutagenesis -- genetics KW - 3' Untranslated Regions -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66785127?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=In+vivo+analysis+of+the+3%27+untranslated+region+of+GB+virus+B+after+in+vitro+mutagenesis+of+an+infectious+cDNA+clone%3A+persistent+infection+in+a+transfected+tamarin.&rft.au=Nam%2C+Jae-Hwan%3BFaulk%2C+Kristina%3BEngle%2C+Ronald+E%3BGovindarajan%2C+Sugantha%3BSt+Claire%2C+Marisa%3BBukh%2C+Jens&rft.aulast=Nam&rft.aufirst=Jae-Hwan&rft.date=2004-09-01&rft.volume=78&rft.issue=17&rft.spage=9389&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 - 2004-09-16 N1 - Date created - 2004-08-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Gen Virol. 2001 Oct;82(Pt 10):2437-48 [11562537] J Virol. 1999 Apr;73(4):3317-25 [10074186] J Med Virol. 2001 Dec;65(4):694-7 [11745933] J Virol. 2002 Jun;76(11):5326-38 [11991961] Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14416-21 [12391335] Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15661-8 [12441397] J Virol. 2003 Mar;77(6):3557-68 [12610131] Virology. 2003 Jun 20;311(1):72-80 [12832204] Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):9962-7 [12907703] Virology. 1999 Sep 1;261(2):216-26 [10497107] J Gen Virol. 1999 Sep;80 ( Pt 9):2337-41 [10501485] Virology. 1999 Sep 30;262(2):470-8 [10502525] J Virol. 2000 Jan;74(2):773-83 [10623739] J Virol. 2000 Feb;74(4):2046-51 [10644379] J Virol. 2000 May;74(9):4291-301 [10756044] J Gen Virol. 2000 Sep;81(Pt 9):2183-8 [10950975] J Viral Hepat. 2000 Sep;7(5):335-42 [10971821] J Virol. 2000 Dec;74(24):11764-72 [11090176] J Virol. 1999 Dec;73(12):10546-50 [10559376] Methods Mol Biol. 2003;226:173-8 [12958498] Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3401-5 [7724574] J Med Virol. 1995 May;46(1):81-90 [7623012] J Virol. 1995 Sep;69(9):5621-30 [7637008] Biochem Biophys Res Commun. 1995 Oct 13;215(2):744-9 [7488017] J Virol. 1996 Jun;70(6):3363-71 [8648666] J Clin Microbiol. 1996 Dec;34(12):3085-91 [8940452] Virology. 1997 Mar 17;229(2):429-36 [9126255] J Virol. 1997 Jul;71(7):4985-9 [9188562] Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8738-43 [9238047] Virology. 1998 Apr 25;244(1):161-72 [9581788] Arch Virol. 1998;143(12):2493-503 [9930205] Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2291-5 [10051634] Gastroenterology. 2001 Nov;121(5):1226-33 [11677216] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification and characterization of a new cross-reactive human immunodeficiency virus type 1-neutralizing human monoclonal antibody. AN - 66782934; 15308718 AB - The identification and characterization of new human monoclonal antibodies (hMAbs) able to neutralize primary human immunodeficiency virus type 1 (HIV-1) isolates from different subtypes may help in our understanding of the mechanisms of virus entry and neutralization and in the development of entry inhibitors and vaccines. For enhanced selection of broadly cross-reactive antibodies, soluble HIV-1 envelope glycoproteins (Envs proteins) from two isolates complexed with two-domain soluble CD4 (sCD4) were alternated during panning of a phage-displayed human antibody library; these two Env proteins (89.6 and IIIB gp140s), and one additional Env (JR-FL gp120) alone and complexed with sCD4 were used for screening. An antibody with relatively long HCDR3 (17 residues), designated m14, was identified that bound to all antigens and neutralized heterologous HIV-1 isolates in multiple assay formats. Fab m14 potently neutralized selected well-characterized subtype B isolates, including JRCSF, 89.6, IIIB, and Yu2. Immunoglobulin G1 (IgG1) m14 was more potent than Fab m14 and neutralized 7 of 10 other clade B isolates; notably, although the potency was on average significantly lower than that of IgG1 b12, IgG1 m14 neutralized two of the isolates with significantly lower 50% inhibitory concentrations than did IgG1 b12. IgG1 m14 neutralized four of four selected clade C isolates with potency higher than that of IgG1 b12. It also neutralized 7 of 17 clade C isolates from southern Africa that were difficult to neutralize with other hMAbs and sCD4. IgG1 m14 neutralized four of seven primary HIV-1 isolates from other clades (A, D, E, and F) much more efficiently than did IgG1 b12; for the other three isolates, IgG b12 was much more potent. Fab m14 bound with high (nanomolar range) affinity to gp120 and gp140 from various isolates; its binding was reduced by soluble CD4 and antibodies recognizing the CD4 binding site (CD4bs) on gp120, and its footprint as defined by alanine-scanning mutagenesis overlaps that of b12. These results suggest that m14 is a novel CD4bs cross-reactive HIV-1-neutralizing antibody that exhibits a different inhibitory profile compared to the only known potent broadly neutralizing CD4bs human antibody, b12, and may have implications for our understanding of the mechanisms of immune evasion and for the development of inhibitors and vaccines. JF - Journal of virology AU - Zhang, Mei-Yun AU - Xiao, Xiaodong AU - Sidorov, Igor A AU - Choudhry, Vidita AU - Cham, Fatim AU - Zhang, Peng Fei AU - Bouma, Peter AU - Zwick, Michael AU - Choudhary, Anil AU - Montefiori, David C AU - Broder, Christopher C AU - Burton, Dennis R AU - Quinnan, Gerald V AU - Dimitrov, Dimiter S AD - Human Immunovirology Group, Laboratory of Experimental and Computational Biology, Center for Cancer Research, National Cancer Institute-Frederick, NIH, Frederick, Maryland 21702-1201, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 9233 EP - 9242 VL - 78 IS - 17 SN - 0022-538X, 0022-538X KW - Antibodies, Monoclonal KW - 0 KW - Antigens, CD4 KW - Epitopes KW - Gene Products, env KW - HIV Antibodies KW - HIV Envelope Protein gp120 KW - Immunoglobulin Fab Fragments KW - Immunoglobulin G KW - Peptide Library KW - env Gene Products, Human Immunodeficiency Virus KW - gp140 envelope protein, Human immunodeficiency virus 1 KW - Alanine KW - OF5P57N2ZX KW - Index Medicus KW - Epitopes -- genetics KW - Humans KW - Immunoglobulin Fab Fragments -- genetics KW - Antigens, CD4 -- immunology KW - Biosensing Techniques KW - HIV Envelope Protein gp120 -- immunology KW - Alanine -- metabolism KW - Molecular Sequence Data KW - Alanine -- genetics KW - Immunoglobulin Fab Fragments -- immunology KW - Epitopes -- chemistry KW - Immunoglobulin G -- isolation & purification KW - Bacteriophages -- genetics KW - Amino Acid Sequence KW - Mutagenesis -- genetics KW - Immunoglobulin G -- immunology KW - Base Sequence KW - Immunoglobulin G -- genetics KW - Kinetics KW - Neutralization Tests KW - Gene Products, env -- immunology KW - Immunoglobulin Fab Fragments -- isolation & purification KW - Epitopes -- immunology KW - Cell Line KW - Genomics KW - HIV-1 -- immunology KW - HIV Antibodies -- isolation & purification KW - Antibodies, Monoclonal -- isolation & purification KW - HIV Antibodies -- immunology KW - Antibodies, Monoclonal -- genetics KW - HIV Antibodies -- genetics KW - HIV-1 -- classification KW - Cross Reactions -- immunology KW - Antibodies, Monoclonal -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66782934?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Identification+and+characterization+of+a+new+cross-reactive+human+immunodeficiency+virus+type+1-neutralizing+human+monoclonal+antibody.&rft.au=Zhang%2C+Mei-Yun%3BXiao%2C+Xiaodong%3BSidorov%2C+Igor+A%3BChoudhry%2C+Vidita%3BCham%2C+Fatim%3BZhang%2C+Peng+Fei%3BBouma%2C+Peter%3BZwick%2C+Michael%3BChoudhary%2C+Anil%3BMontefiori%2C+David+C%3BBroder%2C+Christopher+C%3BBurton%2C+Dennis+R%3BQuinnan%2C+Gerald+V%3BDimitrov%2C+Dimiter+S&rft.aulast=Zhang&rft.aufirst=Mei-Yun&rft.date=2004-09-01&rft.volume=78&rft.issue=17&rft.spage=9233&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 - 2004-09-16 N1 - Date created - 2004-08-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 2002 May 14;99(10):6913-8 [11997472] Biochemistry. 2002 Jun 4;41(22):7176-82 [12033952] J Virol. 2002 Jul;76(14):7293-305 [12072528] J Virol. 2002 Jul;76(14):7306-21 [12072529] Curr Opin Immunol. 2002 Aug;14(4):495-502 [12088685] Nat Rev Immunol. 2002 Sep;2(9):706-13 [12209139] AIDS. 2002 Oct 18;16(15):2019-25 [12370500] J Gen Virol. 2002 Nov;83(Pt 11):2723-32 [12388808] J Virol. 2003 Jan;77(1):560-70 [12477860] J Virol. 2003 Jan;77(1):642-58 [12477867] J Virol. 1991 Jan;65(1):489-93 [1702163] J Immunol. 1991 Jun 15;146(12):4325-32 [1710248] J Virol. 1991 Sep;65(9):4832-8 [1714520] AIDS Res Hum Retroviruses. 1998 May 1;14(7):545-50 [9591708] Science. 1998 Jun 19;280(5371):1884-8 [9632381] J Virol. 1998 Sep;72(9):7099-107 [9696803] J Virol. 1999 May;73(5):4009-18 [10196297] AIDS Res Hum Retroviruses. 1999 Apr 10;15(6):561-70 [10221533] J Virol. 1999 Jun;73(6):5225-30 [10233993] J Virol. 1999 Jul;73(7):5707-13 [10364321] Nat Med. 2000 Feb;6(2):200-6 [10655110] Nat Med. 2000 Feb;6(2):207-10 [10655111] J Virol. 2000 May;74(9):4183-91 [10756031] J Virol. 1991 Nov;65(11):6188-93 [1717717] Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10134-7 [1719545] Res Virol. 1991 Jul-Aug;142(4):247-59 [1724568] J Virol. 1992 Sep;66(9):5635-41 [1380099] J Virol. 1992 Dec;66(12):7538-42 [1433529] J Mol Biol. 1993 Apr 5;230(3):812-23 [8478936] J Virol. 1993 Jul;67(7):3978-88 [7685405] J Virol. 1993 Nov;67(11):6642-7 [7692082] J Virol. 1994 Jun;68(6):4001-8 [7514683] J Virol. 1994 Aug;68(8):4821-8 [7518527] AIDS Res Hum Retroviruses. 1994 Apr;10(4):359-69 [7520721] J Virol. 1994 Nov;68(11):6994-7000 [7933081] Science. 1994 Nov 11;266(5187):1024-7 [7973652] AIDS Res Hum Retroviruses. 1994 Dec;10(12):1651-8 [7888224] AIDS. 1995 Jun;9(6):F1-6 [7662189] AIDS. 1995 Aug;9(8):867-74 [7576320] J Virol. 1996 Feb;70(2):1100-8 [8551569] J Virol. 1996 Mar;70(3):1863-72 [8627711] J Virol. 1996 Oct;70(10):6751-8 [8794312] AIDS Res Hum Retroviruses. 1996 Jul 1;12(10):911-24 [8798976] J Virol. 1996 Dec;70(12):9046-50 [8971041] J Mol Biol. 1997 Apr 4;267(3):684-95 [9126846] J Infect Dis. 1997 May;175(5):1056-62 [9129066] Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10018-23 [9294155] AIDS. 1997;11 Suppl A:S87-98 [9451972] AIDS Res Hum Retroviruses. 1998 Jan 20;14(2):151-5 [9462925] J Infect Dis. 2000 Jul;182(1):326-9 [10882617] J Virol. 2001 Jun;75(11):4964-72 [11333875] Science. 2001 Aug 10;293(5532):1155-9 [11498595] J Virol. 2001 Nov;75(22):10892-905 [11602729] J Virol. 2002 Jan;76(2):644-55 [11752155] Vaccine. 2002 Dec 19;20 Suppl 4:A61-5 [12477430] Virology. 2003 Jan 5;305(1):124-37 [12504547] AIDS. 2003 Feb 14;17(3):301-9 [12556683] J Virol. 2003 Mar;77(5):3119-30 [12584337] Nat Med. 2003 Mar;9(3):343-6 [12579198] J Antimicrob Chemother. 2003 Apr;51(4):757-9 [12654737] J Virol. 2003 May;77(10):5863-76 [12719580] J Virol. 2003 Jul;77(14):8061-71 [12829845] Vaccine. 2003 Jul 28;21(24):3370-3 [12850342] J Virol. 2003 Oct;77(19):10557-65 [12970440] J Immunol Methods. 2003 Dec;283(1-2):17-25 [14659896] J Mol Biol. 2004 Jan 2;335(1):209-19 [14659751] J Virol. 2004 Jan;78(1):146-57 [14671096] J Acquir Immune Defic Syndr. 2004 Feb 1;35(2):169-77 [14722451] Antimicrob Agents Chemother. 2004 Feb;48(2):423-9 [14742190] Antiviral Res. 2004 Mar;61(3):161-4 [15168796] AIDS Res Hum Retroviruses. 2001 Dec 10;17(18):1757-65 [11788027] AIDS. 2002 Jan 25;16(2):227-33 [11807307] J Virol. 2002 Mar;76(5):2233-44 [11836401] J Biol Chem. 2002 May 10;277(19):17291-9 [11782464] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - United States nuclear industry perspective on useful improvements to radiation protection principles. AN - 66774904; 15303064 AB - The current radiation protection framework provides an adequate basis for protecting workers, the public and the environment. Nevertheless, international and national radiation protection organizations are presently engaged in updating, clarifying and enhancing radiation protection principles-and rightly so, given our culture of pursuing excellence in radiation safety through a process of continuous improvement. Accordingly, the nuclear energy industry appreciates the opportunity to provide its perspective on this effort. The nuclear energy industry's perspective is shaped in several ways-as an operator, we carry out a primary responsibility for protecting human health and safety and the environment; as a licensee, we are responsible for complying with government regulations; and as an energy producer, we are responsible for the safe, reliable, and economic generation of electricity for consumers. Our objective in regard to improving radiation protection principles is to help promote an outcome that has a clearly articulated basis in science, is flexible in regard to how it might be applied to a very wide range of current and future regulated activities, and is practical and cost-effective in terms of how it can be implemented and maintained. JF - Health physics AU - Andersen, Ralph L AD - Nuclear Energy Institute, 1776 I Street, NW, Suite 400, Washington, DC 20006-3700, USA. rla@nei.org Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 282 EP - 285 VL - 87 IS - 3 SN - 0017-9078, 0017-9078 KW - Index Medicus KW - United States KW - Occupational Exposure KW - Radiation Dosage KW - Humans KW - Government Agencies KW - Environmental Exposure KW - International Agencies KW - Radiation Protection KW - Nuclear Energy KW - Industry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66774904?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Health+physics&rft.atitle=United+States+nuclear+industry+perspective+on+useful+improvements+to+radiation+protection+principles.&rft.au=Andersen%2C+Ralph+L&rft.aulast=Andersen&rft.aufirst=Ralph&rft.date=2004-09-01&rft.volume=87&rft.issue=3&rft.spage=282&rft.isbn=&rft.btitle=&rft.title=Health+physics&rft.issn=00179078&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-14 N1 - Date created - 2004-08-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fluorescein-methotrexate transport in rat choroid plexus analyzed using confocal microscopy. AN - 66770568; 15126245 AB - One function of the vertebrate choroid plexus (CP) is removal of potentially toxic metabolites and xenobiotics from cerebrospinal fluid (CSF) to blood for subsequent excretion in urine and bile. We have used confocal microscopy and quantitative image analysis to follow transport of the large organic anion fluorescein-methotrexate (FL-MTX) from bath (CSF side) to blood vessels in intact rat CP and found concentrative transport from CSF to blood. With 2 microM FL-MTX in the bath, steady-state fluorescence in the subepithelium and vascular spaces exceeded bath levels by 5- to 10-fold, but fluorescence in epithelial cells was below bath levels. FL-MTX accumulation in subepithelium and vascular spaces was reduced by NaCN, Na removal, and by other organic anions, e.g., MTX, probenecid, and estrone sulfate. Increasing medium K 10-fold had no effect. None of these treatments affected cellular accumulation. However, two observations indicated that apical FL-MTX uptake was indeed mediated: first, cellular accumulation was a saturable function of medium substrate concentration; and second, digoxin and MK-571 reduced FL-MTX accumulation in the subepithelial/vascular spaces but also increased cellular accumulation severalfold. In the presence of digoxin and MK-571, cellular accumulation was concentrative, specific, and Na dependent. Thus transepithelial FL-MTX transport involved the following two mediated steps: Na-dependent uptake at the apical membrane and electroneutral efflux at the basolateral membrane, possibly on Oatp2 and Mrp1. JF - American journal of physiology. Renal physiology AU - Breen, Christopher M AU - Sykes, Destiny B AU - Baehr, Carsten AU - Fricker, Gert AU - Miller, David S AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - F562 EP - F569 VL - 287 IS - 3 SN - 1931-857X, 1931-857X KW - Bronchodilator Agents KW - 0 KW - Enzyme Inhibitors KW - Fluoresceins KW - Organic Anion Transporters KW - Propionates KW - Quinolines KW - fluorescein-methotrexate KW - verlukast KW - 5Q9O54P0H7 KW - Digoxin KW - 73K4184T59 KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Animals KW - Bronchodilator Agents -- pharmacology KW - Propionates -- pharmacology KW - Biological Transport -- drug effects KW - Epithelial Cells -- metabolism KW - Rats KW - Rats, Sprague-Dawley KW - Quinolines -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Biological Transport -- physiology KW - Organic Anion Transporters -- metabolism KW - Digoxin -- pharmacology KW - Male KW - Methotrexate -- pharmacokinetics KW - Methotrexate -- analogs & derivatives KW - Choroid Plexus -- metabolism KW - Fluoresceins -- pharmacokinetics KW - Microscopy, Confocal -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66770568?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+physiology.+Renal+physiology&rft.atitle=Fluorescein-methotrexate+transport+in+rat+choroid+plexus+analyzed+using+confocal+microscopy.&rft.au=Breen%2C+Christopher+M%3BSykes%2C+Destiny+B%3BBaehr%2C+Carsten%3BFricker%2C+Gert%3BMiller%2C+David+S&rft.aulast=Breen&rft.aufirst=Christopher&rft.date=2004-09-01&rft.volume=287&rft.issue=3&rft.spage=F562&rft.isbn=&rft.btitle=&rft.title=American+journal+of+physiology.+Renal+physiology&rft.issn=1931857X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-28 N1 - Date created - 2004-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differences between AGAP1, ASAP1 and Arf GAP1 in substrate recognition: interaction with the N-terminus of Arf1. AN - 66646669; 15212764 AB - The Arf GAPs are a structurally diverse group of proteins that catalyze the hydrolysis of GTP bound to Arf1. Here, we directly compare the role of amino acids 2-17 of Arf1, a GTP- and phospholipid-sensitive switch, for interaction with three Arf GAPs: Arf GAP1, AGAP1 and ASAP1. Sequestration of amino acids 2-17 with an antibody inhibited interaction with the three tested Arf GAPs. Examination of Arf1 mutants also indicated that [2-17]Arf1 is a critical structural determinant of interaction with all three Arf GAPs; however, the effect of specific mutations differed among the GAPs. Compared to wild-type Arf1, Arf1 with the amino terminal 13 ([Delta13]Arf1) and 17 amino acids ([Delta17]Arf1) deleted had 200- and 4000-fold reduced interaction with ASAP1 and 150-fold reduced interaction with AGAP1. In contrast, deletion of the amino terminus of Arf reduced interaction with Arf GAP1 by 5-fold. By analysis of point mutants, we found that lysines 15 and 16 had a greater contribution to productive interaction between Arf1, ASAP1 and AGAP1 than between Arf1 and Arf GAP1. Leucine 8 contributed to the interaction with Arf GAP1 but not with ASAP1 and AGAP1. Amino acids 2-17 of Arf1, isolated from the protein, inhibited GAP activity of Arf GAP1, ASAP1 and AGAP1 and bound directly to ASAP1. Taken together, our results indicate that (i) Arf GAPs interact with amino acids 2-17 of Arf1 and (ii) each subgroup of Arf GAPs has a unique interface with Arf1. JF - Cellular signalling AU - Yoon, Hye-Young AU - Jacques, Kerry AU - Nealon, Beth AU - Stauffer, Stacey AU - Premont, Richard T AU - Randazzo, Paul A AD - Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, Building 37, Room 4118, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 1033 EP - 1044 VL - 16 IS - 9 SN - 0898-6568, 0898-6568 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - Arfgap1 protein, mouse KW - Arfgap3 protein, mouse KW - GTPase-Activating Proteins KW - Immune Sera KW - GTP Phosphohydrolases KW - EC 3.6.1.- KW - ADP-Ribosylation Factor 1 KW - EC 3.6.5.2 KW - ADP-Ribosylation Factors KW - Index Medicus KW - Animals KW - Base Sequence KW - GTP Phosphohydrolases -- metabolism KW - Enzyme Activation -- drug effects KW - Mice KW - Substrate Specificity KW - Protein Binding KW - NIH 3T3 Cells KW - Immune Sera -- pharmacology KW - Protein Transport KW - Mutagenesis KW - Adaptor Proteins, Signal Transducing -- metabolism KW - ADP-Ribosylation Factors -- genetics KW - GTPase-Activating Proteins -- genetics KW - GTPase-Activating Proteins -- metabolism KW - ADP-Ribosylation Factor 1 -- immunology KW - ADP-Ribosylation Factors -- metabolism KW - ADP-Ribosylation Factor 1 -- metabolism KW - ADP-Ribosylation Factor 1 -- genetics KW - Adaptor Proteins, Signal Transducing -- genetics KW - ADP-Ribosylation Factor 1 -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66646669?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+signalling&rft.atitle=Differences+between+AGAP1%2C+ASAP1+and+Arf+GAP1+in+substrate+recognition%3A+interaction+with+the+N-terminus+of+Arf1.&rft.au=Yoon%2C+Hye-Young%3BJacques%2C+Kerry%3BNealon%2C+Beth%3BStauffer%2C+Stacey%3BPremont%2C+Richard+T%3BRandazzo%2C+Paul+A&rft.aulast=Yoon&rft.aufirst=Hye-Young&rft.date=2004-09-01&rft.volume=16&rft.issue=9&rft.spage=1033&rft.isbn=&rft.btitle=&rft.title=Cellular+signalling&rft.issn=08986568&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-07 N1 - Date created - 2004-06-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Does class size in first grade relate to children's academic and social performance or observed classroom processes? AN - 37948901; 2847269 JF - Developmental psychology Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 651 EP - 664 VL - 40 IS - 5 SN - 0012-1649, 0012-1649 KW - Sociology KW - Education KW - Academic achievement KW - Child psychology KW - Psychology KW - Child development KW - Developmental psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/37948901?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aibss&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Developmental+psychology&rft.atitle=Does+class+size+in+first+grade+relate+to+children%27s+academic+and+social+performance+or+observed+classroom+processes%3F&rft.au=&rft.aulast=&rft.aufirst=&rft.date=2004-09-01&rft.volume=40&rft.issue=5&rft.spage=651&rft.isbn=&rft.btitle=&rft.title=Developmental+psychology&rft.issn=00121649&rft_id=info:doi/ LA - English DB - International Bibliography of the Social Sciences (IBSS) N1 - Date revised - 2013-06-12 N1 - Last updated - 2013-09-16 N1 - SubjectsTermNotLitGenreText - 3518 10404; 10404; 2205 2212 10404; 2197 2212 6075 3483; 501 542 8322; 4049 ER - TY - JOUR T1 - Use of microarray for screening radiation induced molecular targets AN - 21268734; 6184266 JF - International Journal of Radiation Oncology, Biology, & Physics AU - Citrin, D AU - Beecken, W AU - Scott, T AU - Goley, E AU - Sproull, M AU - Tofilon, P AU - Camphausen, K AD - Radiation Oncology Branch, National Cancer Institute, Bethesda, MD Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - S360 PB - Elsevier Science Inc., Box 882 New York NY 10159 USA, [mailto:usinfo-f@elsevier.com] VL - 60 IS - 1 SN - 0360-3016, 0360-3016 KW - Biotechnology and Bioengineering Abstracts KW - Radiation KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21268734?accountid=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+Radiation+Oncology%2C+Biology%2C+%26+Physics&rft.atitle=Use+of+microarray+for+screening+radiation+induced+molecular+targets&rft.au=Citrin%2C+D%3BBeecken%2C+W%3BScott%2C+T%3BGoley%2C+E%3BSproull%2C+M%3BTofilon%2C+P%3BCamphausen%2C+K&rft.aulast=Citrin&rft.aufirst=D&rft.date=2004-09-01&rft.volume=60&rft.issue=1&rft.spage=S360&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Radiation+Oncology%2C+Biology%2C+%26+Physics&rft.issn=03603016&rft_id=info:doi/10.1016%2Fj.ijrobp.2004.07.201 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-03-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Radiation DO - http://dx.doi.org/10.1016/j.ijrobp.2004.07.201 ER - TY - JOUR T1 - Multiplex bead array assays for detection of soluble cytokines: Comparisons of sensitivity and quantitative values among kits from multiple manufacturers AN - 20378641; 7760273 AB - Background Multiplex bead array assays permit simultaneous cytometric quantitation of multiple cytokines in solution by capturing these to spectrally distinct beads. Because several manufacturers offer reagents to quantitate the same cytokines on a single instrument, a comparison should be made to determine whether these kits yield similar data and whether these data are comparable to enzyme-linked immunosorbent assay (ELISA). Methods This study compared cytokine detection kits by using Luminex 100. Twenty-six serum samples from seven subjects were analyzed for interferon-, interleukins 1, 6, and 8, and tumor necrosis factor- by using multiplex kits from LINCO Research, Bio-Rad Laboratories, R&D Systems, and BioSource International. Each assay was performed according to the manufacturers' specifications. Standard curves were generated by using reference concentrations supplied by each manufacturer. ELISAs for interleukin-8 were performed by using kits from R&D and BioSource. Results Cytokine levels followed similar patterns, although absolute concentrations differed among kits. ELISA and Luminex values for interleukin-8 were similar in kits from the same manufacturer. Conclusions Because relative cytokine measurements are often valuable when performed serially, it may be possible to make interlaboratory comparisons by using different kits. When comparison of absolute values is crucial, kits from the same supplier should be used. Within-vendor, bead array, and ELISA values appear comparable. JF - Cytometry Part B AU - Khan, Sameena S AU - Smith, Meghan S AU - Reda, Debra AU - Suffredini, Anthony F AU - McCoy Jr, J Philip AD - National Heart, Lung, and Blood Institute, Flow Cytometry Core Facility, National Institutes of Health, Bethesda, Maryland, mccoyj@nhlbi.nih.gov Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 35 EP - 39 PB - John Wiley & Sons, Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 61B IS - 1 SN - 1552-4949, 1552-4949 KW - Biotechnology and Bioengineering Abstracts KW - Interferon KW - Enzyme-linked immunosorbent assay KW - Interleukin 1 KW - Cytokines KW - Quantitation KW - Cytometry KW - Interleukin 8 KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20378641?accountid=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=Cytometry+Part+B&rft.atitle=Multiplex+bead+array+assays+for+detection+of+soluble+cytokines%3A+Comparisons+of+sensitivity+and+quantitative+values+among+kits+from+multiple+manufacturers&rft.au=Khan%2C+Sameena+S%3BSmith%2C+Meghan+S%3BReda%2C+Debra%3BSuffredini%2C+Anthony+F%3BMcCoy+Jr%2C+J+Philip&rft.aulast=Khan&rft.aufirst=Sameena&rft.date=2004-09-01&rft.volume=61B&rft.issue=1&rft.spage=35&rft.isbn=&rft.btitle=&rft.title=Cytometry+Part+B&rft.issn=15524949&rft_id=info:doi/10.1002%2Fcyto.b.20021 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-01-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Enzyme-linked immunosorbent assay; Cytokines; Interleukin 8; Cytometry; Interleukin 1; Interferon; Quantitation DO - http://dx.doi.org/10.1002/cyto.b.20021 ER - TY - JOUR T1 - Mass spectrometric measurement of differential reactivity of cysteine to localize protein-ligand binding sites. AN - 20326681; 7536351 AB - A new method for localizing binding sites of noncovalent drugs on proteins is presented. We have developed an accurate and high-throughput method based on the mass spectrometric measurement of differential reaction yield of cysteine alkylation (MS-DRC). This method, essentially a semiquantitative footprinting approach, is applicable to any type of ligand targeting cysteine-rich proteins because the method measures the reactivity change of each cysteine toward an alkylating agent instead of monitoring the drug itself. Thus, no modification of the drug is needed. In this study, the method is evaluated using tubulin as a model system. Tubulin and drug-treated tubulin were alkylated separately with several alkylating reagents, followed by proteolysis and high-performance liquid chromatography (HPLC)-tandem mass spectrometry (MS/MS) and HPLC-MS. Relative alkylation yields of each cysteine toward the reagents were measured by mass spectrometric quantitation. The reaction yields of each cysteine of two samples were compared to detect a particular cysteine (or cysteines) for which reaction yield was markedly decreased following drug binding. Monobromobimane (mBrB) showed the highest differential.Thus, the MS-DRC method with mBrB was evaluated with various tubulin agents, including the covalent agent T138067 and the noncovalent agents colchicine, podophyllotoxin, and 2-methoxyestradiol. Conformational changes induced by drug binding, as well as sites of direct binding, may be identified. JF - Analytical Biochemistry AU - Kim, Yeoun Jin AU - Pannell, Lewis K AU - Sackett, Dan L AD - National Institute of Diabetes, Digestive, Kidney Diseases, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD 20892, USA, sackettd@mail.nih.gov Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 376 EP - 383 PB - Elsevier Science B.V., P.O. Box 211 Amsterdam 1000 AE Netherlands, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl/] VL - 332 IS - 2 SN - 0003-2697, 0003-2697 KW - Biotechnology and Bioengineering Abstracts KW - Cysteine KW - Reactivity KW - Drug binding KW - Tubulin KW - Mass spectrometry KW - HPLC-MS KW - HPLC-MS/MS KW - Monobromobimane KW - Alkylation KW - T138067 KW - Colchicine KW - Podophyllotoxin KW - High-performance liquid chromatography KW - Proteolysis KW - Alkylating agents KW - Footprinting KW - Mass spectroscopy KW - Drugs KW - Quantitation KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20326681?accountid=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=Analytical+Biochemistry&rft.atitle=Mass+spectrometric+measurement+of+differential+reactivity+of+cysteine+to+localize+protein-ligand+binding+sites.&rft.au=Kim%2C+Yeoun+Jin%3BPannell%2C+Lewis+K%3BSackett%2C+Dan+L&rft.aulast=Kim&rft.aufirst=Yeoun&rft.date=2004-09-01&rft.volume=332&rft.issue=2&rft.spage=376&rft.isbn=&rft.btitle=&rft.title=Analytical+Biochemistry&rft.issn=00032697&rft_id=info:doi/10.1016%2Fj.ab.2004.06.033 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-09-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Alkylating agents; Proteolysis; High-performance liquid chromatography; Footprinting; Cysteine; Podophyllotoxin; Colchicine; Tubulin; Quantitation; Drugs; Mass spectroscopy; Alkylation DO - http://dx.doi.org/10.1016/j.ab.2004.06.033 ER - TY - JOUR T1 - Isolation and characterization of mammalian cells that are undergoing apoptosis by a bovine serum albumin density gradient AN - 20326638; 7536333 AB - When cells are treated with cytotoxic agents, they enter apoptosis asynchronously to yield cells at various stages of cellular deterioration. This mixture makes it difficult to study the biochemical pathways leading to cell death. We have fractionated apoptotic mammalian cells in a simple discontinuous bovine serum albumin (BSA) density gradient centrifugation into five layers, each containing cells at different stages of apoptosis, (1) nonapoptotic, (2) undergoing apoptosis, and (3) mature apoptotic cells, as judged by light and electron microscopy of chromatin condensation and by the extent of DNA fragmentation. Modifications of apoptosis markers including c-Jun N-terminal kinase/stress-activated protein kinase and procaspase 3 cleavage were apparent in those cells that are undergoing apoptosis. Apoptosis-specific histone H2B phosphorylation was highly elevated and DNA fragmentation activity in the cytoplasm was observed in those cells that are undergoing apoptosis, but not much was observed in the cells of other fractions. Results show that apoptotic cells can be fractionated easily by the BSA gradient method, and this method will be invaluable for studying the biochemical processes that drive apoptosis. JF - Analytical Biochemistry AU - Ajiro, Kozo AU - Th'ng, John AU - Yau, Jonathan AU - Nishi, Yoshimi AD - Laboratory of Cell Biology, Research Institute, Aichi Cancer Center, Nagoya, 464-8681, Japan, ajiro@niehs.nih.gov Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 226 EP - 233 PB - Elsevier Science B.V., P.O. Box 211 Amsterdam 1000 AE Netherlands, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl/] VL - 332 IS - 2 SN - 0003-2697, 0003-2697 KW - Biotechnology and Bioengineering Abstracts KW - MAP kinase KW - c-Jun amino-terminal kinase KW - Apoptosis KW - Chromatin KW - Cytotoxic agents KW - Centrifugation KW - DNA fragmentation KW - Bovine serum albumin KW - Mammalian cells KW - Density gradients KW - Phosphorylation KW - Cytoplasm KW - Histone H2B KW - Condensation KW - Electron microscopy KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20326638?accountid=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=Analytical+Biochemistry&rft.atitle=Isolation+and+characterization+of+mammalian+cells+that+are+undergoing+apoptosis+by+a+bovine+serum+albumin+density+gradient&rft.au=Ajiro%2C+Kozo%3BTh%27ng%2C+John%3BYau%2C+Jonathan%3BNishi%2C+Yoshimi&rft.aulast=Ajiro&rft.aufirst=Kozo&rft.date=2004-09-01&rft.volume=332&rft.issue=2&rft.spage=226&rft.isbn=&rft.btitle=&rft.title=Analytical+Biochemistry&rft.issn=00032697&rft_id=info:doi/10.1016%2Fj.ab.2004.05.035 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-09-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - MAP kinase; Apoptosis; c-Jun amino-terminal kinase; Chromatin; Cytotoxic agents; DNA fragmentation; Centrifugation; Phosphorylation; Density gradients; Mammalian cells; Bovine serum albumin; Cytoplasm; Condensation; Histone H2B; Electron microscopy DO - http://dx.doi.org/10.1016/j.ab.2004.05.035 ER - TY - JOUR T1 - CYP1A1 and GSTM1 polymorphisms in relation to lung cancer risk in Chinese women AN - 20189407; 6021243 AB - We examined CYP1A1 (I462V) and GSTM1 null polymorphisms in 200 female cases and 144 female controls selected from a population-based case-control study of lung cancer conducted in northeast China, where the rates of lung cancer among Chinese women are especially high. The CYP1A1 codon 462 point mutation in exon 7 (I462V) causes an Ile-Val substitution near the heme binding site. This mutation correlates with inducibility of aryl hydrocarbon hydrolase (AHH) activity, which activates polycyclic aromatic hydrocarbons (PAHs) in tobacco smoke and in indoor air pollution from coal-burning stoves, a risk factor for lung cancer in this study population. We found that the CYP1A1 I462V genotype (combined ile/val and val/val) was significantly associated with lung cancer risk. The odds ratio (OR) was 2.5 (95% confidence interval [CI], 1.55-4.03) after adjustment for significant risk factors such as age, ever smoking status, family history of cancer, and eye irritation when cooking. The association was more pronounced among non-smokers (OR=3.67; 95% CI, 1.85-7.28) than among smokers (OR=1.74, 95% CI, 0.85-3.54). In contrast, we did not find a significant association with the GSTM1 null genotype. In summary, our case-control study of lung cancer among women in northeast China revealed an elevated risk associated with the CYP1A1 I462V genotype, but no interaction with smoking or indoor air pollution was found. JF - Cancer Letters AU - Yang, X R AU - Wacholder, S AU - Xu, Z AU - Dean, M AU - Clark, V AU - Gold, B AU - Brown, L M AU - Stone, B J AU - Fraumeni, JF Jr AU - Caporaso, N E AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, 6120 Executive Blvd, Bethesda MD 20892, USA, royang@mail.nih.gov Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 197 EP - 204 PB - Elsevier Science Ltd., The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:usinfo-f@elsevier.com], [URL:http://www.elsevier.nl] VL - 213 IS - 2 SN - 0304-3835, 0304-3835 KW - Pollution Abstracts KW - CYP1A1 I462V KW - GSTM1 KW - Lung cancer KW - Chinese women KW - Age KW - Eye KW - Indoor air pollution KW - Genotypes KW - Cancer KW - Smoke KW - Genetics KW - Smoking KW - Tobacco KW - polycyclic aromatic hydrocarbons KW - cooking KW - China, People's Rep. KW - Females KW - Mutation KW - aromatic hydrocarbons KW - P 0000:AIR POLLUTION UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20189407?accountid=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=Cancer+Letters&rft.atitle=CYP1A1+and+GSTM1+polymorphisms+in+relation+to+lung+cancer+risk+in+Chinese+women&rft.au=Yang%2C+X+R%3BWacholder%2C+S%3BXu%2C+Z%3BDean%2C+M%3BClark%2C+V%3BGold%2C+B%3BBrown%2C+L+M%3BStone%2C+B+J%3BFraumeni%2C+JF+Jr%3BCaporaso%2C+N+E&rft.aulast=Yang&rft.aufirst=X&rft.date=2004-09-01&rft.volume=213&rft.issue=2&rft.spage=197&rft.isbn=&rft.btitle=&rft.title=Cancer+Letters&rft.issn=03043835&rft_id=info:doi/10.1016%2Fj.canlet.2004.06.040 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-09-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Age; Eye; Indoor air pollution; Genotypes; Cancer; Smoke; Smoking; Genetics; Tobacco; polycyclic aromatic hydrocarbons; cooking; Females; Mutation; aromatic hydrocarbons; Lung cancer; China, People's Rep. DO - http://dx.doi.org/10.1016/j.canlet.2004.06.040 ER - TY - JOUR T1 - Inhibition of Growth by p205: A Nuclear Protein and Putative Tumor Suppressor Expressed during Myeloid Cell Differentiation AN - 19952703; 6006442 AB - p205 belongs to a family of interferon-inducible proteins called the IFI-200 family, which have been implicated in the regulation of cell growth and differentiation. While p205 is induced in hematopoietic stem cells during myeloid cell differentiation, its function is not known. Therefore, the aim of this study was to determine the role of p205 in regulating proliferation in hematopoietic progenitor cells and in nonhematopoietic cell lines. We found that p205 localizes to the nucleus in hematopoietic and nonhematopoietic cell lines. Transient expression of p205 in murine IL-3-dependent BaF3 and 32D-C123 progenitor cell lines inhibited IL-3-induced growth and proliferation. The closely related IFI-200 family members, p204 and p202, similarly inhibited IL-3- dependent progenitor cell proliferation. p205 also inhibited the proliferation and growth of normal hematopoietic progenitor cells. In nonhematopoietic cell lines, p205 and p204 expression inhibited NIH3T3 cell colony formation in vitro, and microinjection of p205 expression vectors into NIH3T3 fibroblasts inhibited serum-induced proliferation. We have determined the functional domains of p205 necessary for activity, which were identified as the N-terminal domain in apoptosis and interferon response (DAPIN)/PYRIN domain, and the C-terminal retinoblastoma protein (Rb)-binding motif. In addition, we have demonstrated that a putative ataxia telangiectasia, mutated (ATM) kinase phosphorylation site specifically regulates the activity of p205. Taken together, these data suggest that p205 is a potent cell growth regulator whose activity is mediated by its protein-binding domains. We propose that during myelomonocytic cell differentiation, induction of p205 expression contributes to cell growth arrest, thus allowing progenitor cells to differentiate. JF - Stem Cells AU - Dermott, Jonathan M AU - Gooya, John M AU - Asefa, Benyam AU - Weiler, Sarah R AU - Smith, Mark AU - Keller, Jonathan R AD - Laboratory of Molecular Immunoregulation and Basic Research Program, Science Applications International Corporation (SAIC)-Frederick, Inc., Center for Cancer Research, National Cancer Institute at Frederick, Frederick, Maryland, USA Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 832 EP - 848 VL - 22 IS - 5 SN - 1066-5099, 1066-5099 KW - Biotechnology and Bioengineering Abstracts; Oncogenes & Growth Factors Abstracts; Immunology Abstracts KW - Tumor suppressor genes KW - Apoptosis KW - Data processing KW - Lymphocytes B KW - Retinoblastoma protein KW - Myeloid cells KW - Microinjection KW - Fibroblasts KW - Pyrin protein KW - Expression vectors KW - Interferon KW - Ataxia telangiectasia mutated protein KW - Differentiation KW - Stem cells KW - Colonies KW - Phosphorylation KW - Growth regulators KW - interferon-inducible protein KW - Hemopoiesis KW - Nuclei KW - Cell proliferation KW - W 30905:Medical Applications KW - B 26670:Tumor Suppressors KW - F 06910:Microorganisms & Parasites UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19952703?accountid=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+Cell+Biology&rft.atitle=Membrane+insertion+of+anthrax+protective+antigen+and+cytoplasmic+delivery+of+lethal+factor+occur+at+different+stages+of+the+endocytic+pathway&rft.au=Abrami%2C+Laurence%3BLindsay%2C+Margaret%3BParton%2C+Robert+G%3BLeppla%2C+Stephen+H%3BVan+Der+Goot%2C+FGisou&rft.aulast=Abrami&rft.aufirst=Laurence&rft.date=2004-08-30&rft.volume=166&rft.issue=5&rft.spage=645&rft.isbn=&rft.btitle=&rft.title=Journal+of+Cell+Biology&rft.issn=00219525&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-08-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Tumor suppressor genes; Data processing; Apoptosis; Lymphocytes B; Retinoblastoma protein; Microinjection; Myeloid cells; Fibroblasts; Expression vectors; Pyrin protein; Differentiation; Ataxia telangiectasia mutated protein; Interferon; Colonies; Stem cells; Growth regulators; Phosphorylation; interferon-inducible protein; Hemopoiesis; Cell proliferation; Nuclei ER - TY - JOUR T1 - PPARgamma influences susceptibility to DMBA-induced mammary, ovarian and skin carcinogenesis AN - 19807585; 5985929 AB - Peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the nuclear receptor superfamily, plays a role in adipocyte differentiation, type II diabetes, macrophage response to inflammation and is suggested to influence carcinogen-induced colon cancer. Studies done in vitro and in vivo also revealed that PPARgamma ligands might promote differentiation and/or regression of mammary tumors. To directly evaluate the role of PPARgamma in mammary carcinogenesis, PPARgamma wild-type (+/+) or heterozygous (+/-) mice were administered 1 mg 7,12-dimethylbenzaanthracene (DMBA) by gavage once a week for 6 weeks and followed for a total of 25 weeks. Compared with congenic PPARgamma(+/+) littermate controls, PPARgamma(+/-) mice had early evidence for increased susceptibility to DMBA-mediated carcinogenesis based on a 1.6-fold increase in the percentage of mice with skin papillomas, as well as a 1.7-fold increase in the numbers of skin papillomas per mouse (P < 0.05). Similarly, PPARgamma(+/-) mice also had a 1.5-fold decreased survival rate (P = 0.059), and a 1.7-fold increased incidence of total tumors per mouse (P < 0.01). Moreover, PPARgamma(+/-) mice had an almost 3-fold increase in mammary adenocarcinomas (P < 0.05), an over 3-fold increase in ovarian granulosa cell carcinomas (P < 0.05), an over 3-fold increase in malignant tumors (P < 0.02) and a 4.6-fold increase in metastatic incidence. These results are the first to demonstrate an increased susceptibility in vivo of PPARgamma haploinsufficiency to DMBA- mediated carcinogenesis and suggest that PPARgamma may act as a tumor modifier of skin, ovarian and breast cancers. The data also support evidence suggesting a beneficial role for PPARgamma-specific ligands in the chemoprevention of mammary, ovarian and skin carcinogenesis. JF - Carcinogenesis AU - Nicol, Christopher J AU - Yoon, Michung AU - Ward, Jerrold M AU - Yamashita, Masamichi AU - Fukamachi, Katsumi AU - Peters, Jeffrey M AU - Gonzalez, Frank J AD - Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 1747 EP - 1755 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 - 25 IS - 9 SN - 0143-3334, 0143-3334 KW - Toxicology Abstracts KW - Macrophages KW - Granulosa cells KW - Skin KW - Data processing KW - Peroxisome proliferator-activated receptors KW - Mammary gland KW - Nuclear receptors KW - Tumors KW - Colon cancer KW - Inflammation KW - Diabetes mellitus KW - Metastases KW - Differentiation KW - 9,10-Dimethyl-1,2-benzanthracene KW - Adipocytes KW - Carcinogenesis KW - haploinsufficiency KW - Breast cancer KW - Ovarian carcinoma KW - Adenocarcinoma KW - Papilloma KW - X 24490:Other UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19807585?accountid=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=PPARgamma+influences+susceptibility+to+DMBA-induced+mammary%2C+ovarian+and+skin+carcinogenesis&rft.au=Nicol%2C+Christopher+J%3BYoon%2C+Michung%3BWard%2C+Jerrold+M%3BYamashita%2C+Masamichi%3BFukamachi%2C+Katsumi%3BPeters%2C+Jeffrey+M%3BGonzalez%2C+Frank+J&rft.aulast=Nicol&rft.aufirst=Christopher&rft.date=2004-09-01&rft.volume=25&rft.issue=9&rft.spage=1747&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&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 - Macrophages; Granulosa cells; Data processing; Skin; Peroxisome proliferator-activated receptors; Mammary gland; Nuclear receptors; Colon cancer; Tumors; Inflammation; Metastases; Diabetes mellitus; Differentiation; Adipocytes; 9,10-Dimethyl-1,2-benzanthracene; haploinsufficiency; Carcinogenesis; Breast cancer; Ovarian carcinoma; Papilloma; Adenocarcinoma ER - TY - JOUR T1 - Biological pre-treatment of wastewater containing sulfate using anaerobic immobilized cells AN - 19673492; 6021286 AB - Biological reduction of sulfate to sulfide using sulfate reducing bacteria (SRB) was investigated. A respirometer was used to study the sulfide toxicity in the systems fed glucose, the results showed that sulfide would start to inhibit methanogens when the dissolved sulfide and total sulfide concentrations were 276.4 and 304.6 mg/L, respectively. When chemostats were used to study the Monod kinetic coefficients, Y, k sub(d), K sub(s), and k were 0.36 mg VSS (volatile suspended solids) using SRB/mg SO sub(4)-S, 0.05/day, 147.30 mg SO sub(4)- S/L, and 6.50 mg SO sub(4)-S/mg VSS using SRB-d, respectively. Using pure cultural techniques, SRB were found to be 29.45% of the VSS in the chemostats. Sulfate removal using an upflow anaerobic filter packed with immobilized cells was also investigated. Under sulfate loading rates of 0.2 and 0.4 g SO sub(4)-S/L day, and a hydraulic retention time (HRT) of 2 days, a sulfate removal efficiency greater than 93% could be achieved. When the filter was operated under COD (chemical oxygen demand)/S from 10/1 to 5/1 and HRTs of 2, 1 and 0.5 days, sulfate removal efficiency was between 98.1 and 70.9%. It is believed that protection by the immobilized cell structure caused the microbial cells in the filter to tolerate higher dissolved sulfide (447.8 mg/L) and total sulfide (940.3 mg/L) levels, allowing a much higher biomass concentration (13.2-13.5 g VSS/L) to be reached. JF - Journal of Hazardous Materials AU - Kuo, W-C AU - Shu, T-Y AD - Department of Environmental Science and Engineering, National Pingtung University of Science and Technology, Nei Pu, Pingtung 91207, Taiwan, ROC, xwck@mail.npust.edu.tw Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 147 EP - 155 PB - Elsevier Science B.V., P.O. Box 211 Amsterdam 1000 AE Netherlands, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl/] VL - 113 IS - 1-3 SN - 0304-3894, 0304-3894 KW - Toxicology Abstracts; Water Resources Abstracts KW - Sulfide toxicity KW - Sulfate reduction KW - Bubble respirometer KW - Immobilized cells KW - Methane production KW - Sulfates KW - Hydraulics KW - Glucose KW - Chemical Oxygen Demand KW - Hazardous Materials KW - Chemostats KW - Suspended Solids KW - Retention Time KW - Sulfides KW - Sulfur Bacteria KW - Protection KW - Chemical oxygen demand KW - Toxicity KW - Methanogenic bacteria KW - Biomass KW - Sulfate KW - Filters KW - Hydraulic Loading KW - Sulfide KW - Volatiles KW - Structure KW - Kinetics KW - Load Distribution KW - Waste water KW - Wastewater Treatment KW - SW 3040:Wastewater treatment processes KW - X 24490:Other UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19673492?accountid=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=Biological+pre-treatment+of+wastewater+containing+sulfate+using+anaerobic+immobilized+cells&rft.au=Kuo%2C+W-C%3BShu%2C+T-Y&rft.aulast=Kuo&rft.aufirst=W-C&rft.date=2004-09-01&rft.volume=113&rft.issue=1-3&rft.spage=147&rft.isbn=&rft.btitle=&rft.title=Journal+of+Hazardous+Materials&rft.issn=03043894&rft_id=info:doi/10.1016%2Fj.jhazmat.2004.05.033 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-03-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Hydraulics; Glucose; Immobilized cells; Chemical oxygen demand; Toxicity; Biomass; Methanogenic bacteria; Sulfate; Filters; Sulfide; Chemostats; Volatiles; Kinetics; Waste water; Sulfates; Retention Time; Sulfur Bacteria; Sulfides; Protection; Chemical Oxygen Demand; Hydraulic Loading; Hazardous Materials; Suspended Solids; Structure; Load Distribution; Wastewater Treatment DO - http://dx.doi.org/10.1016/j.jhazmat.2004.05.033 ER - TY - JOUR T1 - Eating Disorder or Disordered Eating? Non-normative Eating Patterns in Obese Individuals AN - 19413015; 6042996 AB - Binge eating disorder (BED) and night eating syndrome (NES) are putative eating disorders frequently seen in obese individuals. Data suggest that BED fulfills criteria for a mental disorder. Criteria for NES are evolving but at present do not require distress or functional impairment. It remains unclear whether BED and NES, as they are currently defined, are optimally useful for characterizing distinct patient subgroups. We propose that a distinction be made between "eating disorders" and "non-normative" eating patterns without associated distress or impairment. Although non-normative eating patterns may not be considered mental disorders, they may be very important in terms of their impact on body weight and health. More precise behavioral and metabolic characterization of subgroups with eating disorders and non-normative eating behaviors has important implications for understanding the etiology, pathophysiology, and treatment of obesity. Ultimately, better understanding of the many pathways to increased energy intake may lead to targeted strategies for prevention of overweight and obesity in at-risk individuals and populations. JF - Obesity Research AU - Tanofsky-Kraff, Marian AU - Yanovski, Susan Z AD - Unit on Growth and Obesity, Developmental Endocrinology Branch, National Institute of Child Health and Human Development and. Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Department of Health and Human Services, Bethesda, Maryland. Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 1361 EP - 1366 PB - North American Association for the Study of Obesity, 1090 Amsterdam Ave., Ste. 14K New York NY 10025 USA, [mailto:helener@mindspring.com], [URL:http://www.naaso.org] VL - 12 IS - 9 SN - 1071-7323, 1071-7323 KW - Physical Education Index KW - Obesity KW - Eating disorders KW - Preventive health KW - Strategy KW - Diet (weight control) KW - Patients KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19413015?accountid=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=Obesity+Research&rft.atitle=Eating+Disorder+or+Disordered+Eating%3F+Non-normative+Eating+Patterns+in+Obese+Individuals&rft.au=Tanofsky-Kraff%2C+Marian%3BYanovski%2C+Susan+Z&rft.aulast=Tanofsky-Kraff&rft.aufirst=Marian&rft.date=2004-09-01&rft.volume=12&rft.issue=9&rft.spage=1361&rft.isbn=&rft.btitle=&rft.title=Obesity+Research&rft.issn=10717323&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2007-06-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Obesity; Preventive health; Eating disorders; Strategy; Diet (weight control); Patients ER - TY - JOUR T1 - Differential Monocyte Activation Underlies Strain-Specific Mycobacterium tuberculosis Pathogenesis AN - 18063724; 5992276 AB - In vitro infection of monocytes with Mycobacterium tuberculosis HN878 and related W/Beijing isolates preferentially induced interleukin-4 (IL-4) and IL- 13, which characterize Th2 polarized immunity. In contrast, CDC1551 induced more IL-12 and other molecules associated with phagocyte activation and Th1 protective immunity. The differential cytokine-chemokine response was mediated by extracted lipids, suggesting that these molecules regulate host responses to infection. JF - Infection and Immunity AU - Manca, Claudia AU - Reed, Michael B AU - Freeman, Sherry AU - Mathema, Barun AU - Kreiswirth, Barry AU - Barry, Clifton E AU - Kaplan, Gilla AD - Laboratory of Mycobacterial Immunity and Pathogenesis. Tuberculosis Center, Public Health Research Institute, International Center for Public Health, Newark, New Jersey. Tuberculosis Research Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 5511 EP - 5514 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 72 IS - 9 SN - 0019-9567, 0019-9567 KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - Interleukin 4 KW - Lipids KW - Helper cells KW - Infection KW - Cell activation KW - Interleukin 12 KW - Phagocytes KW - Lymphocytes T KW - Monocytes KW - Mycobacterium tuberculosis 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/18063724?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Differential+Monocyte+Activation+Underlies+Strain-Specific+Mycobacterium+tuberculosis+Pathogenesis&rft.au=Manca%2C+Claudia%3BReed%2C+Michael+B%3BFreeman%2C+Sherry%3BMathema%2C+Barun%3BKreiswirth%2C+Barry%3BBarry%2C+Clifton+E%3BKaplan%2C+Gilla&rft.aulast=Manca&rft.aufirst=Claudia&rft.date=2004-09-01&rft.volume=72&rft.issue=9&rft.spage=5511&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mycobacterium tuberculosis; Interleukin 4; Lymphocytes T; Monocytes; Helper cells; Interleukin 12; Lipids; Cell activation; Phagocytes; Infection ER - TY - JOUR T1 - Level of Maternal IgG Anti-Group B Streptococcus Type III Antibody Correlated with Protection of Neonates against Early-Onset Disease Caused by This Pathogen AN - 18053620; 6008414 AB - The present study estimates the level of maternal immunoglobulin (Ig) G anti-group B streptococcus (GBS) type III required to protect neonates against early-onset disease (EOD) caused by this pathogen. Levels of maternal serum IgG anti-GBS type III, measured by enzyme-linked immunosorbent assay, in 26 case patients (neonates with EOD caused by GBS type III) and 143 matched control subjects (neonates colonized by GBS type III who did not develop EOD) of greater than or equal to 34 weeks gestation were compared. The probability of EOD decreased with increasing levels of maternal IgG anti-GBS type III (P = .01). Neonates whose mothers had greater than or equal to 10 mu g/mL IgG anti-GBS type III had a 91% lower risk for EOD, compared with those whose mothers had levels of <2 mu g/mL. A vaccine that induces IgG anti-GBS type III levels of greater than or equal to 10 mu g/mL in mothers can be predicted to offer a significant degree of protection against EOD caused by this pathogen. JF - Journal of Infectious Diseases AU - Lin, Feng-Ying C AU - Weisman, LE AU - Azimi, PH AU - Philips, JB III AU - Clark, P AU - Regan, J AU - Rhoads, G G AU - Frasch, CE AU - Gray, B M AU - Troendle, J AU - Brenner, R A AU - Moyer, P AU - Clemens, J D AD - National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA Y1 - 2004/09/01/ PY - 2004 DA - 2004 Sep 01 SP - 928 EP - 934 VL - 190 IS - 5 SN - 0022-1899, 0022-1899 KW - Microbiology Abstracts B: Bacteriology KW - Streptococcus KW - Enzyme-linked immunosorbent assay KW - Infectious diseases KW - Guillain-Barre syndrome KW - Gestation KW - Immunoglobulin G KW - Vaccines KW - Neonates KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18053620?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Infectious+Diseases&rft.atitle=Level+of+Maternal+IgG+Anti-Group+B+Streptococcus+Type+III+Antibody+Correlated+with+Protection+of+Neonates+against+Early-Onset+Disease+Caused+by+This+Pathogen&rft.au=Lin%2C+Feng-Ying+C%3BWeisman%2C+LE%3BAzimi%2C+PH%3BPhilips%2C+JB+III%3BClark%2C+P%3BRegan%2C+J%3BRhoads%2C+G+G%3BFrasch%2C+CE%3BGray%2C+B+M%3BTroendle%2C+J%3BBrenner%2C+R+A%3BMoyer%2C+P%3BClemens%2C+J+D&rft.aulast=Lin&rft.aufirst=Feng-Ying&rft.date=2004-09-01&rft.volume=190&rft.issue=5&rft.spage=928&rft.isbn=&rft.btitle=&rft.title=Journal+of+Infectious+Diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Streptococcus; Neonates; Immunoglobulin G; Guillain-Barre syndrome; Infectious diseases; Gestation; Enzyme-linked immunosorbent assay; Vaccines ER - TY - JOUR T1 - Agricultural pesticide use and adenocarcinomas of the stomach and oesophagus AN - 18034737; 5992648 AB - AIMS: To evaluate the risk of the stomach and oesophageal adenocarcinomas associated with farming and agricultural pesticide use. METHODS: Population based case-control study in eastern Nebraska. Telephone interviews were conducted with men and women diagnosed with adenocarcinoma of the stomach (n = 170) or oesophagus (n = 137) between 1988 and 1993, and controls (n = 502) randomly selected from the same geographical area. Unconditional logistic regression was used to calculate adjusted odds ratios (ORs) for farming and for use of individual and chemical classes of insecticides and herbicides, including pesticides classified as nitrosatable (able to form N-nitroso compounds on reaction with nitrite). Non-farmers were used as the reference category for all analyses. RESULTS: Ever living or working on a farm, duration of farming, and size of the farm were not associated with stomach or oesophageal adenocarcinomas. There was no association for either cancer with ever-use of insecticides (stomach OR 0.9, 95% CI 0.6 to 1.4; oesophagus OR 0.7, 95% CI 0.4 to 1.1) or herbicides (stomach OR 0.9, 95% CI 0.5 to 1.4; oesophagus OR 0.7, 95% CI 0.4 to 1.2). Likewise, individual pesticides, including individual nitrosatable pesticides, were not significantly associated with risk. CONCLUSIONS: No significant associations were found between specific agricultural pesticide exposures and the risk of stomach or oesophageal adenocarcinomas among Nebraska farmers. JF - Occupational and Environmental Medicine AU - Lee, W J AU - Lijinsky, W AU - Heineman, E F AU - Markin, R S AU - Weisenburger, D D AU - Ward, M H AD - Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 743 EP - 749 PB - B M J Publishing Group, B.M.A. House Tavistock Sq. London WC1H 9JR UK VL - 61 IS - 9 SN - 1351-0711, 1351-0711 KW - man KW - Health & Safety Science Abstracts; Toxicology Abstracts; Risk Abstracts KW - Risk assessment KW - Esophagus KW - Farms KW - Agrochemicals KW - Cancer KW - Pesticides KW - USA, Nebraska KW - Adenocarcinoma KW - Occupational exposure KW - Stomach KW - R2 23080:Industrial and labor KW - X 24134:Pathology KW - H 5000:Pesticides UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18034737?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+and+Environmental+Medicine&rft.atitle=Agricultural+pesticide+use+and+adenocarcinomas+of+the+stomach+and+oesophagus&rft.au=Lee%2C+W+J%3BLijinsky%2C+W%3BHeineman%2C+E+F%3BMarkin%2C+R+S%3BWeisenburger%2C+D+D%3BWard%2C+M+H&rft.aulast=Lee&rft.aufirst=W&rft.date=2004-09-01&rft.volume=61&rft.issue=9&rft.spage=743&rft.isbn=&rft.btitle=&rft.title=Occupational+and+Environmental+Medicine&rft.issn=13510711&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Esophagus; Farms; Pesticides; Adenocarcinoma; Cancer; Stomach; Occupational exposure; Risk assessment; Agrochemicals; USA, Nebraska ER - TY - JOUR T1 - Chronic inorganic arsenic exposure induces hepatic global and individual gene hypomethylation: implications for arsenic hepatocarcinogenesis AN - 18028003; 5985932 AB - Inorganic arsenic is a human carcinogen that can target the liver, but its carcinogenic mechanisms are still unknown. Global DNA hypomethylation occurs during arsenic-induced malignant transformation in rodent liver cells. DNA hypomethylation can increase gene expression, particularly when occurring in the promoter region CpG sites, and may be a non-genotoxic mechanism of carcinogenesis. Thus, in the present study liver samples of male mice exposed to 0 (control) or 45 p.p.m. arsenic (as NaAsO sub(2)) in the drinking water for 48 weeks were analyzed for gene expression and DNA methylation. Chronic arsenic exposure caused hepatic steatosis, a lesion also linked to consumption of methyl-deficient diets. Microarray analysis of liver samples showed arsenic induced aberrant gene expression including steroid-related genes, cytokines, apoptosis-related genes and cell cycle-related genes. In particular, the expression of the estrogen receptor-alpha (ER-alpha), and cyclin D1 genes were markedly increased. RT-PCR and immunohistochemistry confirmed arsenic-induced increases in hepatic ER-alpha and cyclin D1 transcription and translation products, respectively. Arsenic induced hepatic global DNA hypomethylation, as evidenced by 5-methylcytosine content of DNA and by the methyl acceptance assay. Arsenic also markedly reduced the methylation within the ER-alpha gene promoter region, as assessed by methylation-specific PCR, and this reduction was statistically significant in 8 of 13 CpG sites within the promoter region. Overall, in controls 28.3% of the ER-alpha promoter region CpG sites were methylated, but only 2.9% were methylated after chronic arsenic exposure. Thus, long-term exposure of mice to arsenic in the drinking water can induce aberrant gene expression, global DNA hypomethylation, and the hypomethylation of the ER- alpha gene promoter, all of which could potentially contribute to arsenic hepatocarcinogenesis. JF - Carcinogenesis AU - Chen, Hua AU - Li, Shuanfang AU - Liu, Jie AU - Diwan, Bhalchandra A AU - Barrett, JCarl AU - Waalkes, Michael P AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute at the National Institutes of Environmental Health Sciences, Research Triangle Park, North Carolina, Laboratory of Biosystems and Cancer, National Cancer Institute, Bethesda, Maryland and Basic Research Program, SAIC-Frederick, Frederick, Maryland, USA Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 1779 EP - 1786 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 - 25 IS - 9 SN - 0143-3334, 0143-3334 KW - mice KW - Toxicology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Gene expression KW - Arsenic KW - Carcinogenesis KW - Liver KW - DNA KW - DNA methylation KW - Drinking water KW - Methylation KW - Estrogen receptors KW - cyclin D1 KW - X 24165:Biochemistry KW - X 24162:Chronic exposure KW - N 14550:General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18028003?accountid=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=Chronic+inorganic+arsenic+exposure+induces+hepatic+global+and+individual+gene+hypomethylation%3A+implications+for+arsenic+hepatocarcinogenesis&rft.au=Chen%2C+Hua%3BLi%2C+Shuanfang%3BLiu%2C+Jie%3BDiwan%2C+Bhalchandra+A%3BBarrett%2C+JCarl%3BWaalkes%2C+Michael+P&rft.aulast=Chen&rft.aufirst=Hua&rft.date=2004-09-01&rft.volume=25&rft.issue=9&rft.spage=1779&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Gene expression; Arsenic; Carcinogenesis; DNA methylation; DNA; Liver; Drinking water; Estrogen receptors; Methylation; cyclin D1 ER - TY - JOUR T1 - Development of a Noninvasive Method for Detecting and Monitoring the Time Course of Helicobacter pylori Infection AN - 18025181; 5992131 AB - Helicobacter pylori infection status following experimental inoculation of mice presently requires euthanasia. The purpose of this study was to develop a method for following the time course of H. pylori infection in live experimental animals. Twenty-six C57BL/6, Helicobacter-free female mice were inoculated with H. pylori Sydney strain 1, and 16 mice were sham inoculated. The mice were repeatedly tested during a period of about 1 year with an H. pylori species- specific primer-based PCR analysis of DNA extracted from fecal pellets of mice. The mice were euthanized at 6 months (n = 15) and 10 months (n = 15) to determine their infection status by histology, culture, and PCR of gastric specimens. H. pylori-inoculated mice were tested via the PCR method at 6 and 10 months prior to necropsy. Nine of 13 (69%) and 10 of 13 (77%) mice tested at 6 and 10 months, respectively, were positive. All sham-inoculated mice were negative. These two PCR results suggested a specificity of 100% with a sensitivity range between 69 and 77%. In contrast, sensitivity and specificity rose to 90 and 100% if groups of mice were tested once daily for 4 days. Seventy-seven to 85% of the experimental mice were also positive for H. pylori by culture. The histopathology demonstrated mild to severe gastritis. These findings demonstrate that the persistence or transience of H. pylori infection in live mice can be repeatedly evaluated over time. This method could allow the determination of the time course of infection and the efficacy of medications and/or vaccine without necropsy. JF - Infection and Immunity AU - Nyan, Dougbeh C AU - Welch, Anthony R AU - Dubois, Andre AU - Coleman, William G AD - National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda. Diagnon Corporation, Gaithersburg, Maryland Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 5358 EP - 5364 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 72 IS - 9 SN - 0019-9567, 0019-9567 KW - mice KW - Microbiology Abstracts B: Bacteriology KW - Helicobacter pylori KW - Gastrointestinal tract diseases KW - Animal models KW - Histopathology KW - Polymerase chain reaction KW - Primers KW - Feces KW - Persistent infection KW - J 02855:Human Bacteriology: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18025181?accountid=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=Development+of+a+Noninvasive+Method+for+Detecting+and+Monitoring+the+Time+Course+of+Helicobacter+pylori+Infection&rft.au=Nyan%2C+Dougbeh+C%3BWelch%2C+Anthony+R%3BDubois%2C+Andre%3BColeman%2C+William+G&rft.aulast=Nyan&rft.aufirst=Dougbeh&rft.date=2004-09-01&rft.volume=72&rft.issue=9&rft.spage=5358&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Helicobacter pylori; Gastrointestinal tract diseases; Animal models; Feces; Polymerase chain reaction; Primers; Histopathology; Persistent infection ER - TY - JOUR T1 - Risk factors for completed suicides: a case-control study from Bangalore, India AN - 17810733; 6220644 AB - Suicides are a hidden and unrecognized epidemic in the Indian region, affecting predominantly younger age groups. Information on causative risk factors and mechanisms is not available in the country, which is crucial for designing intervention programmes. To identify and quantify risk factors for completed suicides in the city of Bangalore. A case-control study was conducted with the families of 269 completed suicides and 269 living controls within the broader population of the city using psychological autopsy methods. The study has shown that several factors in the areas of family, marriage, education, occupation, general health, mental health and absence of protective factors contribute significantly for suicides. The cumulative and repetitive interaction of several factors in a complex manner results in suicides. The significant factors were presence of previous suicidal attempt in self (odds ratio (OR) = 42.62), interpersonal conflicts and marital disharmony with spouse (OR = 27.98), alcoholism in self (OR = 23.38), presence of a mental illness (OR = 11.07), sudden economic bankruptcy (OR = 7.1), domestic violence (OR = 6.82) and unemployment (OR = 6.15). Individuals completing suicides did not have a positive outlook towards life, problem-solving approaches and coping skills. The observed findings are at variance with suicidal causation in the West in some areas operating in a different sociocultural and economic environment. The intervention strategies should include prioritized macro and micro level efforts aimed at individual, family and society. JF - Injury Control and Safety Promotion AU - Gururaj, G AU - Isaac, M K AU - Subbakrishna, D K AU - Ranjani, R AD - Department of Epidemiology, WHO Collaborating Centre for Injury Prevention and Safety Promotion, National Institute of Mental Health and Neuro Sciences, PO Box No. 2900, Bangalore-560 029, India, guru@nimhans.kar.nic.in Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 183 EP - 191 VL - 11 IS - 3 SN - 1566-0974, 1566-0974 KW - Risk Abstracts KW - Age KW - Psychology KW - domestic violence KW - Family studies KW - India KW - Education KW - Economics KW - suicide KW - Urban areas KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17810733?accountid=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=Injury+Control+and+Safety+Promotion&rft.atitle=Risk+factors+for+completed+suicides%3A+a+case-control+study+from+Bangalore%2C+India&rft.au=Gururaj%2C+G%3BIsaac%2C+M+K%3BSubbakrishna%2C+D+K%3BRanjani%2C+R&rft.aulast=Gururaj&rft.aufirst=G&rft.date=2004-09-01&rft.volume=11&rft.issue=3&rft.spage=183&rft.isbn=&rft.btitle=&rft.title=Injury+Control+and+Safety+Promotion&rft.issn=15660974&rft_id=info:doi/10.1080%2F156609704%2F233%2F289706 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - India; suicide; Economics; Urban areas; Psychology; domestic violence; Education; Family studies; Age DO - http://dx.doi.org/10.1080/156609704/233/289706 ER - TY - JOUR T1 - Antimicrobial susceptibility trends among Escherichia coli and Shigella spp. isolated from rural Egyptian paediatric populations with diarrhoea between 1995 and 2000 AN - 17794950; 6012230 AB - Antimicrobial susceptibility testing was performed on 3627 isolates of Escherichia coli and 180 isolates of Shigella spp. collected in rural locations from 875 Egyptian children with diarrhoea between 1995 and 2000. The cumulative rates of resistance for E. coli and Shigella spp. were high (respectively, 68.2% and 54.8% for ampicillin, 24.2% and 23.5% for ampicillin-sulbactam, 57.2% and 42.5% for trimethoprim-sulphamethoxazole, and 50.9% and 75.4% for tetracycline). Non-enterotoxigenic E. coli (NETEC) isolates had a consistently higher level of antimicrobial resistance than did enterotoxigenic E. coli (ETEC) isolates. Trend testing showed significant decreases in resistance to ampicillin, ampicillin-sulbactam and tetracycline among all E. coli isolates. Increasing rates of resistance were observed for trimethoprim-sulphamethoxazole in ETEC isolates and Shigella spp., but not in NETEC isolates. Low levels of resistance were observed for all other antimicrobial agents tested. Overall, high levels, but decreasing trends, of resistance to commonly used antimicrobial agents were detected among isolates of E. coli and Shigella spp. from children in rural Egypt. JF - Clinical Microbiology and Infection AU - Putnam, S D AU - Riddle AU - Wierzba, T F AU - Pittner, B T AU - Elyazeed, R A AU - El-Gendy, A AU - Rao, M R AU - Clemens, J D AU - Frenck, R W AD - Enteric Disease Department, Naval Medical Research Center, Silver Spring, MD, USA, Enteric Disease Research Program, Naval Medical Research Unit No. 3, Cairo, Egypt, EPI and Polio Eradication, World Health Organization, Katmandu, Nepal, Department of Immunology, Mayo Clinic, Rochester, MN, Epidemiology Branch, National Institute of Child Health and Human Development, Bethesda, MD, USA and International Vaccine Institute, Seoul, South Korea, putnam@namruz.019 Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 804 EP - 810 PB - Blackwell Science Ltd VL - 10 IS - 9 SN - 1198-743X, 1198-743X KW - Microbiology Abstracts B: Bacteriology KW - Egypt, Arab Rep. KW - Diarrhea KW - Pediatrics KW - Drug resistance KW - Escherichia coli KW - Ampicillin KW - Shigella KW - Children KW - Tetracyclines KW - Antibiotic resistance KW - Antimicrobial agents KW - J 02795:Antibiotic resistance UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17794950?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+physiology.+Renal+physiology&rft.atitle=Fluorescein-methotrexate+transport+in+rat+choroid+plexus+analyzed+using+confocal+microscopy.&rft.au=Breen%2C+Christopher+M%3BSykes%2C+Destiny+B%3BBaehr%2C+Carsten%3BFricker%2C+Gert%3BMiller%2C+David+S&rft.aulast=Breen&rft.aufirst=Christopher&rft.date=2004-09-01&rft.volume=287&rft.issue=3&rft.spage=F562&rft.isbn=&rft.btitle=&rft.title=American+journal+of+physiology.+Renal+physiology&rft.issn=1931857X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Diarrhea; Pediatrics; Drug resistance; Ampicillin; Tetracyclines; Children; Antibiotic resistance; Antimicrobial agents; Escherichia coli; Shigella; Egypt, Arab Rep. DO - http://dx.doi.org/10.1111/j.1469-0691.2004.00927.x ER - TY - JOUR T1 - Probabilities of Death From Breast Cancer and Other Causes Among Female Breast Cancer Patients AN - 17794625; 6006835 AB - BACKGROUND: Among cancer patients, probabilities of death from that cancer and other causes in the presence of competing risks are optimal measures of prognosis and of mortality across demographic groups. We used data on breast cancer patients from the Surveillance, Epidemiology, and End Results (SEER) Program in a competing-risk analysis. METHODS: We determined vital status and cause of death for 395 251 white and 35 259 black female patients with breast cancer diagnosed from January 1, 1973, through December 31, 2000, by use of SEER data. We calculated probabilities of death from breast cancer and other causes according to stage, race, and age at diagnosis; for cases diagnosed from January 1, 1990, to December 31, 2000, we also calculated some such probabilities according to tumor size and estrogen receptor (ER) status. All statistical tests were two-sided. RESULTS: The probability of death from breast cancer after nearly 28 years of follow-up ranged from 0.03 to 0.10 for patients with in situ disease to 0.70 to 0.85 for patients with distant disease, depending on race and age. The probability of death from breast cancer at the end of the follow-up period generally declined with age at diagnosis; the probability among the oldest (=>70 years) compared with the youngest (70 years). Among patients with localized or regional disease and known ER status, the probability of death from breast cancer after nearly 11 years of follow-up ranged from 0.04 to 0.11 for patients with localized ER-positive tumors of 2 cm or less to 0.37 to 0.53 for patients with regional ER-negative tumors. CONCLUSIONS: The probability of death from breast cancer versus other causes varied substantially according to stage, tumor size, ER status, and age at diagnosis in both white and black patients. JF - Journal of the National Cancer Institute AU - Schairer, Catherine AU - Mink, Pamela J AU - Carroll, Leslie AU - Devesa, Susan S AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD (CS, SSD) Y1 - 2004/09/01/ PY - 2004 DA - 2004 Sep 01 SP - 1311 EP - 1321 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 - 96 IS - 17 SN - 0027-8874, 0027-8874 KW - Risk Abstracts KW - Mortality KW - Age KW - Demographics KW - Breast cancer KW - Females KW - Ethnic groups KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17794625?accountid=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=Probabilities+of+Death+From+Breast+Cancer+and+Other+Causes+Among+Female+Breast+Cancer+Patients&rft.au=Schairer%2C+Catherine%3BMink%2C+Pamela+J%3BCarroll%2C+Leslie%3BDevesa%2C+Susan+S&rft.aulast=Schairer&rft.aufirst=Catherine&rft.date=2004-09-01&rft.volume=96&rft.issue=17&rft.spage=1311&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 N1 - SubjectsTermNotLitGenreText - Females; Mortality; Age; Ethnic groups; Breast cancer; Demographics ER - TY - JOUR T1 - Long-Term Interferon- gamma Therapy for Patients with Chronic Granulomatous Disease AN - 17791419; 6056715 AB - Background. Chronic granulomatous disease (CGD) is a rare disorder of phagocytes in which absent production of superoxide and hydrogen peroxide in phagocytes predisposes patients to bacterial and fungal infections. Infections are dramatically reduced by prophylaxis with antibiotics, antifungals, and interferon- gamma (IFN- gamma ). Methods. Seventy-six patients with CGD were enrolled in an uncontrolled, open-label follow-up study to assess the long-term clinical safety and efficacy of IFN- gamma therapy. Patients received IFN- gamma subcutaneously 3 times per week. Results. We observed patients for up to 9 years, for a total observation period of 328.4 patient-years. The incidence of serious infections was 0.30 infections per patient-year; for serious bacterial infections, the incidence was 0.18 cases per patient-year, and for serious fungal infections, it was 0.12 cases per patient-year. Thirty-seven percent of patients reported an adverse event, the most common of which was fever. Twenty-six patients withdrew from the study (3 because of adverse events, 15 because of patient preference, and 8 because of transfer to another trial). There were no life-threatening IFN- gamma -related adverse events and no discernible effects on growth. The overall mortality rate was 1.5% per patient-year. Conclusion. IFN- gamma prophylaxis for CGD appears to be effective and well tolerated over a prolonged period of time. JF - Clinical Infectious Diseases AU - Marciano, B E AU - Wesley, R AU - De Carlo, ES AU - Anderson, V L AU - Barnhart, LA AU - Darnell, D AU - Malech, H L AU - Gallin, JI AU - Holland, S M AD - Laboratories of Host Defenses and Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, and Warren G. Magnuson Clinical Center, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA Y1 - 2004/09/01/ PY - 2004 DA - 2004 Sep 01 SP - 692 EP - 699 VL - 39 IS - 5 SN - 1058-4838, 1058-4838 KW - Microbiology Abstracts B: Bacteriology KW - Fever KW - Mortality KW - Hydrogen peroxide KW - Phagocytes KW - ^g-Interferon KW - Superoxide KW - Chronic infection KW - Prophylaxis KW - Antibiotics KW - Chronic granulomatous disease KW - Clinical trials KW - J 02855:Human Bacteriology: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17791419?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Infectious+Diseases&rft.atitle=Long-Term+Interferon-+gamma+Therapy+for+Patients+with+Chronic+Granulomatous+Disease&rft.au=Marciano%2C+B+E%3BWesley%2C+R%3BDe+Carlo%2C+ES%3BAnderson%2C+V+L%3BBarnhart%2C+LA%3BDarnell%2C+D%3BMalech%2C+H+L%3BGallin%2C+JI%3BHolland%2C+S+M&rft.aulast=Marciano&rft.aufirst=B&rft.date=2004-09-01&rft.volume=39&rft.issue=5&rft.spage=692&rft.isbn=&rft.btitle=&rft.title=Clinical+Infectious+Diseases&rft.issn=10584838&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - ^g-Interferon; Chronic granulomatous disease; Phagocytes; Prophylaxis; Fever; Hydrogen peroxide; Superoxide; Mortality; Chronic infection; Antibiotics; Clinical trials ER - TY - JOUR T1 - Rapid grouping of monoclonal antibodies based on their topographical epitopes by a label-free competitive immunoassay AN - 17755338; 6144551 AB - Topography of epitopes of monoclonal antibodies (MAbs), identified as the mutual competition of the MAbs, can be valuable indicators for the biological functions of MAbs. However, the determination of topographical epitopes is not performed before the functional screening of MAbs, because the requirement for purifying and labeling of MAbs makes the mapping experiment difficult, particularly in the early stage of MAb production. Here we describe a new label-free competitive enzyme-linked immunosorbent assay (LFC-ELISA) for the rapid grouping of MAbs based on the topography of their epitopes. In the LFC-ELISA, the immune complex formed by a competitor, MAb#2, and an antigen is challenged by an indicator, MAb#1 that had been captured on the ELISA plate through a secondary antibody. The MAb#2-antigen immune complex is trapped by MAb#1 only if MAb#1 reacts with an epitope different from that of MAb#2. The immune complex (MAb#2-antigen-MAb#1) is detected with an enzyme-labeled reagent specific to a tag on the antigen. Our experiments using different anti-CD30 MAbs and a CD30-Fc fusion protein as the antigen revealed that the LFC-ELISA performed well with MAbs of different isotypes (IgG1, IgG2a, and IgG2b), and in a practical range of MAb concentrations (0.3-10 mu g/ml) and affinities (0.9-13 nM of Kd). We obtained pairwise competition data from all 26 anti-CD30 MAbs. We then utilized a cluster analysis and a bootstrap method to analyze the competition data for grouping of the MAbs. This objective and automated analysis identified eight distinct topographical epitopes on CD30. The reactivity of the anti-CD30 MAbs in immunoblot, and their inhibiting activity on CD30-CD30-ligand binding correlated with the topographical epitopes. The results show that the LFC-ELISA combined with cluster analysis is a useful new method for grouping MAbs based on their topographical epitopes and can be used in the early stage of MAb production. One useful application is to identify MAbs reacting with different epitopes from a large number of MAbs so that the most appropriate MAbs can be selected for therapeutic use. JF - Journal of Immunological Methods AU - Nagata, S AU - Numata, Y AU - Onda, M AU - Ise, T AU - Hahn, Y AU - Lee, B AU - Pastan, I AD - Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Room 5106, Bethesda, MD 20892-4264, USA, pastani@mail.nih.gov Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 141 EP - 155 VL - 292 IS - 1-2 SN - 0022-1759, 0022-1759 KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Enzyme-linked immunosorbent assay KW - Monoclonal antibodies KW - Immunoassays KW - Epitopes KW - Topography KW - W3 33375:Antibodies KW - F 06711:Monoclonal antibodies, hybridomas, antigens and antisera KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17755338?accountid=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=Rapid+grouping+of+monoclonal+antibodies+based+on+their+topographical+epitopes+by+a+label-free+competitive+immunoassay&rft.au=Nagata%2C+S%3BNumata%2C+Y%3BOnda%2C+M%3BIse%2C+T%3BHahn%2C+Y%3BLee%2C+B%3BPastan%2C+I&rft.aulast=Nagata&rft.aufirst=S&rft.date=2004-09-01&rft.volume=292&rft.issue=1-2&rft.spage=141&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunological+Methods&rft.issn=00221759&rft_id=info:doi/10.1016%2Fj.jim.2004.06.009 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Monoclonal antibodies; Immunoassays; Topography; Enzyme-linked immunosorbent assay; Epitopes DO - http://dx.doi.org/10.1016/j.jim.2004.06.009 ER - TY - JOUR T1 - Marijuana and cannabinoid regulation of brain reward circuits AN - 17708393; 6089852 AB - The reward circuitry of the brain consists of neurons that synaptically connect a wide variety of nuclei. Of these brain regions, the ventral tegmental area (VTA) and the nucleus accumbens (NAc) play central roles in the processing of rewarding environmental stimuli and in drug addiction. The psychoactive properties of marijuana are mediated by the active constituent, Delta super(9)-THC, interacting primarily with CB1 cannabinoid receptors in a large number of brain areas. However, it is the activation of these receptors located within the central brain reward circuits that is thought to play an important role in sustaining the self-administration of marijuana in humans, and in mediating the anxiolytic and pleasurable effects of the drug. Here we describe the cellular circuitry of the VTA and the NAc, define the sites within these areas at which cannabinoids alter synaptic processes, and discuss the relevance of these actions to the regulation of reinforcement and reward. In addition, we compare the effects of Delta super(9)-THC with those of other commonly abused drugs on these reward circuits, and we discuss the roles that endogenous cannabinoids may play within these brain pathways, and their possible involvement in regulating ongoing brain function, independently of marijuana consumption. We conclude that, whereas Delta super(9)-THC alters the activity of these central reward pathways in a manner that is consistent with other abused drugs, the cellular mechanism through which this occurs is likely different, relying upon the combined regulation of several afferent pathways to the VTA. JF - British Journal of Pharmacology AU - Lupica, C R AU - Riegel, A C AU - Hoffman, A F AD - Neurophysiology Section, Cellular Neurobiology Branch, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, U.S. Department of Health and Human Services, Baltimore, MD 21224, USA, clupica@intra.nida.nih.gov Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 227 EP - 234 VL - 143 IS - 2 SN - 0007-1188, 0007-1188 KW - CSA Neurosciences Abstracts; Toxicology Abstracts KW - Drug abuse KW - Anxiolytics KW - Environmental effects KW - Reinforcement KW - Cannabis KW - Self-administration KW - Cannabinoid CB1 receptors KW - Drug addiction KW - Nucleus accumbens KW - ventral tegmentum KW - Tetrahydrocannabinol KW - Reviews KW - X 24180:Social poisons & drug abuse KW - N3 11139:Toxicological and psychoactive drug correlates UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17708393?accountid=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=British+Journal+of+Pharmacology&rft.atitle=Marijuana+and+cannabinoid+regulation+of+brain+reward+circuits&rft.au=Lupica%2C+C+R%3BRiegel%2C+A+C%3BHoffman%2C+A+F&rft.aulast=Lupica&rft.aufirst=C&rft.date=2004-09-01&rft.volume=143&rft.issue=2&rft.spage=227&rft.isbn=&rft.btitle=&rft.title=British+Journal+of+Pharmacology&rft.issn=00071188&rft_id=info:doi/10.1038%2Fsj.bjp.0705931 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cannabis; Reinforcement; Tetrahydrocannabinol; Drug abuse; Drug addiction; Anxiolytics; Nucleus accumbens; ventral tegmentum; Self-administration; Environmental effects; Cannabinoid CB1 receptors; Reviews DO - http://dx.doi.org/10.1038/sj.bjp.0705931 ER - TY - JOUR T1 - Absolute Myocardial Perfusion in Canines Measured by Using Dual-Bolus First- Pass MR Imaging AN - 17688168; 6002801 AB - PURPOSE: To compare fluorescent microsphere measurements of myocardial blood flow (MBF) with qualitative, semiquantitative, and fully quantitative measurements of first-pass perfusion at magnetic resonance (MR) imaging. MATERIALS AND METHODS: Coronary artery occlusion or intracoronary adenosine infusion was successfully performed in 16 beagles; both procedures were performed simultaneously in one animal. MBF was assessed at microsphere analysis. First-pass myocardial perfusion MR imaging was performed during a dual-bolus administration of gadopentetate dimeglumine (0.0025 mmol/kg followed by 0.10 mmol/kg). The absolute myocardial perfusion at MR imaging was calculated by using Fermi function deconvolution methods. Qualitative, semiquantitative, and absolute myocardial perfusion MR imaging measurements were compared with microsphere MBF measurements by using paired t tests, linear correlation, and Bland-Altman analysis. RESULTS: Fully quantitative (ie, absolute) analysis of MBF at MR imaging correlated with microsphere MBF measurement (r = 0.95, P 5.0 mL/min/g). Similar close correlations were observed in endocardial and epicardial segments (representing approximately 0.85 g of the myocardium). With modest increases in MBF, qualitative measurements plateaued in the hyperemic zones. Semiquantitative measurements did not correlate with MBF as well (r = 0.69-0.89); they plateaued around 3.0 mL/min/g. CONCLUSION: Dual-bolus MR imaging enabled accurate measurement of absolute epicardial and endocardial perfusion across a wide range of blood flow rates (0 to >5.0 mL/min/g). Use of qualitative MR imaging measures such as the contrast enhancement ratio led to substantially underestimated hyperemic blood flow measurements. RSNA, 2004 JF - Radiology AU - Christian, Timothy F AU - Rettmann, Dan W AU - Aletras, Anthony H AU - Liao, Steve L AU - Taylor, Joni L AU - Balaban, Robert S AU - Arai, Andrew E AD - Laboratory of Cardiac Energetics, National Heart, Lung and Blood Institute, National Institutes of Health, Department of Health and Human Services, Bldg 10, Rm B1D416, MSC 1061, 10 Center Dr, Bethesda, MD Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 677 EP - 684 PB - Radiological Society of North America, 820 Jorie Blvd. Oak Brook Illinois 60523-2251 USA VL - 232 IS - 3 SN - 0033-8419, 0033-8419 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/17688168?accountid=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=Radiology&rft.atitle=Absolute+Myocardial+Perfusion+in+Canines+Measured+by+Using+Dual-Bolus+First-+Pass+MR+Imaging&rft.au=Christian%2C+Timothy+F%3BRettmann%2C+Dan+W%3BAletras%2C+Anthony+H%3BLiao%2C+Steve+L%3BTaylor%2C+Joni+L%3BBalaban%2C+Robert+S%3BArai%2C+Andrew+E&rft.aulast=Christian&rft.aufirst=Timothy&rft.date=2004-09-01&rft.volume=232&rft.issue=3&rft.spage=677&rft.isbn=&rft.btitle=&rft.title=Radiology&rft.issn=00338419&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-04-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Neonatal abstinence syndrome in methadone-exposed infants is altered by level of prenatal tobacco exposure AN - 17544878; 6418506 AB - Maternal tobacco consumption during pregnancy has been associated with lower birth weight infants, preterm births, intrauterine growth retardation, smaller head circumference and increase in morbidity, yet few studies have examined the role tobacco has on the opiate neonatal abstinence syndrome (NAS). This study examined the effect of prenatal tobacco exposure on NAS for infants born to mothers maintained on methadone during gestation. Twenty-nine pregnant women and their newborn infants participated in this study. Tobacco exposure was based on maternal self-report with 16 women reporting cigarette consumption of 10 or less per day and 13 reporting smoking 20 cigarettes or more a day. The onset, peak, and duration of NAS were examined. Results showed that infants born to mothers who reported smoking 20 or more cigarettes per day had significantly higher NAS peak scores of 9.8 versus 4.8, and took longer to peak (113.0 h versus 37.8 h), than light smokers of 10 or fewer cigarettes per day. We concluded that tobacco use in conjunction with methadone plays an important role in the timing and severity of NAS in prenatally exposed infants. JF - Drug and Alcohol Dependence AU - Choo, R E AU - Huestis, MA AU - Schroeder, J R AU - Shin, A S AU - Jones, HE AD - Chemistry and Drug Metabolism Section, Clinical Pharmacology and Therapeutics Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institute of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224-6823, USA Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 253 EP - 260 VL - 75 IS - 3 SN - 0376-8716, 0376-8716 KW - Toxicology Abstracts KW - Birth weight KW - Tobacco smoking KW - Opiates KW - Prenatal experience KW - Pregnancy KW - Birth KW - Methadone KW - Drug dependence KW - Gestation KW - Cigarette smoking KW - Neonates KW - Infants KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17544878?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+and+Alcohol+Dependence&rft.atitle=Neonatal+abstinence+syndrome+in+methadone-exposed+infants+is+altered+by+level+of+prenatal+tobacco+exposure&rft.au=Choo%2C+R+E%3BHuestis%2C+MA%3BSchroeder%2C+J+R%3BShin%2C+A+S%3BJones%2C+HE&rft.aulast=Choo&rft.aufirst=R&rft.date=2004-09-01&rft.volume=75&rft.issue=3&rft.spage=253&rft.isbn=&rft.btitle=&rft.title=Drug+and+Alcohol+Dependence&rft.issn=03768716&rft_id=info:doi/10.1016%2Fj.drugalcdep.2004.03.012 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Tobacco smoking; Infants; Cigarette smoking; Prenatal experience; Neonates; Drug dependence; Methadone; Birth weight; Gestation; Birth; Pregnancy; Opiates DO - http://dx.doi.org/10.1016/j.drugalcdep.2004.03.012 ER - TY - JOUR T1 - Nicotine serves as an effective reinforcer of intravenous drug-taking behavior in human cigarette smokers AN - 17494023; 6282040 AB - Rationale: Although numerous studies have documented that nicotine can function as an effective reinforcer of intravenous self-administration behavior in animals, it has not been clearly shown to maintain intravenous self-administration behavior above vehicle placebo levels in humans. Objectives: To compare the reinforcing effectiveness of nicotine versus saline placebo in human research volunteers responding under fixed-ratio (FR) schedules of intravenous drug self-administration while systematically increasing response requirements. Methods: Eight male cigarette smokers resided in an inpatient research unit. During 3-h sessions, intravenous injections of nicotine and saline were available concurrently and were contingent on responding (pulling a lever). Nicotine dose (0.75, 1.5, 3.0 mg/injection), time out (TO) value after each injection (1-20 min) and FR response requirement (10-1600) were varied in different subjects over consecutive sessions. Results: Number of nicotine injections/session significantly decreased as dose/injection increased and the number of self-administered nicotine injections was significantly greater than the number of self-administered saline injections across conditions. When FR value was progressively increased over sessions, response rates for nicotine, but not saline, injections increased, with maximal rates at the highest FR values. Rates of responding and injections/session were markedly and significantly higher for nicotine than for saline at FR values of 200 and above. Subjects rated effects of nicotine as both significantly more positive and more negative than saline placebo, with positive ratings significantly higher than negative ratings. Conclusions: Nicotine functioned as a prototypic drug of abuse, serving as an effective reinforcer of intravenous drug-taking behavior in human cigarette smokers. Subjects adjusted their responding to response requirements in a way that maintained relatively constant levels of nicotine injections per session. JF - Psychopharmacology AU - Harvey, Deon M AU - Yasar, Sevil AU - Heishman, Stephen J AU - Panlilio, Leigh V AU - Henningfield, Jack E AU - Goldberg, Steven R AD - DHHS, 5500 Nathan Shock Drive, Baltimore, MD, 21224, USA, sgoldber@intra.nida.nih.gov Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 134 EP - 142 PB - Springer-Verlag (Berlin), Heidelberger Platz 3 Berlin 14197 Germany, [mailto:subscriptions@springer.de], [URL:http://www.springer.de/] VL - 175 IS - 2 SN - 0033-3158, 0033-3158 KW - Toxicology Abstracts KW - Intravenous administration KW - Nicotine KW - Cigarette smoking KW - Reinforcement KW - Self-administration KW - Drug abuse KW - Drug self-administration KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17494023?accountid=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=Psychopharmacology&rft.atitle=Nicotine+serves+as+an+effective+reinforcer+of+intravenous+drug-taking+behavior+in+human+cigarette+smokers&rft.au=Harvey%2C+Deon+M%3BYasar%2C+Sevil%3BHeishman%2C+Stephen+J%3BPanlilio%2C+Leigh+V%3BHenningfield%2C+Jack+E%3BGoldberg%2C+Steven+R&rft.aulast=Harvey&rft.aufirst=Deon&rft.date=2004-09-01&rft.volume=175&rft.issue=2&rft.spage=134&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/10.1007%2Fs00213-004-1818-6 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Nicotine; Intravenous administration; Reinforcement; Cigarette smoking; Self-administration; Drug abuse; Drug self-administration DO - http://dx.doi.org/10.1007/s00213-004-1818-6 ER - TY - JOUR T1 - Enhanced spectral resolution in RNA HCP spectra for measurement of super(3)J sub(C2'P) and super(3)J sub(C4'P) couplings and super(31)P chemical shift changes upon weak alignment AN - 17296949; 6056213 AB - The `out-and-back' 3D HCP experiment, using gradient- and sensitivity-enhanced detection, provides a convenient method for assignment of the super(31)P NMR spectra and accurate measurement of the super(31)P chemical shifts of ribonucleic acids. The super(13)C resolution in such spectra can be doubled, at the cost of a 50% reduction in sensitivity, by combining super(13)C evolution during the super(13)C-\ super(31)P\ de- and rephasing periods. The multiple connectivities observable for a given super(31)P, including correlations to the intranucleotide C5'H sub(2) and C4'H groups, and the C2'H, C3'H and C4'H groups of the preceding nucleotide, permit independent measurements of the super(31)P shift. The super(13)C spectrum of these groups is typically crowded for an RNA molecule in isotropic solution and overlap becomes more problematic in media used to achieve partial alignment. However, many of these correlations are resolvable in the combined-evolution HCP spectrum. The difference in super(31)P chemical shift between isotropic solution and a medium containing liquid crystalline Pf1 provides information on the orientation of phosphate groups. The intensities measured in the 3D HCP spectrum, obtained for an isotropic sample, yield values for the super(3)J sub(C2'P) and super(3)J sub(C4'P) couplings, thereby providing important restraints for the backbone torsion angles epsilon and beta . The experiments are illustrated for a uniformly super(13)C-enriched, 24-residue stem-loop RNA sequence, and results for the helical stem region show close agreement between observed Delta delta ( super(31)P) values and those predicted for a model A-form RNA helix when using a uniform super(31)P CSA tensor. This confirms that Delta delta ( super(31)P) values can be used directly as restraints in refining nucleic acid structures. JF - Journal of Biomolecular NMR AU - O'Neil-Cabello, E AU - Wu, Z AU - Bryce, D L AU - Nikonowicz, E P AU - Bax, A AD - Laboratory of Chemical Physics, NIDDK, National Institutes of Health, Bethesda, MD 20892-0520, U.S.A. Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 61 EP - 70 PB - Kluwer Academic Publishers VL - 30 IS - 1 SN - 0925-2738, 0925-2738 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/17296949?accountid=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+Biomolecular+NMR&rft.atitle=Enhanced+spectral+resolution+in+RNA+HCP+spectra+for+measurement+of+super%283%29J+sub%28C2%27P%29+and+super%283%29J+sub%28C4%27P%29+couplings+and+super%2831%29P+chemical+shift+changes+upon+weak+alignment&rft.au=O%27Neil-Cabello%2C+E%3BWu%2C+Z%3BBryce%2C+D+L%3BNikonowicz%2C+E+P%3BBax%2C+A&rft.aulast=O%27Neil-Cabello&rft.aufirst=E&rft.date=2004-09-01&rft.volume=30&rft.issue=1&rft.spage=61&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biomolecular+NMR&rft.issn=09252738&rft_id=info:doi/10.1023%2FB%3AJNMR.0000042952.66982.38 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-04-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1023/B:JNMR.0000042952.66982.38 ER - TY - JOUR T1 - Detection and quantitation of parvovirus B19 AN - 17275485; 6045406 JF - Journal of Clinical Virology AU - Brown, KE AD - Virus Discovery Group, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Building 10/Room 7C218, 9000 Rockville Pike, Bethesda, MD 20892-1652 USA Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 1 EP - 4 PB - Elsevier B.V. VL - 31 IS - 1 SN - 1386-6532, 1386-6532 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - Parvovirus B19 KW - Detection KW - Quantitation KW - A 01114:Viruses KW - V 22022:Virus assay UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17275485?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Clinical+Virology&rft.atitle=Detection+and+quantitation+of+parvovirus+B19&rft.au=Brown%2C+KE&rft.aulast=Brown&rft.aufirst=KE&rft.date=2004-09-01&rft.volume=31&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Virology&rft.issn=13866532&rft_id=info:doi/10.1016%2Fj.jcv.2004.05.001 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Detection; Quantitation; Parvovirus B19 DO - http://dx.doi.org/10.1016/j.jcv.2004.05.001 ER - TY - JOUR T1 - The solubilizing detergents, Tween 80 and Triton X-100 non-competitively inhibit alpha 7-nicotinic acetylcholine receptor function in Xenopus oocytes. AN - 66724100; 15262057 AB - Because many studies rely upon detergents to solubilize lipophilic agents such as cannabinoid drugs, we examined the effect of commonly employed detergents on the function of the cloned alpha(7) subunit of the nicotinic ACh receptor. Homomeric alpha(7) receptors were expressed in Xenopus oocytes and the two-microelectrode voltage-clamp technique was used to assess their electrophysiological properties. The detergents Tween 80 and Triton X-100 reversibly inhibited ACh (100 microM)-induced inward currents in a concentration-dependent manner, with IC(50) values of 610 nM and 1.4 microM, respectively. The effects of these detergents were independent of membrane potential, and they were not mediated by endogenous Ca(2+)-dependent Cl(-) channels, since they were unaffected by intracellularly injected BAPTA, and recorded in Ca(2+)-free bathing solution containing 2 mM Ba(2+). Both detergents also decreased the maximal effect of ACh, without significantly affecting its EC(50), indicating a non-competitive interaction with the nACh alpha(7) receptors. In contrast to the effects of these detergents, we found that cholic acid (10 microM), DMSO (10 microM) and Tocrisol (0.01% v/v) did not cause a significant effect on nicotinic responses. In conclusion, we demonstrate that the detergents Tween 80 and Triton X-100 are potent inhibitors of neuronal nACh alpha(7) receptors expressed in Xenopus oocytes, and we suggest that studies utilizing these detergents to solubilize lipophilic drugs should be scrutinized for such effects. JF - Journal of neuroscience methods AU - Oz, Murat AU - Spivak, Charles E AU - Lupica, Carl R AD - National Institute on Drug Abuse, NIH/DHHS, Intramural Research Program, Cellular Neurobiology Branch, Cellular Neurophysiology Section, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2004/08/30/ PY - 2004 DA - 2004 Aug 30 SP - 167 EP - 173 VL - 137 IS - 2 SN - 0165-0270, 0165-0270 KW - Chelating Agents KW - 0 KW - Detergents KW - Muscarinic Antagonists KW - Polysorbates KW - RNA, Complementary KW - Receptors, Nicotinic KW - alpha7 Nicotinic Acetylcholine Receptor KW - Barium KW - 24GP945V5T KW - Egtazic Acid KW - 526U7A2651 KW - Atropine KW - 7C0697DR9I KW - Octoxynol KW - 9002-93-1 KW - 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid KW - K22DDW77C0 KW - Acetylcholine KW - N9YNS0M02X KW - Index Medicus KW - Patch-Clamp Techniques -- methods KW - Animals KW - Drug Interactions KW - Dose-Response Relationship, Drug KW - Acetylcholine -- pharmacology KW - RNA, Complementary -- metabolism KW - RNA, Complementary -- chemistry KW - Cloning, Molecular KW - Xenopus laevis KW - Chelating Agents -- pharmacology KW - Chickens KW - Muscarinic Antagonists -- pharmacology KW - Membrane Potentials -- drug effects KW - Atropine -- pharmacology KW - Barium -- pharmacology KW - Female KW - Octoxynol -- pharmacology KW - Egtazic Acid -- analogs & derivatives KW - Polysorbates -- pharmacology KW - Oocytes -- drug effects KW - Receptors, Nicotinic -- drug effects KW - Neural Inhibition -- drug effects KW - Receptors, Nicotinic -- physiology KW - Detergents -- pharmacology KW - Egtazic Acid -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66724100?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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+methods&rft.atitle=The+solubilizing+detergents%2C+Tween+80+and+Triton+X-100+non-competitively+inhibit+alpha+7-nicotinic+acetylcholine+receptor+function+in+Xenopus+oocytes.&rft.au=Oz%2C+Murat%3BSpivak%2C+Charles+E%3BLupica%2C+Carl+R&rft.aulast=Oz&rft.aufirst=Murat&rft.date=2004-08-30&rft.volume=137&rft.issue=2&rft.spage=167&rft.isbn=&rft.btitle=&rft.title=Journal+of+neuroscience+methods&rft.issn=01650270&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-10-08 N1 - Date created - 2004-07-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Membrane insertion of anthrax protective antigen and cytoplasmic delivery of lethal factor occur at different stages of the endocytic pathway AN - 17822387; 6002472 AB - The protective antigen (PA) of anthrax toxin binds to a cell surface receptor, undergoes heptamerization, and binds the enzymatic subunits, the lethal factor (LF) and the edema factor (EF). The resulting complex is then endocytosed. Via mechanisms that depend on the vacuolar ATPase and require membrane insertion of PA, LF and EF are ultimately delivered to the cytoplasm where their targets reside. Here, we show that membrane insertion of PA already occurs in early endosomes, possibly only in the multivesicular regions, but that subsequent delivery of LF to the cytoplasm occurs preferentially later in the endocytic pathway and relies on the dynamics of internal vesicles of multivesicular late endosomes. JF - Journal of Cell Biology AU - Abrami, Laurence AU - Lindsay, Margaret AU - Parton, Robert G AU - Leppla, Stephen H AU - Van Der Goot, FGisou AD - Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland 1211. Institute for Molecular Bioscience, Centre for Microscopy and Microanalysis, and Department of Physiology and Pharmacology, University of Queensland, Brisbane, Australia 4072. Microbial Pathogenesis Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD Y1 - 2004/08/30/ PY - 2004 DA - 2004 Aug 30 SP - 645 EP - 651 PB - Rockefeller University Press, 1114 First Avenue New York NY 10021-8325 USA, [mailto:Bruce.Lyons@rockefeller.edu], [URL:http://www.rockefeller.edu/rupress] VL - 166 IS - 5 SN - 0021-9525, 0021-9525 KW - Microbiology Abstracts B: Bacteriology KW - Cell surface KW - endosomes KW - Adenosinetriphosphatase KW - Lethal factor KW - protective antigen KW - Edema KW - Anthrax KW - Vesicles KW - Bacillus anthracis KW - Toxins KW - J 02832:Antigenic properties and virulence UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17822387?accountid=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+Cell+Biology&rft.atitle=Membrane+insertion+of+anthrax+protective+antigen+and+cytoplasmic+delivery+of+lethal+factor+occur+at+different+stages+of+the+endocytic+pathway&rft.au=Abrami%2C+Laurence%3BLindsay%2C+Margaret%3BParton%2C+Robert+G%3BLeppla%2C+Stephen+H%3BVan+Der+Goot%2C+FGisou&rft.aulast=Abrami&rft.aufirst=Laurence&rft.date=2004-08-30&rft.volume=166&rft.issue=5&rft.spage=645&rft.isbn=&rft.btitle=&rft.title=Journal+of+Cell+Biology&rft.issn=00219525&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bacillus anthracis; protective antigen; Anthrax; endosomes; Lethal factor; Adenosinetriphosphatase; Vesicles; Cell surface; Toxins; Edema ER - TY - JOUR T1 - Retention of aggregated LDL by cultured human coronary artery endothelial cells. AN - 66864359; 15358167 AB - Aggregated LDL (AgLDL) accumulates within the subendothelial space of developing atherosclerotic lesions. We were interested to learn whether endothelial cells can interact with AgLDL. Incubation of endothelial cells with AgLDL resulted in apparent cholesterol retention. Microscopic examination revealed that cholesterol retention resulted mainly from endothelial cell surface attachment of AgLDL. Little AgLDL entered endothelial cells consistent with the small amount of endothelial cell degradation of AgLDL. Although endothelial cell retention of AgLDL was inhibited by LDL, AgLDL retention was not blocked by lactoferrin, C7 anti-LDL receptor monoclonal antibody, or receptor-associated protein, suggesting that LDL receptor family members did not mediate this retention. Surface retention of AgLDL depended on microtubule function and could be regulated by the protein kinase C activator, PMA. Treatment of endothelial cells with PMA either before or during, but not after incubation with AgLDL, inhibited retention of AgLDL. Our findings show that endothelial cells can retain AgLDL but internalize and metabolize little of this AgLDL. Thus, it is unlikely that endothelial cells can transport AgLDL out of atherosclerotic lesions, but it is likely that retention of AgLDL affects endothelial function. JF - Biochemical and biophysical research communications AU - Zhao, Bin AU - Huang, Wei AU - Zhang, Wei-Yang AU - Ishii, Itsuko AU - Kruth, Howard S AD - Section of Experimental Atherosclerosis, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/08/27/ PY - 2004 DA - 2004 Aug 27 SP - 728 EP - 735 VL - 321 IS - 3 SN - 0006-291X, 0006-291X KW - Cholesterol, LDL KW - 0 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Macrophages -- cytology KW - Animals KW - Tetradecanoylphorbol Acetate -- metabolism KW - Cells, Cultured KW - Humans KW - Macrophages -- metabolism KW - Arteries -- metabolism KW - Arteries -- anatomy & histology KW - Endothelial Cells -- ultrastructure KW - Coronary Vessels -- metabolism KW - Endothelium, Vascular -- metabolism KW - Endothelium, Vascular -- cytology KW - Cholesterol, LDL -- metabolism KW - Coronary Vessels -- anatomy & histology KW - Endothelial Cells -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66864359?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mass+spectrometric+measurement+of+differential+reactivity+of+cysteine+to+localize+protein-ligand+binding+sites.&rft.au=Kim%2C+Yeoun+Jin%3BPannell%2C+Lewis+K%3BSackett%2C+Dan+L&rft.aulast=Kim&rft.aufirst=Yeoun&rft.date=2004-09-01&rft.volume=332&rft.issue=2&rft.spage=376&rft.isbn=&rft.btitle=&rft.title=Analytical+Biochemistry&rft.issn=00032697&rft_id=info:doi/10.1016%2Fj.ab.2004.06.033 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-03 N1 - Date created - 2004-09-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - VAMP2-dependent exocytosis regulates plasma membrane insertion of TRPC3 channels and contributes to agonist-stimulated Ca2+ influx. AN - 66817613; 15327778 AB - The mechanism(s) involved in agonist-stimulation of TRPC3 channels is not yet known. Here we demonstrate that TRPC3-N terminus interacts with VAMP2 and alphaSNAP. Further, endogenous and exogenously expressed TRPC3 colocalized and coimmunoprecipitated with SNARE proteins in neuronal and epithelial cells. Imaging of GFP-TRPC3 revealed its localization in the plasma membrane region and in mobile intracellular vesicles. Recovery of TRPC3-GFP fluorescence after photobleaching of the plasma membrane region was decreased by brefeldin-A or BAPTA-AM. Cleavage of VAMP2 with tetanus toxin (TeNT) did not prevent delivery of TRPC3 to the plasma membrane region but reduced its surface expression. TeNT also decreased carbachol and OAG, but not thapsigargin, stimulated Ca2+ influx. Importantly, carbachol, not thapsigargin, increased surface expression of TRPC3 that was attenuated by TeNT and not by BAPTA. In aggregate, these data suggest that VAMP2-dependent exocytosis regulates plasma membrane insertion of TRPC3 channels and contributes to carbachol-stimulation of Ca2+ influx. JF - Molecular cell AU - Singh, Brij B AU - Lockwich, Timothy P AU - Bandyopadhyay, Bidhan C AU - Liu, Xibao AU - Bollimuntha, Sunitha AU - Brazer, So-Ching AU - Combs, Christian AU - Das, Sunit AU - Leenders, A G Miriam AU - Sheng, Zu-Hang AU - Knepper, Mark A AU - Ambudkar, Suresh V AU - Ambudkar, Indu S AD - Secretory Physiology Section, Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, Bethesda, MD 20892, USA. Y1 - 2004/08/27/ PY - 2004 DA - 2004 Aug 27 SP - 635 EP - 646 VL - 15 IS - 4 SN - 1097-2765, 1097-2765 KW - Carrier Proteins KW - 0 KW - Cholinergic Agonists KW - Ion Channels KW - Membrane Proteins KW - Protein Synthesis Inhibitors KW - R-SNARE Proteins KW - Recombinant Fusion Proteins KW - SNARE Proteins KW - Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins KW - TRPC Cation Channels KW - TRPC3 cation channel KW - Tetanus Toxin KW - Vesicular Transport Proteins KW - Brefeldin A KW - 20350-15-6 KW - Carbachol KW - 8Y164V895Y KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Carrier Proteins -- metabolism KW - Neurons -- metabolism KW - Humans KW - Two-Hybrid System Techniques KW - Cholinergic Agonists -- metabolism KW - Carbachol -- metabolism KW - Recombinant Fusion Proteins -- metabolism KW - Rats KW - Protein Synthesis Inhibitors -- metabolism KW - Fluorescence Recovery After Photobleaching KW - Brefeldin A -- metabolism KW - Hippocampus -- cytology KW - Neurons -- cytology KW - Tetanus Toxin -- metabolism KW - Recombinant Fusion Proteins -- genetics KW - Cytoplasmic Vesicles -- physiology KW - Vesicular Transport Proteins -- metabolism KW - Cell Line KW - Exocytosis -- physiology KW - Calcium -- metabolism KW - Membrane Proteins -- metabolism KW - Membrane Proteins -- genetics KW - Cell Membrane -- metabolism KW - Ion Channels -- genetics KW - Ion Channels -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66817613?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=VAMP2-dependent+exocytosis+regulates+plasma+membrane+insertion+of+TRPC3+channels+and+contributes+to+agonist-stimulated+Ca2%2B+influx.&rft.au=Singh%2C+Brij+B%3BLockwich%2C+Timothy+P%3BBandyopadhyay%2C+Bidhan+C%3BLiu%2C+Xibao%3BBollimuntha%2C+Sunitha%3BBrazer%2C+So-Ching%3BCombs%2C+Christian%3BDas%2C+Sunit%3BLeenders%2C+A+G+Miriam%3BSheng%2C+Zu-Hang%3BKnepper%2C+Mark+A%3BAmbudkar%2C+Suresh+V%3BAmbudkar%2C+Indu+S&rft.aulast=Singh&rft.aufirst=Brij&rft.date=2004-08-27&rft.volume=15&rft.issue=4&rft.spage=635&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 - 2004-10-19 N1 - Date created - 2004-08-25 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Identifying novel homozygous deletions by microsatellite analysis and characterization of tumor suppressor candidate 1 gene, TUSC1, on chromosome 9p in human lung cancer. AN - 66817580; 15208665 AB - Loss of heterozygosity (LOH) studies indicate that genetic alterations of chromosome 9p occur in numerous tumor types, suggesting the presence of tumor suppressor genes (TSGs) on chromosome 9p critical in carcinogenesis. Our previous LOH analyses in primary lung tumors led us to propose that chromosome 9p harbors other TSGs important in lung tumorigenesis. In this study, 30 non-small-cell lung cancer and 12 small-cell lung cancer cell lines were screened with 55 markers to identify new regions of homozygous deletion (HD) on chromosome 9p. Three novel noncontiguous homozygously deleted regions were detected and ranged in size from 840 kb to 7.4 Mb. One gene identified in the deletion at D9S126, TUSC1 (tumor suppressor candidate 1), is an intronless gene. Multiplex polymerase chain reaction and Southern blot confirmed the HD of TUSC1. Northern blot analysis of TUSC1 demonstrated two transcripts of approximately 2 and 1.5 kb that are likely generated by alternative polyadenylation signals. Both transcripts are expressed in several human tissues and share an open-reading frame encoding a peptide of 209 amino acids. Analysing cell line cDNAs by reverse transcriptase (RT)-PCR demonstrated downregulation of TUSC1 in cell lines with or without HDs, suggesting that TUSC1 may play a role in lung tumorigenesis. JF - Oncogene AU - Shan, Zhihong AU - Parker, Tracy AU - Wiest, Jonathan S AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-4258, USA. Y1 - 2004/08/26/ PY - 2004 DA - 2004 Aug 26 SP - 6612 EP - 6620 VL - 23 IS - 39 SN - 0950-9232, 0950-9232 KW - DNA, Complementary KW - 0 KW - Index Medicus KW - Polymerase Chain Reaction KW - Animals KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - Mice KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Sequence Deletion KW - Microsatellite Repeats -- genetics KW - Homozygote KW - Genes, Tumor Suppressor KW - Lung Neoplasms -- genetics KW - Chromosomes, Human, Pair 9 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66817580?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Indoor+allergens%2C+asthma%2C+and+asthma-related+symptoms+among+adolescents+in+Wuhan%2C+China.&rft.au=Salo%2C+P%C3%A4ivi+M%3BXia%2C+Jiang%3BJohnson%2C+C+Anderson%3BLi%2C+Yan%3BAvol%2C+Edward+L%3BGong%2C+Jie%3BLondon%2C+Stephanie+J&rft.aulast=Salo&rft.aufirst=P%C3%A4ivi&rft.date=2004-09-01&rft.volume=14&rft.issue=8&rft.spage=543&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 - 2004-09-16 N1 - Date created - 2004-08-26 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AY168647; GENBANK; AY546089 N1 - SuppNotes - Cited By: Genes Chromosomes Cancer. 2000 Mar;27(3):308-18 [10679921] Trends Genet. 2000 Apr;16(4):168-74 [10729832] Adv Cancer Res. 1998;72:141-96 [9338076] Leukemia. 1997 Oct;11(10):1636-40 [9324282] Int J Cancer. 1997 Apr 10;71(2):213-7 [9139845] Cancer Res. 1997 Jan 1;57(1):1-6 [8988029] Br J Cancer. 1999 May;80(3-4):468-76 [10408855] Nat Genet. 1999 Feb;21(2):163-7 [9988266] Genes Chromosomes Cancer. 1998 Jul;22(3):232-40 [9624535] Cancer Res. 1997 Nov 1;57(21):4868-75 [9354451] Cancer Res. 2001 Feb 1;61(3):1154-61 [11221846] Cancer Res. 2002 Jun 1;62(11):3207-13 [12036935] Nat Rev Genet. 2002 Jun;3(6):415-28 [12042769] Gene. 2003 Jan 16;303:55-61 [12559566] Nucleic Acids Res. 1991 Aug 11;19(15):4293 [1870982] Cancer Res. 1993 Oct 15;53(20):4761-3 [8402655] Nature. 1993 Dec 16;366(6456):704-7 [8259215] Cancer Res. 1994 Jan 15;54(2):344-8 [8275465] Oncogene. 1994 May;9(5):1361-5 [8152796] Science. 1994 Apr 15;264(5157):436-40 [8153634] Cancer Res. 1995 Jul 15;55(14):2968-71 [7606711] Nat Genet. 1995 Oct;11(2):210-2 [7550353] Nat Med. 1995 Jul;1(7):686-92 [7585152] Cell. 1995 Dec 15;83(6):993-1000 [8521522] Genes Chromosomes Cancer. 1996 Sep;17(1):14-20 [8889502] Glycoconj J. 1996 Oct;13(5):741-7 [8910001] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evodiamine functions as an agonist for the vanilloid receptor TRPV1. AN - 66778723; 15305207 AB - Evodiamine, a quinozole alkaloid constituent of Evodia rutaecarpa, has been reported previously to induce several responses comparable to capsaicin in animal systems. Here, we characterize evodiamine as an agonist for rat TRPV1 expressed heterologously in CHO cells. Evodiamine bound to rat TRPV1 with a Ki of 5.95 +/- 0.87 microM, as measured by inhibition of [3H] RTX binding (capsaicin, Ki = 1.8 +/- 0.3 microM). Evodiamine was a full agonist for induction of 45Ca2+ uptake, with an EC50 of 856 +/- 43 nM (capsaicin, EC50 = 45 +/- 4 nM) and was competitively antagonized by capsazepine, as revealed by a Schild plot. The pattern of cellular response, as determined by calcium imaging, was similar to that with capsaicin and yielded an EC(50) of 1.03 +/- 0.21 [micro sign]M. Molecular modeling suggested a consistent pattern of overlap between evodiamine and TRPV1 agonists. We conclude that evodiamine represents a novel class of agonists for rat TRPV1, albeit 3-19-fold less potent than capsaicin, and thus represents a new potential class of lead molecules for drug development. JF - Organic & biomolecular chemistry AU - Pearce, Larry V AU - Petukhov, Pavel A AU - Szabo, Tamas AU - Kedei, Noemi AU - Bizik, Fero AU - Kozikowski, Alan P AU - Blumberg, Peter M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, Center for Cancer Research, National Cancer Institute, Building 37, Room 4048, 37 Convent Drive MSC 4255, Bethesda, MD 20892-4255, USA. blumberp@dc37a.nci.nih.gov Y1 - 2004/08/21/ PY - 2004 DA - 2004 Aug 21 SP - 2281 EP - 2286 VL - 2 IS - 16 SN - 1477-0520, 1477-0520 KW - Cations, Divalent KW - 0 KW - Diterpenes KW - Ligands KW - Plant Extracts KW - Quinazolines KW - TRPV Cation Channels KW - resiniferatoxin KW - A5O6P1UL4I KW - evodiamine KW - C01825BVNL KW - capsazepine KW - LFW48MY844 KW - Capsaicin KW - S07O44R1ZM KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Molecular Structure KW - Animals KW - Capsaicin -- chemistry KW - Calcium -- chemistry KW - Models, Biological KW - Capsaicin -- pharmacology KW - Diterpenes -- chemistry KW - Calcium -- metabolism KW - CHO Cells KW - Molecular Conformation KW - Capsaicin -- analogs & derivatives KW - Cations, Divalent -- chemistry KW - Cricetinae KW - TRPV Cation Channels -- agonists KW - TRPV Cation Channels -- metabolism KW - Plant Extracts -- pharmacology KW - Quinazolines -- chemistry KW - Plant Extracts -- chemistry KW - Quinazolines -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66778723?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Organic+%26+biomolecular+chemistry&rft.atitle=Evodiamine+functions+as+an+agonist+for+the+vanilloid+receptor+TRPV1.&rft.au=Pearce%2C+Larry+V%3BPetukhov%2C+Pavel+A%3BSzabo%2C+Tamas%3BKedei%2C+Noemi%3BBizik%2C+Fero%3BKozikowski%2C+Alan+P%3BBlumberg%2C+Peter+M&rft.aulast=Pearce&rft.aufirst=Larry&rft.date=2004-08-21&rft.volume=2&rft.issue=16&rft.spage=2281&rft.isbn=&rft.btitle=&rft.title=Organic+%26+biomolecular+chemistry&rft.issn=14770520&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-06-09 N1 - Date created - 2004-08-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - UvsX recombinase and Dda helicase rescue stalled bacteriophage T4 DNA replication forks in vitro. AN - 66788372; 15194689 AB - The rescue of stalled replication forks via a series of steps that include fork regression, template switching, and fork restoration often has been proposed as a major mechanism for accurately bypassing non-coding DNA lesions. Bacteriophage T4 encodes almost all of the proteins required for its own DNA replication, recombination, and repair. Both recombination and recombination repair in T4 rely on UvsX, a RecA-like recombinase. We show here that UvsX plus the T4-encoded helicase Dda suffice to rescue stalled T4 replication forks in vitro. This rescue is based on two sequential template-switching reactions that allow DNA replication to bypass a non-coding DNA lesion in a non-mutagenic manner. JF - The Journal of biological chemistry AU - Kadyrov, Farid A AU - Drake, John W AD - Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709-2233, USA. Y1 - 2004/08/20/ PY - 2004 DA - 2004 Aug 20 SP - 35735 EP - 35740 VL - 279 IS - 34 SN - 0021-9258, 0021-9258 KW - DNA, Viral KW - 0 KW - DNA-Binding Proteins KW - Membrane Proteins KW - UvsX protein, Enterobacteria phage T4 KW - Viral Proteins KW - DNA Helicases KW - EC 3.6.4.- KW - dda DNA helicase protein, Bacteriophage T4 KW - EC 3.6.4.12 KW - Index Medicus KW - DNA, Viral -- biosynthesis KW - Base Sequence KW - Recombination, Genetic KW - Molecular Sequence Data KW - DNA, Viral -- genetics KW - Viral Proteins -- genetics KW - DNA Helicases -- metabolism KW - Membrane Proteins -- metabolism KW - DNA-Binding Proteins -- genetics KW - DNA Helicases -- genetics KW - Bacteriophage T4 -- metabolism KW - Viral Proteins -- metabolism KW - Bacteriophage T4 -- genetics KW - Membrane Proteins -- genetics KW - DNA Replication KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66788372?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=UvsX+recombinase+and+Dda+helicase+rescue+stalled+bacteriophage+T4+DNA+replication+forks+in+vitro.&rft.au=Kadyrov%2C+Farid+A%3BDrake%2C+John+W&rft.aulast=Kadyrov&rft.aufirst=Farid&rft.date=2004-08-20&rft.volume=279&rft.issue=34&rft.spage=35735&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 - 2005-02-15 N1 - Date created - 2004-08-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Targeting of Scavenger Receptor Class B Type I by Synthetic Amphipathic alpha-Helical-containing Peptides Blocks Lipopolysaccharide (LPS) Uptake and LPS-induced Pro-inflammatory Cytokine Responses in THP-1 Monocyte Cells AN - 18041237; 5986365 AB - Human scavenger receptor class B type I, CLA-1, mediates lipopolysaccharide (LPS) binding and internalization. Because one of the recognition motifs in SR-B1 ligands is the anionic amphipathic alpha-helix, we analyzed the effects of model amphipathic alpha-helical-containing peptides on LPS uptake and LPS-stimulated cytokine production. The L-37pA model peptide, containing two class A amphipathic helices, bound with high affinity (K sub(d) = 0.94 mu g/ml) to CLA-1-expressing HeLa cells with a 10-fold increased capacity when compared with mock transfected HeLa cells. Both LPS and L-37pA colocalized with anti-CLA-1 antibody and directly bound CLA-1 as determined by cross- linking. SR-BI/CLA-1 ligands such as HDL, apoA-I, and L-37pA efficiently competed against iodinated L-37pA. Bacterial LPS, lipoteichoic acid, and hsp60 also competed against iodinated L-37pA. Model peptides blocked uptake of iodinated LPS in both mock transfected and CLA-1-overexpressing HeLa cells. Bound and internalized Alexa-L-37pA and BODIPY-LPS colocalized at the cell surface and perinuclear compartment. Both ligands were predominantly transported to the Golgi complex, colocalizing with the Golgi markers bovine serum albumin- ceramide, anti-Golgin97 antibody, and cholera toxin subunit B. A 100-fold excess of L-37pA nearly eliminated BODIPY-LPS binding and internalization. L-37pA and its D-amino acid analogue, D-37pA peptide were similarly effective in blocking LPS, Gram-positive bacterial wall component lipoteichoic acid and bacterial heat shock protein Gro-EL-stimulated cytokine secretion in THP-1 cells. In the same culture media used for the cytokine stimulation study, neither L-37pA nor D-37pA affected the Limulus amebocyte lysate activity of LPS, indicating that LPS uptake and cytokine stimulation were blocked independently of LPS neutralization. These results demonstrate that amphipathic helices of exchangeable apolipoproteins may represent a general host defense mechanism against inflammation. JF - Journal of Biological Chemistry AU - Bocharov, Alexander V AU - Baranova, Irina N AU - Vishnyakova, Tatyana G AU - Remaley, Alan T AU - Csako, Gyorgy AU - Thomas, Fairwell AU - Patterson, Amy P AU - Eggerman, Thomas L AD - Department of Laboratory Medicine, W. G. Magnuson Clinical Center, NHLBI, and the Division of Diabetes, Endocrinology and Metabolic Diseases, NIDDK, the National Institutes of Health, Bethesda, Maryland Y1 - 2004/08/20/ PY - 2004 DA - 2004 Aug 20 SP - 36072 EP - 36082 PB - American Society for Biochemistry and Molecular Biology, 9650 Rockville Pike Bethesda MD 20814-3996 USA, [mailto:asbmb@asbmb.faseb.org], [URL:http://www.jbc.org] VL - 279 IS - 34 SN - 0021-9258, 0021-9258 KW - man KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - Golgi apparatus KW - Gram-positive bacteria KW - Lipopolysaccharides KW - Cytokines KW - Monocytes KW - scavenger receptors KW - Inflammation KW - F 06733:General KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18041237?accountid=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=Targeting+of+Scavenger+Receptor+Class+B+Type+I+by+Synthetic+Amphipathic+alpha-Helical-containing+Peptides+Blocks+Lipopolysaccharide+%28LPS%29+Uptake+and+LPS-induced+Pro-inflammatory+Cytokine+Responses+in+THP-1+Monocyte+Cells&rft.au=Bocharov%2C+Alexander+V%3BBaranova%2C+Irina+N%3BVishnyakova%2C+Tatyana+G%3BRemaley%2C+Alan+T%3BCsako%2C+Gyorgy%3BThomas%2C+Fairwell%3BPatterson%2C+Amy+P%3BEggerman%2C+Thomas+L&rft.aulast=Bocharov&rft.aufirst=Alexander&rft.date=2004-08-20&rft.volume=279&rft.issue=34&rft.spage=36072&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 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Golgi apparatus; Gram-positive bacteria; Cytokines; Lipopolysaccharides; Monocytes; scavenger receptors; Inflammation ER - TY - JOUR T1 - Detection of HIV-1 and HCV Infections among Antibody-Negative Blood Donors by Nucleic Acid-Amplification Testing AN - 223941326; 15317889 AB - Background Testing of blood donors for human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) RNA by means of nucleic acid amplification was introduced in the United States as an investigational screening test in mid-1999 to identify donations made during the window period before seroconversion. Methods We analyzed all antibody-nonreactive donations that were confirmed to be positive for HIV-1 and HCV RNA on nucleic acid-amplification testing of "minipools" (pools of 16 to 24 donations) by the main blood-collection programs in the United States during the first three years of nucleic acid screening. Results Among 37,164,054 units screened, 12 were confirmed to be positive for HIV-1 RNA -- or 1 in 3.1 million donations -- only 2 of which were detected by HIV-1 p24 antigen testing. For HCV, of 39,721,404 units screened, 170 were confirmed to be positive for HCV RNA, or 1 in 230,000 donations (or 1 in 270,000 on the basis of 139 donations confirmed to be positive for HCV RNA with the use of a more sensitive HCV-antibody test). The respective rates of positive HCV and HIV-1 nucleic acid-amplification tests were 3.3 and 4.1 times as high among first-time donors as among donors who gave blood repeatedly. Follow-up studies of 67 HCV RNA-positive donors demonstrated that seroconversion occurred a median of 35 days after the index donation, followed by a low rate of resolution of viremia; three cases of long-term immunologically silent HCV infection were documented. Conclusions Minipool nucleic acid-amplification testing has helped prevent the transmission of approximately 5 HIV-1 infections and 56 HCV infections annually and has reduced the residual risk of transfusion-transmitted HIV-1 and HCV to approximately 1 in 2 million blood units. JF - The New England Journal of Medicine AU - Stramer, Susan L, PhD AU - Glynn, Simone A, MD, MPH AU - Kleinman, Steven H, MD AU - Strong, D Michael, PhD AU - Caglioti, Sally, MT (ASCP), SBB AU - Wright, David J, PhD AU - Dodd, Roger Y, PhD AU - Busch, Michael P, MD, PhD Y1 - 2004/08/19/ PY - 2004 DA - 2004 Aug 19 SP - 760 EP - 8 CY - Boston PB - Massachusetts Medical Society VL - 351 IS - 8 SN - 00284793 KW - Medical Sciences KW - HIV Antibodies KW - Hepatitis C Antibodies KW - RNA, Viral KW - Alanine Transaminase KW - FDA approval KW - Hepatitis KW - Human immunodeficiency virus--HIV KW - Blood & organ donations KW - Acids KW - United States--US KW - Alanine Transaminase -- blood KW - Hepatitis C -- transmission KW - HIV Infections -- transmission KW - HIV Infections -- blood KW - HIV Antibodies -- blood KW - Hepatitis C -- blood KW - Humans KW - Hepatitis C Antibodies -- blood KW - RNA, Viral -- analysis KW - Viremia -- diagnosis KW - Hepatitis C -- diagnosis KW - HIV-1 -- isolation & purification KW - Nucleic Acid Amplification Techniques KW - Hepacivirus -- isolation & purification KW - Blood Donors KW - HIV Infections -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/223941326?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+Journal+of+Medicine&rft.atitle=Detection+of+HIV-1+and+HCV+Infections+among+Antibody-Negative+Blood+Donors+by+Nucleic+Acid-Amplification+Testing&rft.au=Stramer%2C+Susan+L%2C+PhD%3BGlynn%2C+Simone+A%2C+MD%2C+MPH%3BKleinman%2C+Steven+H%2C+MD%3BStrong%2C+D+Michael%2C+PhD%3BCaglioti%2C+Sally%2C+MT+%28ASCP%29%2C+SBB%3BWright%2C+David+J%2C+PhD%3BDodd%2C+Roger+Y%2C+PhD%3BBusch%2C+Michael+P%2C+MD%2C+PhD&rft.aulast=Stramer&rft.aufirst=Susan&rft.date=2004-08-19&rft.volume=351&rft.issue=8&rft.spage=760&rft.isbn=&rft.btitle=&rft.title=British+Journal+of+Pharmacology&rft.issn=00071188&rft_id=info:doi/10.1038%2Fsj.bjp.0705931 LA - English DB - ProQuest Central N1 - Name - Food & Drug Administration--FDA N1 - Copyright - Copyright © 2004 Massachusetts Medical Society. All rights reserved. N1 - Document feature - Tables; Graphs; References N1 - Last updated - 2014-04-21 N1 - CODEN - NEJMAG N1 - SubjectsTermNotLitGenreText - United States--US ER - TY - JOUR T1 - Frequent downregulation and loss of WWOX gene expression in human hepatocellular carcinoma. AN - 66789547; 15266310 AB - The WWOX (WW-domain containing oxidoreductase) is a candidate tumour suppressor gene spanning the same chromosome region, 16q23, as the second most common fragile site (FS), FRA16D. Deletions detected by comparative genomic hybridisation (CGH) and loss of heterozygosity at microsatellite markers on chromosome 16q are common in many human cancers including hepatocellular carcinoma (HCC). The development of human HCC is closely associated with exposure to oncogenic viruses and chemical carcinogens, agents known to frequently target common FS. We examined the status of WWOX genomic DNA, RNA and protein in 18 cell lines derived from human HCC and found recurrent alterations of the gene. Loss of DNA copy-number confined to band 16q23 was detected by CGH in several cell lines. Although homozygous deletions of the WWOX gene were not detected, WWOX mRNA expression was absent or lower in 60% of cell lines. The occurrence of aberrant WWOX reverse transcription-PCR products with deletion of exons 6-8 correlated significantly with altered WWOX expression. All of the cell lines showing mRNA downregulation had a decreased or undetectable level of WWOX protein as demonstrated by Western blotting with antibody to WWOX. Furthermore, 13 out of the 18 cell lines expressed decreased levels or no WWOX protein when compared with normal liver. These results show that WWOX gene is frequently altered in HCC and raise the possibility that this gene is implicated in hepatocarcinogenesis. JF - British journal of cancer AU - Park, S-W AU - Ludes-Meyers, J AU - Zimonjic, D B AU - Durkin, M E AU - Popescu, N C AU - Aldaz, C M AD - Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-4262, USA. Y1 - 2004/08/16/ PY - 2004 DA - 2004 Aug 16 SP - 753 EP - 759 VL - 91 IS - 4 SN - 0007-0920, 0007-0920 KW - Tumor Suppressor Proteins KW - 0 KW - Oxidoreductases KW - EC 1.- KW - WWOX protein, human KW - EC 1.1.1.- KW - Index Medicus KW - Microsatellite Repeats KW - Loss of Heterozygosity KW - Apoptosis KW - Tumor Cells, Cultured KW - Down-Regulation KW - Humans KW - Chromosome Fragile Sites KW - Reverse Transcriptase Polymerase Chain Reaction KW - Gene Expression Regulation, Neoplastic KW - Liver Neoplasms -- pathology KW - Carcinoma, Hepatocellular -- genetics KW - Carcinoma, Hepatocellular -- pathology KW - Oxidoreductases -- biosynthesis KW - Liver Neoplasms -- genetics KW - Gene Deletion KW - Chromosomes, Human, Pair 16 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66789547?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Frequent+downregulation+and+loss+of+WWOX+gene+expression+in+human+hepatocellular+carcinoma.&rft.au=Park%2C+S-W%3BLudes-Meyers%2C+J%3BZimonjic%2C+D+B%3BDurkin%2C+M+E%3BPopescu%2C+N+C%3BAldaz%2C+C+M&rft.aulast=Park&rft.aufirst=S-W&rft.date=2004-08-16&rft.volume=91&rft.issue=4&rft.spage=753&rft.isbn=&rft.btitle=&rft.title=British+journal+of+cancer&rft.issn=00070920&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-14 N1 - Date created - 2004-08-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cancer Res. 2000 Apr 15;60(8):2140-5 [10786676] Cancer Res. 2000 Feb 15;60(4):1049-53 [10706123] Oncogene. 2001 Aug 23;20(37):5232-8 [11526514] Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11417-22 [11572989] Cancer Res. 2001 Nov 15;61(22):8068-73 [11719429] Nat Rev Cancer. 2001 Dec;1(3):214-21 [11902576] Oncogene. 2002 Mar 14;21(12):1832-40 [11896615] Cancer Res. 2002 Apr 15;62(8):2258-60 [11956080] Cancer Res. 2002 Jul 15;62(14):4054-60 [12124341] Nat Genet. 2002 Aug;31(4):339-46 [12149612] Hepatology. 2002 Nov;36(5):1214-20 [12395332] Int J Oncol. 1998 Jan;12(1):187-96 [9454904] Cell. 2002 Dec 13;111(6):779-89 [12526805] Oncogene. 2003 Jan 23;22(3):445-50 [12545165] J Mol Diagn. 2003 Feb;5(1):48-53 [12552080] Cancer Res. 2003 Feb 15;63(4):878-81 [12591741] Cancer Lett. 2003 Mar 20;192(1):1-17 [12637148] Int J Oncol. 2003 Jul;23(1):133-7 [12792785] Cytogenet Genome Res. 2003;100(1-4):92-100 [14526169] Cytogenet Genome Res. 2003;100(1-4):101-10 [14526170] Cytogenet Genome Res. 2003;101(1):8-16 [14571130] Genes Chromosomes Cancer. 2004 Jan;39(1):71-6 [14603443] Mol Cancer Res. 2003 Nov;1(13):940-7 [14638866] Neoplasia. 2003 Sep-Oct;5(5):390-6 [14670176] Cancer Res. 2003 Dec 15;63(24):8629-33 [14695174] Oncogene. 2004 Feb 12;23(6):1308-13 [14647417] Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4401-6 [15070730] Hum Genet. 1984;67(2):136-42 [6430783] Science. 1987 Jan 16;235(4786):305-11 [3541204] Nucleic Acids Res. 1991 Aug 11;19(15):4293 [1870982] Nat Genet. 1997 Apr;15 Spec No:417-74 [9140409] Hum Mol Genet. 1998 Apr;7(4):755-61 [9499431] Hepatology. 1999 Apr;29(4):1208-14 [10094966] Cancer Genet Cytogenet. 1999 May;111(1):37-44 [10326589] J Clin Oncol. 1999 May;17(5):1618-24 [10334551] Cell. 2000 Jan 7;100(1):57-70 [10647931] Genes Chromosomes Cancer. 2001 Mar;30(3):245-53 [11170281] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pilot clinical trial of dehydroepiandrosterone (DHEA) versus placebo for Sjögren's syndrome. AN - 66824695; 15334433 AB - To screen for potential efficacy and assess feasibility and safety of dehydroepiandrosterone (DHEA) as a treatment for Sjögren's syndrome (SS). A 24-week randomized, double-blinded, pilot trial of oral DHEA (200 mg/day) versus placebo was conducted. The primary comparison was to a hypothesized 20% placebo response rate. If 14 consecutive subjects on DHEA did not respond, a Phase III trial would be considered futile. A placebo group of 14 subjects was planned to verify placebo response rate and estimate sample size required for a definitive trial. Response criteria required 20% improvement in at least 2 of 3 domains. Analysis of covariance was used to adjust for baseline differences and for stratified randomization. Outcome measures included visual analog scale questionnaires for dry eye and dry mouth symptoms, lissamine green ocular dye staining and Schirmer I tests, stimulated salivary flow, IgG, and erythrocyte sedimentation rate (ESR). Randomization resulted in 14 DHEA and 14 placebo group subjects. At baseline, mean +/- SD for DHEA versus placebo groups were Schirmer I tests 4.5 +/- 4.5 versus 5.4 +/- 6.1 mm/5 minutes; Van Bijsterveld score 5.3 +/- 2.1 versus 5.5 +/- 2.2; unstimulated saliva 0.03 +/- 0.05 versus 0.04 +/- 0.10 ml/minute; IgG 1,699 +/- 749 versus 1,712 +/- 621 g/dl; and ESR 40 +/- 31 versus 44 +/- 28 mm/hour. Apart from changes over the trial in dry mouth symptoms, no significant differences were noted between the DHEA and placebo groups for dry eye symptoms, objective measures of ocular dryness, stimulated salivary flow; IgG, or ESR. Four DHEA and one placebo group patient dropped out because of adverse effects. Although 7 subjects met response criteria in the DHEA group, 5 met the criteria in the placebo group, and there was no significant difference between groups. DHEA showed no evidence of efficacy in SS. Without evidence for efficacy, patients with SS should avoid using unregulated DHEA supplements, since long-term adverse consequences of exposure to this hormone are unknown. JF - Arthritis and rheumatism AU - Pillemer, Stanley R AU - Brennan, Michael T AU - Sankar, Vidya AU - Leakan, Rose Anne AU - Smith, Janine A AU - Grisius, Margaret AU - Ligier, Sophie AU - Radfar, Lida AU - Kok, Marc R AU - Kingman, Albert AU - Fox, Philip C AD - National Institute of Dental and Craniofacial Research, Bethesda, Maryland 28092, USA. PillemerS@medimmune.com Y1 - 2004/08/15/ PY - 2004 DA - 2004 Aug 15 SP - 601 EP - 604 VL - 51 IS - 4 SN - 0004-3591, 0004-3591 KW - Adjuvants, Immunologic KW - 0 KW - Placebos KW - Dehydroepiandrosterone KW - 459AG36T1B KW - Abridged Index Medicus KW - Index Medicus KW - Double-Blind Method KW - Humans KW - Treatment Outcome KW - Pilot Projects KW - Middle Aged KW - Female KW - Adjuvants, Immunologic -- administration & dosage KW - Sjogren's Syndrome -- drug therapy KW - Dehydroepiandrosterone -- adverse effects KW - Adjuvants, Immunologic -- adverse effects KW - Dehydroepiandrosterone -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66824695?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Pilot+clinical+trial+of+dehydroepiandrosterone+%28DHEA%29+versus+placebo+for+Sj%C3%B6gren%27s+syndrome.&rft.au=Pillemer%2C+Stanley+R%3BBrennan%2C+Michael+T%3BSankar%2C+Vidya%3BLeakan%2C+Rose+Anne%3BSmith%2C+Janine+A%3BGrisius%2C+Margaret%3BLigier%2C+Sophie%3BRadfar%2C+Lida%3BKok%2C+Marc+R%3BKingman%2C+Albert%3BFox%2C+Philip+C&rft.aulast=Pillemer&rft.aufirst=Stanley&rft.date=2004-08-15&rft.volume=51&rft.issue=4&rft.spage=601&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 - 2004-09-20 N1 - Date created - 2004-08-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Arthritis Rheum. 2005 Aug 15;53(4):626 [16082652] Arthritis Rheum. 2005 Aug 15;53(4):626-7 [16082644] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Poliovirus vaccination during pregnancy, maternal seroconversion to simian virus 40, and risk of childhood cancer. AN - 66763424; 15286015 AB - Before 1963, poliovirus vaccine produced in the United States was contaminated with simian virus 40 (SV40), which causes cancer in animals. To examine whether early-life SV40 infection can cause human cancer, the authors studied 54,796 children enrolled in the US-based Collaborative Perinatal Project (CPP) in 1959-1966, 52 of whom developed cancer by their eighth birthday. Those children whose mothers had received pre-1963 poliovirus vaccine during pregnancy (22.5% of the children) had an increased incidence of neural tumors (hazard ratio = 2.6, 95% confidence interval: 1.0, 6.7; 18 cases) and hematologic malignancies (hazard ratio = 2.8, 95% confidence interval: 1.2, 6.4; 22 cases). For 50 CPP children with cancer and 200 CPP control children, the authors tested paired maternal serum samples from pregnancy for SV40 antibodies using a virus-like particle enzyme immunoassay and a plaque neutralization assay. Overall, mothers exhibited infrequent, low-level SV40 antibody reactivity, and only six case mothers seroconverted by either assay. Using the two SV40 assays, maternal SV40 seroconversion during pregnancy was not consistently related to children's case/control status or mothers' receipt of pre-1963 vaccine. The authors conclude that an increased cancer risk in CPP children whose mothers received pre-1963 poliovirus vaccine was unlikely to have been due to SV40 infection transmitted from mothers to their children. JF - American journal of epidemiology AU - Engels, E A AU - Chen, J AU - Viscidi, R P AU - Shah, K V AU - Daniel, R W AU - Chatterjee, N AU - Klebanoff, M A AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20892, USA. engelse@exchange.nih.gov Y1 - 2004/08/15/ PY - 2004 DA - 2004 Aug 15 SP - 306 EP - 316 VL - 160 IS - 4 SN - 0002-9262, 0002-9262 KW - Antibodies, Viral KW - 0 KW - Poliovirus Vaccines KW - Index Medicus KW - Causality KW - Drug Contamination KW - Maternal Exposure -- statistics & numerical data KW - Humans KW - Seroepidemiologic Studies KW - Child KW - Pregnancy KW - Child, Preschool KW - Infant KW - BK Virus -- immunology KW - Vaccination -- statistics & numerical data KW - Adult KW - Cohort Studies KW - Case-Control Studies KW - Nervous System Neoplasms -- epidemiology KW - Incidence KW - Fibrosarcoma -- epidemiology KW - Hematologic Neoplasms -- epidemiology KW - United States -- epidemiology KW - Male KW - Female KW - Poliomyelitis -- immunology KW - Antibodies, Viral -- blood KW - Pregnancy Complications, Infectious -- prevention & control KW - Pregnancy Complications, Infectious -- immunology KW - Poliomyelitis -- prevention & control KW - Neoplasms -- classification KW - Poliovirus Vaccines -- adverse effects KW - Neoplasms -- epidemiology KW - Simian virus 40 -- immunology KW - Prenatal Exposure Delayed Effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66763424?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Poliovirus+vaccination+during+pregnancy%2C+maternal+seroconversion+to+simian+virus+40%2C+and+risk+of+childhood+cancer.&rft.au=Engels%2C+E+A%3BChen%2C+J%3BViscidi%2C+R+P%3BShah%2C+K+V%3BDaniel%2C+R+W%3BChatterjee%2C+N%3BKlebanoff%2C+M+A&rft.aulast=Engels&rft.aufirst=E&rft.date=2004-08-15&rft.volume=160&rft.issue=4&rft.spage=306&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 - 2004-09-21 N1 - Date created - 2004-08-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Efficient magnetic cell labeling with protamine sulfate complexed to ferumoxides for cellular MRI. AN - 66757118; 15100158 AB - Recently, there have been several reports using various superparamagnetic iron oxide (SPIO) nanoparticles to label mammalian cells for monitoring their temporal and spatial migration in vivo by magnetic resonance imaging (MRI). The purpose of this study was to evaluate the efficiency and toxicity of labeling cells using 2 commercially available Food and Drug Administration (FDA)-approved agents, ferumoxides, a suspension of dextran-coated SPIO used as an MRI contrast agent, and protamine sulfate, conventionally used to reverse heparin anticoagulation but also used ex vivo as a cationic transfection agent. After labeling of human mesenchymal stem cells (MSCs) and hematopoietic (CD34+) stem cells and other mammalian cells with ferumoxides-protamine sulfate complexes (FE-Pro), cellular toxicity, functional capacity, and quantitative cellular iron incorporation were determined. FE-Pro-labeled cells demonstrated no short- or long-term toxicity, changes in differentiation capacity of the stem cells, or changes in phenotype when compared with unlabeled cells. Efficient labeling with FE-Pro was observed with iron content per cell varying between 2.01 +/- 0.1 pg for CD34+ cells and 10.94 +/- 1.86 pg for MSCs with 100% of cells labeled. Cell labeling using these agents should facilitate the translation of this method to clinical trials for evaluation of trafficking of infused or transplanted cells by MRI. JF - Blood AU - Arbab, Ali S AU - Yocum, Gene T AU - Kalish, Heather AU - Jordan, Elaine K AU - Anderson, Stasia A AU - Khakoo, Aarif Y AU - Read, Elizabeth J AU - Frank, Joseph A AD - Laboratory of Diagnostic Radiology Research, National Institutes of Health, Building 10, Room no. B1N256, Bethesda, MD 20892, USA. saali@cc.nih.gov Y1 - 2004/08/15/ PY - 2004 DA - 2004 Aug 15 SP - 1217 EP - 1223 VL - 104 IS - 4 SN - 0006-4971, 0006-4971 KW - Dextrans KW - 0 KW - Magnetite Nanoparticles KW - Molecular Probes KW - Oxides KW - Protamines KW - Iron KW - E1UOL152H7 KW - ferumoxides KW - G6N3J05W84 KW - Ferrosoferric Oxide KW - XM0M87F357 KW - Abridged Index Medicus KW - Index Medicus KW - Cell Movement KW - Cell Proliferation -- drug effects KW - Magnetic Resonance Imaging KW - Animals KW - Protamines -- toxicity KW - Humans KW - Mice KW - Molecular Probes -- pharmacokinetics KW - Drug Evaluation KW - Cell Survival -- drug effects KW - Molecular Probes -- toxicity KW - Protamines -- pharmacokinetics KW - Mesenchymal Stromal Cells -- drug effects KW - Neoplasms -- pathology KW - Iron -- analysis KW - Hematopoietic Stem Cells -- cytology KW - Iron -- pharmacokinetics KW - Oxides -- pharmacokinetics KW - Oxides -- toxicity KW - Iron -- toxicity KW - Molecular Probe Techniques KW - Mesenchymal Stromal Cells -- cytology KW - Hematopoietic Stem Cells -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66757118?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Efficient+magnetic+cell+labeling+with+protamine+sulfate+complexed+to+ferumoxides+for+cellular+MRI.&rft.au=Arbab%2C+Ali+S%3BYocum%2C+Gene+T%3BKalish%2C+Heather%3BJordan%2C+Elaine+K%3BAnderson%2C+Stasia+A%3BKhakoo%2C+Aarif+Y%3BRead%2C+Elizabeth+J%3BFrank%2C+Joseph+A&rft.aulast=Arbab&rft.aufirst=Ali&rft.date=2004-08-15&rft.volume=104&rft.issue=4&rft.spage=1217&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-09 N1 - Date created - 2004-08-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Blood. 2004 Nov 15;104(10):3410-2; author reply 3412-3 [15525839] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HIV transmission risk behavior among men and women living with HIV in 4 cities in the United States. AN - 66694418; 15247559 AB - Determining rates of HIV transmission risk behavior among HIV-positive individuals is a public health priority, especially as infected persons live longer because of improved medical treatments. Few studies have assessed the potential for transmission to the partners of HIV-positive persons who engage in high-risk activities. A total of 3723 HIV-infected persons (1918 men who have sex with men [MSM], 978 women, and 827 heterosexual men) were interviewed in clinics and community-based agencies in Los Angeles, Milwaukee, New York City, and San Francisco from June 2000 to January 2002 regarding sexual and drug use behaviors that confer risk for transmitting HIV. Less than one quarter of women and heterosexual men had 2 or more sexual partners, whereas 59% of MSM reported having multiple partners. Most unprotected vaginal and anal sexual activity took place in the context of relationships with other HIV-positive individuals. Approximately 19% of women, 15.6% of MSM, and 13.1% of heterosexual men engaged in unprotected vaginal or anal intercourse with partners who were HIV-negative or whose serostatus was unknown. The majority of sexually active participants disclosed their serostatus to all partners with whom they engaged in unprotected intercourse. An estimated 30.4 new infections (79.7% as a result of sexual interactions with MSM) would be expected among the sex partners of study participants during the 3-month reporting period. Eighteen percent of 304 participants who injected drugs in the past 3 months reported lending their used injection equipment to others. In addition to the more traditional approaches of HIV test counseling and of focusing on persons not infected, intensive prevention programs for persons with HIV infection are needed to stem the future spread of the virus. JF - Journal of acquired immune deficiency syndromes (1999) AU - Weinhardt, Lance S AU - Kelly, Jeffrey A AU - Brondino, Michael J AU - Rotheram-Borus, Mary Jane AU - Kirshenbaum, Sheri B AU - Chesney, Margaret A AU - Remien, Robert H AU - Morin, Stephen F AU - Lightfoot, Marguerita AU - Ehrhardt, Anke A AU - Johnson, Mallory O AU - Catz, Sheryl L AU - Pinkerton, Steven D AU - Benotsch, Eric G AU - Hong, Daniel AU - Gore-Felton, Cheryl AU - National Institute of Mental Health Healthy Living Project Team AD - Center for AIDS Intervention Research, Medical College of Wisconsin, Milwaukee, WI 53202, USA. lsw@mcw.edu ; National Institute of Mental Health Healthy Living Project Team Y1 - 2004/08/15/ PY - 2004 DA - 2004 Aug 15 SP - 1057 EP - 1066 VL - 36 IS - 5 SN - 1525-4135, 1525-4135 KW - Index Medicus KW - AIDS/HIV KW - Risk-Taking KW - Humans KW - Aged KW - Models, Statistical KW - Sexual Partners KW - Sexual Behavior KW - Aged, 80 and over KW - Needle Sharing KW - Adult KW - Middle Aged KW - Substance Abuse, Intravenous -- complications KW - United States -- epidemiology KW - Female KW - Male KW - HIV Infections -- transmission KW - HIV Infections -- complications KW - HIV Infections -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66694418?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=HIV+transmission+risk+behavior+among+men+and+women+living+with+HIV+in+4+cities+in+the+United+States.&rft.au=Weinhardt%2C+Lance+S%3BKelly%2C+Jeffrey+A%3BBrondino%2C+Michael+J%3BRotheram-Borus%2C+Mary+Jane%3BKirshenbaum%2C+Sheri+B%3BChesney%2C+Margaret+A%3BRemien%2C+Robert+H%3BMorin%2C+Stephen+F%3BLightfoot%2C+Marguerita%3BEhrhardt%2C+Anke+A%3BJohnson%2C+Mallory+O%3BCatz%2C+Sheryl+L%3BPinkerton%2C+Steven+D%3BBenotsch%2C+Eric+G%3BHong%2C+Daniel%3BGore-Felton%2C+Cheryl%3BNational+Institute+of+Mental+Health+Healthy+Living+Project+Team&rft.aulast=Weinhardt&rft.aufirst=Lance&rft.date=2004-08-15&rft.volume=36&rft.issue=5&rft.spage=1057&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 - 2005-09-13 N1 - Date created - 2005-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Repacking of hydrophobic residues in a stable mutant of apocytochrome b562 selected by phage-display and proteolysis. AN - 66670982; 15229877 AB - To test a hydrophobic core-directed protein design approach, we previously have used phage-display and proteolysis to select stably folded proteins from a library of mutants of apocytochrome b562. The consensus sequence of the selected mutants has hydrophilic residues at two of the three positions that are designed to form a hydrophobic core. To understand this unexpected result, we determined the high-resolution structure of one of the selected mutants using multi-dimensional nuclear magnetic resonance (NMR). The structure shows that the two hydrophilic residues in the consensus sequence were on the surface of the structure. Instead, two of their neighboring hydrophobic residues reorganized their side-chain conformations and formed the hydrophobic core. This result suggests that the hydrophobic core-directed protein design by phage-display and proteolysis is a valid method in general but alternative hydrophobic packing needs to be considered in the initial design. The unexpected repacking of the hydrophobic residues also highlights the plastic nature of protein structures. Copyright 2004 Wiley-Liss, Inc. JF - Proteins AU - Feng, Hanqiao AU - Bai, Yawen AD - Laboratory of Biochemistry, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2004/08/15/ PY - 2004 DA - 2004 Aug 15 SP - 426 EP - 429 VL - 56 IS - 3 KW - Cytochrome b Group KW - 0 KW - Peptide Library KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Hydrophobic and Hydrophilic Interactions KW - Protein Structure, Secondary KW - Protein Engineering KW - Computer Simulation KW - Models, Molecular KW - Nuclear Magnetic Resonance, Biomolecular KW - Protein Folding KW - Consensus Sequence KW - Protein Structure, Tertiary KW - Hydrolysis KW - Hydrogen Bonding KW - Cytochrome b Group -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66670982?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proteins&rft.atitle=Repacking+of+hydrophobic+residues+in+a+stable+mutant+of+apocytochrome+b562+selected+by+phage-display+and+proteolysis.&rft.au=Feng%2C+Hanqiao%3BBai%2C+Yawen&rft.aulast=Feng&rft.aufirst=Hanqiao&rft.date=2004-08-15&rft.volume=56&rft.issue=3&rft.spage=426&rft.isbn=&rft.btitle=&rft.title=Proteins&rft.issn=1097-0134&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-20 N1 - Date created - 2004-07-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activity of Staphylococcus epidermidis Phenol-Soluble Modulin Peptides Expressed in Staphylococcus carnosus AN - 18041997; 5990609 AB - Staphylococcus epidermidis releases a group of peptides termed phenol-soluble modulin (PSM) that stimulate macrophages. The structure of 3 peptides (PSM alpha , PSM beta , and PSM gamma ) have been described. We report a fourth peptide (PSM delta ), which is a 23mer with the structure fMSIVSTIIEVVKTIVDIVKKFKK. The gene for each of the 4 peptides was introduced singly into Staphylococcus carnosus, and the PSM-like activity of culture medium and bacterial extract were significantly greater than those of the parent strain. PSM peptides from each of the S. carnosus-expressing strains were purified and analyzed by liquid chromatography-mass spectrometry. The products, which appeared to form aggregates, were active in the activation of human immunodeficiency virus type 1 long-terminal repeat and the production of tumor necrosis factor- alpha by the macrophage cell line THP-1. These findings suggest that PSM peptides are responsible, in part, for the modulin-like activity of staphylococci and may contribute to the development of severe staphylococcal sepsis. JF - Journal of Infectious Diseases AU - Otto, M AU - O'Mahoney, D S AU - Guina, T AU - Klebanoff, S J AD - Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA Y1 - 2004/08/15/ PY - 2004 DA - 2004 Aug 15 SP - 748 EP - 755 VL - 190 IS - 4 SN - 0022-1899, 0022-1899 KW - modulin KW - Microbiology Abstracts B: Bacteriology KW - Macrophages KW - Sepsis KW - Tumor necrosis factor-^a KW - Staphylococcus carnosus KW - Cell lines KW - Staphylococcus epidermidis KW - Phenols KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18041997?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Infectious+Diseases&rft.atitle=Activity+of+Staphylococcus+epidermidis+Phenol-Soluble+Modulin+Peptides+Expressed+in+Staphylococcus+carnosus&rft.au=Otto%2C+M%3BO%27Mahoney%2C+D+S%3BGuina%2C+T%3BKlebanoff%2C+S+J&rft.aulast=Otto&rft.aufirst=M&rft.date=2004-08-15&rft.volume=190&rft.issue=4&rft.spage=748&rft.isbn=&rft.btitle=&rft.title=Journal+of+Infectious+Diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Staphylococcus carnosus; Staphylococcus epidermidis; Phenols; Tumor necrosis factor-^a; Cell lines; Macrophages; Sepsis ER - TY - JOUR T1 - Genome-wide molecular dissection of serotype M3 group A Streptococcus strains causing two epidemics of invasive infections AN - 18016175; 5982709 AB - Molecular factors that contribute to the emergence of new virulent bacterial subclones and epidemics are poorly understood. We hypothesized that analysis of a population-based strain sample of serotype M3 group A Streptococcus (GAS) recovered from patients with invasive infection by using genome-wide investigative methods would provide new insight into this fundamental infectious disease problem. Serotype M3 GAS strains (n = 255) cultured from patients in Ontario, Canada, over 11 years and representing two distinct infection peaks were studied. Genetic diversity was indexed by pulsed-field gel electrophoresis, DNA-DNA microarray, whole-genome PCR scanning, prophage genotyping, targeted gene sequencing, and single-nucleotide polymorphism genotyping. All variation in gene content was attributable to acquisition or loss of prophages, a molecular process that generated unique combinations of proven or putative virulence genes. Distinct serotype M3 genotypes experienced rapid population expansion and caused infections that differed significantly in character and severity. Molecular genetic analysis, combined with immunologic studies, implicated a 4-aa duplication in the extreme N terminus of M protein as a factor contributing to an epidemic wave of serotype M3 invasive infections. This finding has implications for GAS vaccine research. Genome-wide analysis of population-based strain samples cultured from clinically well defined patients is crucial for understanding the molecular events underlying bacterial epidemics. JF - Proceedings of the National Academy of Sciences, USA AU - Beres, Stephen B AU - Sylva, Gail L AU - Sturdevant, Daniel E AU - Granville, Chanel N AU - Liu, Mengyao AU - Ricklefs, Stacy M AU - Whitney, Adeline R AU - Parkins, Larye D AU - Hoe, Nancy P AU - Adams, Gerald J AU - Low, Donald E AU - Deleo, Frank R AU - Mcgeer, Allison AU - Musser, James M AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT Y1 - 2004/08/10/ PY - 2004 DA - 2004 Aug 10 SP - 11833 EP - 11838 PB - National Academy of Sciences, 2101 Constitution Ave. Washington DC 20418 USA VL - 101 IS - 32 SN - 0027-8424, 0027-8424 KW - streptococci KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - Streptococcus KW - Serotypes KW - Genetic diversity KW - Genotypes KW - Infection KW - Virulence KW - Epidemiology KW - J 02855:Human Bacteriology: Others KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18016175?accountid=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=Carcinogenesis&rft.atitle=PPARgamma+influences+susceptibility+to+DMBA-induced+mammary%2C+ovarian+and+skin+carcinogenesis&rft.au=Nicol%2C+Christopher+J%3BYoon%2C+Michung%3BWard%2C+Jerrold+M%3BYamashita%2C+Masamichi%3BFukamachi%2C+Katsumi%3BPeters%2C+Jeffrey+M%3BGonzalez%2C+Frank+J&rft.aulast=Nicol&rft.aufirst=Christopher&rft.date=2004-09-01&rft.volume=25&rft.issue=9&rft.spage=1747&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 - Streptococcus; Virulence; Serotypes; Infection; Genetic diversity; Genotypes; Epidemiology ER - TY - JOUR T1 - Clastogenic effect for cigarette smoking but not areca quid chewing as measured by micronuclei in exfoliated buccal mucosal cells. AN - 66755882; 15279828 AB - The objective of this study was to use the micronuclei from exfoliated buccal mucosal cells to investigate the clastogenic effects of areca quid chewing and cigarette smoking, as well as the interaction between the two. The study population was selected from residents of seven villages recruited for a community-cohort study. A total of 141 subjects were recruited based on the regular consumption of cigarettes and betel quid. Salient personal characteristics were collected from interview using a specially designed questionnaire. Micronuclei were scored on Feulgen/fast green-stained smear preparations of exfoliated cells obtained by scraping the surface of the buccal mucosa. There was no significant interaction between the chewing of betel nut and cigarette smoking. Heavy smoking was positively associated with MN frequency, with areca quid chewing negatively associated. A significant positive trend was demonstrated for the relationship between MN frequency and either daily cigarette consumption or cumulative smoking pack-years. By contrast, negative trends were demonstrated for the analogous relationships with areca quid chewing. These results indicate that heavy smoking, but not areca quid chewing, increases MN formation. These findings suggest that the carcinogenesis of the oral cancers induced by areca quid chewing in Taiwan may be through a pathway other than genotoxicity. JF - Mutation research AU - Wu, Ping-An AU - Loh, Ching-Hui AU - Hsieh, Ling-Ling AU - Liu, Tsung-Yun AU - Chen, Chien-Jen AU - Liou, Saou-Hsing AD - Graduate Institute of Medical Sciences, National Defense Medical Center, National Defense University, Nei-Hu, Taipei, Taiwan, ROC. Y1 - 2004/08/08/ PY - 2004 DA - 2004 Aug 08 SP - 27 EP - 38 VL - 562 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Index Medicus KW - Humans KW - Adult KW - Middle Aged KW - Areca KW - Tobacco KW - Mouth Mucosa -- cytology KW - Smoking -- genetics KW - Micronuclei, Chromosome-Defective UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66755882?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chronic+inorganic+arsenic+exposure+induces+hepatic+global+and+individual+gene+hypomethylation%3A+implications+for+arsenic+hepatocarcinogenesis&rft.au=Chen%2C+Hua%3BLi%2C+Shuanfang%3BLiu%2C+Jie%3BDiwan%2C+Bhalchandra+A%3BBarrett%2C+JCarl%3BWaalkes%2C+Michael+P&rft.aulast=Chen&rft.aufirst=Hua&rft.date=2004-09-01&rft.volume=25&rft.issue=9&rft.spage=1779&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-16 N1 - Date created - 2004-07-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Mutat Res. 2005 Apr 4;582(1-2):163-4; author reply 165-7 [15781221] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inter-rater agreement on chromosome 5 breakage in FISH-based mutagen sensitivity assays (MSAs). AN - 66754707; 15279836 AB - In chromosome breakage assays, validated, universal criteria for selection of cells and classification of chromosome aberrations may enhance their utility for cancer susceptibility screening. To standardize a fluorescence in situ hybridization (FISH) modification of the mutagen sensitivity assay (MSA), scoring criteria were evaluated by web-based validation. Two hundred digital FISH images were assigned random identification numbers. With this set of images, criteria for inclusion of cells and measurement of the frequency of abnormal cells were evaluated by eight observers, all of whom had five or more years of experience. Observers included doctoral and MS/BS level cytogeneticists, and were drawn from a randomized pool of 54 volunteers. Questions addressed were: (1) how uniformly were criteria applied to analysis of a standard digital FISH image set and (2) did concordance vary with educational level? These data suggest inter-rater agreement within a factor of 2 for average breakage frequency, but revealed greater variability in cell selection. These results aid in estimating the components of assay variance due to definitions, technical parameters and biological variables. JF - Mutation research AU - Barker, Peter E AU - Wang, Wendy AU - Wagner, Paul D AU - Pinsky, Paul AD - DNA Technologies Group, Biotechnology Division, Chemical Sciences and Technology Laboratory, NIST-NCI Biomarkers Validation Project, National Institute of Standards and Technology (NIST), Gaithersburg, MD 20899-8311, USA. peter.barker@nist.gov Y1 - 2004/08/08/ PY - 2004 DA - 2004 Aug 08 SP - 133 EP - 142 VL - 562 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Mutagens KW - 0 KW - Index Medicus KW - Humans KW - In Situ Hybridization, Fluorescence KW - Chromosome Aberrations KW - Mutagens -- toxicity KW - Observer Variation KW - Chromosomes, Human, Pair 5 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66754707?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Inter-rater+agreement+on+chromosome+5+breakage+in+FISH-based+mutagen+sensitivity+assays+%28MSAs%29.&rft.au=Barker%2C+Peter+E%3BWang%2C+Wendy%3BWagner%2C+Paul+D%3BPinsky%2C+Paul&rft.aulast=Barker&rft.aufirst=Peter&rft.date=2004-08-08&rft.volume=562&rft.issue=1-2&rft.spage=133&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 - 2004-09-16 N1 - Date created - 2004-07-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Endoplasmic reticulum (ER) stress induced by a neurovirulent mouse retrovirus is associated with prolonged BiP binding and retention of a viral protein in the ER. AN - 66766043; 15178688 AB - Some murine retroviruses cause a spongiform neurodegenerative disease exhibiting pathology resembling that observed in transmissible spongiform encephalopathies. The neurovirulence of these "spongiogenic retroviruses" is determined by the sequence of their respective envelope proteins, although the mechanisms of neurotoxicity are not understood. We have studied a highly neurovirulent virus called FrCasE that causes a rapidly progressive form of this disease. Recently, transcriptional markers of endoplasmic reticulum (ER) stress were detected during the early preclinical period in the brains of FrCasE-infected mice. In contrast, ER stress was not observed in mice infected with an avirulent virus, F43, which carries a different envelope gene, suggesting a role for ER stress in disease pathogenesis. Here we have examined in NIH 3T3 cells the cause of this cellular stress response. The envelope protein of F43 bound BiP, a major ER chaperone, transiently and was processed normally through the secretory pathway. In contrast, the envelope protein of FrCasE bound to BiP for a prolonged period, was retained in the ER, and was degraded by the proteasome. Furthermore, engagement of the FrCasE envelope protein by ER quality control pathways resulted in decreased steady-state levels of this protein, relative to that of F43, both in NIH 3T3 cells and in the brains of infected mice. Thus, the ER stress induced by FrCasE appears to be initiated by inefficient folding of its viral envelope protein, suggesting that the neurodegenerative disease caused by this virus represents a protein misfolding disorder. JF - The Journal of biological chemistry AU - Dimcheff, Derek E AU - Faasse, Mark A AU - McAtee, Frank J AU - Portis, John L AD - Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, NIAID, National Institutes of Health, Hamilton, Montana 59840, USA. Y1 - 2004/08/06/ PY - 2004 DA - 2004 Aug 06 SP - 33782 EP - 33790 VL - 279 IS - 32 SN - 0021-9258, 0021-9258 KW - Heat-Shock Proteins KW - 0 KW - Molecular Chaperones KW - Multienzyme Complexes KW - RNA, Messenger KW - RNA, Viral KW - Viral Envelope Proteins KW - molecular chaperone GRP78 KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - Index Medicus KW - Animals KW - Multienzyme Complexes -- metabolism KW - RNA, Messenger -- analysis KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - NIH 3T3 Cells KW - Microscopy, Fluorescence KW - Mice, Inbred Strains KW - Cysteine Endopeptidases -- metabolism KW - Kinetics KW - Protein Folding KW - Brain -- ultrastructure KW - Cell Line KW - RNA, Viral -- analysis KW - Heat-Shock Proteins -- metabolism KW - Endoplasmic Reticulum -- metabolism KW - Endoplasmic Reticulum -- chemistry KW - Endoplasmic Reticulum -- virology KW - Viral Envelope Proteins -- chemistry KW - Molecular Chaperones -- metabolism KW - Prion Diseases -- virology KW - Retroviridae -- physiology KW - Viral Envelope Proteins -- metabolism KW - Retroviridae Infections -- metabolism KW - Viral Envelope Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66766043?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Endoplasmic+reticulum+%28ER%29+stress+induced+by+a+neurovirulent+mouse+retrovirus+is+associated+with+prolonged+BiP+binding+and+retention+of+a+viral+protein+in+the+ER.&rft.au=Dimcheff%2C+Derek+E%3BFaasse%2C+Mark+A%3BMcAtee%2C+Frank+J%3BPortis%2C+John+L&rft.aulast=Dimcheff&rft.aufirst=Derek&rft.date=2004-08-06&rft.volume=279&rft.issue=32&rft.spage=33782&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 - 2004-10-25 N1 - Date created - 2004-08-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of the role of ubiquitin-interacting motifs in ubiquitin binding and ubiquitylation. AN - 66765953; 15155768 AB - The ubiquitin-interacting motif (UIM) is a short peptide motif with the dual function of binding ubiquitin and promoting ubiquitylation. This motif is conserved throughout eukaryotes and is present in numerous proteins involved in a wide variety of cellular processes including endocytosis, protein trafficking, and signal transduction. We previously reported that the UIMs of epsin were both necessary and sufficient for its ubiquitylation. In this study, we found that many, but not all, UIM-containing proteins were ubiquitylated. When expressed as chimeric fusion proteins, most UIMs promoted ubiquitylation of the chimera. In contrast to previous studies, we found that UIMs do not exclusively promote monoubiquitylation but rather a mixture of mono-, multi-, and polyubiquitylation. However, UIM-dependent polyubiquitylation does not lead to degradation of the modified protein. UIMs also bind polyubiquitin chains of varying lengths and to different degrees, and this activity is required for UIM-dependent ubiquitylation. Mutational analysis of the UIM revealed specific amino acids that are important for both polyubiquitin binding and ubiquitin conjugation. Finally we provide evidence that UIM-dependent ubiquitylation inhibits the interaction of UIM-containing proteins with other ubiquitylated cellular proteins. Our results suggest a new model for the ubiquitylation of UIM-containing proteins. JF - The Journal of biological chemistry AU - Miller, Stephanie L H AU - Malotky, Erica AU - O'Bryan, John P AD - Laboratory of Signal Transduction, NIEHS, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709, USA. Y1 - 2004/08/06/ PY - 2004 DA - 2004 Aug 06 SP - 33528 EP - 33537 VL - 279 IS - 32 SN - 0021-9258, 0021-9258 KW - ANKIB1 protein, human KW - 0 KW - Adaptor Proteins, Vesicular Transport KW - DNAJB2 protein, human KW - Endosomal Sorting Complexes Required for Transport KW - HSP40 Heat-Shock Proteins KW - Heat-Shock Proteins KW - Molecular Chaperones KW - Nerve Tissue Proteins KW - Nuclear Proteins KW - Oligopeptides KW - Peptide Fragments KW - Peptides KW - Phosphoproteins KW - Proteins KW - Recombinant Fusion Proteins KW - Repressor Proteins KW - Ubiquitin KW - Vesicular Transport Proteins KW - epsin KW - hepatocyte growth factor-regulated tyrosine kinase substrate KW - FLAG peptide KW - 98849-88-8 KW - MAP Kinase Kinase Kinase 1 KW - EC 2.7.11.25 KW - MAP Kinase Kinase Kinases KW - MAP3K1 protein, human KW - ATXN3 protein, human KW - EC 3.4.19.12 KW - Ataxin-3 KW - Index Medicus KW - Molecular Chaperones -- genetics KW - Molecular Chaperones -- metabolism KW - Humans KW - Recombinant Fusion Proteins -- chemistry KW - Mutagenesis KW - Recombinant Fusion Proteins -- metabolism KW - Molecular Sequence Data KW - Embryo, Mammalian KW - Signal Transduction KW - Phosphoproteins -- metabolism KW - Heat-Shock Proteins -- metabolism KW - Vesicular Transport Proteins -- genetics KW - Phosphoproteins -- genetics KW - MAP Kinase Kinase Kinases -- genetics KW - Amino Acid Sequence KW - Nerve Tissue Proteins -- genetics KW - Proteins -- metabolism KW - Proteins -- genetics KW - Protein Binding KW - Structure-Activity Relationship KW - Binding Sites KW - MAP Kinase Kinase Kinases -- metabolism KW - Polymerase Chain Reaction KW - Endocytosis KW - Conserved Sequence KW - Transfection KW - Kidney KW - Nerve Tissue Proteins -- metabolism KW - Vesicular Transport Proteins -- metabolism KW - Peptides -- genetics KW - Heat-Shock Proteins -- genetics KW - Cell Line KW - Ubiquitin -- metabolism KW - Peptide Fragments -- chemistry KW - Peptide Fragments -- genetics KW - Peptide Fragments -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66765953?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Analysis+of+the+role+of+ubiquitin-interacting+motifs+in+ubiquitin+binding+and+ubiquitylation.&rft.au=Miller%2C+Stephanie+L+H%3BMalotky%2C+Erica%3BO%27Bryan%2C+John+P&rft.aulast=Miller&rft.aufirst=Stephanie+L&rft.date=2004-08-06&rft.volume=279&rft.issue=32&rft.spage=33528&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 - 2004-10-25 N1 - Date created - 2004-08-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A protein sequestering system reveals control of cellular programs by the transcriptional coactivator HCF-1. AN - 66764238; 15190068 AB - The mammalian transcriptional coactivator HCF-1 is a critical component of the multiprotein herpes simplex virus immediate early gene enhancer core complex. The protein has also been implicated in basic cellular processes such as cell-cycle progression, transcriptional coactivation, and mRNA processing. Functions have been attributed to HCF-1 primarily from analyses of protein-protein interactions and from the cell-cycle-arrested phenotype of an HCF-1 temperature-sensitive mutant. However, neither the mechanisms involved nor specific cellular transcriptional targets have been identified. As the protein is essential for cell viability and proliferation, a genetic system was developed to specifically sequester the nuclear factor in the cell cytoplasm in a regulated manner. This approach exhibits no significant cell toxicity yet clearly demonstrates the requirement of available nuclear HCF-1 for herpes simplex virus immediate early gene expression during productive infection. Additionally, cellular transcriptional events were identified that contribute to understanding the functions ascribed to the protein and implicate the protein in events that impact the regulation of critical cellular processes. JF - The Journal of biological chemistry AU - Khurana, Bharat AU - Kristie, Thomas M AD - Laboratory of Viral Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2004/08/06/ PY - 2004 DA - 2004 Aug 06 SP - 33673 EP - 33683 VL - 279 IS - 32 SN - 0021-9258, 0021-9258 KW - Actins KW - 0 KW - HCFC1 protein, human KW - Host Cell Factor C1 KW - Recombinant Fusion Proteins KW - Transcription Factors KW - Viral Proteins KW - Index Medicus KW - Virus Replication KW - Viral Proteins -- genetics KW - Oligonucleotide Array Sequence Analysis KW - HeLa Cells KW - Cell Nucleus -- metabolism KW - Humans KW - Temperature KW - Transcription, Genetic KW - Amino Acid Sequence KW - Binding Sites KW - Cell Survival KW - Actins -- genetics KW - Cells -- virology KW - Transfection KW - Cytoplasm -- metabolism KW - Molecular Sequence Data KW - Enhancer Elements, Genetic -- genetics KW - Cells -- ultrastructure KW - Mutation KW - Cells -- metabolism KW - Fluorescent Antibody Technique KW - Cell Division KW - Transcription Factors -- physiology KW - Gene Expression Regulation -- physiology KW - Cell Physiological Phenomena KW - Transcription Factors -- chemistry KW - Herpesvirus 1, Human -- physiology KW - Genes, Immediate-Early -- genetics KW - Transcription Factors -- genetics KW - Herpesvirus 1, Human -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66764238?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+protein+sequestering+system+reveals+control+of+cellular+programs+by+the+transcriptional+coactivator+HCF-1.&rft.au=Khurana%2C+Bharat%3BKristie%2C+Thomas+M&rft.aulast=Khurana&rft.aufirst=Bharat&rft.date=2004-08-06&rft.volume=279&rft.issue=32&rft.spage=33673&rft.isbn=&rft.btitle=&rft.title=Contemporary+topics+in+laboratory+animal+science&rft.issn=10600558&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-10-25 N1 - Date created - 2004-08-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - CbpA, a DnaJ Homolog, Is a DnaK Co-chaperone, and Its Activity Is Modulated by CbpM AN - 18017104; 5963689 AB - The DnaK chaperone system, consisting of DnaK, DnaJ, and GrpE, remodels and refolds proteins during both normal growth and stress conditions. CbpA, one of several DnaJ analogs in Escherichia coli, is known to function as a multicopy suppressor for dnaJ mutations and to bind nonspecifically to DNA and preferentially to curved DNA. We found that CbpA functions as a DnaJ-like co- chaperone in vitro. CbpA acted in an ATP-dependent reaction with DnaK and GrpE to remodel inactive dimers of plasmid P1 RepA into monomers active in P1 DNA binding. Additionally, CbpA participated with DnaK in an ATP-dependent reaction to prevent aggregation of denatured rhodanese. The cbpA gene is in an operon with an open reading frame, yccD, which encodes a protein that has some homology to DafA of Thermus thermophilus. DafA is a protein required for the assembly of ring-like particles that contain trimers each of T. thermophilus DnaK, DnaJ, and DafA. The E. coli YccD was isolated because of its potential functional relationship to CbpA. Purified YccD specifically inhibited both the co-chaperone activity and the DNA binding activity of CbpA, suggesting that YccD modulates the activity of CbpA. We named the product of the yccD gene CbpM for "CbpA modulator." JF - Journal of Biological Chemistry AU - Chae, Chi AU - Sharma, Suveena AU - Hoskins, Joel R AU - Wickner, Sue AD - Laboratory of Molecular Biology, NCI, National Institutes of Health, Bethesda, Maryland Y1 - 2004/08/06/ PY - 2004 DA - 2004 Aug 06 SP - 33147 EP - 33153 PB - American Society for Biochemistry and Molecular Biology, 9650 Rockville Pike Bethesda MD 20814-3996 USA, [mailto:asbmb@asbmb.faseb.org], [URL:http://www.jbc.org] VL - 279 IS - 32 SN - 0021-9258, 0021-9258 KW - CbpM protein KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Suppressors KW - Escherichia coli KW - DnaK protein KW - Chaperones KW - Plasmids KW - CbpA protein KW - J 02726:RNA and ribosomes KW - N 14940:Nucleic acid-binding proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18017104?accountid=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=CbpA%2C+a+DnaJ+Homolog%2C+Is+a+DnaK+Co-chaperone%2C+and+Its+Activity+Is+Modulated+by+CbpM&rft.au=Chae%2C+Chi%3BSharma%2C+Suveena%3BHoskins%2C+Joel+R%3BWickner%2C+Sue&rft.aulast=Chae&rft.aufirst=Chi&rft.date=2004-08-06&rft.volume=279&rft.issue=32&rft.spage=33147&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 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Suppressors; DnaK protein; Chaperones; CbpA protein; Plasmids; Escherichia coli ER - TY - JOUR T1 - Loss of Smad3 in acute T-cell lymphoblastic leukemia. AN - 66759392; 15295048 AB - The receptors for transforming growth factor beta (TGF-beta) and their signaling intermediates make up an important tumor-suppressor pathway. The role of one of these intermediates--Smad3--in the pathogenesis of lymphoid neoplasia is unknown. We measured Smad3 messenger RNA (mRNA) and protein in leukemia cells obtained at diagnosis from 19 children with acute leukemia, including 10 with T-cell acute lymphoblastic leukemia (ALL), 7 with pre-B-cell ALL, and 2 with acute nonlymphoblastic leukemia (ANLL). All nine exons of the SMAD3 gene (MADH3) were sequenced. Mice in which one or both alleles of Smad3 were inactivated were used to evaluate the role of Smad3 in the response of normal T cells to TGF-beta and in the susceptibility to spontaneous leukemogenesis in mice in which both alleles of the tumor suppressor p27Kip1 were deleted. Smad3 protein was absent in T-cell ALL but present in pre-B-cell ALL and ANLL. No mutations were found in the MADH3 gene in T-cell ALL, and Smad3 mRNA was present in T-cell ALL and normal T cells at similar levels. In mice, the loss of one allele for Smad3 impairs the inhibitory effect of TGF-beta on the proliferation of normal T cells and works in tandem with the homozygous inactivation of p27Kip1 to promote T-cell leukemogenesis. Loss of Smad3 protein is a specific feature of pediatric T-cell ALL. A reduction in Smad3 expression and the loss of p27Kip1 work synergistically to promote T-cell leukemogenesis in mice. Copyright 2004 Massachusetts Medical Society JF - The New England journal of medicine AU - Wolfraim, Lawrence A AU - Fernandez, Tania M AU - Mamura, Mizuko AU - Fuller, Walter L AU - Kumar, Rajesh AU - Cole, Diane E AU - Byfield, Stacey AU - Felici, Angelina AU - Flanders, Kathleen C AU - Walz, Thomas M AU - Roberts, Anita B AU - Aplan, Peter D AU - Balis, Frank M AU - Letterio, John J AD - Laboratory of Cell Regulation and Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Md, USA. Y1 - 2004/08/05/ PY - 2004 DA - 2004 Aug 05 SP - 552 EP - 559 VL - 351 IS - 6 KW - Cdkn1b protein, mouse KW - 0 KW - Cell Cycle Proteins KW - DNA-Binding Proteins KW - Interleukin-2 KW - RNA, Messenger KW - Receptors, Transforming Growth Factor beta KW - SMAD3 protein, human KW - Smad3 Protein KW - Smad3 protein, mouse KW - Trans-Activators KW - Transforming Growth Factor beta KW - Tumor Suppressor Proteins KW - Cyclin-Dependent Kinase Inhibitor p27 KW - 147604-94-2 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Exons KW - Humans KW - Leukemia, Myeloid, Acute -- metabolism KW - Receptors, Transforming Growth Factor beta -- metabolism KW - Gene Expression KW - Interleukin-2 -- biosynthesis KW - Child KW - Mice KW - Sequence Analysis, DNA KW - RNA, Messenger -- genetics KW - RNA, Messenger -- biosynthesis KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- genetics KW - Mice, Knockout KW - Gene Deletion KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- metabolism KW - Leukemia, Myeloid, Acute -- genetics KW - Adult KW - Signal Transduction KW - Leukemia, T-Cell -- genetics KW - Trans-Activators -- metabolism KW - Leukemia-Lymphoma, Adult T-Cell -- metabolism KW - Leukemia, T-Cell -- metabolism KW - Tumor Suppressor Proteins -- genetics KW - DNA-Binding Proteins -- genetics KW - Leukemia-Lymphoma, Adult T-Cell -- genetics KW - Cell Cycle Proteins -- metabolism KW - T-Lymphocytes -- metabolism KW - Cell Cycle Proteins -- genetics KW - Trans-Activators -- genetics KW - Tumor Suppressor Proteins -- metabolism KW - Transforming Growth Factor beta -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66759392?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Loss+of+Smad3+in+acute+T-cell+lymphoblastic+leukemia.&rft.au=Wolfraim%2C+Lawrence+A%3BFernandez%2C+Tania+M%3BMamura%2C+Mizuko%3BFuller%2C+Walter+L%3BKumar%2C+Rajesh%3BCole%2C+Diane+E%3BByfield%2C+Stacey%3BFelici%2C+Angelina%3BFlanders%2C+Kathleen+C%3BWalz%2C+Thomas+M%3BRoberts%2C+Anita+B%3BAplan%2C+Peter+D%3BBalis%2C+Frank+M%3BLetterio%2C+John+J&rft.aulast=Wolfraim&rft.aufirst=Lawrence&rft.date=2004-08-05&rft.volume=351&rft.issue=6&rft.spage=552&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 - 2004-08-10 N1 - Date created - 2004-08-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: N Engl J Med. 2004 Aug 5;351(6):528-30 [15295044] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular and Cellular Determinants of Skeletal Muscle Atrophy and Hypertrophy AN - 19947536; 5969558 AB - The maintenance of adult skeletal muscle mass is ensured by physical exercise. Accordingly, physiological and pathological situations characterized by either impaired motor neuron activity, reduced gravity (microgravity during space flights), or reduced physical activity result in loss of muscle mass. Furthermore, a plethora of clinical conditions, including cancer, sepsis, diabetes, and AIDS, are associated with varying degrees of muscle atrophy. The cellular and molecular pathways responsible for maintaining the skeletal muscle mass are not well defined. Nonetheless, studies aimed at the understanding of the mechanisms underlying either muscular atrophy or hypertrophy have begun to identify the physiological determinants and clarify the molecular pathways responsible for the maintenance of muscle mass. JF - Signal Transduction Knowledge Environment AU - Sartorelli, Vittorio AU - Fulco, Marcella AD - Muscle Gene Expression Group Laboratory of Muscle Biology, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD Y1 - 2004/08/03/ PY - 2004 DA - 2004 Aug 03 SP - re11 PB - American Association for the Advancement of Science, 1200 New York Avenue, NW Washington DC 20005 USA, [mailto:membership@aaas.org], [URL:http://www.aaas.org] VL - 2004 IS - 244 SN - 1525-8882, 1525-8882 KW - Microbiology Abstracts B: Bacteriology; Virology & AIDS Abstracts KW - Acquired immune deficiency syndrome KW - Space flight KW - Gravity KW - Physical activity KW - Cancer KW - Physical training KW - Diabetes mellitus KW - Motor neurons KW - Microgravity KW - Sepsis KW - Hypertrophy KW - Atrophy KW - Skeletal muscle KW - V 22360:AIDS and HIV KW - J 02400:Human Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19947536?accountid=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=Cytometry+Part+B&rft.atitle=Multiplex+bead+array+assays+for+detection+of+soluble+cytokines%3A+Comparisons+of+sensitivity+and+quantitative+values+among+kits+from+multiple+manufacturers&rft.au=Khan%2C+Sameena+S%3BSmith%2C+Meghan+S%3BReda%2C+Debra%3BSuffredini%2C+Anthony+F%3BMcCoy+Jr%2C+J+Philip&rft.aulast=Khan&rft.aufirst=Sameena&rft.date=2004-09-01&rft.volume=61B&rft.issue=1&rft.spage=35&rft.isbn=&rft.btitle=&rft.title=Cytometry+Part+B&rft.issn=15524949&rft_id=info:doi/10.1002%2Fcyto.b.20021 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-06-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Acquired immune deficiency syndrome; Space flight; Gravity; Physical activity; Cancer; Physical training; Diabetes mellitus; Microgravity; Motor neurons; Hypertrophy; Sepsis; Skeletal muscle; Atrophy ER - TY - JOUR T1 - Neural stem cells redefined. A FACS perspective AN - 856761486; 13859493 AB - Using the generally accepted ontogenetic definition, neural stem cells (NSCs) are characterized as undifferentiated cells originating from the neuroectoderm that have the capacity both to perpetually self-renew without differentiating and to generate multiple types of lineage-restricted progenitors (LRP). LRPs can themselves undergo limited self-renewal, then ultimately differentiate into highly specialized cells that compose the nervous system. However, this physiologically delimited definition of NSCs has been increasingly blurred in the current state of the field, as the great majority of studies have retrospectively inferred the existence of NSCs based on their deferred functional capability rather than prospectively identifying the actual cells that created the outcome. Further complicating the matter is the use of a wide variety of neuroepithelial or neurosphere preparations as a source of putative NSCs, without due consideration that these preparations are themselves composed of heterogeneous populations of both NSCs and LRPs. This article focuses on recent attempts using FACS strategies to prospectively isolate NSCs from different types of LRPs as they appear in vivo and reveals the contrasting differences among these populations at molecular, phenotypic, and functional levels. Thus, the strategies presented here provide a framework for more precise studies of NSC and LRP cell biology in the future. JF - Molecular Neurobiology AU - Maric, Dragan AU - Barker, Jeffery L AD - Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 20892, Bethesda, MD, maricd@ninds.nih.gov Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 49 EP - 76 PB - Humana Press Inc., 999 Riverview Dr., Ste. 208 Totowa NJ 07512 USA VL - 30 IS - 1 SN - 0893-7648, 0893-7648 KW - Biotechnology and Bioengineering Abstracts; CSA Neurosciences Abstracts KW - Flow cytometry KW - Nervous system KW - Neuroectoderm KW - Ontogeny KW - neurospheres KW - Neural stem cells KW - N3 11007:Neurobiology KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/856761486?accountid=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+Neurobiology&rft.atitle=Neural+stem+cells+redefined.+A+FACS+perspective&rft.au=Maric%2C+Dragan%3BBarker%2C+Jeffery+L&rft.aulast=Maric&rft.aufirst=Dragan&rft.date=2004-08-01&rft.volume=30&rft.issue=1&rft.spage=49&rft.isbn=&rft.btitle=&rft.title=Molecular+Neurobiology&rft.issn=08937648&rft_id=info:doi/10.1385%2FMN%3A30%3A1%3A049 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2011-03-01 N1 - Last updated - 2012-03-29 N1 - SubjectsTermNotLitGenreText - Flow cytometry; Nervous system; Neuroectoderm; Ontogeny; neurospheres; Neural stem cells DO - http://dx.doi.org/10.1385/MN:30:1:049 ER - TY - JOUR T1 - Toxicity of commonly-used antimalarial drugs. AN - 734180898; 17291978 JF - Travel medicine and infectious disease AU - Berman, Jonathan AD - Office of Clinical and Regulatory Affairs, National Center for Complementary and Alternative Medicine, National Institutes of Health, 6707 Democracy Boulevard, Suite 401, Bethesda, MD 20892, USA. PY - 2004 SP - 171 EP - 184 VL - 2 IS - 3-4 SN - 1477-8939, 1477-8939 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/734180898?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Travel+medicine+and+infectious+disease&rft.atitle=Toxicity+of+commonly-used+antimalarial+drugs.&rft.au=Berman%2C+Jonathan&rft.aulast=Berman&rft.aufirst=Jonathan&rft.date=2004-08-01&rft.volume=2&rft.issue=3-4&rft.spage=171&rft.isbn=&rft.btitle=&rft.title=Travel+medicine+and+infectious+disease&rft.issn=14778939&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2012-10-02 N1 - Date created - 2007-02-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Therapeutic potential of interleukin-6 in preventing obesity- and alcohol-associated fatty liver transplant failure. AN - 67243330; 15670667 AB - Donor organ shortage significantly hinders orthotopic liver transplantation therapy, the only effective treatment for chronic end-stage liver disease and acute liver failure. Further complicating this matter is the prevalence of steatosis in 13% to 50% of donor livers obtained from obese and alcoholic individuals. When transplanted, these livers are associated with primary nonfunction and an elevated risk of dysfunction. New therapeutic approaches to render marginal fatty livers worthy for clinical transplantation are actively being sought. Study findings obtained from my group show that in vitro treatment with interleukin-6 (IL-6) dramatically reduces mortality, liver injury, and necrapoptosis in steatotic Zucker rat liver isografts. Findings of additional studies indicate that IL-6 induces hepatoprotection of steatotic liver isografts by preventing sinusoidal endothelial cell damage and, consequently, the amelioration of hepatic microcirculation, and by protecting against hepatocyte death, which is likely mediated through activation of signal transducer and activator of transcription 3/Bcl-x(L). Finally, in vitro IL-6 treatment also prevents mortality associated with alcoholic fatty liver transplants. Relative to the protective effect of IL-6 on steatotic Zucker rat liver, IL-6 is less effective in alcoholic fatty livers, which may be due to the inhibitory effects of ethanol on IL-6 activation of signal transducer and activator of transcription 3 in hepatocytes and sinusoidal endothelial cells. Collectively, these results support the assertion that in vitro IL-6 treatment of steatotic livers may render allografts usable for clinical transplantation, thereby decreasing the gap between the short supply of cadaver liver allografts and high demands for replacement livers. Higher concentrations of IL-6 may be required to protect against alcoholic fatty liver isograft injury because alcohol inhibits IL-6 signaling in the liver. JF - Alcohol (Fayetteville, N.Y.) AU - Gao, Bin AD - Section on Liver Biology, Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Park Building Room 120, 12420 Parklawn Drive, MSC 8115, Bethesda, MD 20892, USA. bgao@mail.nih.gov Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 59 EP - 65 VL - 34 IS - 1 SN - 0741-8329, 0741-8329 KW - Interleukin-6 KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Prevalence KW - Obesity -- drug therapy KW - Fatty Liver, Alcoholic -- surgery KW - Interleukin-6 -- therapeutic use KW - Fatty Liver, Alcoholic -- epidemiology KW - Obesity -- surgery KW - Graft Rejection -- metabolism KW - Obesity -- epidemiology KW - Liver Transplantation -- adverse effects KW - Graft Rejection -- prevention & control KW - Fatty Liver, Alcoholic -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67243330?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcohol+%28Fayetteville%2C+N.Y.%29&rft.atitle=Therapeutic+potential+of+interleukin-6+in+preventing+obesity-+and+alcohol-associated+fatty+liver+transplant+failure.&rft.au=Gao%2C+Bin&rft.aulast=Gao&rft.aufirst=Bin&rft.date=2004-08-01&rft.volume=34&rft.issue=1&rft.spage=59&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 - 2005-06-09 N1 - Date created - 2005-01-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adenocarcinoma of ethmoid sinus: an occupational disease. AN - 67242639; 15688904 AB - Sinonasal tumours, particularly those of ethmoidal origin, are rare neoplasms, of which adenocarcinoma is the most frequent histotype in Europe. The association between sinonasal malignancies and exposure to wood or leather dusts has been widely documented, however, the precise tumour site and histology has seldom been reported. In the present study, exposure to wood or leather dusts was investigated in 499 patients diagnosed with sinonasal tumours, who were treated at the Head and Neck Surgery Department of the National Cancer Institute of Milan, Italy, between 1987 and 2001. The original tumour site and histology were carefully assessed. Of the 499 patients evaluated, 249 had ethmoidal tumours; 124 of which adenocarcinomas, affecting 115 males; 9 females. Of the males with adenocarcinoma, 90.4% had been exposed to wood or leather dusts; 16.3% of these had only been exposed for a short time and long before onset of the disease (median exposure 11 years; median latency 31 years). Of the remaining 125 patients with ethmoidal tumours other than adenocarcinomas, only 2 (1.6%) had ever been exposed to these dusts. Non-ethmoidal sinonasal tumours were seen in 250 cases; 17 of these (6.8%) were adenocarcinomas; no exposure to wood or leather dusts was reported in any of these patients. Ethmoid proved to be the sinonasal site affected by adenocarcinomas induced by exposure to wood or leather dusts. Even brief exposure, which may have occurred a very long time before onset of the disease, seems to be sufficient to increase the incidence of this tumour type. No significant correlation was observed between exposure and either non-ethmoidal sinonasal neoplasms or ethmoidal tumours other than adenocarcinomas. JF - Acta otorhinolaryngologica Italica : organo ufficiale della Societa italiana di otorinolaringologia e chirurgia cervico-facciale AU - Bimbi, G AU - Saraceno, M Squadrelli AU - Riccio, S AU - Gatta, G AU - Licitra, L AU - Cantù, G AD - Head and Neck Surgery Department, National Cancer Institute, Milan, Italy. Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 199 EP - 203 VL - 24 IS - 4 SN - 0392-100X, 0392-100X KW - Dust KW - 0 KW - Index Medicus KW - Aged, 80 and over KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Female KW - Paranasal Sinus Neoplasms -- pathology KW - Adenocarcinoma -- etiology KW - Occupational Diseases -- etiology KW - Occupational Exposure -- adverse effects KW - Ethmoid Sinus -- pathology KW - Paranasal Sinus Neoplasms -- surgery KW - Adenocarcinoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67242639?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+otorhinolaryngologica+Italica+%3A+organo+ufficiale+della+Societa+italiana+di+otorinolaringologia+e+chirurgia+cervico-facciale&rft.atitle=Adenocarcinoma+of+ethmoid+sinus%3A+an+occupational+disease.&rft.au=Bimbi%2C+G%3BSaraceno%2C+M+Squadrelli%3BRiccio%2C+S%3BGatta%2C+G%3BLicitra%2C+L%3BCant%C3%B9%2C+G&rft.aulast=Bimbi&rft.aufirst=G&rft.date=2004-08-01&rft.volume=24&rft.issue=4&rft.spage=199&rft.isbn=&rft.btitle=&rft.title=Acta+otorhinolaryngologica+Italica+%3A+organo+ufficiale+della+Societa+italiana+di+otorinolaringologia+e+chirurgia+cervico-facciale&rft.issn=0392100X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-16 N1 - Date created - 2005-02-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Role of fatty liver, dietary fatty acid supplements, and obesity in the progression of alcoholic liver disease: introduction and summary of the symposium. AN - 67226544; 15670659 AB - Alcoholic liver disease is a major cause of illness and death in the United States. In the initial stages of the disease, fat accumulation in hepatocytes leads to the development of fatty liver (steatosis), which is a reversible condition. If alcohol consumption is continued, steatosis may progress to hepatitis and fibrosis, which may lead to liver cirrhosis. Alcoholic fatty liver has long been considered benign; however, increasing evidence supports the idea that it is a pathologic condition. Blunting of the accumulation of fat within the liver during alcohol consumption may block or delay the progression of fatty liver to hepatitis and fibrosis. To achieve this goal, it is important to understand the underlying biochemical and molecular mechanisms by which chronic alcohol consumption leads to fat accumulation in the liver and fatty liver progresses to hepatitis and fibrosis. In addition to alcohol consumption, dietary fatty acids and obesity have been shown to affect the degree of fat accumulation within the liver. Again, it is important to know how these factors modulate the progression of alcoholic liver disease. The National Institute on Alcohol Abuse and Alcoholism and the Office of Dietary Supplements, National Institutes of Health, sponsored a symposium on "Role of Fatty Liver, Dietary Fatty Acid Supplements, and Obesity in the Progression of Alcoholic Liver Disease" in Bethesda, Maryland, USA, October 2003. The following is a summary of the symposium. Alcoholic fatty liver is a pathologic condition that may predispose the liver to further injury (hepatitis and fibrosis) by cytochrome P450 2E1 induction, free radical generation, lipid peroxidation, nuclear factor-kappa B activation, and increased transcription of proinflammatory mediators, including tumor necrosis factor-alpha. Increased acetaldehyde production and lipopolysaccharide-induced Kupffer cell activation may further exacerbate liver injury. Acetaldehyde may promote hepatic fat accumulation by impairing the ability of peroxisome proliferator-activated receptor alpha to bind DNA, and by increasing the synthesis of sterol regulatory binding protein-1. Unsaturated fatty acids (corn oil, fish oil) exacerbate alcoholic liver injury by accentuating oxidative stress, whereas saturated fatty acids are protective. Polyenylphosphatidylcholine may prevent liver injury by down-regulating cytochrome P450 2E1 activity, attenuating oxidative stress, reducing the number of activated hepatic stellate cells, and up-regulating collagenase activity. Nonalcoholic steatohepatitis may develop through several mechanisms, such as oxidative stress, mitochondrial dysfunction and associated impaired fat metabolism, dysregulated cytokine metabolism, insulin resistance, and altered methionine/S-adenosylmethionine/homocysteine metabolism. Obesity (adipose tissue) may contribute to the development of alcoholic liver disease by generating free radicals, increasing tumor necrosis factor-alpha production, inducing insulin resistance, and producing fibrogenic agents, such as angiotensin II, norepinephrine, neuropeptide Y, and leptin. Finally, alcoholic fatty liver transplant failure may be linked to oxidative stress. In vitro treatment of fatty livers with interleukin-6 may render allografts safer for clinical transplantation. JF - Alcohol (Fayetteville, N.Y.) AU - Purohit, Vishnudutt AU - Russo, Denise AU - Coates, Paul M Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 3 EP - 8 VL - 34 IS - 1 KW - Fatty Acids KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Disease Progression KW - Fatty Liver, Alcoholic -- complications KW - Obesity -- pathology KW - Fatty Acids -- adverse effects KW - Fatty Acids -- physiology KW - Fatty Liver, Alcoholic -- pathology KW - Dietary Supplements -- adverse effects KW - Obesity -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67226544?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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+fatty+liver%2C+dietary+fatty+acid+supplements%2C+and+obesity+in+the+progression+of+alcoholic+liver+disease%3A+introduction+and+summary+of+the+symposium.&rft.au=Purohit%2C+Vishnudutt%3BRusso%2C+Denise%3BCoates%2C+Paul+M&rft.aulast=Purohit&rft.aufirst=Vishnudutt&rft.date=2004-08-01&rft.volume=34&rft.issue=1&rft.spage=3&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 - 2005-06-09 N1 - Date created - 2005-01-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical applications of genetics in sporadic cancers. AN - 66985085; 15491025 AB - To describe how genetic information shapes our understanding of carcinogenesis; how genetic information influences recommendations for cancer screening, prevention, diagnosis, and treatment; and how genetic information may affect the prognosis of patients with cancer and the monitoring of anticancer treatment. Medical and nursing literature, textbooks, Internet websites. The Human Genome Project has taken oncology one step further toward accurate diagnosis and treatment of many forms of cancer. There are many genetic traits that can be associated with increased cancer risk, diagnosis, and selection of treatments. Oncology nursing practice is directly affected by the developments of medical genetics. The information gained can be used by nurses at all stages of the cancer continuum when administering these new therapies. JF - Seminars in oncology nursing AU - Kwitkowski, Virginia E AU - Daub, Janine R AD - National Cancer Institute, Center for Cancer Research, Medical Oncology Clinical Research Unit, Bethesda, MD 20892-1906, USA. Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 155 EP - 163 VL - 20 IS - 3 SN - 0749-2081, 0749-2081 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Nursing KW - Nursing Methodology Research KW - Nursing Assessment KW - Risk Factors KW - Humans KW - Databases, Genetic KW - Antineoplastic Agents -- therapeutic use KW - Neoplasms -- diagnosis KW - Neoplasms -- nursing KW - Oncology Nursing -- standards KW - Human Genome Project -- organization & administration KW - Neoplasms -- genetics KW - Oncology Nursing -- education UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66985085?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Clinical+applications+of+genetics+in+sporadic+cancers.&rft.au=Kwitkowski%2C+Virginia+E%3BDaub%2C+Janine+R&rft.aulast=Kwitkowski&rft.aufirst=Virginia&rft.date=2004-08-01&rft.volume=20&rft.issue=3&rft.spage=155&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 - 2004-11-23 N1 - Date created - 2004-10-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytotoxic effect of root extract of Tiliacora racemosa and oil of Semecarpus anacardium nut in human tumour cells. AN - 66984206; 15476314 AB - Tiliacora racemosa and Semecarpus anacardium, the two plants frequently used in Ayurvedic medicine for the treatment of cancerous diseases, have been selected to examine their action in four human tumour cell lines: acute myeloblastic leukaemia (HL-60), chronic myelogenic leukaemia (K-562), breast adenocarcinoma (MCF-7) and cervical epithelial carcinoma (HeLa). In cells grown in appropriate media the ethanol extract of T. racemosa root, the total alkaloids isolated from this organ and S. anacardium nut oil prepared according to the Ayurvedic principle were found to have cytotoxic activity. The alkaloid fraction from T. racemosa had maximum cytotoxicity and was effective against all four cell lines. S. anacardium oil was cytotoxic only in leukaemic cells. These herbal preparations were not cytotoxic towards normal human lymphocytes, suggesting their action is specific for tumour cells. On microscopic examination the cells treated with these agents exhibited characteristic morphological features of apoptosis, such as cell shrinkage, and the formation of apoptotic bodies. Fluorescent staining with propidium iodide revealed distinct chromatin condensation and nuclear fragmentation. The apoptotic index paralleled the cytotoxic parameters, and fragmented DNA extracted free of genomic DNA from treated cells displayed a typical ladder pattern on gel electrophoresis. Apoptosis induced by alkaloids and phenolics, the active principles present in T. racemosa and S. anacardium, respectively, was found to be mediated by the activation of caspases. Copyright (c) 2004 John Wiley & Sons, Ltd. JF - Phytotherapy research : PTR AU - Chakraborty, Sutapa AU - Roy, Madhumita AU - Taraphdar, Amit K AU - Bhattacharya, R K AD - Department of Environmental Carcinogenesis and Toxicology, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata 700 026, India. Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 595 EP - 600 VL - 18 IS - 8 SN - 0951-418X, 0951-418X KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Plant Extracts KW - Plant Oils KW - Index Medicus KW - Plant Roots KW - HeLa Cells -- drug effects KW - HL-60 Cells -- drug effects KW - Dose-Response Relationship, Drug KW - Humans KW - Apoptosis -- drug effects KW - DNA Fragmentation -- drug effects KW - Cell Line, Tumor -- drug effects KW - Fruit KW - K562 Cells -- drug effects KW - Medicine, Ayurvedic KW - Plant Oils -- therapeutic use KW - Plant Extracts -- pharmacology KW - Phytotherapy KW - Semecarpus KW - Plant Oils -- pharmacology KW - Plants, Medicinal KW - Antineoplastic Agents, Phytogenic -- therapeutic use KW - Plant Oils -- administration & dosage KW - Plant Extracts -- therapeutic use KW - Antineoplastic Agents, Phytogenic -- pharmacology KW - Antineoplastic Agents, Phytogenic -- administration & dosage KW - Plant Extracts -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66984206?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Phytotherapy+research+%3A+PTR&rft.atitle=Cytotoxic+effect+of+root+extract+of+Tiliacora+racemosa+and+oil+of+Semecarpus+anacardium+nut+in+human+tumour+cells.&rft.au=Chakraborty%2C+Sutapa%3BRoy%2C+Madhumita%3BTaraphdar%2C+Amit+K%3BBhattacharya%2C+R+K&rft.aulast=Chakraborty&rft.aufirst=Sutapa&rft.date=2004-08-01&rft.volume=18&rft.issue=8&rft.spage=595&rft.isbn=&rft.btitle=&rft.title=Phytotherapy+research+%3A+PTR&rft.issn=0951418X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-02 N1 - Date created - 2004-10-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetics and oncology nursing. AN - 66982253; 15491027 AB - To review oncology nursing practice in the genetic era, how genetic information is used across the cancer care continuum, practice guidelines, and opportunities for genetic nursing education. Published articles. Genetic information in oncology health care is used not only to predict risk but to elucidate disease biology, explain individual variation in vulnerability to environmental carcinogens, diagnose and characterize malignancies, design treatment regimens specific to a cancer's genetic fingerprint, develop new, therapeutic modalities, and clarify modulators of drug metabolism, efficacy, and interactions. With current and emerging genetic discoveries, all oncology nurses will use genetic information in their practice. JF - Seminars in oncology nursing AU - Calzone, Kathleen A AU - Masny, Agnes AD - National Cancer Institute/Center for Cancer Research/Genetics Branch, Bethesda, MD 20883-5105, USA. Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 178 EP - 185 VL - 20 IS - 3 SN - 0749-2081, 0749-2081 KW - Index Medicus KW - Nursing KW - Nursing Methodology Research KW - Education, Nursing, Continuing -- standards KW - Nursing Assessment KW - Human Genome Project KW - Risk Factors KW - Humans KW - Practice Guidelines as Topic KW - Nurse-Patient Relations KW - Clinical Competence KW - Neoplasms -- diagnosis KW - Neoplasms -- nursing KW - Oncology Nursing -- standards KW - Nurse's Role KW - Neoplasms -- genetics KW - Oncology Nursing -- education UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66982253?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Genetics+and+oncology+nursing.&rft.au=Calzone%2C+Kathleen+A%3BMasny%2C+Agnes&rft.aulast=Calzone&rft.aufirst=Kathleen&rft.date=2004-08-01&rft.volume=20&rft.issue=3&rft.spage=178&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 - 2004-11-23 N1 - Date created - 2004-10-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of the current population survey to characterize subpopulations of continued smokers: a national perspective on the "hardcore" smoker phenomenon. AN - 66884421; 15370158 AB - The existence of "hardcore" smokers, those most likely to have substantial difficulty quitting, may have far reaching impact on how to best allocate cessation resources. It has been suggested that hardcore smokers make up only a small fraction of current smokers and therefore do not represent a significant public health problem. However, little is known about the prevalence and nature of this subgroup of smokers in the United States. Based on a national sample, the 1998-1999 Tobacco Use Supplement to the Current Population Survey, we categorized, based on smoking pattern, groups of current smokers who were over age 25 years (N=33,568). We compared hardcore smokers with other groups of current smokers on demographic, environmental, and smoking variables to assess whether hardcore smokers represent a unique group. Hardcore smokers were defined as established daily smokers, consuming 15 or more cigarettes per day with no reported history of quit attempts. Hardcore smokers represent 13.7% of all current smokers and 17.6% of all established smokers. They are more likely to be male, unmarried, not in the work force, and have lower education. They also are more likely to have started smoking at a younger age, smoke more, and are less likely to report contact with smoking restrictions. This analysis suggests that hardcore smokers are distinct from other groups of smokers. These results also indicate that hardcore smokers account for a substantial proportion of smokers and as such may represent a significant public health challenge that needs to be addressed. JF - Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco AU - Augustson, Erik AU - Marcus, Stephen AD - Tobacco Control and Research Branch, DCCPS National Cancer Institute, Bethesda, MD 20892-8318, USA. augustse@mail.nih.gov Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 621 EP - 629 VL - 6 IS - 4 SN - 1462-2203, 1462-2203 KW - Index Medicus KW - Severity of Illness Index KW - Age of Onset KW - Risk Factors KW - Humans KW - Smoking Cessation KW - Health Surveys KW - Adult KW - Aged KW - Middle Aged KW - United States -- epidemiology KW - Male KW - Female KW - Tobacco Use Disorder -- epidemiology KW - Smoking -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66884421?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Use+of+the+current+population+survey+to+characterize+subpopulations+of+continued+smokers%3A+a+national+perspective+on+the+%22hardcore%22+smoker+phenomenon.&rft.au=Augustson%2C+Erik%3BMarcus%2C+Stephen&rft.aulast=Augustson&rft.aufirst=Erik&rft.date=2004-08-01&rft.volume=6&rft.issue=4&rft.spage=621&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 - 2004-12-02 N1 - Date created - 2004-09-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Management of patients receiving antithymocyte globulin for aplastic anemia and myelodysplastic syndrome. AN - 66854243; 15354924 AB - Antithymocyte globulin (ATG) is used commonly in patients with severe aplastic anemia and those undergoing renal transplant. Its utility also is being explored in the treatment of myelodysplastic syndrome, conditioning regimens for hematopoietic stem cell transplant, and prophylaxis of graft-versus-host disease. As indications for ATG expand, knowledge regarding its administration and management of associated toxicities is needed. These toxicities range from life-threatening anaphylaxis associated with the infusion to flu-like symptoms that occur one to two weeks after the infusion. Adverse effects are classified according to the severity and system impacted. Mild toxicities respond to comfort measures and include fever, chills, urticarial rash, and vomiting. Moderate toxicities require acute interventions and include fluid-responsive hypotension, nonischemic chest pain, and reversible oxygen desaturation. Severe toxicities require intensive support and include those refractory to earlier intervention. Management of these toxicities usually is limited to fluid resuscitation and noninvasive monitoring. Occurrence of infusion-related toxicities may require premature discontinuation of therapy. Therefore, an educated healthcare team and interdisciplinary clinical management guidelines are important to ensure the safe administration and complete course of ATG. JF - Clinical journal of oncology nursing AU - Bevans, Margaret F AU - Shalabi, Reem A AD - Clinical Center, National Institutes of Health, Bethesda, MD, USA. mbevans@cc.nih.gov Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 377 EP - 382 VL - 8 IS - 4 SN - 1092-1095, 1092-1095 KW - Antilymphocyte Serum KW - 0 KW - Immunosuppressive Agents KW - Nursing KW - Patient Education as Topic KW - Infusions, Intravenous KW - Humans KW - Drug Monitoring KW - Adult KW - Desensitization, Immunologic KW - Child KW - Drug Hypersensitivity -- therapy KW - Antilymphocyte Serum -- adverse effects KW - Drug Hypersensitivity -- etiology KW - Anemia, Aplastic -- drug therapy KW - Myelodysplastic Syndromes -- drug therapy KW - Immunosuppressive Agents -- therapeutic use KW - Antilymphocyte Serum -- therapeutic use KW - Immunosuppressive Agents -- adverse effects KW - Drug Hypersensitivity -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66854243?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+journal+of+oncology+nursing&rft.atitle=Management+of+patients+receiving+antithymocyte+globulin+for+aplastic+anemia+and+myelodysplastic+syndrome.&rft.au=Bevans%2C+Margaret+F%3BShalabi%2C+Reem+A&rft.aulast=Bevans&rft.aufirst=Margaret&rft.date=2004-08-01&rft.volume=8&rft.issue=4&rft.spage=377&rft.isbn=&rft.btitle=&rft.title=Clinical+journal+of+oncology+nursing&rft.issn=10921095&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-28 N1 - Date created - 2004-09-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Clin J Oncol Nurs. 2004 Dec;8(6):583; author reply 583 [15637953] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Marine toxins and nonmarine toxins: convergence or symbiotic organisms? AN - 66826222; 15332834 AB - Bioactive marine natural products occur only rarely in nonmarine sources. The converse also is true. Divergent evolutionary pathways for the biosynthesis of bioactive secondary metabolites seem to be the rule. Marine biosynthetic pathways lead to a wide variety of different structural classes, among which polyethers, macrolides, terpenes, unusual amino acids/peptides, and alkaloids are notable. Nonmarine biosynthetic pathways also lead to a similar wide variety of structural classes. However, the structures are usually quite different from the marine analogues. The alkaloids of plants are notable, but again there appears little convergence between the marine and nonmarine alkaloids. However, tetrodotoxin, a remarkable, highly polar, marine alkaloid, does occur in various amphibians. The occurrence and possible origin of tetrodotoxin and congeners, including chiriquitoxin, and of the saxitoxin analogue zetekitoxin in amphibians are reviewed. JF - Journal of natural products AU - Daly, John W AD - Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, DHHS, Bethesda, Maryland 20892-0820, USA. jdaly@nih.gov Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 1211 EP - 1215 VL - 67 IS - 8 SN - 0163-3864, 0163-3864 KW - Alkaloids KW - 0 KW - Amphibian Venoms KW - Fish Venoms KW - Marine Toxins KW - Quinazolines KW - Toxins, Biological KW - zetekitoxin AB KW - tetrodonic acid KW - 3270-35-7 KW - Saxitoxin KW - 35523-89-8 KW - Tetrodotoxin KW - 4368-28-9 KW - chiriquitoxin KW - 61132-15-8 KW - Index Medicus KW - Molecular Structure KW - Animals KW - Tetrodotoxin -- chemistry KW - Quinazolines -- chemistry KW - Saxitoxin -- analogs & derivatives KW - Saxitoxin -- chemistry KW - Fish Venoms -- chemistry KW - Amphibian Venoms -- chemistry KW - Alkaloids -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66826222?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+natural+products&rft.atitle=Marine+toxins+and+nonmarine+toxins%3A+convergence+or+symbiotic+organisms%3F&rft.au=Daly%2C+John+W&rft.aulast=Daly&rft.aufirst=John&rft.date=2004-08-01&rft.volume=67&rft.issue=8&rft.spage=1211&rft.isbn=&rft.btitle=&rft.title=Journal+of+natural+products&rft.issn=01633864&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-10-18 N1 - Date created - 2004-08-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ovarian cancer risk associated with varying causes of infertility. AN - 66773545; 15302291 AB - To evaluate the risk of ovarian cancer as related to underlying causes of infertility. Retrospective observational cohort study. Five large reproductive endocrinology practices. A total of 12,193 women evaluated for infertility between 1965 and 1988. None. Ovarian cancer ascertained through 1999. With 45 identified ovarian cancers, this cohort of infertility patients demonstrated a significantly higher rate of ovarian cancer than the general female population (standardized incidence ratio [SIR] = 1.98; 95% confidence interval [CI], 1.4-2.6). The risk was higher for patients with primary infertility (SIR = 2.73) than for those with secondary infertility (SIR = 1.44), and it was particularly high for patients who never subsequently conceived (SIR = 3.33). Women with endometriosis had the highest risk (SIR = 2.48; 95% CI, 1.3-4.2), with a further elevated risk among those with primary infertility (4.19, 2.0-7.7). Comparisons among the infertile women, which allowed calculation of rate ratios (RRs) after adjustment for multiple factors, also showed links with endometriosis. Compared with women with secondary infertility without endometriosis, patients with primary infertility and endometriosis had a RR of 2.72 (95% CI, 1.1-6.7). Determination of ovarian cancer risk should take into account the type of infertility (primary vs. secondary) and underlying causes. Further study of endometriosis may provide insights into ovarian carcinogenesis. JF - Fertility and sterility AU - Brinton, Louise A AU - Lamb, Emmet J AU - Moghissi, Kamran S AU - Scoccia, Bert AU - Althuis, Michelle D AU - Mabie, Jerome E AU - Westhoff, Carolyn L AD - Hormonal and Reproductive Epidemiology Branch, National Cancer Institute, 6120 Executive Boulevard, Bethesda, MD 20852, USA. Brinton@nih.gov Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 405 EP - 414 VL - 82 IS - 2 SN - 0015-0282, 0015-0282 KW - Index Medicus KW - Medical Records KW - Risk Factors KW - Humans KW - Cohort Studies KW - Retrospective Studies KW - Follow-Up Studies KW - Time Factors KW - Female KW - Survival Analysis KW - Ovarian Neoplasms -- mortality KW - Infertility, Female -- complications KW - Ovarian Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66773545?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fertility+and+sterility&rft.atitle=Ovarian+cancer+risk+associated+with+varying+causes+of+infertility.&rft.au=Brinton%2C+Louise+A%3BLamb%2C+Emmet+J%3BMoghissi%2C+Kamran+S%3BScoccia%2C+Bert%3BAlthuis%2C+Michelle+D%3BMabie%2C+Jerome+E%3BWesthoff%2C+Carolyn+L&rft.aulast=Brinton&rft.aufirst=Louise&rft.date=2004-08-01&rft.volume=82&rft.issue=2&rft.spage=405&rft.isbn=&rft.btitle=&rft.title=Fertility+and+sterility&rft.issn=00150282&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-15 N1 - Date created - 2004-08-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I trial of the cyclin-dependent kinase inhibitor flavopiridol in combination with docetaxel in patients with metastatic breast cancer. AN - 66772237; 15297405 AB - The purpose of this study was to determine the toxicities and characterize the pharmacokinetics of docetaxel and flavopiridol in patients with metastatic breast cancer. Docetaxel was administered at an initial dose of 60 mg/m(2) followed in 24 hours by a 72-hour infusion of flavopiridol at 50 mg/m(2)/d every 3 weeks. Because dose-limiting myelosuppression occurred, the schedule was amended to docetaxel, 50 mg/m(2), followed by escalating doses of flavopiridol (starting dose, 26 mg/m(2)/d) as a 1-hour infusion daily for 3 days. Pharmacokinetic studies were performed. Ki67, p53, and phosphorylated retinoblastoma protein (phospho-Rb) in paired tumor and buccal mucosa biopsies (obtained pre- and posttreatment) were examined by immunohistochemistry. Eleven patients were enrolled. Five patients received docetaxel and 72-hour flavopiridol. Dose-limiting toxicity was grade 4 neutropenia. Six patients received docetaxel and 1-hour flavopiridol, and the dose-limiting toxicity was grade 3 hypotension. Pharmacokinetics of flavopiridol and docetaxel were consistent with historical data. Nuclear staining with p53 increased and phospho-Rb decreased in 10 pairs of buccal mucosa biopsies posttreatment (P = 0.002 and P = 0.04, respectively). No significant changes in Ki67, p53, or phospho-Rb were detected in six paired tumors. Two patients sustained stable disease for >3 months (72-hour flavopiridol), and one partial response was observed (1-hour flavopiridol). Docetaxel combined with 72-hour flavopiridol was not feasible because of dose-limiting neutropenia. Dose escalation of a 1-hour infusion of flavopiridol with docetaxel was also not possible. The changes in p53 and phospho-Rb in buccal mucosa suggest that a biological effect with flavopiridol was achieved. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Tan, Antoinette R AU - Yang, Xiaowei AU - Berman, Arlene AU - Zhai, Suoping AU - Sparreboom, Alex AU - Parr, Allyson L AU - Chow, Catherine AU - Brahim, Jaime S AU - Steinberg, Seth M AU - Figg, William D AU - Swain, Sandra M AD - Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20889, USA. Y1 - 2004/08/01/ PY - 2004 DA - 2004 Aug 01 SP - 5038 EP - 5047 VL - 10 IS - 15 SN - 1078-0432, 1078-0432 KW - Biomarkers, Tumor KW - 0 KW - Enzyme Inhibitors KW - Flavonoids KW - Ki-67 Antigen KW - Piperidines KW - Retinoblastoma Protein KW - Taxoids KW - Tumor Suppressor Protein p53 KW - docetaxel KW - 15H5577CQD KW - alvocidib KW - 45AD6X575G KW - Cyclin-Dependent Kinases KW - EC 2.7.11.22 KW - Index Medicus KW - Ki-67 Antigen -- biosynthesis KW - Area Under Curve KW - Mouth Mucosa -- pathology KW - Humans KW - Clinical Trials as Topic KW - Aged KW - Retinoblastoma Protein -- biosynthesis KW - Biopsy KW - Tumor Suppressor Protein p53 -- metabolism KW - Biomarkers, Tumor -- metabolism KW - Phosphorylation KW - Adult KW - Neoplasm Metastasis KW - Middle Aged KW - Mucous Membrane -- pathology KW - Time Factors KW - Immunohistochemistry KW - Female KW - Breast Neoplasms -- drug therapy KW - Enzyme Inhibitors -- administration & dosage KW - Breast Neoplasms -- pathology KW - Flavonoids -- adverse effects KW - Taxoids -- adverse effects KW - Cyclin-Dependent Kinases -- antagonists & inhibitors KW - Breast Neoplasms -- metabolism KW - Piperidines -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Piperidines -- adverse effects KW - Taxoids -- administration & dosage KW - Flavonoids -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66772237?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Phase+I+trial+of+the+cyclin-dependent+kinase+inhibitor+flavopiridol+in+combination+with+docetaxel+in+patients+with+metastatic+breast+cancer.&rft.au=Tan%2C+Antoinette+R%3BYang%2C+Xiaowei%3BBerman%2C+Arlene%3BZhai%2C+Suoping%3BSparreboom%2C+Alex%3BParr%2C+Allyson+L%3BChow%2C+Catherine%3BBrahim%2C+Jaime+S%3BSteinberg%2C+Seth+M%3BFigg%2C+William+D%3BSwain%2C+Sandra+M&rft.aulast=Tan&rft.aufirst=Antoinette&rft.date=2004-08-01&rft.volume=10&rft.issue=15&rft.spage=5038&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 - 2005-03-07 N1 - Date created - 2004-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vitro combination treatment with perifosine and UCN-01 demonstrates synergism against prostate (PC-3) and lung (A549) epithelial adenocarcinoma cell lines. AN - 66771415; 15297428 AB - Antineoplastic agents often achieve antitumor activity at the expense of close to unacceptable toxicity. One potential avenue to improve therapeutic index might combine agents targeting distinct components of the same growth regulatory pathway. This might lead to more complete modulation of the target pathway at concentrations lower than those associated with limiting adventitious toxicities from either agent alone. The protein kinase antagonist UCN-01 is currently used in Phase I/II trials and has recently been demonstrated to inhibit potently PDK1. We have recently documented that the alkylphospholipid perifosine potently also inhibits Akt kinase (PKB) activation by interfering with membrane localization of Akt. This leads to the hypothesis that these two agents might act synergistically through distinct mechanisms in the PI3K/Akt proliferation and survival-related signaling pathway. The synergistic effects of UCN-01 and perifosine, on two cell lines (A-549 and PC-3), were examined using various long-term in vitro assays for cell growth, cell cycle distribution, clonogenicity, survival morphology, and apoptosis. Along with Western blotting experiments were performed to determine whether this synergistic combination of two drugs has significant effect on their downstream targets and on biochemical markers of apoptosis. After 72 h, perifosine at concentrations of 1.5 and 10 microM UCN-01 at 40 and 250 nM did not significantly affect the growth of PC-3 and A459 cells, respectively. However, in combination at the same respective individual concentrations (1.5 microM and 40 nM of perifosine and UCN-01, respectively, in PC-3 cells and 10 microM perifosine and 0.25 microM UCN-01 in the somewhat more resistant A549 cells), virtually complete growth inhibition of both the cell lines resulted. Supra-additive inhibition of growth was also demonstrated in independent clonogenic assays. Mechanistic studies in cell culture models suggest enhanced depletion of the S-phase population in cells treated by the combination. This correlated with enhanced inactivation of Akt along with activation of caspases 3 and 9 and poly(ADP-ribose) polymerase cleavage. Evidence of synergy was formally demonstrated and occurred across a wide range of drug concentrations and was largely independent of the order or sequence of drug addition. As the concentrations of UCN-01 and perifosine causing synergistic inhibition of cell growth are clinically achievable without prominent toxicity, these data support the development of clinical studies with this combination. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Dasmahapatra, Girija P AU - Didolkar, Parijat AU - Alley, Michael C AU - Ghosh, Somiranjan AU - Sausville, Edward A AU - Roy, Krishnendu K AD - Clinical Trials Unit, Developmental Therapeutics Program, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2004/08/01/ PY - 2004 DA - 2004 Aug 01 SP - 5242 EP - 5252 VL - 10 IS - 15 SN - 1078-0432, 1078-0432 KW - Antimetabolites, Antineoplastic KW - 0 KW - Antineoplastic Agents KW - Enzyme Inhibitors KW - Phosphorylcholine KW - 107-73-3 KW - perifosine KW - 2GWV496552 KW - 7-hydroxystaurosporine KW - 7BU5H4V94A KW - Bromodeoxyuridine KW - G34N38R2N1 KW - Staurosporine KW - H88EPA0A3N KW - Index Medicus KW - Immunoblotting KW - Apoptosis KW - Dose-Response Relationship, Drug KW - Humans KW - Cell Line, Tumor KW - Antimetabolites, Antineoplastic -- pharmacology KW - Blotting, Western KW - Bromodeoxyuridine -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Time Factors KW - Antineoplastic Agents -- pharmacology KW - Cell Cycle KW - Signal Transduction KW - Male KW - Female KW - Staurosporine -- administration & dosage KW - Phosphorylcholine -- administration & dosage KW - Lung Neoplasms -- drug therapy KW - Phosphorylcholine -- pharmacology KW - Prostatic Neoplasms -- drug therapy KW - Drug Synergism KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Staurosporine -- analogs & derivatives KW - Phosphorylcholine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66771415?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=In+vitro+combination+treatment+with+perifosine+and+UCN-01+demonstrates+synergism+against+prostate+%28PC-3%29+and+lung+%28A549%29+epithelial+adenocarcinoma+cell+lines.&rft.au=Dasmahapatra%2C+Girija+P%3BDidolkar%2C+Parijat%3BAlley%2C+Michael+C%3BGhosh%2C+Somiranjan%3BSausville%2C+Edward+A%3BRoy%2C+Krishnendu+K&rft.aulast=Dasmahapatra&rft.aufirst=Girija&rft.date=2004-08-01&rft.volume=10&rft.issue=15&rft.spage=5242&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 - 2005-03-07 N1 - Date created - 2004-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phosphorylation of paxillin tyrosines 31 and 118 controls polarization and motility of lymphoid cells and is PMA-sensitive. AN - 66765511; 15252114 AB - Tyrosine phosphorylation of paxillin regulates actin cytoskeleton-dependent changes in cell morphology and motility in adherent cells. In this report we investigated the involvement of paxillin tyrosine phosphorylation in the regulation of actin cytoskeleton-dependent polarization and motility of a non-adherent IL-3-dependent murine pre-B lymphocytic cell line Baf3. We also assessed the effect of phorbol myristate acetate (PMA), a phorbol ester analogous to those currently in clinical trials for the treatment of leukemia, on paxillin phosphorylation. Using tyrosine-to-phenylalanine phosphorylation mutants of paxillin and phosphospecific antibody we demonstrated that IL-3 stimulated phosphorylation of paxillin tyrosine residues 31 and 118, whereas the tyrosines 40 and 181 were constitutively phosphorylated. Phosphorylation of paxillin residues 31 and 118 was required for cell polarization and motility. In the presence of IL-3, PMA dramatically reduced the phosphorylation of residues 31 and 118, which was accompanied by inhibition of cell polarization and motility. This PMA effect was partially recapitulated by expression of exogenous tyrosine 31 and 118 mutants of paxillin. We also demonstrated that PMA inhibited the IL-3-induced and activation-dependent tyrosine phosphorylation of focal adhesion kinase. Thus, our results indicate that phosphorylation of paxillin tyrosine residues 31 and 118 regulates actin-dependent polarization and motility of pre-B Baf3 cells, both of which could be inhibited by PMA. They also suggest that inhibition of upstream signaling by PMA contributes to the decrease of paxillin phosphorylation and subsequent changes in cell morphology. JF - Journal of cell science AU - Romanova, Larisa Y AU - Hashimoto, Shigeru AU - Chay, Kee-Oh AU - Blagosklonny, Mikhail V AU - Sabe, Hisataka AU - Mushinski, J Frederic AD - Molecular Genetics Section, Laboratory of Genetics, National Cancer Institute, NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA. iromanova@partners.org Y1 - 2004/08/01/ PY - 2004 DA - 2004 Aug 01 SP - 3759 EP - 3768 VL - 117 SN - 0021-9533, 0021-9533 KW - Actins KW - 0 KW - Cytoskeletal Proteins KW - Interleukin-3 KW - PXN protein, human KW - Paxillin KW - Phosphoproteins KW - Pxn protein, mouse KW - Tyrosine KW - 42HK56048U KW - Phosphoric Monoester Hydrolases KW - EC 3.1.3.2 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Cell Movement KW - Animals KW - Humans KW - Immunoprecipitation KW - Actins -- metabolism KW - Mice KW - Cell Line, Tumor KW - Lymphocytes KW - B-Lymphocytes -- metabolism KW - Phosphoric Monoester Hydrolases -- metabolism KW - Microscopy, Fluorescence KW - Blotting, Western KW - Phosphorylation KW - Genetic Vectors KW - Interleukin-3 -- metabolism KW - Mutation KW - Immunohistochemistry KW - Cell Line KW - Tyrosine -- chemistry KW - Phosphoproteins -- chemistry KW - Cytoskeletal Proteins -- chemistry KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cytoskeletal Proteins -- metabolism KW - Phosphoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66765511?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cell+science&rft.atitle=Phosphorylation+of+paxillin+tyrosines+31+and+118+controls+polarization+and+motility+of+lymphoid+cells+and+is+PMA-sensitive.&rft.au=Romanova%2C+Larisa+Y%3BHashimoto%2C+Shigeru%3BChay%2C+Kee-Oh%3BBlagosklonny%2C+Mikhail+V%3BSabe%2C+Hisataka%3BMushinski%2C+J+Frederic&rft.aulast=Romanova&rft.aufirst=Larisa&rft.date=2004-08-01&rft.volume=117&rft.issue=&rft.spage=3759&rft.isbn=&rft.btitle=&rft.title=Journal+of+cell+science&rft.issn=00219533&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-04-04 N1 - Date created - 2004-08-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bone marrow-derived immune cells regulate vascular disease through a p27(Kip1)-dependent mechanism. AN - 66765028; 15286808 AB - The cyclin-dependent kinase inhibitors are key regulators of cell cycle progression. Although implicated in carcinogenesis, they inhibit the proliferation of a variety of normal cell types, and their role in diverse human diseases is not fully understood. Here, we report that p27(Kip1) plays a major role in cardiovascular disease through its effects on the proliferation of bone marrow-derived (BM-derived) immune cells that migrate into vascular lesions. Lesion formation after mechanical arterial injury was markedly increased in mice with homozygous deletion of p27(Kip1), characterized by prominent vascular infiltration by immune and inflammatory cells. Vascular occlusion was substantially increased when BM-derived cells from p27(-/-) mice repopulated vascular lesions induced by mechanical injury in p27(+/+) recipients, in contrast to p27(+/+) BM donors. To determine the contribution of immune cells to vascular injury, transplantation was performed with BM derived from RAG(-/-) and RAG(+/+) mice. RAG(+/+) BM markedly exacerbated vascular proliferative lesions compared with what was found in RAG(-/-) donors. Taken together, these findings suggest that vascular repair and regeneration is regulated by the proliferation of BM-derived hematopoietic and nonhematopoietic cells through a p27(Kip1)-dependent mechanism and that immune cells largely mediate these effects. JF - The Journal of clinical investigation AU - Boehm, Manfred AU - Olive, Michelle AU - True, Andrea L AU - Crook, Martin F AU - San, Hong AU - Qu, Xuan AU - Nabel, Elizabeth G AD - Cardiovascular Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 419 EP - 426 VL - 114 IS - 3 SN - 0021-9738, 0021-9738 KW - Cell Cycle Proteins KW - 0 KW - Cyclin-Dependent Kinases KW - EC 2.7.11.22 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Thymectomy KW - Cell Cycle -- physiology KW - Femoral Artery -- injuries KW - Mice KW - Mice, Knockout KW - Gene Deletion KW - Neutrophils -- metabolism KW - Mice, Inbred Strains KW - T-Lymphocytes -- metabolism KW - Cell Division -- immunology KW - Time Factors KW - Bone Marrow Transplantation KW - Cell Cycle -- drug effects KW - Female KW - Male KW - Macrophages -- metabolism KW - Vascular Diseases -- pathology KW - Cell Cycle Proteins -- genetics KW - Gene Expression Regulation -- immunology KW - Vascular Diseases -- genetics KW - Cyclin-Dependent Kinases -- antagonists & inhibitors KW - Bone Marrow Cells -- immunology KW - Cell Cycle Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66765028?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Bone+marrow-derived+immune+cells+regulate+vascular+disease+through+a+p27%28Kip1%29-dependent+mechanism.&rft.au=Boehm%2C+Manfred%3BOlive%2C+Michelle%3BTrue%2C+Andrea+L%3BCrook%2C+Martin+F%3BSan%2C+Hong%3BQu%2C+Xuan%3BNabel%2C+Elizabeth+G&rft.aulast=Boehm&rft.aufirst=Manfred&rft.date=2004-08-01&rft.volume=114&rft.issue=3&rft.spage=419&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biomolecular+NMR&rft.issn=09252738&rft_id=info:doi/10.1023%2FB%3AJNMR.0000042952.66982.38 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-25 N1 - Date created - 2004-08-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Immunol. 2001 Jan 1;166(1):304-12 [11123306] Nat Med. 2000 Nov;6(11):1235-40 [11062534] J Immunol. 2000 Dec 1;165(11):6270-7 [11086062] Science. 2000 Dec 1;290(5497):1779-82 [11099419] Cell. 2001 Feb 23;104(4):503-16 [11239408] Nat Med. 2001 Apr;7(4):382-3 [11283635] Nat Med. 2001 Jun;7(6):693-8 [11385506] Nat Med. 2001 Jun;7(6):738-41 [11385513] J Clin Invest. 2001 Jun;107(11):1411-22 [11390423] J Biol Chem. 2001 Jun 15;276(24):21976-83 [11297537] J Clin Invest. 2001 Jul;108(2):251-9 [11457878] Arterioscler Thromb Vasc Biol. 2001 Dec;21(12):1948-54 [11742869] Circulation. 2002 Mar 5;105(9):1135-43 [11877368] Nat Med. 2002 Apr;8(4):403-9 [11927948] Nature. 2002 Jul 4;418(6893):41-9 [12077603] Circ Res. 2002 Aug 23;91(4):281-91 [12193460] Nat Med. 2002 Nov;8(11):1218-26 [12411948] Nat Med. 2002 Nov;8(11):1249-56 [12411952] N Engl J Med. 2002 Nov 14;347(20):1557-65 [12432042] Mol Cell Biol. 2003 Jan;23(1):359-69 [12482987] Nature. 2002 Dec 19-26;420(6917):868-74 [12490960] Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4754-9 [12665618] N Engl J Med. 2003 Oct 2;349(14):1307-9 [14523135] Blood. 2004 Jan 1;103(1):158-61 [14504088] J Clin Invest. 2004 May;113(9):1258-65 [15124016] Cell. 1992 Mar 6;68(5):869-77 [1547488] Cell. 1994 Jul 15;78(1):59-66 [8033212] Circ Res. 1995 Mar;76(3):412-7 [7532117] Cell. 1996 May 31;85(5):707-20 [8646779] Cell. 1996 May 31;85(5):721-32 [8646780] Cell. 1996 May 31;85(5):733-44 [8646781] J Clin Invest. 1996 Nov 15;98(10):2277-83 [8941644] Science. 1997 Feb 14;275(5302):964-7 [9020076] Exp Hematol. 1999 Feb;27(2):203-9 [10029157] Genes Dev. 1999 Jun 15;13(12):1501-12 [10385618] Nat Med. 2000 Mar;6(3):290-7 [10700231] Nature. 2000 Nov 2;408(6808):92-6 [11081514] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prevalence of and risk factors for depressive symptoms among young adolescents. AN - 66763989; 15289248 AB - To determine the prevalence, risk factors, and risk behaviors associated with depressive symptoms in a nationally representative, cross-sectional sample of young adolescents. A school-based survey collected through self-administered questionnaires in grades 6, 8, and 10 in 1996. Schools in the United States. 9863 students in grades 6, 8, and 10 (average ages, 11, 13, and 15). Depressive symptoms, substance use, somatic symptoms, scholastic behaviors, and involvement in bullying. Eighteen percent of youths reported symptoms of depression. A higher proportion of females (25%) reported depressive symptoms than males (10%). Prevalence of depressive symptoms increased by age for both males and females. Among American Indian youths, 29% reported depressive symptoms, as compared with 22% of Hispanic, 18% of white, 17% of Asian American, and 15% of African American youths. Youths who were frequently involved in bullying, either as perpetrators or as victims, were more than twice as likely to report depressive symptoms than those who were not involved in bullying. A significantly higher percentage of youths who reported using substances reported depressive symptoms as compared with other youths. Similarly, youths who reported experiencing somatic symptoms also reported significantly higher proportions of depressive symptoms than other youths. Depression is a substantial and largely unrecognized problem among young adolescents that warrants an increased need and opportunity for identification and intervention at the middle school level. Understanding differences in prevalence between males and females and among racial/ethnic groups may be important to the recognition and treatment of depression among youths. JF - Archives of pediatrics & adolescent medicine AU - Saluja, Gitanjali AU - Iachan, Ronaldo AU - Scheidt, Peter C AU - Overpeck, Mary D AU - Sun, Wenyu AU - Giedd, Jay N AD - National Institute of Child Health and Human Development, Rockville, MD 20892-7510, USA. salujag@mail.nih.gov Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 760 EP - 765 VL - 158 IS - 8 SN - 1072-4710, 1072-4710 KW - Abridged Index Medicus KW - Index Medicus KW - Violence -- statistics & numerical data KW - Humans KW - Child KW - Comorbidity KW - Ethnic Groups -- statistics & numerical data KW - Age Distribution KW - Cross-Sectional Studies KW - Risk Factors KW - Health Surveys KW - Psychophysiologic Disorders -- epidemiology KW - Adolescent KW - United States -- epidemiology KW - Sex Distribution KW - Female KW - Male KW - Substance-Related Disorders -- epidemiology KW - Prevalence KW - Adolescent Behavior KW - Depression -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66763989?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pediatrics+%26+adolescent+medicine&rft.atitle=Prevalence+of+and+risk+factors+for+depressive+symptoms+among+young+adolescents.&rft.au=Saluja%2C+Gitanjali%3BIachan%2C+Ronaldo%3BScheidt%2C+Peter+C%3BOverpeck%2C+Mary+D%3BSun%2C+Wenyu%3BGiedd%2C+Jay+N&rft.aulast=Saluja&rft.aufirst=Gitanjali&rft.date=2004-08-01&rft.volume=158&rft.issue=8&rft.spage=760&rft.isbn=&rft.btitle=&rft.title=Archives+of+pediatrics+%26+adolescent+medicine&rft.issn=10724710&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-31 N1 - Date created - 2004-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemical-induced DNA damage and human cancer risk. AN - 66763860; 15286742 JF - Nature reviews. Cancer AU - Poirier, Miriam C AD - Carcinogen-DNA Interactions Section, LCCTP, Building 37 Room 4032, National Cancer Institute, National Institutes of Health, 37 Convent Drive MSC-4255, Bethesda, Maryland 20892-4255, USA. poirierm@exchange.nih.gov Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 630 EP - 637 VL - 4 IS - 8 SN - 1474-175X, 1474-175X KW - Carcinogens KW - 0 KW - DNA Adducts KW - Polycyclic Aromatic Hydrocarbons KW - Index Medicus KW - Humans KW - China KW - Cell Transformation, Neoplastic KW - Risk Assessment KW - Esophageal Neoplasms -- prevention & control KW - Esophageal Neoplasms -- chemically induced KW - DNA Damage KW - Esophageal Neoplasms -- physiopathology KW - Neoplasms -- physiopathology KW - Environmental Exposure KW - Carcinogens -- toxicity KW - Polycyclic Aromatic Hydrocarbons -- poisoning KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66763860?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+reviews.+Cancer&rft.atitle=Chemical-induced+DNA+damage+and+human+cancer+risk.&rft.au=Poirier%2C+Miriam+C&rft.aulast=Poirier&rft.aufirst=W-C&rft.date=2004-09-01&rft.volume=113&rft.issue=1-3&rft.spage=147&rft.isbn=&rft.btitle=&rft.title=Journal+of+Hazardous+Materials&rft.issn=03043894&rft_id=info:doi/10.1016%2Fj.jhazmat.2004.05.033 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-24 N1 - Date created - 2004-08-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Nat Rev Cancer. 2004 Sep;4(9):747 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prevalence and co-occurrence of substance use disorders and independent mood and anxiety disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. AN - 66761968; 15289279 AB - Uncertainties exist about the prevalence and comorbidity of substance use disorders and independent mood and anxiety disorders. To present nationally representative data on the prevalence and comorbidity of DSM-IV alcohol and drug use disorders and independent mood and anxiety disorders (including only those that are not substance induced and that are not due to a general medical condition). Face-to-face survey. The United States. Household and group quarters' residents. Prevalence and associations of substance use disorders and independent mood and anxiety disorders. The prevalences of 12-month DSM-IV independent mood and anxiety disorders in the US population were 9.21% (95% confidence interval [CI], 8.78%-9.64%) and 11.08% (95% CI, 10.43%-11.73%), respectively. The rate of substance use disorders was 9.35% (95% CI, 8.86%-9.84%). Only a few individuals with mood or anxiety disorders were classified as having only substance-induced disorders. Associations between most substance use disorders and independent mood and anxiety disorders were positive and significant (P<.05). Substance use disorders and mood and anxiety disorders that develop independently of intoxication and withdrawal are among the most prevalent psychiatric disorders in the United States. Associations between most substance use disorders and independent mood and anxiety disorders were overwhelmingly positive and significant, suggesting that treatment for a comorbid mood or anxiety disorder should not be withheld from individuals with substance use disorders. JF - Archives of general psychiatry AU - Grant, Bridget F AU - Stinson, Frederick S AU - Dawson, Deborah A AU - Chou, S Patricia AU - Dufour, Mary C AU - Compton, Wilson AU - Pickering, Roger P AU - Kaplan, Kenneth AD - Laboratory of Epidemiology and Biometry, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892-9304, USA. bgrant@willco.niaaa.nih.gov Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 807 EP - 816 VL - 61 IS - 8 SN - 0003-990X, 0003-990X KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Diagnosis, Dual (Psychiatry) KW - Aged KW - Comorbidity KW - Depressive Disorder -- epidemiology KW - Psychiatric Status Rating Scales KW - Adult KW - Depressive Disorder -- diagnosis KW - Middle Aged KW - Adolescent KW - United States -- epidemiology KW - Diagnostic and Statistical Manual of Mental Disorders KW - Female KW - Male KW - Prevalence KW - Substance-Related Disorders -- diagnosis KW - Mood Disorders -- diagnosis KW - Anxiety Disorders -- diagnosis KW - Mood Disorders -- epidemiology KW - Anxiety Disorders -- epidemiology KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66761968?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+general+psychiatry&rft.atitle=Prevalence+and+co-occurrence+of+substance+use+disorders+and+independent+mood+and+anxiety+disorders%3A+results+from+the+National+Epidemiologic+Survey+on+Alcohol+and+Related+Conditions.&rft.au=Grant%2C+Bridget+F%3BStinson%2C+Frederick+S%3BDawson%2C+Deborah+A%3BChou%2C+S+Patricia%3BDufour%2C+Mary+C%3BCompton%2C+Wilson%3BPickering%2C+Roger+P%3BKaplan%2C+Kenneth&rft.aulast=Grant&rft.aufirst=Bridget&rft.date=2004-08-01&rft.volume=61&rft.issue=8&rft.spage=807&rft.isbn=&rft.btitle=&rft.title=Archives+of+general+psychiatry&rft.issn=0003990X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-17 N1 - Date created - 2004-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Natural history of lipid abnormalities and fat redistribution among human immunodeficiency virus-infected children receiving long-term, protease inhibitor-containing, highly active antiretroviral therapy regimens. AN - 66761430; 15286262 AB - To characterize the type and frequency of biochemical lipid abnormalities and physical changes in body composition associated with the use of protease inhibitor (PI)-containing antiretroviral therapy among human immunodeficiency virus-infected children treated for up to 6 years. A retrospective study of human immunodeficiency virus-infected pediatric patients enrolled in research protocols between August 1995 and December 2001 was performed. All patients who had received a PI for > or =2 years as part of their investigational antiretroviral treatment regimens during the study period were eligible. Of the 110 patients identified as having received PI therapy, 94 met the study criteria. Of the 94 patients evaluated, 9 patients (10%) developed fat redistribution as well as dyslipidemia, 49 patients (52%) developed dyslipidemia without associated physical changes, and 36 patients (38%) exhibited no elevation of lipid levels or physical signs of fat redistribution. For all 9 patients with fat redistribution, the onset of the physical changes was closely associated with changes during pubertal development. Fat redistribution was also associated with lower viral loads and higher, more sustained levels of dyslipidemia. The onset of dyslipidemia and fat redistribution peaked between 10 and 15 years of age. Among pediatric patients receiving PI therapy, there seems to be an age range in which children are at greater risk of developing hypercholesterolemia and subsequent fat redistribution, suggesting that unidentified physiologic changes associated with puberty may predispose pediatric patients treated with PI therapy to developing lipodystrophy. JF - Pediatrics AU - Taylor, Perdita AU - Worrell, Carol AU - Steinberg, Seth M AU - Hazra, Rohan AU - Jankelevich, Shirley AU - Wood, Lauren V AU - Zwerski, Sheryl AU - Yarchoan, Robert AU - Zeichner, Steven AD - Pediatric HIV Working Group, HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2004/08// PY - 2004 DA - August 2004 SP - e235 EP - e242 VL - 114 IS - 2 KW - HIV Protease Inhibitors KW - 0 KW - Lipids KW - Abridged Index Medicus KW - Index Medicus KW - Lipids -- blood KW - Age Factors KW - Analysis of Variance KW - Humans KW - Retrospective Studies KW - Child KW - Child, Preschool KW - Infant KW - Risk Factors KW - Adolescent KW - Female KW - Male KW - Puberty KW - HIV-Associated Lipodystrophy Syndrome -- etiology KW - Antiretroviral Therapy, Highly Active -- adverse effects KW - HIV Infections -- complications KW - HIV Infections -- blood KW - Hypercholesterolemia -- etiology KW - HIV Infections -- drug therapy KW - HIV Protease Inhibitors -- therapeutic use KW - HIV Protease Inhibitors -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66761430?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Natural+history+of+lipid+abnormalities+and+fat+redistribution+among+human+immunodeficiency+virus-infected+children+receiving+long-term%2C+protease+inhibitor-containing%2C+highly+active+antiretroviral+therapy+regimens.&rft.au=Taylor%2C+Perdita%3BWorrell%2C+Carol%3BSteinberg%2C+Seth+M%3BHazra%2C+Rohan%3BJankelevich%2C+Shirley%3BWood%2C+Lauren+V%3BZwerski%2C+Sheryl%3BYarchoan%2C+Robert%3BZeichner%2C+Steven&rft.aulast=Taylor&rft.aufirst=Perdita&rft.date=2004-08-01&rft.volume=114&rft.issue=2&rft.spage=e235&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 - 2004-12-27 N1 - Date created - 2004-08-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Discovery of new potentially defective alleles of human CYP2C9. AN - 66758479; 15284535 AB - CYP2C9 is a clinically important enzyme, responsible for the metabolism of numerous clinically important therapeutic drugs. In the present study, we discovered 38 single nucleotide polymorphisms in CYP2C9 by resequencing of genomic DNA from 92 individuals from three different racial groups. Haplotype analysis predicted that there are at least 21 alleles of CYP2C9 in this group of individuals. Six new alleles were identified that contained coding changes: L19I (CYP2C9*7), R150H (CYP2C9*8), H251R (CYP2C9*9), E272G (CYP2C9*10), R335W(CYP2C9*11) and P489S (CYP2C9*12). When expressed in a bacterial cDNA expression system, several alleles exhibited altered catalytic activity. CYP2C9*11 appeared to be a putative poor metabolizer allele, exhibiting a three-fold increase in the Km and more than a two-fold decrease in the intrinsic clearance for tolbutamide. Examination of the crystal structure of human CYP2C9 reveals that R335 is located in the turn between the J and J' helices and forms a hydrogen-bonding ion pair with D341 from the J' helix. Abolishing this interaction in CYP2C9*11 individuals could destabilize the secondary structure and alter the substrate affinity. This new putative poor metabolizer (PM) allele was found in Africans. A second potentially PM allele CYP2C9*12 found in a racially unidentified sample also exhibited a modest decrease in the Vmax and the intrinsic clearance for tolbutamide in a recombinant system. Further clinical studies are needed to determine the effect of these new polymorphisms on the metabolism of CYP2C9 substrates. JF - Pharmacogenetics AU - Blaisdell, Joyce AU - Jorge-Nebert, Lucia F AU - Coulter, Sherry AU - Ferguson, Stephen S AU - Lee, Su-Jun AU - Chanas, Brian AU - Xi, Tina AU - Mohrenweiser, Harvey AU - Ghanayem, Burhan AU - Goldstein, Joyce A AD - Laboratory of Pharmacology and Chemistry, Human Metabolism Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA, DNA. Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 527 EP - 537 VL - 14 IS - 8 SN - 0960-314X, 0960-314X KW - Recombinant Proteins KW - 0 KW - Tolbutamide KW - 982XCM1FOI KW - CYP2C9 protein, human KW - EC 1.14.13.- KW - Cytochrome P-450 CYP2C9 KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - Index Medicus KW - Models, Molecular KW - Humans KW - Recombinant Proteins -- genetics KW - Asian Continental Ancestry Group KW - Genotype KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- isolation & purification KW - Alleles KW - Haplotypes -- genetics KW - Transfection KW - Recombinant Proteins -- metabolism KW - European Continental Ancestry Group KW - African Continental Ancestry Group KW - Aryl Hydrocarbon Hydroxylases -- metabolism KW - Tolbutamide -- metabolism KW - Aryl Hydrocarbon Hydroxylases -- genetics KW - Polymorphism, Single Nucleotide -- genetics KW - Ethnic Groups -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66758479?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Discovery+of+new+potentially+defective+alleles+of+human+CYP2C9.&rft.au=Blaisdell%2C+Joyce%3BJorge-Nebert%2C+Lucia+F%3BCoulter%2C+Sherry%3BFerguson%2C+Stephen+S%3BLee%2C+Su-Jun%3BChanas%2C+Brian%3BXi%2C+Tina%3BMohrenweiser%2C+Harvey%3BGhanayem%2C+Burhan%3BGoldstein%2C+Joyce+A&rft.aulast=Blaisdell&rft.aufirst=Joyce&rft.date=2004-08-01&rft.volume=14&rft.issue=8&rft.spage=527&rft.isbn=&rft.btitle=&rft.title=Pharmacogenetics&rft.issn=0960314X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-10 N1 - Date created - 2004-07-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structure-function defects of human mitochondrial DNA polymerase in autosomal dominant progressive external ophthalmoplegia. AN - 66754774; 15258572 AB - Progressive external ophthalmoplegia (PEO) is a mitochondrial disorder associated with mutations in the POLG gene encoding the mitochondrial DNA polymerase (pol gamma). Four autosomal dominant mutations that cause PEO encode the amino acid substitutions G923D, R943H, Y955C and A957S in the polymerase domain of pol gamma. A homology model of the pol gamma catalytic domain in complex with DNA was developed to investigate the effects of these mutations. Two mutations causing the most severe disease phenotype, Y955C and R943H, change residues that directly interact with the incoming dNTP. Polymerase mutants exhibit 0.03-30% wild-type polymerase activity and a 2- to 35-fold decrease in nucleotide selectivity in vitro. The reduced selectivity and catalytic efficiency of the autosomal dominant PEO mutants predict in vivo dysfunction, and the extent of biochemical defects correlates with the clinical severity of the disease. JF - Nature structural & molecular biology AU - Graziewicz, Maria A AU - Longley, Matthew J AU - Bienstock, Rachelle J AU - Zeviani, Massimo AU - Copeland, William C AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 770 EP - 776 VL - 11 IS - 8 SN - 1545-9993, 1545-9993 KW - Bacterial Proteins KW - 0 KW - Nucleotides KW - Tyrosine KW - 42HK56048U KW - DNA KW - 9007-49-2 KW - DNA polymerase gamma KW - EC 2.7.7.- KW - RNA-Directed DNA Polymerase KW - EC 2.7.7.49 KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Glycine KW - TE7660XO1C KW - Index Medicus KW - Glycine -- chemistry KW - Models, Molecular KW - DNA -- metabolism KW - Humans KW - Catalytic Domain KW - Nucleotides -- chemistry KW - RNA-Directed DNA Polymerase -- metabolism KW - Protein Binding KW - Structure-Activity Relationship KW - Tyrosine -- chemistry KW - Mutagenesis, Site-Directed KW - Amino Acid Motifs KW - Bacterial Proteins -- chemistry KW - Genes, Dominant KW - Kinetics KW - Protein Folding KW - DNA -- chemistry KW - Crystallography, X-Ray KW - Mutation KW - Mitochondria -- enzymology KW - Ophthalmoplegia, Chronic Progressive External -- genetics KW - Ophthalmoplegia, Chronic Progressive External -- enzymology KW - DNA-Directed DNA Polymerase -- metabolism KW - DNA-Directed DNA Polymerase -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66754774?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+structural+%26+molecular+biology&rft.atitle=Structure-function+defects+of+human+mitochondrial+DNA+polymerase+in+autosomal+dominant+progressive+external+ophthalmoplegia.&rft.au=Graziewicz%2C+Maria+A%3BLongley%2C+Matthew+J%3BBienstock%2C+Rachelle+J%3BZeviani%2C+Massimo%3BCopeland%2C+William+C&rft.aulast=Graziewicz&rft.aufirst=Maria&rft.date=2004-08-01&rft.volume=11&rft.issue=8&rft.spage=770&rft.isbn=&rft.btitle=&rft.title=Nature+structural+%26+molecular+biology&rft.issn=15459993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-16 N1 - Date created - 2004-07-28 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 1D8Y; PDB; 1T7P; 2KTQ; 3DBP N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The transcription factor NRF2 protects against pulmonary fibrosis. AN - 66752968; 15208274 AB - The molecular mechanisms of pulmonary fibrosis are poorly understood, although reactive oxygen species are thought to have an important role. NRF2 is a transcription factor that protects cells and tissues from oxidative stress by activating protective antioxidant and detoxifying enzymes. We hypothesized that NRF2 protects lungs from injury and fibrosis induced by bleomycin, an anti-neoplastic agent that causes pulmonary fibrosis in susceptible patients. To test this hypothesis, mice with targeted deletion of Nrf2 (Nrf2-/-) and wild-type (Nrf2+/+) mice were treated with bleomycin or vehicle, and pulmonary injury and fibrotic responses were compared. Bleomycin-induced increases in lung weight, epithelial cell death, and inflammation were significantly greater in Nrf2-/- mice than in Nrf2+/+ mice. Indices of lung fibrosis (hydroxyproline content, collagen accumulation, fibrotic score, cell proliferation) were significantly greater in bleomycin-treated Nrf2-/- mice, compared with Nrf2+/+ mice. NRF2 expression and activity were elevated in Nrf2+/+ mice by bleomycin. Bleomycin caused greater up-regulation of several NRF2-inducible antioxidant enzyme genes and protein products in Nrf2+/+ mice compared with Nrf2-/- mice. Further, bleomycin-induced transcripts and protein levels of lung injury and fibrosis markers were significantly attenuated in Nrf2+/+ mice compared with Nrf2-/- mice. Results demonstrated that NRF2 has a critical role in protection against pulmonary fibrosis, presumably through enhancement of cellular antioxidant capacity. This study has important implications for the development of intervention strategies against fibrosis. JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Cho, Hye-Youn AU - Reddy, Sekhar P M AU - Yamamoto, Masayuki AU - Kleeberger, Steven R AD - Department of Environmental Health Sciences, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA. cho2@niehs.nih.gov Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 1258 EP - 1260 VL - 18 IS - 11 KW - Biomarkers KW - 0 KW - Tenascin KW - Tissue Inhibitor of Metalloproteinase-1 KW - Bleomycin KW - 11056-06-7 KW - RNA KW - 63231-63-0 KW - Collagen KW - 9007-34-5 KW - Hydroxyproline KW - RMB44WO89X KW - Index Medicus KW - Animals KW - Mice, Inbred ICR KW - Lung -- chemistry KW - Cell Division -- drug effects KW - Collagen -- analysis KW - Bleomycin -- toxicity KW - Mice KW - Lung -- pathology KW - Organ Size KW - RNA -- biosynthesis KW - Mice, Knockout KW - Hydroxyproline -- analysis KW - Bronchoalveolar Lavage Fluid -- chemistry KW - Enzyme Induction -- drug effects KW - Tenascin -- analysis KW - Lung -- drug effects KW - Tissue Inhibitor of Metalloproteinase-1 -- genetics KW - Male KW - Tissue Inhibitor of Metalloproteinase-1 -- biosynthesis KW - Pulmonary Fibrosis -- chemically induced KW - Pulmonary Fibrosis -- prevention & control KW - Pulmonary Fibrosis -- metabolism KW - Pulmonary Fibrosis -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66752968?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+transcription+factor+NRF2+protects+against+pulmonary+fibrosis.&rft.au=Cho%2C+Hye-Youn%3BReddy%2C+Sekhar+P+M%3BYamamoto%2C+Masayuki%3BKleeberger%2C+Steven+R&rft.aulast=Cho&rft.aufirst=Hye-Youn&rft.date=2004-08-01&rft.volume=18&rft.issue=11&rft.spage=1258&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 - 2005-02-08 N1 - Date created - 2004-07-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prolonged fever of unknown origin and hemophagocytosis evolving into acute lymphoblastic leukemia. AN - 66750483; 15282670 AB - Hemophagocytic syndrome (HPS) is an unusual acute syndrome presenting with fever, hepatosplenomegaly, and cytopenias. The hallmark of HPS is the accumulation of activated macrophages that engulf hematopoietic cells in the reticuloendothelial system. Most cases of HPS in adults are secondary to infection or malignancy, and thus investigation of the underlying disease is necessary. We describe a patient with prolonged fever, HPS, and chromosomal abnormalities in the bone marrow who underwent thorough evaluation for the cause of his symptoms. A final diagnosis of acute lymphoblastic leukemia (ALL) was established in a fourth, repeated bone marrow biopsy performed more than 2 months after the first presenting symptom appeared. This unusual case demonstrates the importance of cytogenetic abnormalities found in cases of HPS and the importance of repeated testing when an underlying disease is suspected. Copyright 2004 Wiley-Liss, Inc. JF - American journal of hematology AU - Goldschmidt, Neta AU - Gural, Alexander AU - Kornberg, Abraham AU - Spectre, Galia AU - Shopen, Andrei AU - Paltiel, Ora AD - Department of Hematology, Hadassah Medical Center, Jerusalem, Israel. goldschn@mail.nih.gov Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 364 EP - 367 VL - 76 IS - 4 SN - 0361-8609, 0361-8609 KW - Antibodies, Monoclonal KW - 0 KW - Antibodies, Monoclonal, Murine-Derived KW - Cytarabine KW - 04079A1RDZ KW - Rituximab KW - 4F4X42SYQ6 KW - Vincristine KW - 5J49Q6B70F KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Prednisone KW - VB0R961HZT KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Karyotyping KW - Bone Marrow -- pathology KW - Humans KW - Vincristine -- administration & dosage KW - Disease Progression KW - Doxorubicin -- administration & dosage KW - Cytarabine -- administration & dosage KW - Antibodies, Monoclonal -- administration & dosage KW - Splenomegaly -- etiology KW - Chromosome Aberrations KW - Middle Aged KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Pancytopenia -- etiology KW - Methotrexate -- administration & dosage KW - Prednisone -- administration & dosage KW - Male KW - Remission Induction KW - Histiocytosis, Non-Langerhans-Cell -- pathology KW - Histiocytosis, Non-Langerhans-Cell -- etiology KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- pathology KW - Fever of Unknown Origin -- etiology KW - Histiocytosis, Non-Langerhans-Cell -- genetics KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- complications KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66750483?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+hematology&rft.atitle=Prolonged+fever+of+unknown+origin+and+hemophagocytosis+evolving+into+acute+lymphoblastic+leukemia.&rft.au=Goldschmidt%2C+Neta%3BGural%2C+Alexander%3BKornberg%2C+Abraham%3BSpectre%2C+Galia%3BShopen%2C+Andrei%3BPaltiel%2C+Ora&rft.aulast=Goldschmidt&rft.aufirst=Neta&rft.date=2004-08-01&rft.volume=76&rft.issue=4&rft.spage=364&rft.isbn=&rft.btitle=&rft.title=American+journal+of+hematology&rft.issn=03618609&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-16 N1 - Date created - 2004-07-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Am J Hematol. 2005 Mar;78(3):246-7 [15726603] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Arsenic-induced alterations in the contact hypersensitivity response in Balb/c mice. AN - 66743874; 15276424 AB - Previous studies in our laboratory indicate that arsenic alters secretion of growth promoting and inflammatory cytokines in the skin that can regulate the migration and maturation of Langerhans cells (LC) during allergic contact dermatitis. Therefore, we hypothesized that arsenic may modulate hypersensitivity responses to cutaneous sensitizing agents by altering cytokine production, LC migration, and T-cell proliferation. To investigate this hypothesis, we examined the induction and elicitation phases of dermal sensitization. Mice exposed to 50 mg/l arsenic in the drinking water for 4 weeks demonstrated a reduction in lymph node cell (LNC) proliferation and ear swelling following sensitization with 2,4-dinitrofluorobenzene (DNFB), compared to control mice. LC and T-cell populations in the draining lymph nodes of DNFB-sensitized mice were evaluated by fluorescence-activated cell sorting; activated LC were reduced in cervical lymph nodes, suggesting that LC migration may be altered following arsenic exposure. Lymphocytes from arsenic-treated animals sensitized with fluorescein isothiocyanate (FITC) exhibited reduced proliferative responses following T-cell mitogen stimulation in vitro; however, lymphocyte proliferation from nonsensitized, arsenic-treated mice was comparable to controls. Arsenic exposure also reduced the number of thioglycollate-induced peritoneal macrophages and circulating neutrophils. These studies demonstrate that repeated, prolonged exposure to nontoxic concentrations of sodium arsenite alters immune cell populations and results in functional changes in immune responses, specifically attenuation of contact hypersensitivity. JF - Toxicology and applied pharmacology AU - Patterson, Rachel AU - Vega, Libia AU - Trouba, Kevin AU - Bortner, Carl AU - Germolec, Dori AD - Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 2004/08/01/ PY - 2004 DA - 2004 Aug 01 SP - 434 EP - 443 VL - 198 IS - 3 SN - 0041-008X, 0041-008X KW - Arsenites KW - 0 KW - Cytokines KW - Enzyme Inhibitors KW - Sodium Compounds KW - sodium arsenite KW - 48OVY2OC72 KW - Dinitrofluorobenzene KW - D241E059U6 KW - Index Medicus KW - Lymph Nodes -- metabolism KW - Animals KW - Dinitrofluorobenzene -- toxicity KW - Mice KW - Flow Cytometry KW - Mice, Inbred BALB C KW - Lymph Nodes -- drug effects KW - Female KW - Sodium Compounds -- therapeutic use KW - Sodium Compounds -- pharmacology KW - Arsenites -- pharmacology KW - Enzyme Inhibitors -- therapeutic use KW - Dermatitis, Contact -- prevention & control KW - Cytokines -- biosynthesis KW - Dermatitis, Contact -- immunology KW - Enzyme Inhibitors -- pharmacology KW - Arsenites -- therapeutic use KW - Immunization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66743874?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Arsenic-induced+alterations+in+the+contact+hypersensitivity+response+in+Balb%2Fc+mice.&rft.au=Patterson%2C+Rachel%3BVega%2C+Libia%3BTrouba%2C+Kevin%3BBortner%2C+Carl%3BGermolec%2C+Dori&rft.aulast=Patterson&rft.aufirst=Rachel&rft.date=2004-08-01&rft.volume=198&rft.issue=3&rft.spage=434&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 - 2004-09-14 N1 - Date created - 2004-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytotoxicity of oxidized low-density lipoprotein in cultured RPE cells is dependent on the formation of 7-ketocholesterol. AN - 66742567; 15277510 AB - To determine which components present in oxidized LDL are responsible for the cytotoxicity associated with its internalization by culture ARPE19 cells. ARPE19 cells were grown in 24-well and 96-well plates. Cell viability was measured by MTT and/or adenosine triphosphate (ATP) content. LDL was oxidized with Cu(+2) and oxysterol content analyzed by a novel HPLC method. OxLDL showed increased cytotoxicity with prolonged oxidation. Analysis of the oxLDL showed a predominance of the 7-oxygenated products, 7 alpha-hydroxycholesterol (7 alpha HCh), 7 beta-hydroxycholesterol (7 beta HCh), and 7-ketocholesterol (7kCh). Addition of these oxysterols to the ARPE19 cell in free form indicated that 7kCh is the most cytotoxic of the oxysterols but at physiologically unrealistic concentrations. Partitioning of individual oxysterols into nonoxidized LDL at concentrations similar to those found in the oxLDL also indicated that 7kCh is the most cytotoxic of the oxysterols. Transition metals are tightly bound by LDL and play an important role in the oxidation of LDL, but do not seem to enhance its cytotoxicity directly. Prolonged oxidation of LDL increases the levels of 7kCh due to further oxidation of 7 alpha HCh and 7 beta HCh. The formation of 7KCh seems to be responsible for most of the cytotoxicity associated with oxLDL internalization in ARPE19 cells. JF - Investigative ophthalmology & visual science AU - Rodriguez, Ignacio R AU - Alam, Shahabuddin AU - Lee, Jung Wha AD - Laboratory of Retinal Cell and Molecular Biology, Section on Mechanisms of Retinal Diseases, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. rodriguezi@nei.nih.gov Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 2830 EP - 2837 VL - 45 IS - 8 SN - 0146-0404, 0146-0404 KW - Hydroxycholesterols KW - 0 KW - Ketocholesterols KW - Lipoproteins, LDL KW - Tetrazolium Salts KW - Thiazoles KW - Transition Elements KW - oxidized low density lipoprotein KW - cholest-5-en-3 beta,7 alpha-diol KW - 566-26-7 KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - thiazolyl blue KW - EUY85H477I KW - 7-ketocholesterol KW - O7676FE78M KW - Index Medicus KW - Oxidation-Reduction KW - Hydroxycholesterols -- metabolism KW - Transition Elements -- toxicity KW - Thiazoles -- metabolism KW - Cells, Cultured KW - Humans KW - Adenosine Triphosphate -- metabolism KW - Drug Synergism KW - Time Factors KW - Tetrazolium Salts -- metabolism KW - Chromatography, High Pressure Liquid KW - Cell Survival KW - Pigment Epithelium of Eye -- drug effects KW - Pigment Epithelium of Eye -- metabolism KW - Lipoproteins, LDL -- toxicity KW - Ketocholesterols -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66742567?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cytotoxicity+of+oxidized+low-density+lipoprotein+in+cultured+RPE+cells+is+dependent+on+the+formation+of+7-ketocholesterol.&rft.au=Rodriguez%2C+Ignacio+R%3BAlam%2C+Shahabuddin%3BLee%2C+Jung+Wha&rft.aulast=Rodriguez&rft.aufirst=Ignacio&rft.date=2004-08-01&rft.volume=45&rft.issue=8&rft.spage=2830&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 - 2004-08-31 N1 - Date created - 2004-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cannabinoid antagonist SR-141716 inhibits endotoxic hypotension by a cardiac mechanism not involving CB1 or CB2 receptors. AN - 66741803; 15059774 AB - Endocannabinoids and CB1 receptors have been implicated in endotoxin (LPS)-induced hypotension: LPS stimulates the synthesis of anandamide in macrophages, and the CB1 antagonist SR-141716 inhibits the hypotension induced by treatment of rats with LPS or LPS-treated macrophages. Recent evidence indicates the existence of cannabinoid receptors distinct from CB1 or CB2 that are inhibited by SR-141716 but not by other CB1 antagonists such as AM251. In pentobarbital-anesthetized rats, intravenous injection of 10 mg/kg LPS elicited hypotension associated with profound decreases in cardiac contractility, moderate tachycardia, and an increase in lower body vascular resistance. Pretreatment with 3 mg/kg SR-141716 prevented the hypotension and decrease in cardiac contractility, slightly attenuated the increase in peripheral resistance, and had no effect on the tachycardia caused by LPS, whereas pretreatment with 3 mg/kg AM251 did not affect any of these responses. SR-141716 also elicited an acute reversal of the hypotension and decreased contractility when administered after the response to LPS had fully developed. The LPS-induced hypotension and its inhibition by SR-141716 were similar in pentobarbital-anesthetized wild-type, CB1(-/-), and CB1(-/-)/CB2(-/-) mice. We conclude that SR-141716 inhibits the acute hemodynamic effects of LPS by interacting with a cardiac receptor distinct from CB1 or CB2 that mediates negative inotropy and may be activated by anandamide or a related endocannabinoid released during endotoxemia. JF - American journal of physiology. Heart and circulatory physiology AU - Bátkai, Sándor AU - Pacher, Pál AU - Járai, Zoltán AU - Wagner, Jens A AU - Kunos, George AD - National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892-8115, USA. Y1 - 2004/08// PY - 2004 DA - August 2004 SP - H595 EP - H600 VL - 287 IS - 2 SN - 0363-6135, 0363-6135 KW - Cannabinoids KW - 0 KW - Endotoxins KW - Piperidines KW - Pyrazoles KW - Receptor, Cannabinoid, CB1 KW - Receptor, Cannabinoid, CB2 KW - AM 251 KW - 3I4FA44MAI KW - rimonabant KW - RML78EN3XE KW - Index Medicus KW - Receptor, Cannabinoid, CB2 -- metabolism KW - Hemodynamics -- drug effects KW - Animals KW - Receptor, Cannabinoid, CB1 -- metabolism KW - Vascular Resistance -- drug effects KW - Mice KW - Myocardial Contraction -- drug effects KW - Receptor, Cannabinoid, CB2 -- deficiency KW - Mice, Knockout KW - Rats KW - Heart Rate -- drug effects KW - Rats, Sprague-Dawley KW - Male KW - Receptor, Cannabinoid, CB1 -- deficiency KW - Piperidines -- pharmacology KW - Hypotension -- chemically induced KW - Pyrazoles -- pharmacology KW - Hypotension -- prevention & control KW - Hypotension -- physiopathology KW - Heart -- physiopathology KW - Cannabinoids -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66741803?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+physiology.+Heart+and+circulatory+physiology&rft.atitle=Cannabinoid+antagonist+SR-141716+inhibits+endotoxic+hypotension+by+a+cardiac+mechanism+not+involving+CB1+or+CB2+receptors.&rft.au=B%C3%A1tkai%2C+S%C3%A1ndor%3BPacher%2C+P%C3%A1l%3BJ%C3%A1rai%2C+Zolt%C3%A1n%3BWagner%2C+Jens+A%3BKunos%2C+George&rft.aulast=B%C3%A1tkai&rft.aufirst=S%C3%A1ndor&rft.date=2004-08-01&rft.volume=287&rft.issue=2&rft.spage=H595&rft.isbn=&rft.btitle=&rft.title=American+journal+of+physiology.+Heart+and+circulatory+physiology&rft.issn=03636135&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-03 N1 - Date created - 2004-07-27 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: J Pharmacol Exp Ther. 2003 Jan;304(1):179-84 [12490589] Biochem Pharmacol. 2002 Dec 15;64(12):1785-91 [12445868] Circulation. 2003 Feb 18;107(6):896-904 [12591762] Mol Pharmacol. 2003 Mar;63(3):699-705 [12606780] J Cardiovasc Pharmacol. 2003 Apr;41(4):657-64 [12658069] Br J Pharmacol. 2003 Apr;138(7):1320-32 [12711633] J Biol Chem. 2003 Nov 7;278(45):45034-9 [12949078] Clin Pharmacol Ther. 1975 Sep;18(3):287-97 [1164818] Circulation. 1976 Apr;53(4):703-7 [1253395] Proc Natl Acad Sci U S A. 1990 Mar;87(5):1932-6 [2308954] J Crit Care. 1993 Jun;8(2):117-27 [8102078] Nature. 1993 Sep 2;365(6441):61-5 [7689702] FEBS Lett. 1994 Aug 22;350(2-3):240-4 [8070571] Eur J Pharmacol. 1995 May 24;278(3):279-83 [7589169] Br J Pharmacol. 1996 Aug;118(8):2023-8 [8864538] Am J Physiol. 1997 Feb;272(2 Pt 2):H843-50 [9124447] J Pharmacol Exp Ther. 1997 Jun;281(3):1030-7 [9190833] Naunyn Schmiedebergs Arch Pharmacol. 1997 Aug;356(2):197-202 [9272725] Life Sci. 1997;61(14):PL 191-7 [9335234] Nature. 1997 Dec 4;390(6659):518-21 [9394002] J Cardiovasc Pharmacol. 1998 Apr;31(4):479-83 [9554792] FASEB J. 1998 Aug;12(11):1035-44 [9707176] Science. 1999 Jan 15;283(5400):401-4 [9888857] Am J Physiol. 1999 Jun;276(6 Pt 2):H2085-93 [10362691] J Cardiovasc Pharmacol. 1999 Jul;34(1):64-9 [10413069] Nature. 1999 Jul 29;400(6743):452-7 [10440374] Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1393-8 [12538878] Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):14136-41 [10570211] Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14228-33 [10588688] Br J Pharmacol. 1999 Dec;128(8):1772-8 [10588933] Hypertension. 2000 Feb;35(2):679-84 [10679517] Biochem J. 2000 Mar 15;346 Pt 3:835-40 [10698714] J Pharmacol Exp Ther. 2000 Jul;294(1):27-32 [10871291] Jpn J Pharmacol. 2000 Mar;82(3):261-4 [10887957] Shock. 2000 Oct;14(4):441-6 [11049107] Chem Phys Lipids. 2000 Nov;108(1-2):159-68 [11106789] Naunyn Schmiedebergs Arch Pharmacol. 2001 Mar;363(3):267-75 [11284440] Nature. 2001 Apr 12;410(6830):822-5 [11298451] Crit Care Med. 2001 Mar;29(3):609-17 [11373429] Anal Biochem. 2001 Jul 1;294(1):73-82 [11412008] Nat Med. 2001 Jul;7(7):827-32 [11433348] J Am Coll Cardiol. 2001 Dec;38(7):2048-54 [11738314] Anesthesiology. 2001 Dec;95(6):1396-405 [11748398] Gastroenterology. 2002 Jan;122(1):85-93 [11781284] Br J Pharmacol. 2002 Mar;135(5):1191-8 [11877326] Am J Physiol Heart Circ Physiol. 2002 Jun;282(6):H2046-54 [12003810] Br J Pharmacol. 2002 Jun;136(4):581-7 [12055136] J Am Coll Cardiol. 2002 Sep 4;40(5):1006-16 [12225730] Neuropharmacology. 2002 Sep;43(4):503-10 [12367597] Behav Pharmacol. 2002 Sep;13(5-6):451-63 [12394421] Comment In: Am J Physiol Heart Circ Physiol. 2005 Jan;288(1):H451; author reply H451-2 [15598874] N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Mouse susceptibility to anthrax lethal toxin is influenced by genetic factors in addition to those controlling macrophage sensitivity. AN - 66737458; 15271901 AB - Bacillus anthracis lethal toxin (LT) produces symptoms of anthrax in mice and induces rapid lysis of macrophages (M phi) derived from certain inbred strains. We used nine inbred strains and two inducible nitric oxide synthase (iNOS) knockout C57BL/6J strains polymorphic for the LT M phi sensitivity Kif1C locus to analyze the role of M phi sensitivity (to lysis) in LT-mediated cytokine responses and lethality. LT-mediated induction of cytokines KC, MCP-1/JE, MIP-2, eotaxin, and interleukin-1 beta occurred only in mice having LT-sensitive M phi. However, while iNOS knockout C57BL/6J mice having LT-sensitive M phi were much more susceptible to LT than the knockout mice with LT-resistant M phi, a comparison of susceptibilities to LT in the larger set of inbred mouse strains showed a lack of correlation between M phi sensitivity and animal susceptibility to toxin. For example, C3H/HeJ mice, harboring LT-sensitive M phi and having the associated LT-mediated cytokine response, were more resistant than mice with LT-resistant M phi and no cytokine burst. Toll-like receptor 4 (Tlr4)-deficient, lipopolysaccharide-nonresponsive mice were not more resistant to LT. We also found that CAST/Ei mice are uniquely sensitive to LT and may provide an economical bioassay for toxin-directed therapeutics. The data indicate that while the cytokine response to LT in mice requires M phi lysis and while M phi sensitivity in the C57BL/6J background is sufficient for BALB/cJ-like mortality of that strain, the contribution of M phi sensitivity and cytokine response to animal susceptibility to LT differs among other inbred strains. Thus, LT-mediated lethality in mice is influenced by genetic factors in addition to those controlling M phi lysis and cytokine response and is independent of Tlr4 function. JF - Infection and immunity AU - Moayeri, Mahtab AU - Martinez, Nathaniel W AU - Wiggins, Jason AU - Young, Howard A AU - Leppla, Stephen H AD - Microbial Pathogenesis Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 4439 EP - 4447 VL - 72 IS - 8 SN - 0019-9567, 0019-9567 KW - Antigens, Bacterial KW - 0 KW - Bacterial Toxins KW - anthrax toxin KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Nitric Oxide Synthase Type II KW - Nos2 protein, mouse KW - Index Medicus KW - Mice, Inbred Strains KW - Animals KW - Disease Susceptibility KW - Nitric Oxide Synthase -- genetics KW - Mice, Inbred C57BL KW - Mice KW - Mice, Knockout KW - Macrophages, Peritoneal -- physiology KW - Antigens, Bacterial -- toxicity KW - Bacillus anthracis -- pathogenicity KW - Macrophages, Peritoneal -- drug effects KW - Bacterial Toxins -- toxicity KW - Antigens, Bacterial -- immunology KW - Genetic Predisposition to Disease KW - Bacterial Toxins -- immunology KW - Anthrax -- mortality KW - Anthrax -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66737458?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+immunity&rft.atitle=Mouse+susceptibility+to+anthrax+lethal+toxin+is+influenced+by+genetic+factors+in+addition+to+those+controlling+macrophage+sensitivity.&rft.au=Moayeri%2C+Mahtab%3BMartinez%2C+Nathaniel+W%3BWiggins%2C+Jason%3BYoung%2C+Howard+A%3BLeppla%2C+Stephen+H&rft.aulast=Moayeri&rft.aufirst=Mahtab&rft.date=2004-08-01&rft.volume=72&rft.issue=8&rft.spage=4439&rft.isbn=&rft.btitle=&rft.title=Infection+and+immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-20 N1 - Date created - 2004-07-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1990 Jun;87(12):4828-32 [2191302] J Biol Chem. 2003 Feb 28;278(9):7413-21 [12488448] Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10198-201 [8234277] Ann N Y Acad Sci. 1995 Jul 21;762:499-501 [7668571] Mol Med. 1998 Feb;4(2):87-95 [9508786] Mol Microbiol. 1998 Jul;29(2):581-91 [9720874] Behav Brain Res. 1998 Sep;95(1):135-42 [9754885] J Bacteriol. 1962 Jun;83:1274-80 [13866126] J Clin Invest. 2003 Sep;112(5):670-82 [12952916] Am J Pathol. 2003 Nov;163(5):1735-41 [14578173] J Infect Dis. 1966 Apr;116(2):123-38 [4956203] J Infect Dis. 1966 Jun;116(3):377-89 [4957317] J Infect Dis. 1968 Feb;118(1):114-24 [5640983] Infect Immun. 1986 Mar;51(3):795-800 [3081444] Science. 1962 Dec 21;138(3547):1331-3 [14033353] Curr Biol. 2001 Oct 2;11(19):1503-11 [11591317] Science. 2002 Sep 20;297(5589):2048-51 [12202685] Infect Immun. 1993 Jan;61(1):245-52 [8380282] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cellular repair of oxidatively induced DNA base lesions is defective in prostate cancer cell lines, PC-3 and DU-145. AN - 66736484; 15044326 AB - Mutagenic oxidative DNA base damage increases with age in prostatic tissue. Various factors may influence this increase including: increased production of reactive oxygen species, increased susceptibility to oxidative stress, alterations in detoxifying enzyme levels or defects in DNA repair. Using liquid chromatography/mass spectrometry and gas chromatography/mass spectrometry, we show increased levels of oxidative DNA base lesions, 8-hydroxyguanine (8-oxoG), 8-hydroxyadenine (8-oxoA) and 5-hydroxycytosine (5OHC) over the baseline in PC-3 and DU-145 prostate cancer cells following exposure to ionizing radiation and a repair period. Nuclear extracts from PC-3 and DU-145 prostate cancer cell lines are defective in the incision of 8-oxoG, 5OHC and thymine glycol (TG) relative to the non-malignant prostate cell line. Consistent with reduced expression of OGG1 2a, incision of 8-oxoG is reduced in PC-3 and DU-145 mitochondrial extracts. We also show a correlation between severely defective incision of TG and 5OHC and reduced levels of NTH1 in PC-3 mitochondria. The antioxidant enzymes, glutathione peroxidase (GPx), catalase and superoxide dismutases (SOD1, SOD2), have altered expression patterns in these cancer cell lines. Genetic analysis of the OGG1 gene reveals that both PC-3 and DU-145 cell lines harbor polymorphisms associated with a higher susceptibility to certain cancers. These data suggest that the malignant phenotype in PC-3 and DU-145 cell lines may be associated with defects in base excision repair and alterations in expression of antioxidant enzymes. JF - Carcinogenesis AU - Trzeciak, Andrzej R AU - Nyaga, Simon G AU - Jaruga, Pawel AU - Lohani, Althaf AU - Dizdaroglu, Miral AU - Evans, Michele K AD - Laboratory of Cellular and Molecular Biology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224-6825, USA. Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 1359 EP - 1370 VL - 25 IS - 8 SN - 0143-3334, 0143-3334 KW - Antioxidants KW - 0 KW - 8-hydroxyadenine KW - 21149-26-8 KW - 8-hydroxyguanine KW - 5614-64-2 KW - Guanine KW - 5Z93L87A1R KW - 5-hydroxycytosine KW - 75321-30-1 KW - Cytosine KW - 8J337D1HZY KW - DNA KW - 9007-49-2 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 - Electron Transport Complex IV KW - EC 1.9.3.1 KW - Adenine KW - JAC85A2161 KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Comet Assay KW - Polymorphism, Genetic KW - Cell Nucleus -- metabolism KW - Dose-Response Relationship, Drug KW - Humans KW - Superoxide Dismutase -- metabolism KW - Cell Line, Tumor KW - Catalase -- metabolism KW - Blotting, Western KW - Glutathione Peroxidase -- metabolism KW - Antioxidants -- pharmacology KW - Kinetics KW - Gas Chromatography-Mass Spectrometry KW - Mitochondria -- metabolism KW - Electron Transport Complex IV -- metabolism KW - Time Factors KW - Male KW - Cell Division KW - DNA Damage KW - Cytosine -- pharmacology KW - Oxygen -- metabolism KW - Prostatic Neoplasms -- genetics KW - DNA -- chemistry KW - Guanine -- analogs & derivatives KW - Cytosine -- analogs & derivatives KW - Adenine -- analogs & derivatives KW - Guanine -- pharmacology KW - Adenine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66736484?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cellular+repair+of+oxidatively+induced+DNA+base+lesions+is+defective+in+prostate+cancer+cell+lines%2C+PC-3+and+DU-145.&rft.au=Trzeciak%2C+Andrzej+R%3BNyaga%2C+Simon+G%3BJaruga%2C+Pawel%3BLohani%2C+Althaf%3BDizdaroglu%2C+Miral%3BEvans%2C+Michele+K&rft.aulast=Trzeciak&rft.aufirst=Andrzej&rft.date=2004-08-01&rft.volume=25&rft.issue=8&rft.spage=1359&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-10 N1 - Date created - 2004-07-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Raloxifene and its role in breast cancer prevention. AN - 66733533; 15270657 AB - Raloxifene (Evista, Eli Lilly), a selective estrogen receptor modulator (SERM) and ligand for the estrogen receptor (ER), competes with endogenous estrogen for ER binding. Raloxifene is approved for the prevention and treatment of osteoporosis, and shows promise as a breast cancer prevention drug. Raloxifene may be a preferred agent over tamoxifen due to its side-effect profile; in particular, it does not stimulate the endometrium and is not associated with endometrial cancer. The mechanisms for the differential tissue effects of raloxifene compared with other SERMs are not completely understood; the roles of ERalpha and -beta, classic and alternative signaling pathways, and drug conformation are discussed in this review. The utility of raloxifene will depend on the outcome of trials that are now underway, as well as acceptance by high-risk women and their healthcare practitioners. JF - Expert review of anticancer therapy AU - Eng-Wong, Jennifer AU - Zujewski, Jo Anne AD - National Cancer Institute, Medical Oncology Clinical Research Unit, Bldg 10, Rm 12N226, Bethesda, MD 20892, USA. engwongj@mail.nih.gov Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 523 EP - 532 VL - 4 IS - 4 SN - 1473-7140, 1473-7140 KW - Estrogen Antagonists KW - 0 KW - Raloxifene Hydrochloride KW - 4F86W47BR6 KW - Index Medicus KW - Risk Factors KW - Humans KW - Clinical Trials as Topic KW - Chemoprevention KW - Signal Transduction KW - Female KW - Osteoporosis -- prevention & control KW - Estrogen Antagonists -- pharmacology KW - Raloxifene Hydrochloride -- pharmacology KW - Estrogen Antagonists -- adverse effects KW - Raloxifene Hydrochloride -- therapeutic use KW - Breast Neoplasms -- prevention & control KW - Raloxifene Hydrochloride -- adverse effects KW - Estrogen Antagonists -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66733533?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+review+of+anticancer+therapy&rft.atitle=Raloxifene+and+its+role+in+breast+cancer+prevention.&rft.au=Eng-Wong%2C+Jennifer%3BZujewski%2C+Jo+Anne&rft.aulast=Eng-Wong&rft.aufirst=Jennifer&rft.date=2004-08-01&rft.volume=4&rft.issue=4&rft.spage=523&rft.isbn=&rft.btitle=&rft.title=Expert+review+of+anticancer+therapy&rft.issn=14737140&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-21 N1 - Date created - 2004-07-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Severe disabling sensory-motor polyneuropathy during oxaliplatin-based chemotherapy. AN - 66729629; 15269607 AB - Oxaliplatin-based combination chemotherapy is an option for first-line therapy of metastatic colorectal cancer. It is associated with acute hyperexcitability of motor and sensory nerves, and a cumulative sensory axonal neuropathy. We describe a 56-year-old male with metastatic colorectal cancer treated with oxaliplatin and capecitabine who developed a rapidly ascending motor and sensory neuropathy, which rendered him wheelchair-bound. Heightened clinical suspicion for possible oxaliplatin-induced motor neuropathies may be warranted. JF - Anti-cancer drugs AU - Leonard, Gregory D AU - Wagner, Michael R AU - Quinn, Mary G AU - Grem, Jean L AD - National Cancer Institute-Navy Medical Oncology, Bethesda, MD, USA. Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 733 EP - 735 VL - 15 IS - 7 SN - 0959-4973, 0959-4973 KW - Organoplatinum Compounds KW - 0 KW - oxaliplatin KW - 04ZR38536J KW - Deoxycytidine KW - 0W860991D6 KW - Capecitabine KW - 6804DJ8Z9U KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Severity of Illness Index KW - Organoplatinum Compounds -- adverse effects KW - Organoplatinum Compounds -- administration & dosage KW - Humans KW - Fluorouracil -- analogs & derivatives KW - Middle Aged KW - Disabled Persons KW - Male KW - Deoxycytidine -- adverse effects KW - Deoxycytidine -- analogs & derivatives KW - Colonic Neoplasms -- drug therapy KW - Deoxycytidine -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Polyneuropathies -- chemically induced KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66729629?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Severe+disabling+sensory-motor+polyneuropathy+during+oxaliplatin-based+chemotherapy.&rft.au=Leonard%2C+Gregory+D%3BWagner%2C+Michael+R%3BQuinn%2C+Mary+G%3BGrem%2C+Jean+L&rft.aulast=Leonard&rft.aufirst=Gregory&rft.date=2004-08-01&rft.volume=15&rft.issue=7&rft.spage=733&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 - 2004-11-15 N1 - Date created - 2004-07-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interleukin-1beta-induced mucin production in human airway epithelium is mediated by cyclooxygenase-2, prostaglandin E2 receptors, and cyclic AMP-protein kinase A signaling. AN - 66728441; 15266025 AB - We reported recently that interleukin (IL)-1beta exposure resulted in a prolonged increase in MUC5AC mucin production in normal, well differentiated, human tracheobronchial epithelial (NHTBE) cell cultures, without significantly increasing MUC5AC mRNA (Am J Physiol 286:L320-L330, 2004). The goal of the present study was to elucidate the signaling pathways involved in IL-1beta-induced MUC5AC production. We found that IL-1beta increased cyclooxygenase-2 (COX-2) mRNA expression and prostaglandin (PG) E(2) production and that the COX-2 inhibitor celecoxib suppressed IL-1beta-induced MUC5AC production. Addition of exogenous PGE(2) to NHTBE cultures also increased MUC5AC production and IL-1beta-induced Muc5ac hypersecretion in tracheas from wild-type but not from COX-2-/- mice. NHTBE cells expressed all four E-prostanoid (EP) receptor subtypes and misoprostol, an EP2 and EP4 agonist, increased MUC5AC production, whereas sulprostone, an EP1 and EP3 agonist, did not. Furthermore, specific protein kinase A (PKA) inhibitors blocked IL-1beta and PGE(2)-induced MUC5AC production. However, neither inhibition of epidermal growth factor receptor (EGFR) activation with the tyrosine kinase inhibitor 4-(3-chloroanilino)-6,7-dimethoxyquinazoline HCl (AG-1478) or EGFR blocking antibody nor inhibition of extracellular signal-regulated kinase/P-38 mitogen activated protein kinases with specific inhibitors blocked IL-1beta stimulation of MUC5AC mucin production. We also observed that tumor necrosis factor (TNF)-alpha, platelet activating factor (PAF), and lipopolysaccharide (LPS) induced COX-2 and increased MUC5AC production that was blocked by celecoxib, suggesting a common signaling pathway of inflammatory mediator-induced MUC5AC production in NHTBE cells. We conclude that the induction of MUC5AC by IL-1beta, TNF-alpha, PAF, and LPS involves COX-2- generated PGE(2), activation of EP2 and/or EP4 receptor(s), and cAMP-PKA-mediated signaling. JF - Molecular pharmacology AU - Gray, Thomas AU - Nettesheim, Paul AU - Loftin, Charles AU - Koo, Ja-Seok AU - Bonner, James AU - Peddada, Shyamal AU - Langenbach, Robert AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. grayt@niehs.nih.gov Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 337 EP - 346 VL - 66 IS - 2 SN - 0026-895X, 0026-895X KW - Interleukin-1 KW - 0 KW - Isoenzymes KW - Lipopolysaccharides KW - Membrane Proteins KW - Mucins KW - PTGER1 protein, human KW - PTGER2 protein, human KW - PTGER3 protein, human KW - PTGER4 protein, human KW - Ptger1 protein, mouse KW - Ptger2 protein, mouse KW - Ptger3 protein, mouse KW - Ptger4 protein, mouse KW - Receptors, Prostaglandin E KW - Receptors, Prostaglandin E, EP1 Subtype KW - Receptors, Prostaglandin E, EP2 Subtype KW - Receptors, Prostaglandin E, EP3 Subtype KW - Receptors, Prostaglandin E, EP4 Subtype KW - Tumor Necrosis Factor-alpha KW - Cyclic AMP KW - E0399OZS9N KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - PTGS2 protein, human KW - Prostaglandin-Endoperoxide Synthases KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Dinoprostone KW - K7Q1JQR04M KW - Index Medicus KW - Receptor, Epidermal Growth Factor -- metabolism KW - Dose-Response Relationship, Drug KW - Humans KW - Lipopolysaccharides -- pharmacology KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Bronchi -- cytology KW - Cells, Cultured KW - Dinoprostone -- metabolism KW - Cyclic AMP -- metabolism KW - Trachea -- metabolism KW - Trachea -- drug effects KW - Receptors, Prostaglandin E -- metabolism KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Signal Transduction -- physiology KW - Interleukin-1 -- pharmacology KW - Prostaglandin-Endoperoxide Synthases -- metabolism KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - Epithelium -- metabolism KW - Mucins -- biosynthesis KW - Isoenzymes -- genetics KW - Isoenzymes -- metabolism KW - Epithelium -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66728441?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmacology&rft.atitle=Interleukin-1beta-induced+mucin+production+in+human+airway+epithelium+is+mediated+by+cyclooxygenase-2%2C+prostaglandin+E2+receptors%2C+and+cyclic+AMP-protein+kinase+A+signaling.&rft.au=Gray%2C+Thomas%3BNettesheim%2C+Paul%3BLoftin%2C+Charles%3BKoo%2C+Ja-Seok%3BBonner%2C+James%3BPeddada%2C+Shyamal%3BLangenbach%2C+Robert&rft.aulast=Gray&rft.aufirst=Thomas&rft.date=2004-08-01&rft.volume=66&rft.issue=2&rft.spage=337&rft.isbn=&rft.btitle=&rft.title=Molecular+pharmacology&rft.issn=0026895X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-30 N1 - Date created - 2004-07-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of cysteines and charged amino acids in extracellular loops of the human Ca(2+) receptor in cell surface expression and receptor activation processes. AN - 66727651; 15117879 AB - The Ca(2+) receptor is a plasma-membrane bound G protein-coupled receptor stimulated by extracellular calcium [Ca(2+)](o) and other di- and poly-cations. We investigated the role in receptor activation of all the charged amino acid residues and cysteines in the three extracellular loops (EL1, 2, and 3) of the human Ca(2+) receptor by alanine-scanning mutagenesis. The mutant receptors were transiently expressed in HEK-293 cells, and cell surface expression patterns were analyzed by endoglycosidase-H digestion, immunoblotting, intact cell ELISA, and hydrolysis of phosphoinositides (PI) induced by [Ca(2+)](o.) The mutation of Cys677 and Cys765 located in EL1 and EL2, respectively, ablated PI hydrolysis completely, showed less than 5% cell surface expression of the wild-type receptor, and were not properly glycosylated. Replacement of the charged residues by using a single mutation or multiple alanine mutations in EL1, 2, and 3 produced only minor changes in receptor activation, except for Glu767 and Lys831. The E767A and K831A mutations in EL2 and EL3, respectively, showed gain-of-function by significantly enhancing apparent [Ca(2+)](o) affinity. E767A and K831A exhibited EC(50) values of 2.1 and 2.8 mm, respectively, for [Ca(2+)](o)-stimulated PI hydrolysis as opposed to EC(50) value of 4.2 mm for the wild-type receptor. Like E767A, substitutions of Glu767 with Gln and Lys was similarly activating, whereas Asp substitution displayed wild-type [Ca(2+)](o) sensitivity. Substitution of Lys831 with Glu but not with Gln showed similar activating effect as Ala replacement. A double-mutant E767K/K831E in which charged residues were switched positions showed impaired cell surface expression and failed to respond to [Ca(2+)](o.) Taken together, these results suggest that in ELs, two cysteines form critical disulfide links, and the side chains of Glu767 and Lys831 are probably involved in ionic interactions with other prospective oppositely charged residues. Some of these interactions could be important for receptor folding and also may contribute to keep the Ca(2+) receptor transmembrane helix bundle in an inactive conformation. JF - Endocrinology AU - Ray, Kausik AU - Ghosh, Sanchita P AU - Northup, John K AD - Laboratory of Cellular Biology, National Institute on Deafness and Other Communication Disorders, Rockville, Maryland 20850, USA. rayk@nidcd.nih.gov. Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 3892 EP - 3903 VL - 145 IS - 8 SN - 0013-7227, 0013-7227 KW - Receptors, Calcium-Sensing KW - 0 KW - Cysteine KW - K848JZ4886 KW - Calcium KW - SY7Q814VUP KW - Abridged Index Medicus KW - Index Medicus KW - Calcium -- metabolism KW - Cells, Cultured KW - Humans KW - Protein Folding KW - Signal Transduction KW - Molecular Weight KW - Structure-Activity Relationship KW - Receptors, Calcium-Sensing -- chemistry KW - Receptors, Calcium-Sensing -- physiology KW - Cysteine -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66727651?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+role+of+cysteines+and+charged+amino+acids+in+extracellular+loops+of+the+human+Ca%282%2B%29+receptor+in+cell+surface+expression+and+receptor+activation+processes.&rft.au=Ray%2C+Kausik%3BGhosh%2C+Sanchita+P%3BNorthup%2C+John+K&rft.aulast=Ray&rft.aufirst=Kausik&rft.date=2004-08-01&rft.volume=145&rft.issue=8&rft.spage=3892&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-17 N1 - Date created - 2004-07-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nkx2.1 transcription factor in lung cells and a transforming growth factor-beta1 heterozygous mouse model of lung carcinogenesis. AN - 66720233; 15264213 AB - The Nkx2.1 homeobox gene and transforming growth factor-beta1 (TGF-beta1) are essential for organogenesis and differentiation of the mouse lung. NKX2.1 is a marker of human lung carcinomas, but it is not known whether this gene participates in early tumorigenesis. Addition of TGF-beta1 to TGF-beta1-responsive nontumorigenic mouse lung cells cotransfected with a NKX2.1Luc luciferase reporter and either a Sp1 or Sp3 plasmid showed a significant increase or decrease, respectively, in NKX2.1Luc transcription. Cotransfection of Sp3 and dominant-negative TGF-beta type II receptor plasmids negated the effect of Sp1. Cotransfected Sp1 plasmid with either dominant-negative Smad2 or Smad3 or Smad4 plasmids significantly decreased NKX2.1Luc transcription. Electrophoretic mobility shift assays revealed binding of Sp1 and Smad4 to the NKX2.1 promoter. With a TGF-beta1 heterozygous mouse model, Nkx2.1 mRNA and protein in lungs of TGF-beta1 heterozygous mice were significantly lower compared to wildtype (WT) littermates. Competitive reverse transcription (RT)-polymerase chain reaction (PCR) and immunostaining showed that Nkx2.1 mRNA and protein decreased significantly in adenomas and adenocarcinomas compared to normal lung tissue. Our in vitro data showed that regulation of Nkx2.1 by TGF-beta1 occurs through TGF-beta type II receptor and Smad signaling, with Sp1 and Sp3 in lung cells. Our in vivo data showed reduced Nkx2.1 in lungs of TGF-beta1 heterozygous mice compared to WT mice, that is detectable in adenomas, and that is further reduced in carcinogenesis, and that correlates with reduction of Sp1, Sp3, and Smads in lung adenocarcinomas. Our findings suggest that reduced Nkx2.1 and TGF-beta1 signaling components may contribute to tumorigenesis in the lungs of TGF-beta1 heterozygous mice. JF - Molecular carcinogenesis AU - Kang, Yang AU - Hebron, Haroun AU - Ozbun, Laurent AU - Mariano, Jennifer AU - Minoo, Parviz AU - Jakowlew, Sonia B AD - National Cancer Institute, Cell and Cancer Biology Branch, Rockville, Maryland 20850, USA. Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 212 EP - 231 VL - 40 IS - 4 SN - 0899-1987, 0899-1987 KW - Nuclear Proteins KW - 0 KW - RNA, Messenger KW - Receptors, Transforming Growth Factor beta KW - Transcription Factors KW - Transforming Growth Factor beta KW - thyroid nuclear factor 1 KW - Tritium KW - 10028-17-8 KW - Thymidine KW - VC2W18DGKR KW - Index Medicus KW - Thymidine -- metabolism KW - Receptors, Transforming Growth Factor beta -- genetics KW - Animals KW - Blotting, Northern KW - Tritium -- metabolism KW - RNA, Messenger -- metabolism KW - Gene Expression Regulation, Neoplastic -- physiology KW - Disease Models, Animal KW - Mice KW - Receptors, Transforming Growth Factor beta -- biosynthesis KW - Immunohistochemistry KW - Lung Neoplasms -- etiology KW - Nuclear Proteins -- genetics KW - Transcription Factors -- metabolism KW - Cell Transformation, Neoplastic -- metabolism KW - Lung Neoplasms -- genetics KW - Lung -- metabolism KW - Transforming Growth Factor beta -- genetics KW - Nuclear Proteins -- metabolism KW - Transforming Growth Factor beta -- metabolism KW - Transcription Factors -- genetics KW - Lung Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66720233?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+carcinogenesis&rft.atitle=Nkx2.1+transcription+factor+in+lung+cells+and+a+transforming+growth+factor-beta1+heterozygous+mouse+model+of+lung+carcinogenesis.&rft.au=Kang%2C+Yang%3BHebron%2C+Haroun%3BOzbun%2C+Laurent%3BMariano%2C+Jennifer%3BMinoo%2C+Parviz%3BJakowlew%2C+Sonia+B&rft.aulast=Kang&rft.aufirst=Yang&rft.date=2004-08-01&rft.volume=40&rft.issue=4&rft.spage=212&rft.isbn=&rft.btitle=&rft.title=Molecular+carcinogenesis&rft.issn=08991987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-17 N1 - Date created - 2004-07-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Substrate specificity of Xenopus matrix metalloproteinase stromelysin-3. AN - 66706793; 15254771 AB - The matrix metalloproteinase stromelysin-3 (ST3 or MMP11) was initially identified as a breast carcinoma associated protease and has since been shown to be highly expressed in diverse carcinomas and in developmental processes that involve extensive cell death (apoptosis) and tissue remodeling. Unlike other MMPs, purified ST3 has little activity toward known extracellular matrix (ECM) proteins in vitro but cleaves strongly a few non-ECM, extracellular proteins, including human alpha1-proteinase inhibitor (alpha1-PI). To investigate the possibility of alpha1-PI as a conserved physiological substrate for ST3 during vertebrate development, we analyzed the ability of Xenopus laevis ST3 catalytic domain to cleave frog alpha1-PI. Surprisingly, we found the ST3 failed to recognize the site in alpha1-PI equivalent to the major cleavage site in human alpha1-PI by mammalian ST3. Sequence and mutagenic analysis revealed that multiple substitutions at P2-P3' positions between human and Xenopus alpha1-PI contributed to the inability of Xenopus alpha1-PI to be cleaved by ST3. Our studies showed that (A)(G/A)(A)(M)(F/A)(L) (P3-P3') as a preferred cleavage site for ST3. We further demonstrated that mutations in the cleavage sites affected cleavage by ST3 differently from several other MMPs. These findings, together with earlier reports on ST3, showed that ST3 has distinct substrate specificities compared to other MMPs. Our results further suggest that alpha1-PI is unlikely to be a physiological substrate for ST3, at least with regard to evolutionarily conserved developmental processes. JF - International journal of molecular medicine AU - Amano, Tosikazu AU - Fu, Liezhen AU - Sahu, Shelley AU - Markey, Meghan AU - Shi, Yun-Bo AD - Section on Molecular Morphogenesis, Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 233 EP - 239 VL - 14 IS - 2 SN - 1107-3756, 1107-3756 KW - alpha 1-Antitrypsin KW - 0 KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Matrix Metalloproteinase 11 KW - EC 3.4.24.- KW - Metalloendopeptidases KW - Index Medicus KW - Animals KW - alpha 1-Antitrypsin -- chemistry KW - Extracellular Matrix -- metabolism KW - alpha 1-Antitrypsin -- metabolism KW - DNA Mutational Analysis KW - Humans KW - Catalytic Domain KW - Protein Binding KW - Evolution, Molecular KW - Binding Sites KW - Mutagenesis KW - Mutagenesis, Site-Directed KW - Xenopus KW - Substrate Specificity KW - Protein Structure, Tertiary KW - Green Fluorescent Proteins -- metabolism KW - Metalloendopeptidases -- metabolism KW - Metalloendopeptidases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66706793?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+molecular+medicine&rft.atitle=Substrate+specificity+of+Xenopus+matrix+metalloproteinase+stromelysin-3.&rft.au=Amano%2C+Tosikazu%3BFu%2C+Liezhen%3BSahu%2C+Shelley%3BMarkey%2C+Meghan%3BShi%2C+Yun-Bo&rft.aulast=Amano&rft.aufirst=Tosikazu&rft.date=2004-08-01&rft.volume=14&rft.issue=2&rft.spage=233&rft.isbn=&rft.btitle=&rft.title=International+journal+of+molecular+medicine&rft.issn=11073756&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-04 N1 - Date created - 2004-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional reconstitution of gamma-secretase through coordinated expression of presenilin, nicastrin, Aph-1, and Pen-2. AN - 66697934; 15248287 AB - The gamma-secretase complex has emerged as an unusual membrane-bound aspartyl protease with the ability to cleave certain substrate proteins at peptide bonds believed to be buried within the hydrophobic environment of the lipid bilayer. This cleavage is responsible for a key biochemical step in signaling from several different cell-surface receptors, and it is also crucial in generating the neurotoxic amyloid peptides that are central to the pathogenesis of Alzheimer's disease. Active gamma-secretase is a multimeric protein complex consisting of at least four different proteins, presenilin, nicastrin, Aph-1, and Pen-2, with presenilin serving as the catalytically active core of the aspartyl protease. Presenilin itself undergoes endoproteolytic maturation, a process that is tightly regulated during the assembly and maturation of gamma-secretase, and that depends on the three cofactors nicastrin, Aph-1, and Pen-2. Recent studies have demonstrated that presenilin and its three cofactors are likely to be the major proteins needed for functional reconstitution of active gamma-secretase and have begun to elucidate the specific functions of the cofactors in the ordered assembly of gamma-secretase. Published 2004 Wiley-Liss, Inc. JF - Journal of neuroscience research AU - Periz, Goran AU - Fortini, Mark E AD - Laboratory of Protein Dynamics and Signaling, National Cancer Institute, Frederick, Maryland 21701, USA. Y1 - 2004/08/01/ PY - 2004 DA - 2004 Aug 01 SP - 309 EP - 322 VL - 77 IS - 3 SN - 0360-4012, 0360-4012 KW - Macromolecular Substances KW - 0 KW - Membrane Glycoproteins KW - Membrane Proteins KW - PSEN1 protein, human KW - PSENEN protein, human KW - Presenilin-1 KW - nicastrin protein KW - APH1A protein, human KW - EC 3.4.- KW - Amyloid Precursor Protein Secretases KW - Endopeptidases KW - Peptide Hydrolases KW - Aspartic Acid Endopeptidases KW - EC 3.4.23.- KW - BACE1 protein, human KW - EC 3.4.23.46 KW - Index Medicus KW - Animals KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Membrane Glycoproteins -- biosynthesis KW - Membrane Glycoproteins -- physiology KW - Membrane Proteins -- biosynthesis KW - Endopeptidases -- metabolism KW - Endopeptidases -- physiology KW - Membrane Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66697934?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Functional+reconstitution+of+gamma-secretase+through+coordinated+expression+of+presenilin%2C+nicastrin%2C+Aph-1%2C+and+Pen-2.&rft.au=Periz%2C+Goran%3BFortini%2C+Mark+E&rft.aulast=Periz&rft.aufirst=Goran&rft.date=2004-08-01&rft.volume=77&rft.issue=3&rft.spage=309&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 - 2004-09-09 N1 - Date created - 2004-07-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chronic alcohol consumption accelerates liver injury in T cell-mediated hepatitis: alcohol disregulation of NF-kappaB and STAT3 signaling pathways. AN - 66691603; 15064234 AB - Alcohol consumption is a major risk factor accelerating the progression of liver disease in patients with chronic hepatitis virus infection. However, the mechanism underlying the enhanced susceptibility of alcoholics to liver injury is not fully understood. Here, we demonstrate that chronic ethanol consumption increases the susceptibility of C57BL/6 mice to concanavalin A (Con A)-induced T cell-mediated hepatitis. Injection of a low dose of Con A (5 microg/g) causes severe liver damage in ethanol-fed mice as evidenced by a significant elevation of serum alanine aminotransaminase levels, massive necrosis, and infiltration of leukocytes but only slightly induces liver injury in control pair-fed mice. In ethanol-fed mice, the activation and cytotoxicity of natural killer T cells, cells that play key roles in Con A-induced T cell hepatitis, are not significantly enhanced relative to pair-fed mice. Moreover, Con A-induced activation of hepatic NF-kappaB is increased, whereas activation of STAT1 and STAT3 is attenuated in ethanol-fed mice. Consistent with this result, the expression of chemokines and adhesion molecules [such as ICAM-1, macrophage inflammatory protein (MIP)-1, MIP-2, and MCP-1] controlled by NF-kappaB is upregulated, whereas STAT1-controlled expression of chemokines (such as MIG and IP-10) is downregulated in ethanol-fed mice compared with pair-fed mice. In conclusion, chronic alcohol consumption accelerates T cell-mediated hepatitis via upregulation of the NF-kappaB signaling pathway and subsequently enhances expression of chemokines/adhesive molecules and recruitment of leukocytes into the liver. Downregulation of the antiapoptotic STAT3 signal may also contribute to alcohol potentiation of T cell hepatitis. JF - American journal of physiology. Gastrointestinal and liver physiology AU - Jaruga, Barbara AU - Hong, Feng AU - Kim, Won-Ho AU - Sun, Rui AU - Fan, Saijun AU - Gao, Bin AD - Section on Liver Biology, NIAAA/NIH, Park Bldg. Rm. 120, 12420 Parklawn Dr., MSC 8115, Bethesda, MD 20892, USA. Y1 - 2004/08// PY - 2004 DA - August 2004 SP - G471 EP - G479 VL - 287 IS - 2 SN - 0193-1857, 0193-1857 KW - Cell Adhesion Molecules KW - 0 KW - Chemokines KW - DNA-Binding Proteins KW - NF-kappa B KW - STAT3 Transcription Factor KW - Stat3 protein, mouse KW - Trans-Activators KW - Concanavalin A KW - 11028-71-0 KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Animals KW - Chemokines -- metabolism KW - Concanavalin A -- adverse effects KW - Hepatocytes KW - Leukocytes -- pathology KW - Mice, Inbred C57BL KW - Cell Adhesion Molecules -- metabolism KW - Mice KW - Monocytes KW - Time Factors KW - Male KW - Killer Cells, Natural -- drug effects KW - T-Lymphocytes KW - Trans-Activators -- metabolism KW - Liver -- physiopathology KW - Liver -- pathology KW - Chemical and Drug Induced Liver Injury -- pathology KW - Ethanol -- pharmacology KW - Signal Transduction -- drug effects KW - Alcohol Drinking KW - NF-kappa B -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66691603?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+physiology.+Gastrointestinal+and+liver+physiology&rft.atitle=Chronic+alcohol+consumption+accelerates+liver+injury+in+T+cell-mediated+hepatitis%3A+alcohol+disregulation+of+NF-kappaB+and+STAT3+signaling+pathways.&rft.au=Jaruga%2C+Barbara%3BHong%2C+Feng%3BKim%2C+Won-Ho%3BSun%2C+Rui%3BFan%2C+Saijun%3BGao%2C+Bin&rft.aulast=Jaruga&rft.aufirst=Barbara&rft.date=2004-08-01&rft.volume=287&rft.issue=2&rft.spage=G471&rft.isbn=&rft.btitle=&rft.title=American+journal+of+physiology.+Gastrointestinal+and+liver+physiology&rft.issn=01931857&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-30 N1 - Date created - 2004-07-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A population-based study of vaginal human papillomavirus infection in hysterectomized women. AN - 66687159; 15243917 AB - We compared point prevalences and determinants of human papillomavirus (HPV) DNA detection by testing enrollment vaginal specimens from hysterectomized women (n=569) and enrollment cervical specimens from nonhysterectomized women (n=6098) >or=30 years old, using MY09/MY11 L1 consensus-primer polymerase chain reaction. The subjects were participating in a population-based cohort study (n=10,049) in Guanacaste, Costa Rica, that was initiated in 1993. Non-cancer-associated HPV types, especially types 61, 71, and 72, were detected more frequently in the vaginal specimens from hysterectomized women (23.7% [95% confidence interval [CI], 20.3%-27.4%]) than in the cervical specimens from nonhysterectomized women (16.7% [95% CI, 15.7%-17.6%]) (P=.0001). There was no difference between the prevalences of cancer-associated HPV types in hysterectomized women and those in nonhysterectomized women; in both groups, the prevalence of HPV DNA was greater in women with multiple lifetime sex partners. We infer from our data that the cervical transformation zone may not be needed for cancer-associated HPV infection but may be uniquely susceptible to HPV-induced carcinogenesis; we also infer that specific phylogenetic groups of HPV (i.e., A3/A4/A15) may have a predilection for vaginal epithelium. JF - The Journal of infectious diseases AU - Castle, Philip E AU - Schiffman, Mark AU - Bratti, M Concepcion AU - Hildesheim, Allan AU - Herrero, Rolando AU - Hutchinson, Martha L AU - Rodriguez, Ana Cecilia AU - Wacholder, Sholom AU - Sherman, Mark E AU - Kendall, Hortense AU - Viscidi, Raphael P AU - Jeronimo, Jose AU - Schussler, John E AU - Burk, Robert D AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892-7234, USA. castlep@mail.nih.gov Y1 - 2004/08/01/ PY - 2004 DA - 2004 Aug 01 SP - 458 EP - 467 VL - 190 IS - 3 SN - 0022-1899, 0022-1899 KW - Antibodies, Viral KW - 0 KW - DNA, Viral KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Aged KW - Antibodies, Viral -- blood KW - Polymerase Chain Reaction KW - Uterine Cervical Neoplasms -- epidemiology KW - Aged, 80 and over KW - DNA, Viral -- analysis KW - Adult KW - Cohort Studies KW - Vagina -- virology KW - Cervix Uteri -- virology KW - Middle Aged KW - Female KW - Uterine Cervical Neoplasms -- virology KW - Prevalence KW - Vaginal Diseases -- virology KW - Papillomavirus Infections -- epidemiology KW - Vaginal Diseases -- epidemiology KW - Papillomaviridae -- classification KW - Hysterectomy KW - Papillomaviridae -- isolation & purification KW - Papillomavirus Infections -- virology KW - Papillomaviridae -- genetics KW - Papillomaviridae -- immunology KW - Population Surveillance UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66687159?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+infectious+diseases&rft.atitle=A+population-based+study+of+vaginal+human+papillomavirus+infection+in+hysterectomized+women.&rft.au=Castle%2C+Philip+E%3BSchiffman%2C+Mark%3BBratti%2C+M+Concepcion%3BHildesheim%2C+Allan%3BHerrero%2C+Rolando%3BHutchinson%2C+Martha+L%3BRodriguez%2C+Ana+Cecilia%3BWacholder%2C+Sholom%3BSherman%2C+Mark+E%3BKendall%2C+Hortense%3BViscidi%2C+Raphael+P%3BJeronimo%2C+Jose%3BSchussler%2C+John+E%3BBurk%2C+Robert+D&rft.aulast=Castle&rft.aufirst=Philip&rft.date=2004-08-01&rft.volume=190&rft.issue=3&rft.spage=458&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 - 2004-08-24 N1 - Date created - 2004-07-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulated expression of pathogen-associated molecular pattern molecules in Staphylococcus epidermidis: quorum-sensing determines pro-inflammatory capacity and production of phenol-soluble modulins. AN - 66679322; 15236642 AB - Phenol-soluble modulin (PSM) is a peptide complex produced by the nosocomial pathogen Staphylococcus epidermidis that has a strong capacity to activate the human innate immune response. We developed a novel method based on liquid chromatography-mass spectrometry (LC-MS) to quantify the production of the individual PSM components. Each PSM peptide was abundant in most of the 76 S epidermidis strains tested. Importantly, none of the PSM components were secreted by an agr mutant strain, indicating that PSM synthesis is regulated strictly by the agr quorum-sensing system. Furthermore, the agr mutant strain failed to elicit production of TNFalpha by human myeloid cells and induced significantly less neutrophil chemotaxis compared with the wild-type strain. Thus, quorum-sensing in S. epidermidis dramatically influenced activation of human host defence. We propose that an agr quorum-sensing mechanism facilitates growth and survival in infected hosts by adapting production of the pro-inflammatory PSMs to the stage of infection. JF - Cellular microbiology AU - Vuong, Cuong AU - Dürr, Manuela AU - Carmody, Aaron B AU - Peschel, Andreas AU - Klebanoff, Seymour J AU - Otto, Michael AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, 903 S 4th Street, Hamilton, MT 59840, USA. Y1 - 2004/08// PY - 2004 DA - August 2004 SP - 753 EP - 759 VL - 6 IS - 8 SN - 1462-5814, 1462-5814 KW - Bacterial Toxins KW - 0 KW - staphylococcal delta toxin KW - Index Medicus KW - Virulence KW - Mass Spectrometry KW - Humans KW - Inflammation -- etiology KW - Chromatography, Liquid KW - Mutation KW - Inflammation -- pathology KW - Bacterial Toxins -- metabolism KW - Bacterial Toxins -- analysis KW - Staphylococcus epidermidis -- metabolism KW - Staphylococcus epidermidis -- physiology KW - Staphylococcus epidermidis -- pathogenicity KW - Bacterial Toxins -- toxicity KW - Staphylococcal Infections -- microbiology KW - Staphylococcal Infections -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66679322?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+microbiology&rft.atitle=Regulated+expression+of+pathogen-associated+molecular+pattern+molecules+in+Staphylococcus+epidermidis%3A+quorum-sensing+determines+pro-inflammatory+capacity+and+production+of+phenol-soluble+modulins.&rft.au=Vuong%2C+Cuong%3BD%C3%BCrr%2C+Manuela%3BCarmody%2C+Aaron+B%3BPeschel%2C+Andreas%3BKlebanoff%2C+Seymour+J%3BOtto%2C+Michael&rft.aulast=Vuong&rft.aufirst=Cuong&rft.date=2004-08-01&rft.volume=6&rft.issue=8&rft.spage=753&rft.isbn=&rft.btitle=&rft.title=Cellular+microbiology&rft.issn=14625814&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-10-05 N1 - Date created - 2004-07-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fmoc-based chemical synthesis and selective binding to supercoiled DNA of the p53 C-terminal segment and its phosphorylated and acetylated derivatives AN - 21157353; 11338236 AB - The C-terminal domain of p53 comprises a linker, the tetramerization domain and the regulatory domain, and contains at least seven sites of potential post-translational modification. An improved strategy was developed for the synthesis of large peptides that contain phosphorylated amino acids and p53(303-393), a 91-amino acid peptide, and three post-translationally modified derivatives were synthesized through the sequential condensation of three partially protected segments. Peptide thiolesters were prepared using the sulfonamide-based safety-catch resin approach and employing Fmoc-based solid-phase peptide synthesis. At the N-terminus of the middle building block, a photolabile protecting group, 3,4-dimethoxy-6-nitrobenzyloxycarbonyl, was incorporated to differentiate the N-terminal amino group from the side-chain amino groups. Two sequential couplings were accomplished following this protection strategy. The synthetic products, p53(303-393) and its phosphorylated or acetylated derivatives, exhibited the ability to bind specifically to supercoiled DNA, which is one of the characteristics of this domain. Published in 2004 by the European Peptide Society and John Wiley & Sons, Ltd. JF - Journal of Peptide Science AU - Teruya, Kenta AU - Murphy, Angela C AU - Burlin, Tom AU - Appella, Ettore AU - Mazur, Sharlyn J AD - National Cancer Institute, NIH, 37 Convent Drive, Bethesda, MD 20892, USA, mazurs@mail.nih.gov Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 479 EP - 493 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 USA VL - 10 IS - 8 SN - 1075-2617, 1075-2617 KW - Biochemistry Abstracts 2: Nucleic Acids; Biotechnology and Bioengineering Abstracts KW - Amino groups KW - Resins KW - Amino acids KW - Post-translation KW - DNA KW - Condensation KW - thiolesters KW - Peptide synthesis KW - Protecting groups KW - p53 protein KW - N-Terminus KW - W 30940:Products KW - N 14835:Protein-Nucleic Acids Association UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21157353?accountid=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+Peptide+Science&rft.atitle=Fmoc-based+chemical+synthesis+and+selective+binding+to+supercoiled+DNA+of+the+p53+C-terminal+segment+and+its+phosphorylated+and+acetylated+derivatives&rft.au=Teruya%2C+Kenta%3BMurphy%2C+Angela+C%3BBurlin%2C+Tom%3BAppella%2C+Ettore%3BMazur%2C+Sharlyn+J&rft.aulast=Teruya&rft.aufirst=Kenta&rft.date=2004-08-01&rft.volume=10&rft.issue=8&rft.spage=479&rft.isbn=&rft.btitle=&rft.title=Journal+of+Peptide+Science&rft.issn=10752617&rft_id=info:doi/10.1002%2Fpsc.552 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-01-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Resins; Amino groups; Amino acids; Post-translation; DNA; thiolesters; Condensation; Peptide synthesis; Protecting groups; N-Terminus; p53 protein DO - http://dx.doi.org/10.1002/psc.552 ER - TY - JOUR T1 - Pharmacogenetics of tipifarnib (R115777) transport and metabolism in cancer patients AN - 20859737; 6650339 AB - The purpose of this study was to perform exploratory relationships between the pharmacokinetics of the farnesyl transferase inhibitor, tipifarnib (R115777, Zarnestra) and allelic variants of genes coding for ATP binding-cassette transporters and drug-metabolizing enzymes. Twenty-eight patients with advanced solid tumors were treated with tipifarnib administered orally at a dose of 200 or 300 mg. Blood samples were collected for pharmacokinetics and genotyping of 10 variants in genes encoding P-glycoprotein (ABCB1), cytochrome P450 isozymes CYP3A4 and CYP3A5, and UDP glucuronosyltransferase isozyme UGT1A1. The homozygous T-allele of ABCB1*8 (1236C > T) was associated with a trend for a higher area under the curve of tipifarnib as compared to patients with only one or no variant alleles [mean ( plus or minus SD), 5,303 plus or minus 1,620 ng.h/mL vs. 3,619 plus or minus 1,275 ng.h/mL; P = 0.047). No statistically significant differences were observed with any other genetic variant (P > 0.15). Overall, this study indicates that ABCB1 genotype might be correlated with tipifarnib pharmacokinetics, although considerable overlap in exposure measures between genotype groups was observed. JF - Investigational New Drugs AU - Sparreboom, Alex AU - Marsh, Sharon AU - Mathijssen, Ron HJ AU - Verweij, Jaap AU - McLeod, Howard L AD - National Cancer Institute, Bethesda, MD, USA Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 285 EP - 289 PB - Springer-Verlag (Heidelberg), Tiergartenstrasse 17 Heidelberg 69121 Germany, [mailto:subscriptions@springer.de], [URL:http://www.springer.de/] VL - 22 IS - 3 SN - 0167-6997, 0167-6997 KW - Genetics Abstracts; Biotechnology and Bioengineering Abstracts KW - Glucuronosyltransferase KW - Solid tumors KW - Genotyping KW - Statistical analysis KW - Enzymes KW - ATP KW - Genotypes KW - Pharmacogenetics KW - Pharmacokinetics KW - P-Glycoprotein KW - Isoenzymes KW - Cytochrome P450 KW - Metabolism KW - G 07880:Human Genetics KW - W 30920:Tissue Engineering UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20859737?accountid=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=Investigational+New+Drugs&rft.atitle=Pharmacogenetics+of+tipifarnib+%28R115777%29+transport+and+metabolism+in+cancer+patients&rft.au=Sparreboom%2C+Alex%3BMarsh%2C+Sharon%3BMathijssen%2C+Ron+HJ%3BVerweij%2C+Jaap%3BMcLeod%2C+Howard+L&rft.aulast=Sparreboom&rft.aufirst=Alex&rft.date=2004-08-01&rft.volume=22&rft.issue=3&rft.spage=285&rft.isbn=&rft.btitle=&rft.title=Investigational+New+Drugs&rft.issn=01676997&rft_id=info:doi/10.1023%2FB%3ADRUG.0000026254.97350.fe LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-09-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Glucuronosyltransferase; Solid tumors; Genotyping; Statistical analysis; ATP; Enzymes; Genotypes; Pharmacokinetics; Pharmacogenetics; P-Glycoprotein; Isoenzymes; Cytochrome P450; Metabolism DO - http://dx.doi.org/10.1023/B:DRUG.0000026254.97350.fe ER - TY - JOUR T1 - Bioeconomics of Managing the Spread of Exotic Pest Species with Barrier Zones AN - 20133638; 6120793 AB - Exotic pests are serious threats to North American ecosystems; thus, economic analysis of decisions about eradication, stopping, or slowing their spread may be critical to ecosystem management. The proposed bioeconomic model assumes that the rate of population expansion can be reduced (even to negative values in a case of eradication) if certain management actions are taken along the population front. The area of management can be viewed as a dynamic barrier zone that moves together with the population front. The lower is the target rate of spread, the higher would be both benefits and costs of the project. The problem is to find the optimal target rate of spread at which the present value of net benefits from managing population spread reaches its maximum value. If a population spreads along an infinite habitat strip, the target rate of spread is optimal if the slope of the cost function versus the rate of spread is equal to the ratio of the average pest-related damage per unit time and unit area to the discount rate. In a more complex model where the potential area of expansion is limited, two local maxima of net benefits may exist: one for eradication and another for slowing the spread. If both maxima are present, their heights are compared and the strategy that corresponds to a higher value of net benefits is selected. The optimal strategy changes from eradication to slowing the spread and finally to doing nothing as the area occupied by the species increases. The model shows that slowing the spread of pest species generates economic benefits even if a relatively small area remains uninfested. The cost of slowing the spread can be estimated from a model of population expansion via establishment of isolated colonies beyond the moving front. The model is applied to managing the spread of the gypsy moth (Lymantria dispar) populations in the United States. JF - Risk Analysis AU - Sharov, A A AD - National Institute on Aging, Baltimore, MD, USA, Sharoval@grc.nia.nih.gov Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 879 EP - 892 VL - 24 IS - 4 SN - 0272-4332, 0272-4332 KW - Gypsy Moth KW - Entomology Abstracts; Sustainability Science Abstracts; ASFA 1: Biological Sciences & Living Resources KW - North America KW - population levels KW - Barriers KW - Ecosystems KW - Habitat preferences KW - Pest control KW - Habitat KW - Nearctic Region KW - Models KW - USA KW - Lymantriidae KW - pests KW - Infestation KW - Colonies KW - Economics KW - Ecosystem management KW - Economic analysis KW - Introduced species KW - Economic benefits KW - Lymantria dispar KW - economic analysis KW - M3 1010:Issues in Sustainable Development KW - Z 05350:Medical, Veterinary, and Agricultural Entomology KW - Q1 08485:Species interactions: pests and control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20133638?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Assamodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Risk+Analysis&rft.atitle=Bioeconomics+of+Managing+the+Spread+of+Exotic+Pest+Species+with+Barrier+Zones&rft.au=Sharov%2C+A+A&rft.aulast=Sharov&rft.aufirst=A&rft.date=2004-08-01&rft.volume=24&rft.issue=4&rft.spage=879&rft.isbn=&rft.btitle=&rft.title=Risk+Analysis&rft.issn=02724332&rft_id=info:doi/10.1111%2Fj.0272-4332.2004.00486.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-12-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Barriers; Economic analysis; Ecosystem management; Introduced species; Economic benefits; Colonies; Infestation; Economics; Habitat preferences; Pest control; Models; pests; population levels; Ecosystems; Habitat; economic analysis; Lymantriidae; Lymantria dispar; North America; USA; Nearctic Region DO - http://dx.doi.org/10.1111/j.0272-4332.2004.00486.x ER - TY - JOUR T1 - Global Gene Expression Profile of Nasopharyngeal Carcinoma by Laser Capture Microdissection and Complementary DNA Microarrays AN - 19937671; 5969439 AB - A number of genetic and epigenetic changes underlying the development of nasopharyngeal carcinomas have recently been identified. However, there is still limited information on the nature of the genes and gene products whose aberrant expression and activity promote the malignant conversion of nasopharyngeal epithelium. Here, we have performed a genome-wide transcriptome analysis by probing cDNA microarrays with fluorescent-labeled amplified RNA derived from laser capture microdissected cells procured from normal nasopharyngeal epithelium and areas of metaplasia-dysplasia and carcinoma from EBV-associated nasopharyngeal carcinomas. This approach enabled the identification of genes differentially expressed in each cell population, as well as numerous genes whose expression can help explain the aggressive clinical nature of this tumor type. For example, genes indicating cell cycle aberrations (cyclin D2, cyclin B1, activator of S-phase kinase, and the cell cycle checkpoint kinase, CHK1) and invasive-metastatic potential (matrix metalloproteinase 11, v-Ral, and integrin beta sub(4)) were highly expressed in tumor cells. In contrast, genes underexpressed in tumors included genes involved in apoptosis (B-cell CLL/lymphoma 6, secretory leukocyte protease inhibitor, and calpastatin), cell structure (keratin 7 and carcinoembryonic antigen-related cell adhesion molecule 6), and putative tumor suppressor genes (H-Ras-like suppressor 3, retinoic acid receptor responder 1, and growth arrested specific 8) among others. Gene expression patterns also suggested alterations in the Wnt/ beta -catenin and transforming growth factor beta pathways in nasopharyngeal carcinoma. Thus, expression profiles indicate that aberrant expression of growth, survival, and invasion-promoting genes may contribute to the molecular pathogenesis of nasopharyngeal carcinoma. Ultimately, this approach may facilitate the identification of clinical useful markers of disease progression and novel potential therapeutic targets for nasopharyngeal carcinoma. JF - Clinical Cancer Research AU - Sriuranpong, Virote AU - Mutirangura, Apiwat AU - Gillespie, John W AU - Patel, Vyomesh AU - Amornphimoltham, Panomwat AU - Molinolo, Alfredo A AU - Kerekhanjanarong, Veerachai AU - Supanakorn, Siripornchai AU - Supiyaphun, Pakpoom AU - Rangdaeng, Samreung AU - Voravud, Narin AU - Gutkind, JSilvio AD - Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, and Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, Maryland Y1 - 2004/08/01/ PY - 2004 DA - 2004 Aug 01 SP - 4944 EP - 4958 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 USA, [URL:http://www.aacr.org/] VL - 10 IS - 15 SN - 1078-0432, 1078-0432 KW - Genetics Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Biotechnology and Bioengineering Abstracts KW - Tumor suppressor genes KW - Apoptosis KW - Wnt protein KW - Cell cycle KW - Survival KW - Matrix metalloproteinase KW - DNA microarrays KW - Tumor cells KW - Gene expression KW - epigenetics KW - Cyclin B1 KW - Cytology KW - Epithelium KW - cyclin D2 KW - Lymphoma KW - Retinoic acid receptors KW - Lymphocytes B KW - Proteinase inhibitors KW - Leukocytes KW - Tumors KW - catenin KW - Keratin KW - Nasopharyngeal carcinoma KW - RNA KW - Transforming growth factor- beta KW - Lasers KW - CHK1 protein KW - Chronic lymphatic leukemia KW - Calpastatin KW - Cell adhesion molecules KW - W 30915:Pharmaceuticals & Vaccines KW - G 07730:Development & Cell Cycle KW - N 14825:Gene Regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19937671?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Cancer+Research&rft.atitle=Global+Gene+Expression+Profile+of+Nasopharyngeal+Carcinoma+by+Laser+Capture+Microdissection+and+Complementary+DNA+Microarrays&rft.au=Sriuranpong%2C+Virote%3BMutirangura%2C+Apiwat%3BGillespie%2C+John+W%3BPatel%2C+Vyomesh%3BAmornphimoltham%2C+Panomwat%3BMolinolo%2C+Alfredo+A%3BKerekhanjanarong%2C+Veerachai%3BSupanakorn%2C+Siripornchai%3BSupiyaphun%2C+Pakpoom%3BRangdaeng%2C+Samreung%3BVoravud%2C+Narin%3BGutkind%2C+JSilvio&rft.aulast=Sriuranpong&rft.aufirst=Virote&rft.date=2004-08-01&rft.volume=10&rft.issue=15&rft.spage=4944&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&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 - Tumor suppressor genes; Wnt protein; Apoptosis; Cell cycle; Matrix metalloproteinase; Survival; Tumor cells; DNA microarrays; Gene expression; Cyclin B1; epigenetics; Cytology; Epithelium; cyclin D2; Lymphoma; Retinoic acid receptors; Lymphocytes B; Leukocytes; Proteinase inhibitors; Tumors; Nasopharyngeal carcinoma; Keratin; catenin; RNA; Transforming growth factor- beta; CHK1 protein; Lasers; Calpastatin; Chronic lymphatic leukemia; Cell adhesion molecules ER - TY - JOUR T1 - Prevalence of multiple chronic disease risk factors 2001 National Health Interview Survey AN - 19637312; 8790683 AB - Background: Four common factors-cigarette smoking, risky drinking of alcoholic beverages, physical inactivity, and overweight-contribute substantially to chronic disease prevalence. Methods We used data from the 2001 National Health Interview Survey to provide an up-to-date picture of multiple risk factor prevalence and clustering in the U.S. population. We conducted a multinomial logit analysis to examine the independent association between each covariate and the dependent ordinal risk factor variable with three levels (none or one risk factor, two risk factors, and three or four risk factors). Results Seventeen percent of the sample of 29,183 subjects had three or more risk factors. For the entire sample, the mean number of risk factors was 1.68 (95% confidence interval [CI]=1.66-1.70). Many demographic and health factors were significantly associated with the mean number of risk factors including gender, age, ethnic/racial categories, education, martial status, presence of chronic diseases, level of mental distress, country of birth, and presence and type of health insurance. Using the risk factor score as the ordinal dependent variable, adjusted odds for having a risk score of three or four versus zero or one were as follows: men aged <65, 2.49 (95% CI=2.29-2.72); education attainment of high school graduate or less, 3.24 (95% CI=2.86-3.67); and individuals with high levels of mental distress, 2.06 (95% CI=1.65-2.58). Conclusions Our analyses confirm earlier reports of the high prevalence of multiple, clustered behavioral risk factors and underline the challenge this presents for primary care and public health systems. JF - American Journal of Preventive Medicine AU - Fine, Lawrence J AU - Philogene, G Stephane AU - Gramling, Robert AU - Coups, Elliot J AU - Sinha, Sarbajit AD - Office of Behavioral and Social Sciences Research, Office of the Director, National Institutes of Health, Bethesda, Maryland, USA, FineL@od.nih.gov Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 18 EP - 24 PB - Elsevier Science, The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl] VL - 27 IS - 2 SN - 0749-3797, 0749-3797 KW - Risk Abstracts KW - demography KW - Age KW - Insurance KW - Public health KW - Smoking KW - Education KW - USA KW - Gender KW - physical activity KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19637312?accountid=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+Preventive+Medicine&rft.atitle=Prevalence+of+multiple+chronic+disease+risk+factors+2001+National+Health+Interview+Survey&rft.au=Fine%2C+Lawrence+J%3BPhilogene%2C+G+Stephane%3BGramling%2C+Robert%3BCoups%2C+Elliot+J%3BSinha%2C+Sarbajit&rft.aulast=Fine&rft.aufirst=Lawrence&rft.date=2004-08-01&rft.volume=27&rft.issue=2&rft.spage=18&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Preventive+Medicine&rft.issn=07493797&rft_id=info:doi/10.1016%2Fj.amepre.2004.04.017 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-02-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - USA; Education; Insurance; Gender; physical activity; Public health; Smoking; demography; Age DO - http://dx.doi.org/10.1016/j.amepre.2004.04.017 ER - TY - JOUR T1 - Patterns of Pesticide Use and Their Determinants Among Wives of Farmer Pesticide Applicators in the Agricultural Health Study AN - 18060808; 6019973 AB - Pesticide exposure among farmers' wives is poorly characterized. Using questionnaire data from a cohort study of licensed pesticide applicators and their spouses, we investigated patterns of pesticide use among farmers' wives (n = 31,173). Wives reported a wide range of pesticide use: 36% never used pesticides during their lifetimes, whereas the heaviest pesticide users (10%) reported lifetime use of 3 or more agricultural pesticides plus commonly used residential pesticides. We identified 5 ordinal pesticide-use categories and studied factors associated with each category through polytomous logistic regression. Engaging in field work and household hygiene practices that could increase exposure were associated with pesticide use, and associations appeared to strengthen with increasing pesticide use category. Farm women reporting the heaviest pesticide use could exacerbate their exposure by engaging in practices that could increase pesticide contact. JF - Journal of Occupational and Environmental Medicine AU - Kirrane, E F AU - Hoppin, JA AU - Umbach, D M AU - Samanic, C AU - Sandler, D P AD - Epidemiology Branch, NIH, MD A3 05, Box 12233, Research Triangle Park, NC 27709, USA, hoppin1@niehs.nih.gov Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 856 EP - 865 VL - 46 IS - 8 SN - 1076-2752, 1076-2752 KW - Toxicology Abstracts; Health & Safety Science Abstracts KW - Farms KW - Agrochemicals KW - Exposure KW - Pesticides KW - Residential areas KW - Hygiene KW - Occupational exposure KW - H 5000:Pesticides KW - X 24222:Analytical procedures KW - X 24136:Environmental impact UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18060808?accountid=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+Occupational+and+Environmental+Medicine&rft.atitle=Patterns+of+Pesticide+Use+and+Their+Determinants+Among+Wives+of+Farmer+Pesticide+Applicators+in+the+Agricultural+Health+Study&rft.au=Kirrane%2C+E+F%3BHoppin%2C+JA%3BUmbach%2C+D+M%3BSamanic%2C+C%3BSandler%2C+D+P&rft.aulast=Kirrane&rft.aufirst=E&rft.date=2004-08-01&rft.volume=46&rft.issue=8&rft.spage=856&rft.isbn=&rft.btitle=&rft.title=Journal+of+Occupational+and+Environmental+Medicine&rft.issn=10762752&rft_id=info:doi/10.1097%2F01.jom.0000135521.15169.3e LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Occupational exposure; Residential areas; Pesticides; Agrochemicals; Hygiene; Exposure; Farms DO - http://dx.doi.org/10.1097/01.jom.0000135521.15169.3e ER - TY - JOUR T1 - Animal models for arsenic carcinogenesis: inorganic arsenic is a transplacental carcinogen in mice AN - 18054701; 6045937 AB - Inorganic arsenic is a known human carcinogen causing tumors of the skin, urinary bladder, lung, liver, kidney, and possibly other organs. However, the animal models for inorganic arsenic carcinogenesis have been limited and development has been problematic. Gestation is often a period of high sensitivity to carcinogenesis so we investigated inorganic arsenite as a transplacental carcinogen in mice. Pregnant C3H mice were exposed to sodium arsenite (0, 42.5, and 85 ppm as arsenic) in the drinking water for a brief period during gestation (from gestation day 8 to 18), with no further arsenic exposure or other treatments. The offsprings were monitored up to 90 weeks. Transplacental inorganic arsenic exposure produced a dose-dependent induction of tumors in the liver, adrenal, lung, and ovary in the offsprings after they had reached adulthood. This included hepatocellular carcinoma (HCC), a tumor associated with arsenic exposure in humans. These tumors occurred when mice became adults in the absence of any other treatments and well after arsenic exposure had ended. Genomic analysis of liver tumors and tumor-surrounding tissues revealed several patterns of aberrant gene expression associated with transplacental arsenic carcinogenesis. This animal model demonstrated that inorganic arsenic could act as a 'complete' transplacental carcinogen in mice. In addition, other important animal models for inorganic arsenic as a skin tumor co-promoter or as a co-carcinogen are discussed. The development of these animal models should advance our understanding of the mechanisms of inorganic arsenic carcinogenesis. JF - Toxicology and Applied Pharmacology AU - Waalkes, M P AU - Liu, J AU - Ward, J M AU - Diwan, BA 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 - 2004/08/01/ PY - 2004 DA - 2004 Aug 01 SP - 377 EP - 384 PB - Elsevier Inc. VL - 198 IS - 3 SN - 0041-008X, 0041-008X KW - mice KW - Toxicology Abstracts KW - Arsenic KW - Sodium arsenite KW - Skin KW - Urinary bladder KW - Animal models KW - Offspring KW - Carcinogens KW - Gene expression KW - Lung KW - Genomic analysis KW - Gestation KW - Carcinogenesis KW - Kidney KW - Ovaries KW - Hepatocellular carcinoma KW - X 24165:Biochemistry KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18054701?accountid=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=Animal+models+for+arsenic+carcinogenesis%3A+inorganic+arsenic+is+a+transplacental+carcinogen+in+mice&rft.au=Waalkes%2C+M+P%3BLiu%2C+J%3BWard%2C+J+M%3BDiwan%2C+BA&rft.aulast=Waalkes&rft.aufirst=M&rft.date=2004-08-01&rft.volume=198&rft.issue=3&rft.spage=377&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+Applied+Pharmacology&rft.issn=0041008X&rft_id=info:doi/10.1016%2Fj.taap.2003.10.028 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Arsenic; Carcinogenesis; Animal models; Carcinogens; Gestation; Offspring; Skin; Lung; Sodium arsenite; Ovaries; Gene expression; Hepatocellular carcinoma; Urinary bladder; Genomic analysis; Kidney DO - http://dx.doi.org/10.1016/j.taap.2003.10.028 ER - TY - JOUR T1 - Translation repression by an RNA polymerase elongation complex AN - 18054361; 6003910 AB - Bacteriophage lambda N and bacterial Nus proteins together with a unique site NUT in the leader of the early viral N gene transcript bind RNA polymerase (RNAP) and form a highly processive antitermination complex; N bound at NUT also represses N translation. In this study, we investigate whether N and NUT cause N translation repression as part of the antitermination complex by testing conditions that inhibit the formation of the N-modified transcription complex for their effect on N-mediated translation repression. We show that nus and nut mutations that in combination destabilize multiple interactions in the antitermination complex prevent N-mediated translation repression. Likewise, transcription of the nut-N region by T7 RNAP, which does not lead to the assembly of an effective antitermination complex when N is supplied, eliminates translation repression. We also demonstrate that a unique mutant beta subunit of RNAP reduces N-mediated translation repression, and that overexpression of transcription factor NusA suppresses this defect. We conclude that the N-modified RNAP transcription complex is necessary to repress N translation. JF - Molecular Microbiology AU - Wilson, H R AU - Zhou, J AU - Yu, D AU - Court, D L AD - Molecular Control and Genetics Section, Gene Regulation and Chromosome Biology, National Cancer Institute-Frederick, Frederick, MD 21702-1201, USA., court@ncifcrf.gov Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 821 EP - 828 PB - Blackwell Science Ltd VL - 53 IS - 3 SN - 0950-382X, 0950-382X KW - antitermination KW - Virology & AIDS Abstracts; Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Phages KW - Translation KW - Elongation KW - double prime N gene KW - Bacteria KW - DNA-directed RNA polymerase KW - Transcription factors KW - Transcription KW - Mutation KW - Gene silencing KW - J 02726:RNA and ribosomes KW - V 22070:Phage-host interactions including lysogeny & transduction KW - N 14551:Virus & phage infections UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18054361?accountid=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=Translation+repression+by+an+RNA+polymerase+elongation+complex&rft.au=Wilson%2C+H+R%3BZhou%2C+J%3BYu%2C+D%3BCourt%2C+D+L&rft.aulast=Wilson&rft.aufirst=H&rft.date=2004-08-01&rft.volume=53&rft.issue=3&rft.spage=821&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1111%2Fj.1365-2958.2004.04170.x LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Phages; Bacteria; double prime N gene; Elongation; Translation; DNA-directed RNA polymerase; Transcription factors; Transcription; Mutation; Gene silencing DO - http://dx.doi.org/10.1111/j.1365-2958.2004.04170.x ER - TY - JOUR T1 - High-resolution genome-wide mapping of histone modifications AN - 18019482; 5993744 AB - The expression patterns of eukaryotic genomes are controlled by their chromatin structure, consisting of nucleosome subunits in which DNA of approximately 146 bp is wrapped around a core of 8 histone molecules. Post-translational histone modifications play an essential role in modifying chromatin structure. Here we apply a combination of SAGE and chromatin immunoprecipitation (ChIP) protocols to determine the distribution of hyperacetylated histones H3 and H4 in the Saccharomyces cerevisiae genome. We call this approach genome-wide mapping technique (GMAT). Using GMAT, we find that the highest acetylation levels are detected in the 5' end of a gene's coding region, but not in the promoter. Furthermore, we show that the histone acetyltransferase, GCN5p, regulates H3 acetylation in the promoter and 5' end of the coding regions. These findings indicate that GMAT should find valuable applications in mapping target sites of chromatin-modifying enzymes. JF - Nature Biotechnology AU - Roh, T-Y AU - Ngau, W C AU - Cui, K AU - Landsman, D AU - Zhao, K AD - Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland 20892, USA, zhaok@nhlbi.nih.gov Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 1013 EP - 1016 VL - 22 IS - 8 SN - 1087-0156, 1087-0156 KW - budding yeast KW - Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Medical and Pharmaceutical Biotechnology Abstracts KW - Histones KW - Serial analysis of gene expression KW - Chromatin KW - Saccharomyces cerevisiae KW - Acetylation KW - DNA KW - Gene mapping KW - N 14040:Genome/chromosome structure & maintenance KW - W3 33243:Molecular methods KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18019482?accountid=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=High-resolution+genome-wide+mapping+of+histone+modifications&rft.au=Roh%2C+T-Y%3BNgau%2C+W+C%3BCui%2C+K%3BLandsman%2C+D%3BZhao%2C+K&rft.aulast=Roh&rft.aufirst=T-Y&rft.date=2004-08-01&rft.volume=22&rft.issue=8&rft.spage=1013&rft.isbn=&rft.btitle=&rft.title=Nature+Biotechnology&rft.issn=10870156&rft_id=info:doi/10.1038%2Fnbt990 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Saccharomyces cerevisiae; Serial analysis of gene expression; Histones; Chromatin; Acetylation; DNA; Gene mapping DO - http://dx.doi.org/10.1038/nbt990 ER - TY - JOUR T1 - Application of a Statistical Dynamic Model Investigating the Short-Term Cellular Kinetics Induced by Riddelliine, a Hepatic Endothelial Carcinogen AN - 18007981; 5945833 AB - In recent studies, riddelliine, a pyrrolizidine alkaloid, was found to increase rates of replication and apoptosis and induce hemangiosarcoma in the liver of rats and mice. To analyze DNA replication and apoptosis data taken from the same animals, we have developed a predictive mathematical model for describing BrdU labeling and apoptotic processes. The model allows the incorporation of simple diurnal patterns in cellular kinetics and is applied to data on hepatocytes and endothelial cells taken from riddelliine exposed rats. Predictions from the model were used with multivariable nonlinear regression techniques to estimate replication and apoptotic rate constants for both cell types and all treatment groups. Hypothesis tests were used with the predicted rates to separate the competing effects of riddelliine on replication and apoptosis of hepatocytes and endothelial cells as well as compare replication rates between cell types. That estimated replication rates were found to be significantly higher for endothelial cells supports the supposition of induction of hemangiosarcoma by riddelliine in the liver. JF - Toxicological Sciences AU - Smith, Marjo V AU - Nyska, Abraham AU - Portier, Chris AD - Constella Health Sciences, 2605 Meridian Parkway, Durham, North Carolina 27713 and National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27713 Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 258 EP - 267 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 - 80 IS - 2 SN - 1096-6080, 1096-6080 KW - hemangiosarcoma KW - mice KW - pyrrolizidine alkaloid KW - rats KW - riddelliine KW - Toxicology Abstracts KW - Prediction KW - Endothelial cells KW - DNA biosynthesis KW - Alkaloids KW - Mathematical models KW - Apoptosis KW - Replication KW - Hepatocytes KW - DNA KW - Liver KW - X 24173:Animals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18007981?accountid=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=Toxicological+Sciences&rft.atitle=Application+of+a+Statistical+Dynamic+Model+Investigating+the+Short-Term+Cellular+Kinetics+Induced+by+Riddelliine%2C+a+Hepatic+Endothelial+Carcinogen&rft.au=Smith%2C+Marjo+V%3BNyska%2C+Abraham%3BPortier%2C+Chris&rft.aulast=Smith&rft.aufirst=Marjo&rft.date=2004-08-01&rft.volume=80&rft.issue=2&rft.spage=258&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Endothelial cells; Prediction; DNA biosynthesis; Alkaloids; Apoptosis; Mathematical models; Hepatocytes; Replication; Liver; DNA ER - TY - JOUR T1 - Three-Dimensional Electron Microscopic Imaging of Membrane Invaginations in Escherichia coli Overproducing the Chemotaxis Receptor Tsr AN - 17991438; 5952582 AB - Electron tomography is a powerful method for determining the three- dimensional structures of large macromolecular assemblies, such as cells, organelles, and multiprotein complexes, when crystallographic averaging methods are not applicable. Here we used electron tomographic imaging to determine the molecular architecture of Escherichia coli cells engineered to overproduce the bacterial chemotaxis receptor Tsr. Tomograms constructed from fixed, cryosectioned cells revealed that overproduction of Tsr led to formation of an extended internal membrane network composed of stacks and extended tubular structures. We present an interpretation of the tomogram in terms of the packing arrangement of Tsr using constraints derived from previous X-ray and electron- crystallographic studies of receptor clusters. Our results imply that the interaction between the cytoplasmic ends of Tsr is likely to stabilize the presence of the membrane networks in cells overproducing Tsr. We propose that membrane invaginations that are potentially capable of supporting axial interactions between receptor clusters in apposing membranes could also be present in wild-type E. coli and that such receptor aggregates could play an important role in signal transduction during bacterial chemotaxis. JF - Journal of Bacteriology AU - Lefman, Jonathan AU - Zhang, Peijun AU - Hirai, Teruhisa AU - Weis, Robert M AU - Juliani, Jemma AU - Bliss, Donald AU - Kessel, Martin AU - Bos, Erik AU - Peters, Peter J AU - Subramaniam, Sriram AD - Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland Y1 - 2004/08/01/ PY - 2004 DA - 2004 Aug 01 SP - 5052 EP - 5061 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 186 IS - 15 SN - 0021-9193, 0021-9193 KW - Tsr protein KW - Microbiology Abstracts B: Bacteriology KW - Cell membranes KW - Escherichia coli KW - Receptors KW - Tomography KW - Invaginations KW - Chemotaxis KW - Signal transduction KW - J 02721:Cell cycle, morphology and motility UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17991438?accountid=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=Three-Dimensional+Electron+Microscopic+Imaging+of+Membrane+Invaginations+in+Escherichia+coli+Overproducing+the+Chemotaxis+Receptor+Tsr&rft.au=Lefman%2C+Jonathan%3BZhang%2C+Peijun%3BHirai%2C+Teruhisa%3BWeis%2C+Robert+M%3BJuliani%2C+Jemma%3BBliss%2C+Donald%3BKessel%2C+Martin%3BBos%2C+Erik%3BPeters%2C+Peter+J%3BSubramaniam%2C+Sriram&rft.aulast=Lefman&rft.aufirst=Jonathan&rft.date=2004-08-01&rft.volume=186&rft.issue=15&rft.spage=5052&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Cell membranes; Receptors; Tomography; Invaginations; Chemotaxis; Signal transduction; Escherichia coli ER - TY - JOUR T1 - Age and gender affect ventricular-vascular coupling during aerobic exercise AN - 17883635; 6086755 AB - Objectives The goal of this study was to examine the age-associated differences in ventricular-vascular coupling, defined by the ratio of arterial elastance (EaI) to left ventricular systolic elastance (E sub(LV)I), and its components, at rest and during exercise. Background Ejection fraction (EF) increases during exercise, but the EF reserve decreases with aging. Ejection fraction is inversely related to EaI/E sub(LV)I, an index of the interaction between arterial and ventricular properties, which is an important determinant of cardiac performance. Thus, age differences in EaI/E sub(LV)I during exercise, due to age differences in EaI, E sub(LV)I, or both, may help to explain the age deficit in EF reserve. Methods We noninvasively characterized EaI/E sub(LV)I = end-systolic volume index (ESVI)/stroke volume index (SVI) and its two determinants EaI = end-systolic pressure/SVI, and E sub(LV)I = end-systolic pressure/ESVI, at rest and during exercise in 239 healthy men and women (age range, 21 to 87 years). Blood pressures were assessed with cuff sphygomanometry, and cardiac volumes with gated blood pool scintingraphy. Results Resting EaI/E sub(LV)I was not age related in men or women. In both sexes, EaI/E sub(LV)I decreased during exercise and declined to a lesser extent in older subjects. There were gender differences in the components of EaI/E sub(LV)I during exercise: EaI was greater in older versus young women (p = 0.01) but was unaffected by age in men. Left ventricular systolic elastance increased to a greater extent in young versus older subjects (p = 0.0001 for men, P = 0.07 for women). Conclusions Age-associated differences in EaI/E sub(LV)I occur in both genders during exercise. Sub-optimal ventricular-vascular coupling helps to explain the age-associated blunting of maximal exercise EF, and its underlying mechanisms appear to differ between men and women. JF - Journal of the American College of Cardiology AU - Najjar, S S AU - Schulman, S P AU - Gerstenblith, G AU - Fleg, J L AU - Kass, DA AU - O'Connor, F AU - Becker, L C AU - Lakatta, E G AD - Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive,, Baltimore, Maryland 21224,, USA Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 611 EP - 617 VL - 44 IS - 3 SN - 0735-1097, 0735-1097 KW - Physical Education Index KW - Age KW - Aerobics KW - Heart (stroke volume) KW - Gerontology KW - Stress KW - Adults KW - Exercise KW - Sex differences KW - Blood pressure KW - Blood KW - Cardiac output KW - Rest KW - Performance KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17883635?accountid=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+the+American+College+of+Cardiology&rft.atitle=Age+and+gender+affect+ventricular-vascular+coupling+during+aerobic+exercise&rft.au=Najjar%2C+S+S%3BSchulman%2C+S+P%3BGerstenblith%2C+G%3BFleg%2C+J+L%3BKass%2C+DA%3BO%27Connor%2C+F%3BBecker%2C+L+C%3BLakatta%2C+E+G&rft.aulast=Najjar&rft.aufirst=S&rft.date=2004-08-01&rft.volume=44&rft.issue=3&rft.spage=611&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+College+of+Cardiology&rft.issn=07351097&rft_id=info:doi/10.1016%2Fj.jacc.2004.04.041 LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Exercise; Adults; Gerontology; Sex differences; Age; Rest; Stress; Performance; Blood; Aerobics; Heart (stroke volume); Blood pressure; Cardiac output DO - http://dx.doi.org/10.1016/j.jacc.2004.04.041 ER - TY - JOUR T1 - RNAi quashes polyQ AN - 17881341; 5994264 AB - RNA interference in the brain inhibits neurodegeneration in a polyglutamine disease, SCA1. Is this now the way forward for the clinical treatment of certain genetic disorders?. JF - Nature Medicine AU - Caplen, N J AD - Gene Silencing Section, Office of Science and Technology Partnerships, Office of the Director, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA, ncaplen@mail.nih.gov Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 775 VL - 10 IS - 8 SN - 1078-8956, 1078-8956 KW - Biotechnology and Bioengineering Abstracts; CSA Neurosciences Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Medical and Pharmaceutical Biotechnology Abstracts KW - polyglutamine diseases KW - Hereditary diseases KW - Brain KW - ataxin KW - Neurodegeneration KW - Neurodegenerative diseases KW - Movement disorders KW - Reviews KW - Polyglutamine KW - RNA-mediated interference KW - Spinocerebellar ataxia KW - N 14100:Reviews KW - W3 33243:Molecular methods KW - N3 11011:Motor systems and movement disorders KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17881341?accountid=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=RNAi+quashes+polyQ&rft.au=Caplen%2C+N+J&rft.aulast=Caplen&rft.aufirst=N&rft.date=2004-08-01&rft.volume=10&rft.issue=8&rft.spage=775&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 N1 - SubjectsTermNotLitGenreText - ataxin; RNA-mediated interference; Hereditary diseases; Brain; Neurodegenerative diseases; Polyglutamine; Reviews; Movement disorders; Spinocerebellar ataxia; Neurodegeneration; polyglutamine diseases ER - TY - JOUR T1 - Simultaneous Quantification of Opiates, Cocaine, and Metabolites in Hair by LC-APCI-MS/MS AN - 17825522; 6129970 AB - A quantitative LC-APCI-MS/MS method for simultaneous measurement of opiates, cocaine, and metabolites in hair was developed and validated. Cocaine and opiates were extracted from pulverized hair via sonication in methanol at 37 degree C for 3 h. Samples were cleaned up using solid-phase extraction. LC separation was achieved in 20 min with identification and quantification by selected reaction monitoring. Calibration by linear regression analysis utilized deuterated internal standards and a weighting factor of 1/x (R super(2) > 0.998). Limits of quantification (LOQ) ranged from 17 to 50 pg/mg for cocaine and metabolites and were 83 pg/mg for opiates. Standard curves were linear from the LOQ to 5000 pg/mg for cocaine and metabolites, except benzoylecgonine (2500 pg/mg). Opiate standard curves were linear from the LOQ to 12500 pg/mg. Accuracy ranged from 84 to 115% for all quantitative analytes. Precision, % relative standard deviation, was less than 11.0% for all analytes. Methanolic sonication produced less than 5% hydrolysis of cocaine and 6-acetylmorphine. The method should be useful for studying cocaine and opiate distribution into hair. JF - Analytical Chemistry (Washington) AU - Scheidweiler, K B AU - Huestis, MA AD - Chemistry and Drug Metabolism Section, Intramural Research Program, National Institute on Drug Abuse, 5500 Nathan Shock Drive, Baltimore, Maryland 21224, USA Y1 - 2004/08/01/ PY - 2004 DA - 2004 Aug 01 SP - 4358 EP - 4363 VL - 76 IS - 15 SN - 0003-2700, 0003-2700 KW - Toxicology Abstracts KW - Opiates KW - Standard deviation KW - Methanol KW - Regression analysis KW - Metabolites KW - Cocaine KW - Hair KW - Hydrolysis KW - Sonication KW - X 24222:Analytical procedures KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17825522?accountid=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=Analytical+Chemistry+%28Washington%29&rft.atitle=Simultaneous+Quantification+of+Opiates%2C+Cocaine%2C+and+Metabolites+in+Hair+by+LC-APCI-MS%2FMS&rft.au=Scheidweiler%2C+K+B%3BHuestis%2C+MA&rft.aulast=Scheidweiler&rft.aufirst=K&rft.date=2004-08-01&rft.volume=76&rft.issue=15&rft.spage=4358&rft.isbn=&rft.btitle=&rft.title=Analytical+Chemistry+%28Washington%29&rft.issn=00032700&rft_id=info:doi/10.1021%2Fac049555t LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-05-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Standard deviation; Opiates; Methanol; Regression analysis; Metabolites; Cocaine; Hydrolysis; Hair; Sonication DO - http://dx.doi.org/10.1021/ac049555t ER - TY - JOUR T1 - Stress Dose of Hydrocortisone Is Not Beneficial in Patients with Classic Congenital Adrenal Hyperplasia Undergoing Short-Term, High-Intensity Exercise AN - 17820736; 5964659 AB - Classic congenital adrenal hyperplasia (CAH) is associated with impaired function of the adrenal cortex and medulla leading to decreased production of cortisol and epinephrine. As a result, the normal exercise-induced rise in blood glucose is markedly blunted in such individuals. We examined whether an extra dose of hydrocortisone, similar to that given during other forms of physical stress such as intercurrent illness, would normalize blood glucose levels during exercise in patients with CAH. We studied hormonal, metabolic, and cardiorespiratory parameters in response to a standardized high-intensity exercise protocol in nine adolescent patients with classic CAH. Patients were assigned to receive either an additional morning dose of hydrocortisone or placebo, in addition to their usual glucocorticoid and mineralocorticoid replacement in a randomized, double-blind, crossover design 1 h before exercising. Although plasma cortisol levels approximately doubled after administration of the additional hydrocortisone dose compared with the usual single dose, fasting and exercise-induced blood glucose levels did not differ. In addition, no differences were observed in the serum concentrations of the glucose-modulating hormones epinephrine, insulin, glucagon, and GH and of the metabolic parameters lactate and free fatty acids. Although maximal heart rate was slightly higher after stress dosing (193 +/- 3 vs. 191 +/- 3 beats/min, mean +/- SEM, P < 0.05), this did not affect exercise performance or perceived exertion. We conclude that patients with classic CAH do not benefit from additional hydrocortisone during short-term, high-intensity exercise. Although this has not been tested with long-term exercise, a high degree of caution should be used when considering the frequent use of additional hydrocortisone administration with exercise, given the adverse side effects of glucocorticoid excess. JF - Journal of Clinical Endocrinology and Metabolism AU - Weise, Martina AU - Drinkard, Bart AU - Mehlinger, Sarah L AU - Holzer, Stuart M AU - Eisenhofer, Graeme AU - Charmandari, Evangelia AU - Chrousos, George P AU - Merke, Deborah P AD - Pediatric and Reproductive Endocrinology Branch (S.L.M., S.M.H., E.C., G.P.C., D.P.M.), Developmental Endocrinology Branch (M.W.), National Institute of Child Health and Human Development, The Warren Grant Magnuson Clinical Center (B.D., D.P.M.) and Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke (G.E.), National Institutes of Health, Bethesda, Maryland Y1 - 2004/08/01/ PY - 2004 DA - 2004 Aug 01 SP - 3679 EP - 3684 PB - Endocrine Society, 4350 East West Highway Suite 500 Bethesda MD 20814-4426 USA, [mailto:societyservices@endo-society.org], [URL:http://www.endo-society.org/] VL - 89 IS - 8 SN - 0021-972X, 0021-972X KW - Physical Education Index KW - Perceived exertion KW - Lipids KW - Adolescence KW - Heart rate KW - Stress KW - Blood glucose KW - Patients KW - Illness KW - Hormones KW - Physical stress KW - Exercise (intensity) KW - Lactic acid KW - Cardiorespiratory KW - Performance KW - Endocrine system KW - Metabolism KW - PE 090:Sports Medicine & Exercise Sport Science UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17820736?accountid=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+Clinical+Endocrinology+and+Metabolism&rft.atitle=Stress+Dose+of+Hydrocortisone+Is+Not+Beneficial+in+Patients+with+Classic+Congenital+Adrenal+Hyperplasia+Undergoing+Short-Term%2C+High-Intensity+Exercise&rft.au=Weise%2C+Martina%3BDrinkard%2C+Bart%3BMehlinger%2C+Sarah+L%3BHolzer%2C+Stuart+M%3BEisenhofer%2C+Graeme%3BCharmandari%2C+Evangelia%3BChrousos%2C+George+P%3BMerke%2C+Deborah+P&rft.aulast=Weise&rft.aufirst=Martina&rft.date=2004-08-01&rft.volume=89&rft.issue=8&rft.spage=3679&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Endocrinology+and+Metabolism&rft.issn=0021972X&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Patients; Endocrine system; Hormones; Blood glucose; Stress; Metabolism; Heart rate; Adolescence; Lipids; Cardiorespiratory; Performance; Physical stress; Exercise (intensity); Illness; Perceived exertion; Lactic acid ER - TY - JOUR T1 - Perspectives on alcohol consumption: liver polyunsaturated fatty acids and essential fatty acid metabolism AN - 17796664; 6141277 AB - In this article, subjects diagnosed with alcoholic liver disease are shown to have lower concentrations of several polyunsaturated fatty acids (PUFAs), including 18:2n6, 18:3n6, 20:3n6, 18:3n3, 22:5n3, and 22:6n3, but not 20:4n6 and 22:4n6, nor 22:5n6, in the total lipid extracts of their livers compared with findings for specimens obtained from patients diagnosed with primary biliary cirrhosis and from control subjects. Findings of studies in animals have demonstrated that prolonged alcohol consumption reduces liver polyunsaturate content. However, the effect of ethanol on the elongation/desaturation of essential fatty acids is complex, as in vitro study results indicate that the direction of the effect of alcohol may be related to the dose of alcohol. Findings of studies in hepatocyte cell culture indicate that ethanol increased delta-5 and delta-6 desaturase activities throughout a broad concentration range. In contrast, lower liver desaturase activity has been reported in animals consuming high concentrations of alcohol (36%-40% energy) over a period of several months. Findings from in vivo isotope tracers studies in nonhuman primates and felines indicate that prolonged periods of moderate (mean consumption 2.6 g kg super(-1) d super(-1) and 1.2 g kg super(-1) d super(-1), respectively) alcohol consumption had no effect on the uptake of either linoleic (18:2n6) or alpha-linolenic (18:3n3) acids into the plasma and lead to an increased incorporation of these deuterated precursors into 20:4n6 and 22:6n3. Thus, this likely reflects a stimulated, rather than an inhibited, production of long-chain PUFAs. In numerous studies in various species, investigators have documented that alcohol consumption can increase the level of lipid peroxidation in tissues, and sustained periods of ethanol-induced peroxidation can deplete tissues of PUFAs. A hypothesis to rationalize the long-term effects of alcohol consumption on liver PUFA concentration that takes into consideration the effect of ethanol on essential fatty acid metabolism is presented. JF - Alcohol AU - Salem, N AD - Section of Nutritional Neuroscience, Laboratory of Membrane Biochemistry and Biophysics, Division of Intramural Clinical and Biological Research, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Room 3C-07, Rockville, MD 20852, USA, nsalem@niaaa.nih.gov Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 27 EP - 33 PB - Elsevier Science Inc., Box 882 New York NY 10159 USA, [mailto:usinfo-f@elsevier.com] VL - 34 IS - 1 SN - 0741-8329, 0741-8329 KW - Toxicology Abstracts KW - Fatty liver KW - Essential fatty acids KW - Human beings KW - Animals KW - Docosahexaenoic acid KW - Arachidonic acid KW - Fatty acid desaturation KW - Metabolism KW - Ethanol KW - Isotopes KW - Liver diseases KW - Peroxidation KW - Hepatocytes KW - Lipids KW - Cell culture KW - Alcoholics KW - Lipid peroxidation KW - Long-term effects KW - Elongation KW - Tracers KW - Fatty acids KW - Polyunsaturated fatty acids KW - desaturase KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17796664?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcohol&rft.atitle=Perspectives+on+alcohol+consumption%3A+liver+polyunsaturated+fatty+acids+and+essential+fatty+acid+metabolism&rft.au=Salem%2C+N&rft.aulast=Salem&rft.aufirst=N&rft.date=2004-08-01&rft.volume=34&rft.issue=1&rft.spage=27&rft.isbn=&rft.btitle=&rft.title=Alcohol&rft.issn=07418329&rft_id=info:doi/10.1016%2Fj.alcohol.2004.07.009 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Isotopes; Liver diseases; Peroxidation; Hepatocytes; Lipids; Cell culture; Lipid peroxidation; Alcoholics; Long-term effects; Tracers; Elongation; Fatty acids; Polyunsaturated fatty acids; Fatty liver; desaturase; Metabolism; Ethanol DO - http://dx.doi.org/10.1016/j.alcohol.2004.07.009 ER - TY - JOUR T1 - Biokinetics and Subchronic Toxic Effects of Oral Arsenite, Arsenate, Monomethylarsonic Acid, and Dimethylarsinic Acid in v-Ha-ras Transgenic (Tg.AC) Mice AN - 17757486; 6047506 AB - Previous research demonstrated that 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment increased the number of skin papillomas in v-Ha-ras transgenic (Tg.AC) mice that had received sodium arsenite [(As(III)] in drinking water, indicating that this model is useful for studying the toxic effects of arsenic in vivo. Because the liver is a known target of arsenic, we examined the pathophysiologic and molecular effects of inorganic and organic arsenical exposure on Tg.AC mouse liver in this study. Tg.AC mice were provided drinking water containing As(III), sodium arsenate [As(V)], monomethylarsonic acid [(MMA(V)], and 1,000 ppm dimethylarsinic acid [DMA(V)] at dosages of 150, 200, 1,500, or 1,000 ppm as arsenic, respectively, for 17 weeks. Control mice received unaltered water. Four weeks after initiation of arsenic treatment, TPA at a dose of 1.25 mu g/200 mu L acetone was applied twice a week for 2 weeks to the shaved dorsal skin of all mice, including the controls not receiving arsenic. In some cases arsenic exposure reduced body weight gain and caused mortality (including moribundity). Arsenical exposure resulted in a dose-dependent accumulation of arsenic in the liver that was unexpectedly independent of chemical species and produced hepatic global DNA hypomethylation. cDNA microarray and reverse transcriptase-polymerase chain reaction analysis revealed that all arsenicals altered the expression of numerous genes associated with toxicity and cancer. However, organic arsenicals [MMA(V) and DMA(V)] induced a pattern of gene expression dissimilar to that of inorganic arsenicals. In summary, subchronic exposure of Tg.AC mice to inorganic or organic arsenicals resulted in toxic manifestations, hepatic arsenic accumulation, global DNA hypomethylation, and numerous gene expression changes. These effects may play a role in arsenic-induced hepatotoxicity and carcinogenesis and may be of particular toxicologic relevance. JF - Environmental Health Perspectives AU - Xie, Yaxiong AU - Trouba, K J AU - Liu, J AU - Waalkes, M P AU - Germolec AD - Environmental Immunology, National Institute of Environmental Health Sciences, P.O. Box 12233, Mail Drop C1-03, Research Triangle Park, NC 27709, USA, germolec@niehs.nih.gov Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 1255 EP - 1263 VL - 112 IS - 12 SN - 0091-6765, 0091-6765 KW - monomethylarsonic acid KW - Toxicology Abstracts KW - Mortality KW - Arsenic KW - Sodium arsenite KW - Skin KW - Animal models KW - Toxicity KW - Transgenic mice KW - sodium arsenate KW - DNA microarrays KW - TPA KW - Cancer KW - 12-O-Tetradecanoylphorbol-13-acetate KW - Carcinogenesis KW - DNA KW - Liver KW - Polymerase chain reaction KW - Papilloma KW - Drinking water KW - Body weight gain KW - dimethylarsinic acid KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17757486?accountid=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=Biokinetics+and+Subchronic+Toxic+Effects+of+Oral+Arsenite%2C+Arsenate%2C+Monomethylarsonic+Acid%2C+and+Dimethylarsinic+Acid+in+v-Ha-ras+Transgenic+%28Tg.AC%29+Mice&rft.au=Xie%2C+Yaxiong%3BTrouba%2C+K+J%3BLiu%2C+J%3BWaalkes%2C+M+P%3BGermolec&rft.aulast=Xie&rft.aufirst=Yaxiong&rft.date=2004-08-01&rft.volume=112&rft.issue=12&rft.spage=1255&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/10.1289%2Ftxg.7152 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-05-01 N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Mortality; Arsenic; Skin; Sodium arsenite; Animal models; Toxicity; sodium arsenate; Transgenic mice; DNA microarrays; 12-O-Tetradecanoylphorbol-13-acetate; Cancer; TPA; Carcinogenesis; Liver; DNA; Polymerase chain reaction; Body weight gain; Drinking water; Papilloma; dimethylarsinic acid DO - http://dx.doi.org/10.1289/txg.7152 ER - TY - JOUR T1 - Gene Interaction Network Suggests Dioxin Induces a Significant Linkage between Aryl Hydrocarbon Receptor and Retinoic Acid Receptor Beta AN - 17757455; 6047503 AB - Gene expression arrays (gene chips) have enabled researchers to roughly quantify the level of mRNA expression for a large number of genes in a single sample. Several methods have been developed for the analysis of gene array data including clustering, outlier detection, and correlation studies. Most of these analyses are aimed at a qualitative identification of what is different between two samples and/or the relationship between two genes. We propose a quantitative, statistically sound methodology for the analysis of gene regulatory networks using gene expression data sets. The method is based on Bayesian networks for direct quantification of gene expression networks. Using the gene expression changes in HPL1A lung airway epithelial cells after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin at levels of 0.1, 1.0, and 10.0 nM for 24 hr, a gene expression network was hypothesized and analyzed. The method clearly demonstrates support for the assumed network and the hypothesis linking the usual dioxin expression changes to the retinoic acid receptor system. Simulation studies demonstrated the method works well, even for small samples. JF - Environmental Health Perspectives AU - Toyoshiba, Hiroyoshi AU - Yamanaka, Takeharu AU - Sone, Hideko AU - Parham, F M AU - Walker, N J AU - Martinez, J AU - Portier, C J AD - National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709, USA, portier@niehs.nih.gov Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 1217 EP - 1224 VL - 112 IS - 12 SN - 0091-6765, 0091-6765 KW - Toxicology Abstracts KW - Gene expression KW - Epithelial cells KW - Retinoic acid receptors KW - Bayesian analysis KW - Lung KW - Sound KW - Aryl hydrocarbon receptors KW - Dioxin KW - Respiratory tract KW - X 24222:Analytical procedures UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17757455?accountid=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=Gene+Interaction+Network+Suggests+Dioxin+Induces+a+Significant+Linkage+between+Aryl+Hydrocarbon+Receptor+and+Retinoic+Acid+Receptor+Beta&rft.au=Toyoshiba%2C+Hiroyoshi%3BYamanaka%2C+Takeharu%3BSone%2C+Hideko%3BParham%2C+F+M%3BWalker%2C+N+J%3BMartinez%2C+J%3BPortier%2C+C+J&rft.aulast=Toyoshiba&rft.aufirst=Hiroyoshi&rft.date=2004-08-01&rft.volume=112&rft.issue=12&rft.spage=1217&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/10.1289%2Ftxg.7020 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-05-01 N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Gene expression; Epithelial cells; Retinoic acid receptors; Lung; Bayesian analysis; Sound; Aryl hydrocarbon receptors; Dioxin; Respiratory tract DO - http://dx.doi.org/10.1289/txg.7020 ER - TY - JOUR T1 - Prediction equations for resting energy expenditure in overweight and normal-weight black and white children AN - 17738647; 6086679 AB - Background: Accurate estimation of children's resting energy expenditure (REE) is important for planning dietary therapy. Objective: Our objective was to compare the utility of 5 REE prediction equations in a diverse sample of young children. Design: REE was obtained in 502 black and white girls and boys aged 6-11 y by using indirect calorimetry at 4 US sites. Measured REE and REE predicted from the equations were compared. Results: None of the equations provided both accurate and unbiased estimates of REE. Two new sets of sex-specific equations including race as a factor were generated and evaluated. One set used easily measured variables--females: REE = 0.046 x weight - 4.492 x 1/height super(2) - 0.151 x race + 5.841; males: REE = 0.037 x weight - 4.67 x 1/height super(2) - 0.159 x race + 6.792--and accounted for 72% and 69%, respectively, of REE variance. The other set used body-composition variables--females: REE = 0.101 x fat-free mass + 0.025 x fat mass + 0.293 x height super(3) - 0.185 x race + 1.643; males: REE = 0.078 x fat-free mass + 0.026 x fat mass - 2.646 x 1/height super(2) - 0.244 x race + 4.8--and accounted for 75% and 71%, respectively, of REE variance. When split by race and adiposity, the small bias generated could be corrected to within 0.25 MJ (60 kcal) of the mean measured value. Conclusion: Sex-specific equations must take race into account to predict REE adequately in children. JF - American Journal of Clinical Nutrition AU - McDuffie, J R AU - Adler-Wailes, D C AU - Elberg, J AU - Steinberg, EN AU - Fallon, E M AU - Tershakovec, A M AU - Arslanian, SA AU - Delany, J P AU - Bray, G A AU - Yanovski, JA AD - Unit on Growth and Obesity, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA Y1 - 2004/08/01/ PY - 2004 DA - 2004 Aug 01 SP - 365 EP - 373 VL - 80 IS - 2 SN - 0002-9165, 0002-9165 KW - Physical Education Index KW - Ethnic differences KW - Energy cost KW - Obesity KW - Nutrition (effects) KW - Children KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17738647?accountid=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+Clinical+Nutrition&rft.atitle=Prediction+equations+for+resting+energy+expenditure+in+overweight+and+normal-weight+black+and+white+children&rft.au=McDuffie%2C+J+R%3BAdler-Wailes%2C+D+C%3BElberg%2C+J%3BSteinberg%2C+EN%3BFallon%2C+E+M%3BTershakovec%2C+A+M%3BArslanian%2C+SA%3BDelany%2C+J+P%3BBray%2C+G+A%3BYanovski%2C+JA&rft.aulast=McDuffie&rft.aufirst=J&rft.date=2004-08-01&rft.volume=80&rft.issue=2&rft.spage=365&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Clinical+Nutrition&rft.issn=00029165&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Energy cost; Children; Ethnic differences; Obesity; Nutrition (effects) ER - TY - JOUR T1 - Prevalence of Overweight among Inner City Hispanic-American Children and Adolescents AN - 17712913; 6024873 AB - OBJECTIVE: National surveys have pointed to a particularly high risk of pediatric overweight among U.S. Hispanics. However, the data have been primarily from the Mexican-American community. We studied the prevalence of overweight and clinical comorbidities in children and youth of predominantly El Salvadoran ancestry. RESEARCH METHODS AND PROCEDURES: A sample of 309 Hispanic youth, 6-18 years was surveyed from two inner city Washington, DC, clinics. BMI; triceps skinfold (TSF) and subscapular skinfold thickness (SSSF); bioelectrical impedance analysis (BIA); and blood pressure measures were obtained, along with information regarding physical activity, sedentary behavior, dietary history, family, and personal medical history. RESULTS: Thirty-eight percent were overweight (BMI => 95th percentile) and 22% at risk for overweight (BMI 85-94th percentile). Thirty-four percent had TSF => 90th percentile and 29% had SSSF => 90th percentile. Fifty-one percent of males and 70% of females had body fat > 30%. Compared to their nonoverweight counterparts, overweight youth had significantly higher systolic blood pressure (111.4 +/- 1.3 vs. 104.5 +/- 0.9 mm Hg, p < 0.0001). Among children younger than 11 years, overweight was associated with onset of adrenarche (23% vs. 10%, p = 0.01). Participation in one or more sports teams was negatively correlated with overweight) p = 0.04). DISCUSSION: The prevalence of overweight and at risk for overweight in this sample was twice the national average for U.S. children and 1.7 times greater than that of Mexican-American children in national surveys. Overweight was associated with advanced pubertal development, high body fat, elevated blood pressure, and decreased sports participation. JF - Obesity Research AU - Mirza, Nazrat M AU - Kadow, Kathleen AU - Palmer, Matilde AU - Solano, Heidi AU - Rosche, Claire AU - Yanovski, Jack A AD - Children's National Medical Center, Washington, DC. Unit on Growth and Obesity, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland. Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 1298 EP - 1310 PB - North American Association for the Study of Obesity, 1090 Amsterdam Ave., Ste. 14K New York NY 10025 USA, [mailto:helener@mindspring.com], [URL:http://www.naaso.org] VL - 12 IS - 8 SN - 1071-7323, 1071-7323 KW - Hispanics KW - Risk Abstracts; Physical Education Index KW - Obesity KW - Physical activity KW - Adolescence KW - Surveys KW - Children KW - Blood pressure KW - Sports (participation) KW - Ethnic groups KW - Adolescents KW - Urban areas KW - Urban environment KW - R2 23060:Medical and environmental health KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17712913?accountid=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=Obesity+Research&rft.atitle=Prevalence+of+Overweight+among+Inner+City+Hispanic-American+Children+and+Adolescents&rft.au=Mirza%2C+Nazrat+M%3BKadow%2C+Kathleen%3BPalmer%2C+Matilde%3BSolano%2C+Heidi%3BRosche%2C+Claire%3BYanovski%2C+Jack+A&rft.aulast=Mirza&rft.aufirst=Nazrat&rft.date=2004-08-01&rft.volume=12&rft.issue=8&rft.spage=1298&rft.isbn=&rft.btitle=&rft.title=Obesity+Research&rft.issn=10717323&rft_id=info:doi/ LA - English DB - Physical Education Index; ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Obesity; Children; Adolescence; Blood pressure; Sports (participation); Urban environment; Surveys; Urban areas; Adolescents; Ethnic groups; Physical activity ER - TY - JOUR T1 - Gene Therapy Progress and Prospects. Downregulating gene expression: the impact of RNA interference AN - 17711855; 5994586 AB - The control and maintenance of gene expression is critical for cell development and differentiation. Over the last 2 years, our understanding of the role of RNA as a regulator of gene expression has significantly increased. Small RNA molecules are key elements of a machinery that trigger chromosomal modifications, post-transcriptional gene silencing and protein translational blockade depending on the source, the RNA and the nature of the interaction with the target nucleic acid. Currently, the best characterized of this group of RNA-mediated gene regulation pathways is the post-transcriptional gene silencing mechanism known as RNA interference. RNAi is triggered by double-stranded RNA (dsRNA), which induces the formation of a ribonucleoprotein complex that mediates sequence-specific cleavage of the transcript cognate with the input dsRNA. RNAi has been adapted as a functional genomics tool and it has potential as a therapeutic approach. This review will summarize our current understanding of the RNAi mechanism and the various applications of RNAi-based technologies. JF - Gene Therapy AU - Caplen, N J AD - Gene Silencing Section, Office of the Director, Center for Cancer Research, National Cancer Institute, Building 37, Room 3128B, Bethesda, MD 20892, USA Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 1241 EP - 1248 VL - 11 IS - 16 SN - 0969-7128, 0969-7128 KW - Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Gene therapy KW - Double-stranded RNA KW - Gene expression KW - Gene regulation KW - Reviews KW - Ribonucleoproteins KW - RNA-mediated interference KW - Post-transcription KW - Gene silencing KW - N 14100:Reviews 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/17711855?accountid=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=Gene+Therapy+Progress+and+Prospects.+Downregulating+gene+expression%3A+the+impact+of+RNA+interference&rft.au=Caplen%2C+N+J&rft.aulast=Caplen&rft.aufirst=N&rft.date=2004-08-01&rft.volume=11&rft.issue=16&rft.spage=1241&rft.isbn=&rft.btitle=&rft.title=Gene+Therapy&rft.issn=09697128&rft_id=info:doi/10.1038%2Fsj.gt.3302324 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - RNA-mediated interference; Gene expression; Gene therapy; Gene silencing; Ribonucleoproteins; Reviews; Double-stranded RNA; Gene regulation; Post-transcription DO - http://dx.doi.org/10.1038/sj.gt.3302324 ER - TY - JOUR T1 - Human Mesenchymal Progenitor Cell-Based Tissue Engineering of a Single-Unit Osteochondral Construct AN - 17701426; 6072194 AB - A desirable strategy for articular cartilage repair is to surgically replace the damaged area with an in vitro-engineered osteochondral plug. We report here the development of a novel osteochondral construct using human trabecular bone-derived mesenchymal progenitor cells and a biodegradable poly-D,L-lactic acid scaffold. The cartilage layer was fabricated by press-coating a chondrifying high-density cell pellet onto the scaffold, which was then loaded with cells previously initiated to undergo osteogenesis. The composite was then cultured in a cocktail medium formulated to maintain both chondrogenesis and osteogenesis. Macroscopically, the construct consisted of a cartilage-like layer adherent to, and overlying, a dense bone-like component. RT-PCR, immunohistochemistry, and histology revealed hyaline-like cartilage and bone with an interface resembling the native osteochondral junction. All parameters, including mechanical properties, improved with increased culture time. The single-cell source nature of the construct, which minimizes handling while maximizing biocompatibility, suggests applicability for articular cartilage repair. JF - Tissue Engineering AU - Tuli, R AU - Nandi, S AU - Li, W-J AU - Tuli, S AU - Huang, X AU - Manner, P A AU - Laquerriere, P AU - Noeth, U AU - Hall, D J AU - Tuan, R S AD - Cartilage Biology and Orthopedics Branch, National Institute of Arthritis, and Musculoskeletal, and Skin Diseases, National Institutes of Health, Building 50, Room 1503, 50 South Drive, MSC 8022, Bethesda, MD 20892-8022, USA, tuanr@mail.nih.gov Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 1169 EP - 1179 VL - 10 IS - 7-8 SN - 1076-3279, 1076-3279 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Cell culture KW - biocompatibility KW - Stem cells KW - Polymerase chain reaction KW - Cartilage (articular) KW - Mechanical properties KW - Osteogenesis KW - Tissue engineering KW - poly-D,L-lactic acid KW - scaffolds KW - Immunohistochemistry 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/17701426?accountid=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=Human+Mesenchymal+Progenitor+Cell-Based+Tissue+Engineering+of+a+Single-Unit+Osteochondral+Construct&rft.au=Tuli%2C+R%3BNandi%2C+S%3BLi%2C+W-J%3BTuli%2C+S%3BHuang%2C+X%3BManner%2C+P+A%3BLaquerriere%2C+P%3BNoeth%2C+U%3BHall%2C+D+J%3BTuan%2C+R+S&rft.aulast=Tuli&rft.aufirst=R&rft.date=2004-08-01&rft.volume=10&rft.issue=7-8&rft.spage=1169&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 N1 - SubjectsTermNotLitGenreText - Stem cells; scaffolds; Cartilage (articular); Tissue engineering; Osteogenesis; Mechanical properties; biocompatibility; Immunohistochemistry; Chondrogenesis; Polymerase chain reaction; poly-D,L-lactic acid; Cell culture ER - TY - JOUR T1 - Physical activity and risk of coronary heart disease in India AN - 17559629; 6406893 AB - Background Physical exercise has been inversely associated with coronary heart disease (CHD) risk in Western populations; however, the association has not been examined in India where physical inactivity levels in urban areas are now comparable with the West. Methods We conducted a hospital-based case-control study and collected data from 350 cases of acute myocardial infarction and 700 controls matched on age, gender, and hospital in New Delhi and Bangalore. We used conditional logistic regression to control for the matching and other risk factors. Results Of the controls, 48% participated in some form of leisure-time exercise compared with 38% of cases. In age- and sex-adjusted analyses, people in the highest level of leisure-time exercise (>145 metabolic equivalents [MET]-minutes per day, equivalent to 36 minutes of brisk walking per day) had a relative risk of 0.45 (95% CI: 0.31, 0.66) compared with non-exercisers. Multivariate adjustment for other risk factors did not substantially alter the association. We observed a positive association between non-work sedentary activity and CHD risk; people with >3.6 hours per day of sedentary activity (for example, television viewing) had an elevated risk of 1.88 (95% CI: 1.09, 3.20) compared with <70 minutes per day in multivariate analysis. Conclusion Leisure-time exercise, including as much as 35-40 minutes per day of brisk walking, was protective for CHD risk and sedentary lifestyles were positively associated with risk of CHD. Given limited resources for care of CHD in India and the important role of physical exercise in disease risk in urban India, improvements in physical activity should be promoted. JF - International Journal of Epidemiology AU - Rastogi, T AU - Vaz, M AU - Spiegelman, D AU - Reddy, K S AU - Bharathi, A V AU - Stampfer, MJ AU - Willett, W C AU - Ascherio, A AD - NEB, Division of Cancer Epidemiology & Genetics, National Cancer Institute, NIH, DHHS, 6120 Executive Blvd, EPS 320, Rockville MD 20852 USA, trastogi@post.harvard.edu Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 759 EP - 767 VL - 33 IS - 4 SN - 0300-5771, 0300-5771 KW - Risk Abstracts; Physical Education Index KW - Age KW - Physical activity KW - Promotion KW - Walking KW - Exercise KW - India KW - Risk factors KW - Analysis KW - Gender KW - Television KW - Cardiovascular diseases KW - Health promotion KW - Urban areas KW - Hospitals KW - Heart diseases KW - Urban environment KW - R2 23060:Medical and environmental health KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17559629?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Epidemiology&rft.atitle=Physical+activity+and+risk+of+coronary+heart+disease+in+India&rft.au=Rastogi%2C+T%3BVaz%2C+M%3BSpiegelman%2C+D%3BReddy%2C+K+S%3BBharathi%2C+A+V%3BStampfer%2C+MJ%3BWillett%2C+W+C%3BAscherio%2C+A&rft.aulast=Rastogi&rft.aufirst=T&rft.date=2004-08-01&rft.volume=33&rft.issue=4&rft.spage=759&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Epidemiology&rft.issn=03005771&rft_id=info:doi/10.1093%2Fije%2Fdyh042 LA - English DB - Physical Education Index; ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Urban environment; Exercise; Analysis; Heart diseases; Risk factors; Walking; Hospitals; Television; Promotion; Age; Gender; India; Urban areas; Physical activity; Cardiovascular diseases; Health promotion DO - http://dx.doi.org/10.1093/ije/dyh042 ER - TY - JOUR T1 - Imaging of myocardial infarction for diagnosis and intervention using real-time interactive MRI without ECG-gating or breath-holding AN - 17380507; 6494140 AB - Current methods for MRI of infarcted myocardium require ECG-gating and breath-holding during contrast-enhanced segmented k-space inversion-recovery (IR) imaging. However, ECG-gating can be problematic in MRI, and breath-holding can be difficult for some patients. This work demonstrates that infarcted tissue can be visualized without ECG-gating or breath-holding with the use of intermittent inversion pulses during real-time (RT) interactive imaging with steady-state free precession (SSFP). The sequence generates a RT image stream containing a myocardium-nulled image every few frames, which allows nearly simultaneous observation of both infarcted regions and wall motion. First-pass perfusion and wall motion can be simultaneously observed with minor parameter modifications. This method may reduce diagnostic scan time, expand the target population, improve patient comfort, and facilitate targeted, interventional treatment of infarcted myocardium. Supplementary material for this article can be found on the MRM website at http://www.interscience.wiley.com/jpages/0740-3194/suppmat/index.h tml. JF - Magnetic Resonance in Medicine AU - Guttman, Michael A AU - Dick, Alexander J AU - Raman, Venkatesh K AU - Arai, Andrew E AU - Lederman, Robert J AU - McVeigh, Elliot R AD - NIH/NHLBI, 10 Center Dr., Building 10, Room B1D416, Bethesda, MD 20892-1061, USA, mguttman@nih.gov Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 354 EP - 361 PB - John Wiley & Sons, Ltd. VL - 52 IS - 2 SN - 0740-3194, 0740-3194 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Heart KW - Perfusion KW - Magnetic resonance imaging KW - N.M.R. KW - Myocardial infarction KW - Myocardium KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17380507?accountid=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=Imaging+of+myocardial+infarction+for+diagnosis+and+intervention+using+real-time+interactive+MRI+without+ECG-gating+or+breath-holding&rft.au=Guttman%2C+Michael+A%3BDick%2C+Alexander+J%3BRaman%2C+Venkatesh+K%3BArai%2C+Andrew+E%3BLederman%2C+Robert+J%3BMcVeigh%2C+Elliot+R&rft.aulast=Guttman&rft.aufirst=Michael&rft.date=2004-08-01&rft.volume=52&rft.issue=2&rft.spage=354&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.20174 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-03-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Magnetic resonance imaging; Myocardium; N.M.R.; Perfusion; Heart; Myocardial infarction DO - http://dx.doi.org/10.1002/mrm.20174 ER - TY - JOUR T1 - Sensitivity of femoral orientation estimates to condylar surface and MR image plane location AN - 17378668; 6482101 AB - Purpose To define the femoral anatomic region that provides the most reliable reference for measuring femoral orientation, from which patellofemoral and tibiofemoral orientation can be measured. Materials and Methods After a three-dimensional image-based osteo-alignment procedure, two independent estimates of distal femoral orientation, the anterior (AFA) and posterior femoral angles (PFA), were acquired. These sets were comprised of 31 axial femoral orientation estimates each (obtained across a region 10 mm above to. JF - Journal of Magnetic Resonance Imaging AU - Shibanuma, N AU - Sheehan, F T AU - Lipsky, P E AU - Stanhope, S J AD - Building 10, Room 6s235, MSC 1604, National Institutes of Health, Bethesda, MD 20892-1604, USA, fsheehan@cc.nih.gov Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 300 EP - 305 VL - 20 IS - 2 SN - 1053-1807, 1053-1807 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Magnetic resonance imaging KW - Femur KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17378668?accountid=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=Sensitivity+of+femoral+orientation+estimates+to+condylar+surface+and+MR+image+plane+location&rft.au=Shibanuma%2C+N%3BSheehan%2C+F+T%3BLipsky%2C+P+E%3BStanhope%2C+S+J&rft.aulast=Shibanuma&rft.aufirst=N&rft.date=2004-08-01&rft.volume=20&rft.issue=2&rft.spage=300&rft.isbn=&rft.btitle=&rft.title=Journal+of+Magnetic+Resonance+Imaging&rft.issn=10531807&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-07-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Magnetic resonance imaging; Femur ER - TY - JOUR T1 - Measures of Accuracy for Active Shoulder Movements at 3 Different Speeds With Kinesthetic and Visual Feedback AN - 17337589; 6384854 AB - To compare measures of end point accuracy (EPA) for 2 feedback conditions: (1) visual and kinesthetic feedback and (2) kinesthetic feedback alone, during shoulder movements, at 3 different speeds. Shoulder joint kinesthesia is typically reported with EPA measures, such as constant error. Reporting multiple measures of EPA, such as variable error and absolute error, could provide a more detailed description of performance. Subjects were seated with the shoulder abducted 90 degree in the scapular plane and externally rotated 75 degree , with the forearm placed in a custom shoulder wheel. Subjects internally rotated the shoulder 27 degree to a target position at 48 degree of shoulder external rotation for both conditions. Motion analysis was used to determine peak angular velocity and 3 EPA measures for shoulder movements. Each EPA measure was compared between the 2 feedback conditions and among the 3 speeds with a separate 2-way analysis of variance. Movements performed with kinesthetic feedback alone, measured by constant error (P<.01), variable error (P<.01), and absolute error (P<.01), were less accurate than movements performed with visual and kinesthetic feedback. Faster movements were less accurate when measured by constant error (P = .01) and absolute error (P<.01) than slower movements. Subjects tended to overshoot the target in the absence of visual feedback; however, movement speed played minimal role in the overshooting. Multiple measures of EPA, such as constant, variable, and absolute error during simple restricted shoulder movements may provide additional information regarding the evaluation of a motor performance or identify different central nervous system control mechanisms for joint kinesthesia. JF - Journal of Orthopaedic & Sports Physical Therapy AU - Brindle, T J AU - Nitz, A J AU - Uhl, T L AU - Kifer, E AU - Shapiro, R AD - Physical Disabilities Branch, National Institutes of Health, Bethesda, MD, USA Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 468 EP - 478 VL - 34 IS - 8 SN - 0190-6011, 0190-6011 KW - Physical Education Index KW - PE 100:Kinesiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17337589?accountid=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+Orthopaedic+%26+Sports+Physical+Therapy&rft.atitle=Measures+of+Accuracy+for+Active+Shoulder+Movements+at+3+Different+Speeds+With+Kinesthetic+and+Visual+Feedback&rft.au=Brindle%2C+T+J%3BNitz%2C+A+J%3BUhl%2C+T+L%3BKifer%2C+E%3BShapiro%2C+R&rft.aulast=Brindle&rft.aufirst=T&rft.date=2004-08-01&rft.volume=34&rft.issue=8&rft.spage=468&rft.isbn=&rft.btitle=&rft.title=Journal+of+Orthopaedic+%26+Sports+Physical+Therapy&rft.issn=01906011&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-03-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Radio frequency continuous-wave and time-domain EPR imaging and Overhauser-enhanced magnetic resonance imaging of small animals: instrumental developments and comparison of relative merits for functional imaging AN - 17122147; 6755180 AB - Electron paramagnetic resonance (EPR) imaging in the continuous wave (CW) and time-domain modes, as well as Overhauser-enhanced magnetic resonance imaging in vivo is described. The review is based mainly on the CW and time-domain EPR instrumentation at 300 MHz developed in our laboratory, and the relative merits of these methods for functional in vivo imaging of small animals to assess hypoxia and tissue redox status are described. Overhauser imaging of small animals at magnetic fields in the range 10-15 mT that is being carried out in our laboratory for tumor imaging and the evaluation of tumor hypoxia based on quantitative evaluation of Overhauser enhancement is also described. Alternate approaches to spectral-spatial imaging using the transverse decay constants to infer in situ line widths and hence in vivo pO sub(2) using CW and time-domain EPR imaging are also discussed. The nature of the spin probes used, the quality of the images obtained in all the three methods, the achievable resolution, limitations and possible future directions in small animal functional imaging with these modalities are summarized. JF - NMR in Biomedicine AU - Subramanian, Sankaran AU - Matsumoto, Ken-Ichiro AU - Mitchell, James B AU - Krishna, Murali C AD - Biomedical Imaging Section, Radiation Biology Branch, CCR, NCI, NIH, Bethesda, MD 20892, USA, murali@helix.nih.gov Y1 - 2004/08// PY - 2004 DA - Aug 2004 SP - 263 EP - 294 PB - John Wiley & Sons, Ltd. VL - 17 IS - 5 SN - 0952-3480, 0952-3480 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - E.S.R. KW - Magnetic fields KW - Hypoxia KW - Reviews KW - Magnetic resonance imaging KW - N.M.R. KW - Nuclear Overhauser effect KW - Spin probes KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17122147?accountid=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=NMR+in+Biomedicine&rft.atitle=Radio+frequency+continuous-wave+and+time-domain+EPR+imaging+and+Overhauser-enhanced+magnetic+resonance+imaging+of+small+animals%3A+instrumental+developments+and+comparison+of+relative+merits+for+functional+imaging&rft.au=Subramanian%2C+Sankaran%3BMatsumoto%2C+Ken-Ichiro%3BMitchell%2C+James+B%3BKrishna%2C+Murali+C&rft.aulast=Subramanian&rft.aufirst=Sankaran&rft.date=2004-08-01&rft.volume=17&rft.issue=5&rft.spage=263&rft.isbn=&rft.btitle=&rft.title=NMR+in+Biomedicine&rft.issn=09523480&rft_id=info:doi/10.1002%2Fnbm.897 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-05-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - E.S.R.; Magnetic fields; Reviews; Hypoxia; Magnetic resonance imaging; N.M.R.; Nuclear Overhauser effect; Spin probes DO - http://dx.doi.org/10.1002/nbm.897 ER - TY - JOUR T1 - Arsenic transport by the human multidrug resistance protein 1 (MRP1/ABCC1). Evidence that a tri-glutathione conjugate is required. AN - 66743064; 15161912 AB - Inorganic arsenic is an established human carcinogen, but its metabolism is incompletely defined. The ATP binding cassette protein, multidrug resistance protein (MRP1/ABCC1), transports conjugated organic anions (e.g. leukotriene C(4)) and also co-transports certain unmodified xenobiotics (e.g. vincristine) with glutathione (GSH). MRP1 also confers resistance to arsenic in association with GSH; however, the mechanism and the species of arsenic transported are unknown. Using membrane vesicles prepared from the MRP1-overexpressing lung cancer cell line, H69AR, we found that MRP1 transports arsenite (As(III)) only in the presence of GSH but does not transport arsenate (As(V)) (with or without GSH). The non-reducing GSH analogs L-gamma-glutamyl-L-alpha-aminobutyryl glycine and S-methyl GSH did not support As(III) transport, indicating that the free thiol group of GSH is required. GSH-dependent transport of As(III) was 2-fold higher at pH 6.5-7 than at a more basic pH, consistent with the formation and transport of the acid-stable arsenic triglutathione (As(GS)(3)). Immunoblot analysis of H69AR vesicles revealed the unexpected membrane association of GSH S-transferase P1-1 (GSTP1-1). Membrane vesicles from an MRP1-transfected HeLa cell line lacking membrane-associated GSTP1-1 did not transport As(III) even in the presence of GSH but did transport synthetic As(GS)(3). The addition of exogenous GSTP1-1 to HeLa-MRP1 vesicles resulted in GSH-dependent As(III) transport. The apparent K(m) of As(GS)(3) for MRP1 was 0.32 microM, suggesting a remarkably high relative affinity. As(GS)(3) transport by MRP1 was osmotically sensitive and was inhibited by several conjugated organic anions (MRP1 substrates) as well as the metalloid antimonite (K(i) 2.8 microM). As(GS)(3) transport experiments using MRP1 mutants with substrate specificities differing from wild-type MRP1 suggested a commonality in the substrate binding pockets of As(GS)(3) and leukotriene C(4). Finally, human MRP2 also transported As(GS)(3). In conclusion, MRP1 transports inorganic arsenic as a tri-GSH conjugate, and GSTP1-1 may have a synergistic role in this process. JF - The Journal of biological chemistry AU - Leslie, Elaine M AU - Haimeur, Anass AU - Waalkes, Michael P AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2004/07/30/ PY - 2004 DA - 2004 Jul 30 SP - 32700 EP - 32708 VL - 279 IS - 31 SN - 0021-9258, 0021-9258 KW - Anions KW - 0 KW - Antibodies, Monoclonal KW - Carcinogens KW - Multidrug Resistance-Associated Proteins KW - Oligopeptides KW - Protein Isoforms KW - Sulfhydryl Compounds KW - Aspartic Acid KW - 30KYC7MIAI KW - ophthalmic acid KW - 3A60475Q1Q KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Glutathione KW - GAN16C9B8O KW - Leucine KW - GMW67QNF9C KW - Cadmium Chloride KW - J6K4F9V3BA KW - Lysine KW - K3Z4F929H6 KW - Arsenic KW - N712M78A8G KW - multidrug resistance-associated protein 1 KW - Y49M64GZ4Q KW - Index Medicus KW - Microscopy, Confocal KW - Animals KW - Humans KW - Hydrogen-Ion Concentration KW - Biological Transport KW - Drug Resistance KW - Leucine -- chemistry KW - Aspartic Acid -- chemistry KW - Genetic Vectors KW - Time Factors KW - Immunoblotting KW - Lysine -- chemistry KW - Dose-Response Relationship, Drug KW - Antibodies, Monoclonal -- metabolism KW - HeLa Cells KW - Cadmium Chloride -- pharmacology KW - Glutathione Transferase -- metabolism KW - Cell Line, Tumor KW - Mice KW - Antibodies, Monoclonal -- chemistry KW - Osmosis KW - Transfection KW - Kinetics KW - Oligopeptides -- pharmacology KW - Substrate Specificity KW - Cell Membrane -- metabolism KW - Mutation KW - Cell Line KW - Arsenic -- pharmacokinetics KW - Arsenic -- metabolism KW - Glutathione -- metabolism KW - Multidrug Resistance-Associated Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66743064?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Arsenic+transport+by+the+human+multidrug+resistance+protein+1+%28MRP1%2FABCC1%29.+Evidence+that+a+tri-glutathione+conjugate+is+required.&rft.au=Leslie%2C+Elaine+M%3BHaimeur%2C+Anass%3BWaalkes%2C+Michael+P&rft.aulast=Leslie&rft.aufirst=Elaine&rft.date=2004-07-30&rft.volume=279&rft.issue=31&rft.spage=32700&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 - 2004-09-10 N1 - Date created - 2004-07-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional redundancy of the human CCL4 and CCL4L1 chemokine genes. AN - 66682860; 15240137 AB - CCL4 and CCL4L1 are two CC chemokine genes located at chromosome 17q21 whose mature proteins differ at only a single amino acid. Abundant functional information exists for CCL4, however, CCL4L1 has only recently been recognized as a distinct gene, thus information describing it is wanting. The CCL4L1 protein was synthesized in Escherichia coli and compared with the CCL4 protein. Competitive binding studies using HEK-293/CCR5 cells produced comparable EC50 values for the two proteins. Similarly, chemotaxis assays with cells expressing CCR1, CCR3, or CCR5 revealed no substantial differences. CCL4L1 was somewhat more effective at inhibiting HIV-1 replication in PBMCs than was CCL4, however the difference was not statistically significant. These data combined with the observation of individual variation in CCL4L1 gene copy number [Eur. J. Immunol. 32 (2002) 3016, Genomics 83 (2004) 735] support the contention that the CCL4 and CCL4L1 proteins have redundant functions. JF - Biochemical and biophysical research communications AU - Howard, O M Zack AU - Turpin, Jim A AU - Goldman, Robert AU - Modi, William S AD - Laboratory of Molecular Immunoregulation, NCI-Frederick, Frederick, MD 21702, USA. Y1 - 2004/07/30/ PY - 2004 DA - 2004 Jul 30 SP - 927 EP - 931 VL - 320 IS - 3 SN - 0006-291X, 0006-291X KW - CCL4 protein, human KW - 0 KW - CCL4L1 protein, human KW - Chemokine CCL4 KW - Chemokines KW - Chemokines, CC KW - Macrophage Inflammatory Proteins KW - Proteins KW - Receptors, CCR5 KW - Index Medicus KW - Chemokines -- metabolism KW - Chemokines -- chemistry KW - Chemokines -- pharmacology KW - Chemokines -- genetics KW - Virus Replication -- drug effects KW - Humans KW - Molecular Sequence Data KW - Lethal Dose 50 KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Cell Line KW - Structure-Activity Relationship KW - Kidney -- metabolism KW - Chemotaxis -- physiology KW - Kidney -- drug effects KW - Chemokines, CC -- genetics KW - Proteins -- genetics KW - Proteins -- metabolism KW - Proteins -- pharmacology KW - Chemokines, CC -- metabolism KW - Proteins -- chemistry KW - Chemokines, CC -- pharmacology KW - HIV-1 -- growth & development KW - HIV-1 -- drug effects KW - Receptors, CCR5 -- metabolism KW - Chemokines, CC -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66682860?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Functional+redundancy+of+the+human+CCL4+and+CCL4L1+chemokine+genes.&rft.au=Howard%2C+O+M+Zack%3BTurpin%2C+Jim+A%3BGoldman%2C+Robert%3BModi%2C+William+S&rft.aulast=Howard&rft.aufirst=O+M&rft.date=2004-07-30&rft.volume=320&rft.issue=3&rft.spage=927&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 - 2004-08-26 N1 - Date created - 2004-07-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Investigating the Role of the Little Finger Domain of Y-family DNA Polymerases in Low Fidelity Synthesis and Translesion Replication AN - 17999938; 5964061 AB - Dpo4 and Dbh are Y-family polymerases that originate from two closely related strains of Sulfolobaceae: Quite surprisingly, however, the two polymerases exhibit different enzymatic properties in vitro. For example, Dpo4 can replicate past a variety of DNA lesions, yet Dbh does so with a much lower efficiency. When replicating undamaged DNA, Dpo4 is prone to make base pair substitutions, whereas Dbh predominantly makes single-base deletions. Overall, the two proteins are 54% identical, but the greatest divergence is found in their respective little finger (LF) domains, which are only 41% identical. To investigate the role of the LF domain in the fidelity and lesion-bypassing abilities of Y-family polymerases, we have generated chimeras of Dpo4 and Dbh in which their LF domains have been interchanged. Interestingly, by replacing the LF domain of Dbh with that of Dpo4, the enzymatic properties of the chimeric enzyme are more Dpo4-like in that the enzyme is more processive, can bypass an abasic site and a thymine-thymine cyclobutane pyrimidine dimer, and predominantly makes base pair substitutions when replicating undamaged DNA. The converse is true for the Dpo4-LF-Dbh chimera, which is more Dbh-like in its processivity and ability to bypass DNA adducts and generate single-base deletion errors. Our studies indicate that the unique but variable LF domain of Y-family polymerases plays a major role in determining the enzymatic and biological properties of each individual Y-family member. JF - Journal of Biological Chemistry AU - Boudsocq, Francois AU - Kokoska, Robert J AU - Plosky, Brian S AU - Vaisman, Alexandra AU - Ling, Hong AU - Kunkel, Thomas A AU - Yang, Wei AU - Woodgate, Roger AD - Section on DNA Replication, Repair, and Mutagenesis, Laboratory of Genomic Integrity, NICHD, National Institutes of Health, Bethesda, Maryland Y1 - 2004/07/30/ PY - 2004 DA - 2004 Jul 30 SP - 32932 EP - 32940 PB - American Society for Biochemistry and Molecular Biology, 9650 Rockville Pike Bethesda MD 20814-3996 USA, [mailto:asbmb@asbmb.faseb.org], [URL:http://www.jbc.org] VL - 279 IS - 31 SN - 0021-9258, 0021-9258 KW - Dpo4 protein KW - LF domain KW - Dbh protein KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Replication KW - DNA-directed DNA polymerase KW - Enzymatic activity KW - Sulfolobaceae KW - J 02725:DNA KW - N 14722:DNA polymerases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17999938?accountid=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=Investigating+the+Role+of+the+Little+Finger+Domain+of+Y-family+DNA+Polymerases+in+Low+Fidelity+Synthesis+and+Translesion+Replication&rft.au=Boudsocq%2C+Francois%3BKokoska%2C+Robert+J%3BPlosky%2C+Brian+S%3BVaisman%2C+Alexandra%3BLing%2C+Hong%3BKunkel%2C+Thomas+A%3BYang%2C+Wei%3BWoodgate%2C+Roger&rft.aulast=Boudsocq&rft.aufirst=Francois&rft.date=2004-07-30&rft.volume=279&rft.issue=31&rft.spage=32932&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Sulfolobaceae; Enzymatic activity; Replication; DNA-directed DNA polymerase ER - TY - JOUR T1 - Interaction of noncompetitive inhibitors with an immobilized alpha3beta4 nicotinic acetylcholine receptor investigated by affinity chromatography, quantitative-structure activity relationship analysis, and molecular docking. AN - 66733329; 15267239 AB - A large number of drug substances act as noncompetitive inhibitors (NCIs) of the nicotinic acetylcholine receptor (nAChR) by blocking the ion flux through the channel. An affinity chromatography technique has been developed for investigating the interactions between NCIs and the alpha3beta4 subtype of neuronal nAChR. The data obtained from the chromatographic study were used to construct QSAR models of the NCI-nAChR binding with both electronic and steric parameters observed as important descriptors. A molecular model of the transmembrane domain of the alpha3beta4 subtype of nAChR was constructed and used to simulate the docking of a series of NCIs. A key aspect of the model was the discovery of the cleft produced by the incorporation of the bulky phenylalanine moiety into the nonpolar section of the lumen by the beta4 subunit. Quantitatively, the results of docking simulations modeled the experimental affinity data better than QSAR results. The computational approach, combined with the modeling of NCI-nAChR interaction by affinity chromatography, can be used to predict possible toxicities and adverse interactions. JF - Journal of medicinal chemistry AU - Jozwiak, Krzysztof AU - Ravichandran, Sarangan AU - Collins, Jack R AU - Wainer, Irving W AD - Gerontology Research Center, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, Maryland 21224, USA. Y1 - 2004/07/29/ PY - 2004 DA - 2004 Jul 29 SP - 4008 EP - 4021 VL - 47 IS - 16 SN - 0022-2623, 0022-2623 KW - Ligands KW - 0 KW - Nicotinic Antagonists KW - Protein Subunits KW - Receptors, Nicotinic KW - Dextromethorphan KW - 7355X3ROTS KW - Index Medicus KW - Chromatography, Affinity KW - Sequence Alignment KW - Quantitative Structure-Activity Relationship KW - Dextromethorphan -- chemistry KW - Neurons -- chemistry KW - Models, Molecular KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Molecular Conformation KW - Protein Subunits -- chemistry KW - Nicotinic Antagonists -- chemistry KW - Receptors, Nicotinic -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66733329?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Interaction+of+noncompetitive+inhibitors+with+an+immobilized+alpha3beta4+nicotinic+acetylcholine+receptor+investigated+by+affinity+chromatography%2C+quantitative-structure+activity+relationship+analysis%2C+and+molecular+docking.&rft.au=Jozwiak%2C+Krzysztof%3BRavichandran%2C+Sarangan%3BCollins%2C+Jack+R%3BWainer%2C+Irving+W&rft.aulast=Jozwiak&rft.aufirst=Krzysztof&rft.date=2004-07-29&rft.volume=47&rft.issue=16&rft.spage=4008&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 - 2004-08-24 N1 - Date created - 2004-07-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutational analysis of ABCG2: role of the GXXXG motif. AN - 66720746; 15260487 AB - ABCG2 (BCRP/MXR/ABCP) is a half-transporter associated with multidrug resistance that presumably homodimerizes for function. It has a conserved GXXXG motif in its first transmembrane segment, a motif that has been linked with dimerization in other proteins, e.g., glycophorin A. We substituted either or both glycines of this GXXXG motif with leucines to evaluate the impact on drug transport, ATP hydrolysis, cross-linking, and susceptibility to degradation. All mutants also carried the R482G gain-of-function mutation, and all migrated to the cell surface. The mutations resulted in lost transport for rhodamine 123 and impaired mitoxantrone, pheophorbide a, and BODIPY-prazosin transport, particularly in the double leucine mutant (G406L/G410L). Basal ATPase activity of the G406L/G410L mutant was comparable to the empty vector transfected cells with no substrate induction. Despite impaired function, the mutants retained susceptibility to cross-linking using either disuccinimidyl suberate (DSS) or the reducible dithiobis(succinimidyl propionate) (DSP) and demonstrated a high molecular weight complex under nonreducing conditions. Mutations to alanine at the same positions yielded fully functional transporters. Finally, we exposed cells to mitoxantrone to promote folding and processing of the mutant proteins, which in the leucine mutants resulted in increased amounts detected on immunoblot and by immunofluorescence. These studies support a hypothesis that the GXXXG motif promotes proper packing of the transmembrane segments in the functional ABCG2 homodimer, although it does not solely arbitrate dimerization. JF - Biochemistry AU - Polgar, Orsolya AU - Robey, Robert W AU - Morisaki, Kuniaki AU - Dean, Michael AU - Michejda, Christopher AU - Sauna, Zuben E AU - Ambudkar, Suresh V AU - Tarasova, Nadya AU - Bates, Susan E AD - Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland 20892, USA. Y1 - 2004/07/27/ PY - 2004 DA - 2004 Jul 27 SP - 9448 EP - 9456 VL - 43 IS - 29 SN - 0006-2960, 0006-2960 KW - ABCG2 protein, human KW - 0 KW - ATP Binding Cassette Transporter, Sub-Family G, Member 2 KW - Neoplasm Proteins KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Humans KW - Molecular Sequence Data KW - Flow Cytometry KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Cell Line KW - Amino Acid Motifs KW - Neoplasm Proteins -- genetics KW - ATP-Binding Cassette Transporters -- genetics KW - ATP-Binding Cassette Transporters -- chemistry KW - Neoplasm Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66720746?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutational+analysis+of+ABCG2%3A+role+of+the+GXXXG+motif.&rft.au=Polgar%2C+Orsolya%3BRobey%2C+Robert+W%3BMorisaki%2C+Kuniaki%3BDean%2C+Michael%3BMichejda%2C+Christopher%3BSauna%2C+Zuben+E%3BAmbudkar%2C+Suresh+V%3BTarasova%2C+Nadya%3BBates%2C+Susan+E&rft.aulast=Polgar&rft.aufirst=Orsolya&rft.date=2004-07-27&rft.volume=43&rft.issue=29&rft.spage=9448&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-20 N1 - Date created - 2004-07-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - MRI detection of single particles for cellular imaging AN - 17681959; 5963847 AB - There is rapid growth in the use of MRI for molecular and cellular imaging. Much of this work relies on the high relaxivity of nanometer-sized, ultrasmall dextran-coated iron oxide particles. Typically, millions of dextran-coated ultrasmall iron oxide particles must be loaded into cells for efficient detection. Here we show that single, micrometer-sized iron oxide particles (MPIOs) can be detected by MRI in vitro in agarose samples, in cultured cells, and in mouse embryos. Experiments studying effects of MRI resolution and particle size from 0.76 to 1.63 mu m indicated that effects can be readily detected from single MPIOs at 50- mu m resolution and significant signal effects could be detected at resolutions as low as 200 mu m. Cultured cells were labeled with fluorescent MPIOs such that single particles were present in individual cells. These single particles in single cells could be detected both by MRI and fluorescence microscopy. Finally, single particles injected into single-cell-stage mouse embryos could be detected at embryonic day 11.5, demonstrating that even after many cell divisions, daughter cells still carry individual particles. These results demonstrate that MRI can detect single particles and indicate that single-particle detection will be useful for cellular imaging. JF - Proceedings of the National Academy of Sciences, USA AU - Shapiro, Erik M AU - Skrtic, Stanko AU - Sharer, Kathryn AU - Hill, Jonathan M AU - Dunbar, Cynthia E AU - Koretsky, Alan P AD - Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke and Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD Y1 - 2004/07/27/ PY - 2004 DA - 2004 Jul 27 SP - 10901 EP - 10906 PB - National Academy of Sciences, 2101 Constitution Ave. Washington DC 20418 USA VL - 101 IS - 30 SN - 0027-8424, 0027-8424 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/17681959?accountid=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=MRI+detection+of+single+particles+for+cellular+imaging&rft.au=Shapiro%2C+Erik+M%3BSkrtic%2C+Stanko%3BSharer%2C+Kathryn%3BHill%2C+Jonathan+M%3BDunbar%2C+Cynthia+E%3BKoretsky%2C+Alan+P&rft.aulast=Shapiro&rft.aufirst=Erik&rft.date=2004-07-27&rft.volume=101&rft.issue=30&rft.spage=10901&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-04-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Myocardial protection at a crossroads: the need for translation into clinical therapy. AN - 66739977; 15271864 AB - Over the past 30 years, hundreds of experimental interventions (both pharmacologic and nonpharmacologic) have been reported to protect the ischemic myocardium in experimental animals; however, with the exception of early reperfusion, none has been translated into clinical practice. The National Heart, Lung, and Blood Institute convened a working group to discuss the reasons for the failure to translate potential therapies for protecting the heart from ischemia and reperfusion and to recommend new approaches to accomplish this goal. The Working Group concluded that cardioprotection in the setting of acute myocardial infarction, cardiac surgery, and cardiac arrest is at a crossroads. Present basic research approaches to identify cardioprotective therapies are inefficient and counterproductive. For 3 decades, significant resources have been invested in single-center studies that have often yielded inconclusive results. A new paradigm is needed to obviate many of the difficulties associated with translation of basic science findings. The Working Group urged a new focus on translational research that emphasizes efficacy and clinically relevant outcomes, and recommended the establishment of a system for rigorous preclinical testing of promising cardioprotective agents with clinical trial-like approaches (ie, blinded, randomized, multicenter, and adequately powered studies using standardized methods). A national preclinical research consortium would enable rational translation of important basic science findings into clinical use. The Working Group recommended that the National Institutes of Health proactively intervene to remedy current problems that impede translation of cardioprotective therapies. Their specific recommendations include the establishment of a preclinical consortium and the performance of 2 clinical studies that are likely to demonstrate effectiveness (phase III clinical trials of adenosine in acute myocardial infarction and cardiac surgery). JF - Circulation research AU - Bolli, Roberto AU - Becker, Lance AU - Gross, Garrett AU - Mentzer, Robert AU - Balshaw, David AU - Lathrop, David A AU - NHLBI Working Group on the Translation of Therapies for Protecting the Heart from Ischemia AD - Heart Research Program, Division of Heart and Vascular Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health & Human Services, Bethesda, Md 20892, USA. ; NHLBI Working Group on the Translation of Therapies for Protecting the Heart from Ischemia Y1 - 2004/07/23/ PY - 2004 DA - 2004 Jul 23 SP - 125 EP - 134 VL - 95 IS - 2 KW - Cardiotonic Agents KW - 0 KW - Guanidines KW - Sodium-Hydrogen Antiporter KW - Sulfones KW - cariporide KW - 7E3392891K KW - eniporide KW - 7IGF9182QU KW - Index Medicus KW - Myocardial Infarction -- pathology KW - Animals KW - Clinical Trials, Phase III as Topic KW - Guanidines -- administration & dosage KW - Humans KW - Clinical Trials as Topic KW - Drug Utilization KW - Sulfones -- administration & dosage KW - Sulfones -- adverse effects KW - Prospective Studies KW - Guanidines -- therapeutic use KW - Sulfones -- therapeutic use KW - Coronary Artery Bypass KW - Treatment Outcome KW - Sodium-Hydrogen Antiporter -- antagonists & inhibitors KW - Guanidines -- adverse effects KW - Drug Evaluation, Preclinical KW - Myocardial Infarction -- drug therapy KW - Myocardial Ischemia -- surgery KW - Myocardial Ischemia -- drug therapy KW - Myocardial Reperfusion Injury -- drug therapy KW - Cardiotonic Agents -- therapeutic use KW - Myocardial Ischemia -- prevention & control KW - Myocardial Reperfusion Injury -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66739977?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Circulation+research&rft.atitle=Myocardial+protection+at+a+crossroads%3A+the+need+for+translation+into+clinical+therapy.&rft.au=Bolli%2C+Roberto%3BBecker%2C+Lance%3BGross%2C+Garrett%3BMentzer%2C+Robert%3BBalshaw%2C+David%3BLathrop%2C+David+A%3BNHLBI+Working+Group+on+the+Translation+of+Therapies+for+Protecting+the+Heart+from+Ischemia&rft.aulast=Bolli&rft.aufirst=Roberto&rft.date=2004-07-23&rft.volume=95&rft.issue=2&rft.spage=125&rft.isbn=&rft.btitle=&rft.title=Circulation+research&rft.issn=1524-4571&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-08 N1 - Date created - 2004-07-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Influence of DNA structure on DNA polymerase beta active site function: extension of mutagenic DNA intermediates. AN - 66717877; 15145936 AB - In the ternary substrate complex of DNA polymerase (pol) beta, the nascent base pair (templating and incoming nucleotides) is sandwiched between the duplex DNA terminus and polymerase. To probe molecular interactions in the dNTP-binding pocket, we analyzed the kinetic behavior of wild-type pol beta on modified DNA substrates that alter the structure of the DNA terminus and represent mutagenic intermediates. The DNA substrates were modified to 1) alter the sequence of the duplex terminus (matched and mismatched), 2) introduce abasic sites near the nascent base pair, and 3) insert extra bases in the primer or template strands to mimic frameshift intermediates. The results indicate that the nucleotide insertion efficiency (k(cat)/K(m), dGTP-dC) is highly dependent on the sequence identity of the matched (i.e. Watson-Crick base pair) DNA terminus (template/primer, G/C approximately A/T > T/A approximately C/G). Mismatches at the primer terminus strongly diminish correct nucleotide insertion efficiency but do not affect DNA binding affinity. Transition intermediates are generally extended more easily than transversions. Most mismatched primer termini decrease the rate of insertion and binding affinity of the incoming nucleotide. In contrast, the loss of catalytic efficiency with homopurine mismatches at the duplex DNA terminus is entirely due to the inability to insert the incoming nucleotide, since K(d)((dGTP)) is not affected. Abasic sites and extra nucleotides in and around the duplex terminus decrease catalytic efficiency and are more detrimental to the nascent base pair binding pocket when situated in the primer strand than the equivalent position in the template strand. JF - The Journal of biological chemistry AU - Beard, William A AU - Shock, David D AU - Wilson, Samuel H AD - Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2004/07/23/ PY - 2004 DA - 2004 Jul 23 SP - 31921 EP - 31929 VL - 279 IS - 30 SN - 0021-9258, 0021-9258 KW - DNA KW - 9007-49-2 KW - DNA Polymerase beta KW - EC 2.7.7.- KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Frameshift Mutation KW - Base Sequence KW - Kinetics KW - Humans KW - Base Pair Mismatch KW - In Vitro Techniques KW - Binding, Competitive KW - Catalytic Domain KW - Substrate Specificity KW - Mutagenesis KW - DNA -- metabolism KW - DNA Polymerase beta -- chemistry KW - DNA -- genetics KW - DNA -- chemistry KW - DNA Polymerase beta -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66717877?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Influence+of+DNA+structure+on+DNA+polymerase+beta+active+site+function%3A+extension+of+mutagenic+DNA+intermediates.&rft.au=Beard%2C+William+A%3BShock%2C+David+D%3BWilson%2C+Samuel+H&rft.aulast=Beard&rft.aufirst=William&rft.date=2004-07-23&rft.volume=279&rft.issue=30&rft.spage=31921&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 - 2004-09-21 N1 - Date created - 2004-07-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The trihelical bundle subdomain of the GGA proteins interacts with multiple partners through overlapping but distinct sites. AN - 66716689; 15143060 AB - The Golgi-localized, gamma-adaptin ear-containing, ARF-binding (GGA) proteins are monomeric clathrin adaptors that mediate the sorting of cargo at the trans-Golgi network and endosomes. The GGAs contain four different domains named Vps27, Hrs, Stam (VHS); GGAs and TOM1 (GAT); hinge; and gamma-adaptin ear (GAE). The VHS domain recognizes transmembrane cargo, whereas the hinge and GAE regions bind clathrin and accessory proteins, respectively. The GAT domain is a polyfunctional module that interacts with various partners including the small GTPase ARF, the endosomal fusion regulator Rabaptin-5, ubiquitin, and the product of the tumor susceptibility gene 101 (TSG101). Previous x-ray crystallographic analyses showed that the GAT region is composed of two subdomains, an N-terminal helix-loop-helix containing the ARF binding site, and a C-terminal triple alpha-helical (trihelical) bundle. In this study, we define the Rabaptin-5 binding site on the GGA1-GAT domain and its relationship to the binding sites for ubiquitin and TSG101. Our observations show that Rabaptin-5, ubiquitin, and TSG101 bind to overlapping but distinct binding sites on the trihelical bundle. The different GAT binding partners engage in both competitive and cooperative interactions that may be important for the function of the GGAs in protein sorting. JF - The Journal of biological chemistry AU - Mattera, Rafael AU - Puertollano, Rosa AU - Smith, William J AU - Bonifacino, Juan S AD - Cell Biology and Metabolism Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2004/07/23/ PY - 2004 DA - 2004 Jul 23 SP - 31409 EP - 31418 VL - 279 IS - 30 SN - 0021-9258, 0021-9258 KW - Adaptor Proteins, Vesicular Transport KW - 0 KW - Carrier Proteins KW - GGA adaptor proteins KW - RABEP1 protein, human KW - Recombinant Proteins KW - Vesicular Transport Proteins KW - ADP-Ribosylation Factor 1 KW - EC 3.6.5.2 KW - ADP-Ribosylation Factors KW - rab GTP-Binding Proteins KW - Index Medicus KW - Vesicular Transport Proteins -- genetics KW - Models, Molecular KW - ADP-Ribosylation Factor 1 -- genetics KW - Humans KW - Two-Hybrid System Techniques KW - ADP-Ribosylation Factor 1 -- chemistry KW - Amino Acid Sequence KW - Recombinant Proteins -- genetics KW - rab GTP-Binding Proteins -- genetics KW - rab GTP-Binding Proteins -- chemistry KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- metabolism KW - ADP-Ribosylation Factor 1 -- metabolism KW - In Vitro Techniques KW - Molecular Sequence Data KW - Vesicular Transport Proteins -- metabolism KW - Recombinant Proteins -- chemistry KW - Binding Sites -- genetics KW - rab GTP-Binding Proteins -- metabolism KW - Sequence Homology, Amino Acid KW - Protein Structure, Tertiary KW - Vesicular Transport Proteins -- chemistry KW - Amino Acid Substitution KW - ADP-Ribosylation Factors -- genetics KW - Carrier Proteins -- metabolism KW - Carrier Proteins -- chemistry KW - ADP-Ribosylation Factors -- metabolism KW - Carrier Proteins -- genetics KW - ADP-Ribosylation Factors -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66716689?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+trihelical+bundle+subdomain+of+the+GGA+proteins+interacts+with+multiple+partners+through+overlapping+but+distinct+sites.&rft.au=Mattera%2C+Rafael%3BPuertollano%2C+Rosa%3BSmith%2C+William+J%3BBonifacino%2C+Juan+S&rft.aulast=Mattera&rft.aufirst=Rafael&rft.date=2004-07-23&rft.volume=279&rft.issue=30&rft.spage=31409&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 - 2004-09-21 N1 - Date created - 2004-07-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Higher versus Lower Positive End-Expiratory Pressures in Patients with the Acute Respiratory Distress Syndrome AN - 223939921; 15269312 AB - Background Most patients requiring mechanical ventilation for acute lung injury and the acute respiratory distress syndrome (ARDS) receive positive end-expiratory pressure (PEEP) of 5 to 12 cm of water. Higher PEEP levels may improve oxygenation and reduce ventilator-induced lung injury but may also cause circulatory depression and lung injury from overdistention. We conducted this trial to compare the effects of higher and lower PEEP levels on clinical outcomes in these patients. Methods We randomly assigned 549 patients with acute lung injury and ARDS to receive mechanical ventilation with either lower or higher PEEP levels, which were set according to different tables of predetermined combinations of PEEP and fraction of inspired oxygen. Results Mean (±SD) PEEP values on days 1 through 4 were 8.3±3.2 cm of water in the lower-PEEP group and 13.2±3.5 cm of water in the higher-PEEP group (P<0.001). The rates of death before hospital discharge were 24.9 percent and 27.5 percent, respectively (P=0.48; 95 percent confidence interval for the difference between groups, -10.0 to 4.7 percent). From day 1 to day 28, breathing was unassisted for a mean of 14.5±10.4 days in the lower-PEEP group and 13.8±10.6 days in the higher-PEEP group (P=0.50). Conclusions These results suggest that in patients with acute lung injury and ARDS who receive mechanical ventilation with a tidal-volume goal of 6 ml per kilogram of predicted body weight and an end-inspiratory plateau-pressure limit of 30 cm of water, clinical outcomes are similar whether lower or higher PEEP levels are used. JF - The New England Journal of Medicine AU - Brower, R G AU - Lanken, P N AU - MacIntyre, N AU - Matthay MA AU - Morris, A AU - Ancukiewicz, M AU - Schoenfeld, D AU - Thompson, B T AU - National Heart, Lung, and Blood Institute ARDS Clinical Trials Network AD - National Heart, Lung, and Blood Institute ARDS Clinical Trials Network Y1 - 2004/07/22/ PY - 2004 DA - 2004 Jul 22 SP - 327 EP - 36 CY - Boston PB - Massachusetts Medical Society VL - 351 IS - 4 SN - 00284793 KW - Medical Sciences KW - Biological Markers KW - Interleukin-6 KW - Pulmonary Surfactant-Associated Protein D KW - Intercellular Adhesion Molecule-1 KW - Ventilators KW - Lungs KW - Injuries KW - Respiratory distress syndrome KW - Mortality KW - Proteins KW - Respiratory Distress Syndrome, Adult -- mortality KW - Intercellular Adhesion Molecule-1 -- blood KW - Humans KW - Pulmonary Surfactant-Associated Protein D -- blood KW - Aged KW - Respiratory Physiological Phenomena KW - Biological Markers -- blood KW - Interleukin-6 -- blood KW - Respiratory Distress Syndrome, Adult -- blood KW - Hospital Mortality KW - Adult KW - Treatment Outcome KW - Respiratory Distress Syndrome, Adult -- physiopathology KW - Middle Aged KW - Female KW - Male KW - Positive-Pressure Respiration -- methods KW - Respiratory Distress Syndrome, Adult -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/223939921?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+Journal+of+Medicine&rft.atitle=Higher+versus+Lower+Positive+End-Expiratory+Pressures+in+Patients+with+the+Acute+Respiratory+Distress+Syndrome&rft.au=Brower%2C+R+G%3BLanken%2C+P+N%3BMacIntyre%2C+N%3BMatthay+MA%3BMorris%2C+A%3BAncukiewicz%2C+M%3BSchoenfeld%2C+D%3BThompson%2C+B+T%3BNational+Heart%2C+Lung%2C+and+Blood+Institute+ARDS+Clinical+Trials+Network&rft.aulast=Brower&rft.aufirst=R&rft.date=2004-07-22&rft.volume=351&rft.issue=4&rft.spage=327&rft.isbn=&rft.btitle=&rft.title=The+New+England+Journal+of+Medicine&rft.issn=00284793&rft_id=info:doi/ LA - English DB - ProQuest Central N1 - Copyright - Copyright © 2004 Massachusetts Medical Society. All rights reserved. N1 - Document feature - Tables; Graphs; Diagrams; References N1 - Last updated - 2014-04-21 N1 - CODEN - NEJMAG ER - TY - JOUR T1 - Neural activity protects hypothalamic magnocellular neurons against axotomy-induced programmed cell death. AN - 66732014; 15269267 AB - Axotomy typically leads to retrograde neuronal degeneration in the CNS. Studies in the hypothalamo-neurohypophysial system (HNS) have suggested that neural activity is supportive of magnocellular neuronal (MCN) survival after axotomy. In this study, we directly test this hypothesis by inhibiting neural activity in the HNS, both in vivo and in vitro, by the use of tetrodotoxin (TTX). After median eminence compression to produce axonal injury, unilateral superfusion of 3 microM TTX into the rat supraoptic nucleus (SON), delivered with the use of a miniature osmotic pump for 2 weeks in vivo, produced a decrease in the number of surviving MCNs in the TTX-treated SON, compared with the contralateral untreated side of the SON. In vitro application of 2.5 microM TTX for 2 weeks to the SON in organotypic culture produced a 73% decrease in the surviving MCNs, compared with untreated control cultures. Raising the extracellular KCl in the culture medium to 25 mM rescued the MCNs from the axotomy- and TTX-induced cell death. These data support the proposal that after axotomy, neural activity is neuroprotective in the HNS. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Shahar, Tal AU - House, Shirley B AU - Gainer, Harold AD - Laboratory of Neurochemistry, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-4130, USA. Y1 - 2004/07/21/ PY - 2004 DA - 2004 Jul 21 SP - 6553 EP - 6562 VL - 24 IS - 29 KW - Tetrodotoxin KW - 4368-28-9 KW - Potassium Chloride KW - 660YQ98I10 KW - Index Medicus KW - Animals KW - Axotomy KW - Synaptic Transmission -- drug effects KW - Potassium Chloride -- pharmacology KW - Rats KW - Tetrodotoxin -- toxicity KW - Rats, Sprague-Dawley KW - Neurites -- ultrastructure KW - Cell Survival -- drug effects KW - Neurites -- drug effects KW - Median Eminence -- surgery KW - Organ Culture Techniques KW - Male KW - Apoptosis KW - Supraoptic Nucleus -- cytology KW - Nerve Degeneration -- physiopathology KW - Neurons -- cytology KW - Nerve Degeneration -- pathology KW - Neurons -- physiology KW - Supraoptic Nucleus -- physiopathology KW - Supraoptic Nucleus -- drug effects KW - Neurons -- pathology KW - Nerve Degeneration -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66732014?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Neural+activity+protects+hypothalamic+magnocellular+neurons+against+axotomy-induced+programmed+cell+death.&rft.au=Shahar%2C+Tal%3BHouse%2C+Shirley+B%3BGainer%2C+Harold&rft.aulast=Shahar&rft.aufirst=Tal&rft.date=2004-07-21&rft.volume=24&rft.issue=29&rft.spage=6553&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 - 2005-03-21 N1 - Date created - 2004-07-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: J Neurosci. 2004 Aug 4;24(31):1 p following 7014 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dynamic characterization of a DNA repair enzyme: NMR studies of [methyl-13C]methionine-labeled DNA polymerase beta. AN - 66702336; 15248749 AB - Crystallographic characterization of DNA polymerase beta (pol beta) has suggested that multiple-domain and subdomain motions occur during substrate binding and catalysis. NMR studies of [methyl-(13)C]methionine-labeled pol beta were conducted to characterize the structural and dynamic response to ligand binding. The enzyme contains seven methionine residues, one of which is at the amino terminus and is partially removed by the expression system. Three of the methyl resonances were readily assigned using site-directed mutants. Assignment of the resonances of Met155, Met158, and Met191 was more difficult due to the spatial proximity of these residues, so that assignments were based on NOESY-HSQC data and on the response to paramagnetic Co(2+) addition, as well as shift perturbations observed for the site-directed mutants. The response of the methyl resonances to substrate binding was evaluated by the serial addition of a template oligonucleotide, a downstream 5'-phosphorylated oligonucleotide, and a primer oligonucleotide to create a two-nucleotide-gapped DNA substrate. Addition of the single-stranded template DNA resulted in selective broadening of the methyl resonance of Met18 in the 8 kDa lyase domain, and this resonance then shifted and sharpened upon addition of a 5'-phosphate-terminated downstream complementary oligonucleotide. Conversion of the two-nucleotide-gapped DNA substrate to a single-nucleotide-gapped substrate by incorporation of ddCMP produced a small perturbation of the Met236 resonance, which makes contact with the primer strand in the crystal structure. The addition of a second equivalent of ddCTP to form the pol beta-DNA-ddCTP ternary complex resulted in significant shifts for the resonances corresponding to Met155, Met191, Met236, and Met282. The Met155 methyl resonance is severely broadened, while the Met191 and Met282 resonances exhibit significant but less extreme broadening. Since only Met236 makes contact with the substrate, the effects on Met155, Met236, and Met282 result from indirect conformational and dynamic perturbations. Previous crystallographic characterization of this abortive complex indicated that a polymerase subdomain or segment (alpha-helix N) repositions itself to form one face of the binding pocket for the nascent base pair. Met282 serves as a probe for motion in this segment. Addition of Mg(2+)-dATP to pol beta in the absence of DNA produced qualitatively similar but much smaller effects on Met191 and Met155, but did not strongly perturb Met282, leading to the conclusion that Mg(2+)-dATP alone is insufficient to produce the large conformational changes that are observed in the abortive complex involving the gapped DNA with a blocked primer and ddNTP. Thus, the NMR data indicate that the nucleotide-DNA interaction appears to be essential for conformational activation. JF - Biochemistry AU - Bose-Basu, Bidisha AU - DeRose, Eugene F AU - Kirby, Thomas W AU - Mueller, Geoffrey A AU - Beard, William A AU - Wilson, Samuel H AU - London, Robert E AD - Laboratory of Structural Biology, NIEHS, NIH, Research Triangle Park, North Carolina 27709, USA. Y1 - 2004/07/20/ PY - 2004 DA - 2004 Jul 20 SP - 8911 EP - 8922 VL - 43 IS - 28 SN - 0006-2960, 0006-2960 KW - Carbon Isotopes KW - 0 KW - Deoxycytosine Nucleotides KW - Oligonucleotides KW - DNA Polymerase beta KW - EC 2.7.7.- KW - DNA Repair Enzymes KW - EC 6.5.1.- KW - Index Medicus KW - Molecular Structure KW - Animals KW - Motion KW - Oligonucleotides -- pharmacology KW - Deoxycytosine Nucleotides -- chemistry KW - Protein Conformation -- drug effects KW - Mutation, Missense KW - Protein Binding KW - Rats KW - Mutagenesis, Site-Directed KW - Deoxycytosine Nucleotides -- pharmacology KW - Oligonucleotides -- chemistry KW - Nuclear Magnetic Resonance, Biomolecular -- methods KW - DNA Polymerase beta -- chemistry KW - DNA Repair Enzymes -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66702336?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dynamic+characterization+of+a+DNA+repair+enzyme%3A+NMR+studies+of+%5Bmethyl-13C%5Dmethionine-labeled+DNA+polymerase+beta.&rft.au=Bose-Basu%2C+Bidisha%3BDeRose%2C+Eugene+F%3BKirby%2C+Thomas+W%3BMueller%2C+Geoffrey+A%3BBeard%2C+William+A%3BWilson%2C+Samuel+H%3BLondon%2C+Robert+E&rft.aulast=Bose-Basu&rft.aufirst=Bidisha&rft.date=2004-07-20&rft.volume=43&rft.issue=28&rft.spage=8911&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-09 N1 - Date created - 2004-07-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synthesis of a bromotyrosine-derived natural product inhibitor of mycothiol-S-conjugate amidase. AN - 66643258; 15203162 AB - Recently we described the structures of two new bromotyrosine-derived alkaloids that inhibit the detoxification enzyme mycothiol-S-conjugate amidase (MCA) from Mycobacterium tuberculosis. Here we describe a concise total synthesis of bromotyrosine oxime 1. The six-step synthesis of 1 utilized a trifluoromethyloxazole intermediate, whose hydrolysis product underwent alkylation and coupling to agmatine to give the inhibitor in approximately 40% overall yield. Oxime 1 inhibited MCA and its homolog AcGI deacetylase with IC(50) values of 30 and 150 microM, respectively. JF - Bioorganic & medicinal chemistry letters AU - Fetterolf, Brandon 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 - 2004/07/16/ PY - 2004 DA - 2004 Jul 16 SP - 3785 EP - 3788 VL - 14 IS - 14 SN - 0960-894X, 0960-894X KW - Anti-Infective Agents KW - 0 KW - Bacterial Proteins KW - Hydrocarbons, Fluorinated KW - Oxazoles KW - Oximes KW - bromotyrosine KW - Tyrosine KW - 42HK56048U KW - Amidohydrolases KW - EC 3.5.- KW - N-acetyl-1-D-inosityl-2-amino-2-deoxy-alpha-D-glucopyranoside deacetylase KW - EC 3.5.1.- KW - mycothiol S-conjugate amidase KW - Index Medicus KW - Hydrocarbons, Fluorinated -- chemistry KW - Kinetics KW - Oxazoles -- chemistry KW - Inhibitory Concentration 50 KW - Oximes -- chemistry KW - Hydrolysis KW - Structure-Activity Relationship KW - Alkylation KW - Amidohydrolases -- metabolism KW - Mycobacterium tuberculosis -- enzymology KW - Tyrosine -- pharmacology KW - Anti-Infective Agents -- pharmacology KW - Amidohydrolases -- antagonists & inhibitors KW - Tyrosine -- analogs & derivatives KW - Mycobacterium tuberculosis -- drug effects KW - Anti-Infective Agents -- chemical synthesis KW - Tyrosine -- chemical synthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66643258?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Synthesis+of+a+bromotyrosine-derived+natural+product+inhibitor+of+mycothiol-S-conjugate+amidase.&rft.au=Fetterolf%2C+Brandon%3BBewley%2C+Carole+A&rft.aulast=Fetterolf&rft.aufirst=Brandon&rft.date=2004-07-16&rft.volume=14&rft.issue=14&rft.spage=3785&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 - 2005-02-07 N1 - Date created - 2004-06-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I/II study of infusional vinblastine with the P-glycoprotein antagonist valspodar (PSC 833) in renal cell carcinoma. AN - 66733837; 15269145 AB - P-glycoprotein (Pgp) inhibitors have been under clinical evaluation for drug resistance reversal for over a decade. Valspodar (PSC 833) inhibits Pgp-mediated efflux but delays drug clearance, requiring reduction of anticancer drug dosage. We designed an infusional schedule for valspodar and vinblastine to mimic infusional vinblastine alone. The study was designed to determine the maximally tolerated dose of vinblastine, while attempting to understand the pharmacokinetic interactions between vinblastine and valspodar and to determine the response rate in patients with metastatic renal cell cancer. Thirty-nine patients received continuous infusion valspodar and vinblastine. Vinblastine was administered for 3 days to compensate for the expected delay in clearance and the required dose reduction. Valspodar was administered initially at a dose of 10 mg/kg/d; the dose of vinblastine varied. The maximum-tolerated dose of vinblastine was 1.3 mg/m(2)/d. As suggested previously, serum valspodar concentrations exceeded those needed for Pgp inhibition. Consequently, the dose of valspodar was reduced to 5 mg/kg, allowing a vinblastine dose of 2.1 mg/m(2)/d to be administered. Pharmacodynamic studies demonstrated continued inhibition of Pgp at lower valspodar doses by functional assay in Pgp-expressing CD56+ cells and by (99m)Tc-sestamibi imaging. A 15-fold range in cytochrome p450 activity was observed, as measured by midazolam clearance. No major responses were observed. These results suggest that the pharmacokinetic impact of cytochrome P450 inhibition by valspodar can be reduced although not eliminated, while preserving Pgp inhibition, thus separating the pharmacokinetic and pharmacodynamic activities of valspodar. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Bates, Susan E AU - Bakke, Susan AU - Kang, Min AU - Robey, Robert W AU - Zhai, Suoping AU - Thambi, Paul AU - Chen, Clara C AU - Patil, Sheela AU - Smith, Tom AU - Steinberg, Seth M AU - Merino, Maria AU - Goldspiel, Barry AU - Meadows, Beverly AU - Stein, Wilfred D AU - Choyke, Peter AU - Balis, Frank AU - Figg, William D AU - Fojo, Tito AD - Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA. sebates@helix.nih.gov Y1 - 2004/07/15/ PY - 2004 DA - 2004 Jul 15 SP - 4724 EP - 4733 VL - 10 IS - 14 SN - 1078-0432, 1078-0432 KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Cyclosporins KW - P-Glycoprotein KW - Vinblastine KW - 5V9KLZ54CY KW - valspodar KW - Q7ZP55KF3X KW - Index Medicus KW - Infusions, Intravenous KW - Area Under Curve KW - Dose-Response Relationship, Drug KW - Humans KW - Fatigue -- chemically induced KW - Metabolic Clearance Rate KW - Aged KW - Constipation -- chemically induced KW - P-Glycoprotein -- antagonists & inhibitors KW - Antineoplastic Agents, Phytogenic -- pharmacokinetics KW - Antineoplastic Agents, Phytogenic -- adverse effects KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Adolescent KW - Antineoplastic Agents, Phytogenic -- administration & dosage KW - Male KW - Female KW - Cyclosporins -- adverse effects KW - Carcinoma, Renal Cell -- pathology KW - Kidney Neoplasms -- pathology KW - Kidney Neoplasms -- drug therapy KW - Carcinoma, Renal Cell -- metabolism KW - Cyclosporins -- pharmacokinetics KW - Vinblastine -- pharmacokinetics KW - Kidney Neoplasms -- metabolism KW - Vinblastine -- administration & dosage KW - Carcinoma, Renal Cell -- drug therapy KW - Vinblastine -- adverse effects KW - Cyclosporins -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66733837?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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%2FII+study+of+infusional+vinblastine+with+the+P-glycoprotein+antagonist+valspodar+%28PSC+833%29+in+renal+cell+carcinoma.&rft.au=Bates%2C+Susan+E%3BBakke%2C+Susan%3BKang%2C+Min%3BRobey%2C+Robert+W%3BZhai%2C+Suoping%3BThambi%2C+Paul%3BChen%2C+Clara+C%3BPatil%2C+Sheela%3BSmith%2C+Tom%3BSteinberg%2C+Seth+M%3BMerino%2C+Maria%3BGoldspiel%2C+Barry%3BMeadows%2C+Beverly%3BStein%2C+Wilfred+D%3BChoyke%2C+Peter%3BBalis%2C+Frank%3BFigg%2C+William+D%3BFojo%2C+Tito&rft.aulast=Bates&rft.aufirst=Susan&rft.date=2004-07-15&rft.volume=10&rft.issue=14&rft.spage=4724&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 - 2005-01-19 N1 - Date created - 2004-07-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Using germ-line genetic variation to investigate and treat cancer. AN - 66689887; 15239980 AB - For many years, there has been spirited debate as to the relative importance of environmental and genetic factors in the pathogenesis of cancer. Current efforts to annotate the human genome for germ-line genetic variants should establish the foundation for dissecting the contribution of genetics to the risk for cancer susceptibility. Population-based studies should be conducted to determine the influence of germline genetic variation on cancer outcomes, including the efficacy of anti-cancer drugs and the risk for life-threatening toxicities. Although we are early in the investigation of the influence of germline genetics on cancer outcomes, it is likely that, in the future, it will be possible to individualize therapeutic interventions. In turn, knowledge of genetic risk factors could afford opportunities for prevention, early intervention and minimization of deleterious toxicities associated with cancer therapy. JF - Drug discovery today AU - Savage, Sharon A AU - Chanock, Stephen J AD - Section of Genomic Variation, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 2004/07/15/ PY - 2004 DA - 2004 Jul 15 SP - 610 EP - 618 VL - 9 IS - 14 SN - 1359-6446, 1359-6446 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Humans KW - Male KW - Female KW - Neoplasms -- drug therapy KW - Microsatellite Repeats -- genetics KW - Genome, Human KW - Antineoplastic Agents -- therapeutic use KW - Polymorphism, Single Nucleotide -- genetics KW - Polymorphism, Single Nucleotide -- physiology KW - Neoplasms -- genetics KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66689887?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+discovery+today&rft.atitle=Using+germ-line+genetic+variation+to+investigate+and+treat+cancer.&rft.au=Savage%2C+Sharon+A%3BChanock%2C+Stephen+J&rft.aulast=Savage&rft.aufirst=Sharon&rft.date=2004-07-15&rft.volume=9&rft.issue=14&rft.spage=610&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 completed - 2004-08-31 N1 - Date created - 2004-07-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 2-amino-O4-benzylpteridine derivatives: potent inactivators of O6-alkylguanine-DNA alkyltransferase. AN - 66686363; 15239666 AB - 2-amino-O4-benzylpteridine (1), 2-amino-O4-benzyl-6,7-dimethylpteridine (2), 2-amino-O4-benzyl-6-hydroxymethylpteridine (4), 2-amino-O4-benzylpteridine-6-carboxylic acid (5), 2-amino-O4-benzyl-6-formylpteridine (6), and O4-benzylfolic acid (7) are shown to be as potent or more potent inactivators of the human DNA repair protein O6-alkylguanine-DNA alkyltransferase (alkyltransferase) in vitro than O6-benzylguanine, the prototype alkyltransferase inactivator currently in clinical trials. Additionally, the negatively charged (at physiological pH) inactivators 2-amino-O4-benzylpteridine-6-carboxylic acid (5) and O4-benzylfolate (7) are far more water soluble than O6-benzylguanine. The activity of O4-benzylfolic acid (7) is particularly noteworthy because it is roughly 30 times more active than O6-benzylguanine against the wild-type alkyltransferase and is even capable of inactivating the P140K mutant alkyltransferase that is resistant to inactivation by O6-benzylguanine. All the pteridine derivatives except 2-amino-O4-benzylpteridine-6-carboxylic acid are effective in enhancing cell killing by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). However, the effectiveness of O4-benzylfolate as an adjuvant for cell killing by BCNU appears to be a function of a cell's alpha-folate receptor expression. Thus, O4-benzylfolate is least effective as an adjuvant in A549 cells (which express little if any receptor), is moderately effective in HT29 cells (which express low levels of the receptor), but is very effective in KB cells (which are known to express high levels of the alpha-folate receptor). Therefore, O4-benzylfolic acid shows promise as an agent for possible tumor-selective alkyltransferase inactivation, which suggests it may prove to be superior to O6-benzylguanine as a chemotherapy adjuvant. JF - Journal of medicinal chemistry AU - Nelson, Michael E AU - Loktionova, Natalia A AU - Pegg, Anthony E AU - Moschel, Robert C AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, P.O. Box B, Building 538, Frederick, MD 21702, USA. Y1 - 2004/07/15/ PY - 2004 DA - 2004 Jul 15 SP - 3887 EP - 3891 VL - 47 IS - 15 SN - 0022-2623, 0022-2623 KW - Pteridines KW - 0 KW - O(6)-Methylguanine-DNA Methyltransferase KW - EC 2.1.1.63 KW - Index Medicus KW - Drug Screening Assays, Antitumor KW - Humans KW - Cell Line, Tumor KW - Chemotherapy, Adjuvant KW - Structure-Activity Relationship KW - Pteridines -- chemistry KW - Pteridines -- pharmacology KW - O(6)-Methylguanine-DNA Methyltransferase -- antagonists & inhibitors KW - O(6)-Methylguanine-DNA Methyltransferase -- chemistry KW - Pteridines -- chemical synthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66686363?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=2-amino-O4-benzylpteridine+derivatives%3A+potent+inactivators+of+O6-alkylguanine-DNA+alkyltransferase.&rft.au=Nelson%2C+Michael+E%3BLoktionova%2C+Natalia+A%3BPegg%2C+Anthony+E%3BMoschel%2C+Robert+C&rft.aulast=Nelson&rft.aufirst=Michael&rft.date=2004-07-15&rft.volume=47&rft.issue=15&rft.spage=3887&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 - 2004-08-12 N1 - Date created - 2004-07-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cholera toxin prevents Th1-mediated autoimmune disease by inducing immune deviation. AN - 66685294; 15240661 AB - Cholera toxin (CT), a major enterotoxin produced by Vibrio cholerae, is known for its properties as a mucosal adjuvant that promotes Th2 or mixed Th1 + Th2 responses. In this study, we explore the ability of CT to act as a systemic adjuvant to counteract the Th1 response leading to experimental autoimmune uveitis. We report that susceptible B10.RIII mice immunized with a uveitogenic regimen of the retinal Ag interphotoreceptor retinoid-binding protein could be protected from disease by a single systemic injection of as little as 2 micro g of CT at the time of immunization. The protected mice were not immunosuppressed, but rather displayed evidence of immune deviation. Subsequent adaptive responses to interphotoreceptor retinoid-binding protein showed evidence of Th2 enhancement, as indicated by reduced delayed-type hypersensitivity in the context of enhanced Ag-specific lymphocyte proliferation and IL-4 production. Ag-specific production of several other cytokines, including IFN-gamma, was not appreciably altered. The inhibitory effect of CT was dependent on the enzymatic A subunit of CT, because the cell-binding B subunit alone could not block disease development. Mice given CT displayed detectable IL-4 levels in their serum within hours of CT administration. This innate IL-4 production was critical for protection, as infusion of neutralizing Ab against IL-4 to mice, given a uveitogenic immunization and treated with CT, counteracted immune deviation and abrogated protection. Our data indicate that systemic administration of CT inhibits experimental autoimmune uveitis by skewing the response to the uveitogenic autoantigen to a nonpathogenic phenotype. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Su, Shao-Bo AU - Silver, Phyllis B AU - Wang, Peng AU - Chan, Chi-Chao AU - Caspi, Rachel R AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/07/15/ PY - 2004 DA - 2004 Jul 15 SP - 755 EP - 761 VL - 173 IS - 2 SN - 0022-1767, 0022-1767 KW - Adjuvants, Immunologic KW - 0 KW - Autoantigens KW - Cholera Toxin KW - 9012-63-9 KW - Abridged Index Medicus KW - Index Medicus KW - Uveitis -- prevention & control KW - Animals KW - Uveitis -- pathology KW - Autoantigens -- immunology KW - Uveitis -- immunology KW - Mice KW - Autoimmune Diseases -- prevention & control KW - Th1 Cells -- drug effects KW - Autoimmune Diseases -- pathology KW - Cholera Toxin -- pharmacology KW - Adjuvants, Immunologic -- pharmacology KW - Autoimmune Diseases -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66685294?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Cholera+toxin+prevents+Th1-mediated+autoimmune+disease+by+inducing+immune+deviation.&rft.au=Su%2C+Shao-Bo%3BSilver%2C+Phyllis+B%3BWang%2C+Peng%3BChan%2C+Chi-Chao%3BCaspi%2C+Rachel+R&rft.aulast=Su&rft.aufirst=Shao-Bo&rft.date=2004-07-15&rft.volume=173&rft.issue=2&rft.spage=755&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 - 2004-08-27 N1 - Date created - 2004-07-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ethics and Standard of Care in Clinical Trials/From the Authors AN - 199644921; 15242856 JF - American Journal of Respiratory and Critical Care Medicine AU - Brower, Roy G AU - Gordon, Bernard AU - Morris, Alan AU - Miller, Franklin G AU - Silverman, Henry J Y1 - 2004/07/15/ PY - 2004 DA - 2004 Jul 15 SP - 198 EP - 9; author reply 199 CY - New York PB - American Thoracic Society VL - 170 IS - 2 SN - 1073449X KW - Medical Sciences--Respiratory Diseases KW - Pulmonary Medicine -- standards KW - Humans KW - Respiratory Distress Syndrome, Adult -- therapy KW - Clinical Trials as Topic -- standards KW - Clinical Trials as Topic -- ethics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/199644921?accountid=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=American+Journal+of+Respiratory+and+Critical+Care+Medicine&rft.atitle=Ethics+and+Standard+of+Care+in+Clinical+Trials%2FFrom+the+Authors&rft.au=Brower%2C+Roy+G%3BGordon%2C+Bernard%3BMorris%2C+Alan%3BMiller%2C+Franklin+G%3BSilverman%2C+Henry+J&rft.aulast=Brower&rft.aufirst=Roy&rft.date=2004-07-15&rft.volume=170&rft.issue=2&rft.spage=198&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Respiratory+and+Critical+Care+Medicine&rft.issn=1073449X&rft_id=info:doi/ LA - English DB - ProQuest Central N1 - Copyright - Copyright American Thoracic Society Jul 15, 2004 N1 - Last updated - 2017-01-07 ER - TY - JOUR T1 - Immunization of Patients with the hTERT:540-548 Peptide Induces Peptide-Reactive T Lymphocytes That Do Not Recognize Tumors Endogenously Expressing Telomerase AN - 19400415; 5956877 AB - PURPOSE: Telomerase is an attractive target antigen for cancer immunotherapies because it is expressed in >85% of human tumors but is rarely found in normal tissues. A HLA-A*0201-restricted T-cell epitope was previously identified within telomerase reverse transcriptase hTERT:540-548. This peptide was reported to induce CTL that recognized tumor cells and transfectants that endogenously expressed telomerase. Therefore, we initiated a clinical protocol to evaluate the therapeutic and immunological efficacy of this peptide. Experimental Design: Fourteen patients with metastatic cancers were vaccinated with hTERT:540-548 emulsified in incomplete Freund's adjuvant. RESULTS: In 7 patients, peripheral blood mononuclear cells collected after immunization recognized hTERT:540-548, whereas those collected before vaccination did not. However, none of these CTLs recognized tumors that endogenously expressed telomerase, and none of the patients had an objective clinical response. Several highly avid T-cell clones were generated that recognized T2 cells pulsed with <1 nM hTERT:540-548, but none of these recognized HLA-A*0201 super(+) hTERT super(+) tumors or cells transduced with the human telomerase reverse transcriptase (hTERT) gene. Also, an antibody specific for hTERT:540-548/HLA-A*0201 complexes stained peptide-pulsed cells but not telomerase super(+) tumors. CONCLUSIONS: Our results are discordant with previous studies and those of a clinical trial that claimed peripheral blood mononuclear cells from patients vaccinated with peptide-pulsed dendritic cells lysed hTERT super(+) tumors. However, our findings are consistent with a previous study that demonstrated that the hTERT:540-548 peptide is cleaved in the proteasome. These results suggest that hTERT:540-548 is not presented on the surfaces of tumor cells in the context of HLA-A*0201 and will not be useful for the immunotherapy of patients with cancer. JF - Clinical Cancer Research AU - Parkhurst, Maria R AU - Riley, John P AU - Igarashi, Takehito AU - Li, Yong AU - Robbins, Paul F AU - Rosenberg, Steven A AD - National Cancer Institute, Surgery Branch and National Heart, Lung, and Blood Institute, Hematology Branch, NIH, Bethesda, Maryland Y1 - 2004/07/15/ PY - 2004 DA - 2004 Jul 15 SP - 4688 EP - 4698 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 USA, [URL:http://www.aacr.org/] VL - 10 IS - 14 SN - 1078-0432, 1078-0432 KW - Genetics Abstracts; Immunology Abstracts; Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Histocompatibility antigen HLA KW - Immunotherapy KW - proteasomes KW - Tumors KW - telomerase reverse transcriptase KW - Clinical trials KW - Tumor cells KW - Vaccination KW - Cancer KW - Metastases KW - Dendritic cells KW - Antibodies KW - Cytotoxicity KW - Peripheral blood mononuclear cells KW - Lymphocytes T KW - Freund's adjuvant KW - Telomerase reverse transcriptase KW - Epitopes KW - G 07880:Human Genetics KW - F 06915:Cancer Immunology KW - N 14835:Protein-Nucleic Acids Association KW - W 30915:Pharmaceuticals & Vaccines UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19400415?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Cancer+Research&rft.atitle=Immunization+of+Patients+with+the+hTERT%3A540-548+Peptide+Induces+Peptide-Reactive+T+Lymphocytes+That+Do+Not+Recognize+Tumors+Endogenously+Expressing+Telomerase&rft.au=Parkhurst%2C+Maria+R%3BRiley%2C+John+P%3BIgarashi%2C+Takehito%3BLi%2C+Yong%3BRobbins%2C+Paul+F%3BRosenberg%2C+Steven+A&rft.aulast=Parkhurst&rft.aufirst=Maria&rft.date=2004-07-15&rft.volume=10&rft.issue=14&rft.spage=4688&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&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 - Histocompatibility antigen HLA; Immunotherapy; proteasomes; telomerase reverse transcriptase; Tumors; Vaccination; Tumor cells; Clinical trials; Cancer; Metastases; Dendritic cells; Peripheral blood mononuclear cells; Cytotoxicity; Antibodies; Lymphocytes T; Freund's adjuvant; Telomerase reverse transcriptase; Epitopes ER - TY - JOUR T1 - Engagement of the Pathogen Survival Response Used by Group A Streptococcus to Avert Destruction by Innate Host Defense AN - 18038963; 5945914 AB - Neutrophils are a critical component of human innate host defense and efficiently kill the vast majority of invading microorganisms. However, bacterial pathogens such as group A Streptococcus (GAS) successfully avert destruction by neutrophils to cause human infections. Relatively little is known about how pathogens detect components of the innate immune system to respond and survive within the host. In this study, we show that inactivation of a two- component gene regulatory system designated Ihk-Irr significantly attenuates streptococcal virulence in mouse models of soft tissue infection and bacteremia. Microarray analysis of wild-type and irr-negative mutant (irr mutant) GAS strains revealed that Ihk-Irr influenced expression of 20% of all transcripts in the pathogen genome. Notably, at least 11 genes involved in cell wall synthesis, turnover, and/or modification were down-regulated in the irr mutant strain. Compared with the wild-type strain, significantly more of the irr mutant strain was killed by human neutrophil components that destroy bacteria by targeting the cell envelope (cell wall and/or membrane). Unexpectedly, expression of ihk and irr was dramatically increased in the wild-type strain exposed to these same neutrophil products under conditions that favored cell envelope damage. We report a GAS mechanism for detection of innate host defense that initiates the pathogen survival response, in which cell wall synthesis is critical. Importantly, our studies identify specific genes in the pathogen survival response as potential targets to control human infections. JF - Journal of Immunology AU - Voyich, Jovanka M AU - Braughton, Kevin R AU - Sturdevant, Daniel E AU - Vuong, Cuong AU - Kobayashi, Scott D AU - Porcella, Stephen F AU - Otto, Michael 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, Hamilton, MT 59840 Y1 - 2004/07/15/ PY - 2004 DA - 2004 Jul 15 SP - 1194 EP - 1201 PB - American Association of Immunologists, 9650 Rockville Pike Bethesda MD 20814-3998 USA, [URL:http://www.jimmunol.org/] VL - 173 IS - 2 SN - 0022-1767, 0022-1767 KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Cell survival KW - Streptococcus KW - Bacteria KW - Immune system KW - Cell envelopes KW - Animal models KW - Leukocytes (neutrophilic) KW - Bacteremia KW - Pathogens KW - DNA microarrays KW - Streptococcus pyogenes KW - Virulence KW - Soft tissues KW - Cell walls KW - J 02833:Immune response and immune mechanisms KW - F 06800:Viruses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18038963?accountid=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=Engagement+of+the+Pathogen+Survival+Response+Used+by+Group+A+Streptococcus+to+Avert+Destruction+by+Innate+Host+Defense&rft.au=Voyich%2C+Jovanka+M%3BBraughton%2C+Kevin+R%3BSturdevant%2C+Daniel+E%3BVuong%2C+Cuong%3BKobayashi%2C+Scott+D%3BPorcella%2C+Stephen+F%3BOtto%2C+Michael%3BMusser%2C+James+M%3BDeLeo%2C+Frank+R&rft.aulast=Voyich&rft.aufirst=Jovanka&rft.date=2004-07-15&rft.volume=173&rft.issue=2&rft.spage=1194&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunology&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Streptococcus pyogenes; Streptococcus; Pathogens; Leukocytes (neutrophilic); Cell walls; Cell envelopes; DNA microarrays; Bacteremia; Immune system; Soft tissues; Virulence; Bacteria; Cell survival; Animal models ER - TY - JOUR T1 - Divinyl Sulfone as a Postdigestion Modifier for Enhancing the a sub(1) Ion in MS/MS and Postsource Decay: Potential Applications in Proteomics AN - 17302675; 6129556 AB - Divinyl sulfone reacts at pH 8-9 with the alpha -amino groups of N-terminal residues, proline, the epsilon -amino groups of lysine, and the histidine side chains of peptides. This reaction leads to great enhancement of the abundance of the normally weak or missing "a sub(1)" fragment ion in MS/MS analysis defining the N-terminal residue of a peptide in a digest. This provides "one-step Edman-like" information that, together with a fairly accurately determined mass, often enables one to correctly identify a protein or family of proteins. The applicability of this procedure in proteomics was demonstrated with several peptides and tryptic digests of protein mixtures by LC-MS/MS experiments using a QTOF and MALDI-PSD analyses. Advantages of this approach are its simple chemistry, retention of charge multiplicity, and possibly, shortening of database search time. Used with other MS/MS data, it provides higher confidence in the scores and identification of a protein found in peptide mass fingerprinting. Moreover, this approach has an advantage in "de novo" sequencing due to its ability to decipher the first amino acid of a peptide whose information is normally unavailable in MS/MS spectra. JF - Analytical Chemistry (Washington) AU - Boja, E S AU - Sokoloski, E A AU - Fales, H M AD - Laboratory of Biophysical Chemistry, NHLBI, NIH, 50 South Drive, Bethesda, Maryland 20892-8014, USA Y1 - 2004/07/15/ PY - 2004 DA - 2004 Jul 15 SP - 3958 EP - 3970 VL - 76 IS - 14 SN - 0003-2700, 0003-2700 KW - Divinyl sulfone 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/17302675?accountid=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=Analytical+Chemistry+%28Washington%29&rft.atitle=Divinyl+Sulfone+as+a+Postdigestion+Modifier+for+Enhancing+the+a+sub%281%29+Ion+in+MS%2FMS+and+Postsource+Decay%3A+Potential+Applications+in+Proteomics&rft.au=Boja%2C+E+S%3BSokoloski%2C+E+A%3BFales%2C+H+M&rft.aulast=Boja&rft.aufirst=E&rft.date=2004-07-15&rft.volume=76&rft.issue=14&rft.spage=3958&rft.isbn=&rft.btitle=&rft.title=Analytical+Chemistry+%28Washington%29&rft.issn=00032700&rft_id=info:doi/10.1021%2Fac049774e LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-06-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1021/ac049774e ER - TY - JOUR T1 - Direct action of estradiol on gonadotropin-releasing hormone-1 neuronal activity via a transcription-dependent mechanism. AN - 66713414; 15254088 AB - Pulsatile secretion of gonadotropin-releasing hormone-1 (GnRH-1) is essential for reproduction. GnRH-1 induces gonadotropin release and is regulated by 17beta-estradiol (E2). Although a subpopulation of GnRH-1 neurons expresses estrogen receptor (ER) beta, it is unclear whether E2 acts directly on GnRH-1 neurons or indirectly through interneuronal connections. To test the hypothesis that E2 acts directly on GnRH-1 neurons to regulate neuronal activity, we used calcium imaging to monitor intracellular calcium oscillations in GnRH-1 neurons maintained in nasal explants. TTX was used to minimize synaptic input from other cells. Consistent with previous studies, TTX reduced the activity of individual GnRH-1 neurons to a basal level, while the population of cells maintained synchronized calcium oscillations. Exposure of GnRH-1 cells to TTX plus E2 increased the number of calcium peaks/cell, percentage of cells with > or =10 peaks, mean peak amplitude, and percentage of cells that contributed to each calcium pulse in explants maintained in vitro for 7 d (7 div) compared with TTX alone. These effects were induced within 30 min and were not mimicked by 17alpha-estradiol, E2 conjugated to BSA (which does not cross the plasma membrane), or seen at 21 div, when the percentage of GnRH-1 cells expressing ERbeta transcripts declines. In addition, these effects were inhibited by the ER antagonist ICI 182,780 and prevented by inhibition of gene transcription. These data suggest that, via ERbeta, E2 can rapidly act as a hormone-activated transcription complex and are the first to show that E2 directly increases GnRH-1 neuronal activity and synchronization. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Temple, Jennifer L AU - Laing, Eric AU - Sunder, Anushka 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 - 2004/07/14/ PY - 2004 DA - 2004 Jul 14 SP - 6326 EP - 6333 VL - 24 IS - 28 KW - Estrogen Receptor Modulators KW - 0 KW - Estrogen Receptor beta KW - Fluorescent Dyes KW - Organic Chemicals KW - Sodium Channel Blockers KW - calcium green KW - 138067-55-7 KW - fulvestrant KW - 22X328QOC4 KW - Gonadotropin-Releasing Hormone KW - 33515-09-2 KW - Tetrodotoxin KW - 4368-28-9 KW - Estradiol KW - 4TI98Z838E KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Fluorescent Dyes -- analysis KW - Animals KW - Transcription, Genetic -- drug effects KW - Calcium -- analysis KW - Humans KW - Estrogen Receptor beta -- drug effects KW - Mice KW - Nasal Mucosa -- cytology KW - Secretory Rate KW - Adenocarcinoma -- pathology KW - Breast Neoplasms -- pathology KW - Sodium Channel Blockers -- pharmacology KW - Tetrodotoxin -- pharmacology KW - Organ Culture Techniques KW - Calcium Signaling KW - Female KW - Estrogen Receptor Modulators -- pharmacology KW - Estradiol -- analogs & derivatives KW - Neurons -- drug effects KW - Estradiol -- pharmacology KW - Gonadotropin-Releasing Hormone -- secretion KW - Neurons -- secretion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66713414?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Direct+action+of+estradiol+on+gonadotropin-releasing+hormone-1+neuronal+activity+via+a+transcription-dependent+mechanism.&rft.au=Temple%2C+Jennifer+L%3BLaing%2C+Eric%3BSunder%2C+Anushka%3BWray%2C+Susan&rft.aulast=Temple&rft.aufirst=Jennifer&rft.date=2004-07-14&rft.volume=24&rft.issue=28&rft.spage=6326&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 - 2004-12-13 N1 - Date created - 2004-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Subunit-specific regulation of NMDA receptor endocytosis. AN - 66713084; 15254094 AB - At excitatory synapses, both NMDA and AMPA receptors are localized to the postsynaptic density (PSD). However, unlike AMPA receptors, synaptic NMDA receptors are stable components of the PSD. Even so, surface-expressed NMDA receptors undergo endocytosis, which is more robust early in development and declines during synaptic development. We investigated the subunit-specific contributions to NMDA receptor endocytosis, specifically defining the endocytic motifs and endocytic pathways preferred by the NR2A and NR2B subunits. We find that NR2A and NR2B have distinct endocytic motifs encoded in their distal C termini and that these interact with clathrin adaptor complexes with differing affinities. We also find that NR2A and NR2B sort into different intracellular pathways after endocytosis, with NR2B preferentially trafficking through recycling endosomes. In mature cultures, we find that NR2B undergoes more robust endocytosis than NR2A, consistent with previous studies showing that NR2A is more highly expressed at stable synaptic sites. Our findings demonstrate fundamental differences between NR2A and NR2B that help clarify developmental changes in NMDA receptor trafficking and surface expression. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Lavezzari, Gabriela AU - McCallum, Jennifer AU - Dewey, Colleen M AU - Roche, Katherine W AD - National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2004/07/14/ PY - 2004 DA - 2004 Jul 14 SP - 6383 EP - 6391 VL - 24 IS - 28 KW - Adaptor Protein Complex 2 KW - 0 KW - Membrane Glycoproteins KW - NR2A NMDA receptor KW - NR2B NMDA receptor KW - Nerve Tissue Proteins KW - Protein Subunits KW - Receptors, N-Methyl-D-Aspartate KW - Recombinant Fusion Proteins KW - TGOLN2 protein, human KW - Tgoln2 protein, rat KW - postsynaptic density proteins KW - Index Medicus KW - Animals KW - Neurons -- metabolism KW - Cerebral Cortex -- metabolism KW - HeLa Cells KW - Humans KW - Two-Hybrid System Techniques KW - Endosomes -- metabolism KW - Structure-Activity Relationship KW - Recombinant Fusion Proteins -- metabolism KW - Rats KW - Mutagenesis, Site-Directed KW - Rats, Sprague-Dawley KW - Protein Interaction Mapping KW - Amino Acid Motifs KW - Transfection KW - Hippocampus -- growth & development KW - Hippocampus -- cytology KW - Nerve Tissue Proteins -- metabolism KW - Synapses -- metabolism KW - Protein Transport KW - Adaptor Protein Complex 2 -- metabolism KW - Membrane Glycoproteins -- metabolism KW - Receptors, N-Methyl-D-Aspartate -- physiology KW - Receptors, N-Methyl-D-Aspartate -- chemistry KW - Endocytosis -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66713084?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Subunit-specific+regulation+of+NMDA+receptor+endocytosis.&rft.au=Lavezzari%2C+Gabriela%3BMcCallum%2C+Jennifer%3BDewey%2C+Colleen+M%3BRoche%2C+Katherine+W&rft.aulast=Lavezzari&rft.aufirst=Gabriela&rft.date=2004-07-14&rft.volume=24&rft.issue=28&rft.spage=6383&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 - 2004-12-13 N1 - Date created - 2004-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Export from the endoplasmic reticulum of assembled N-methyl-d-aspartic acid receptors is controlled by a motif in the c terminus of the NR2 subunit. AN - 66682090; 15102836 AB - Functional N-methyl-d-aspartic acid (NMDA) receptors are formed from the assembly of NR1 and NR2 subunits. When expressed alone, the major NR1 splice variant and the NR2 subunits are retained in the endoplasmic reticulum (ER), reflecting a quality control mechanism found in many complex multisubunit proteins to ensure that only fully assembled and properly folded complexes reach the cell surface. Recent studies have identified an RRR motif in the C terminus of the NR1 subunit, which controls the ER retention of the unassembled subunit. Here we investigated the mechanisms controlling the ER retention of the NR2 subunit and the export of the assembled complex from the ER. We found that Tac chimeras of the C terminus of the NR2B subunit show that an ER retention signal is also present in the NR2B subunit. In assembled complexes, ER retention signals on the individual subunits must be overcome to allow the complex to leave the ER. One common mechanism involves mutual masking of the signals on the individual subunits. Our data do not support such a mechanism for regulating the release of assembled NMDA receptors from the ER. We found that the motif, HLFY, immediately following transmembrane domain 4 of the NR2 subunit, is required for the assembled complex to exit from the ER. Mutation of this motif allowed the assembly of NR1 and NR2 subunits into a complex that was functional, based on MK-801 binding, but it is retained in the ER. These results are consistent with HLFY functioning as a signal that is necessary for the release of the assembled functional NMDA receptor complex from the ER. JF - The Journal of biological chemistry AU - Hawkins, Lynda M AU - Prybylowski, Kate AU - Chang, Kai AU - Moussan, Caroline AU - Stephenson, F Anne AU - Wenthold, Robert J AD - Laboratory of Neurochemistry, NIDCD, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2004/07/09/ PY - 2004 DA - 2004 Jul 09 SP - 28903 EP - 28910 VL - 279 IS - 28 SN - 0021-9258, 0021-9258 KW - Excitatory Amino Acid Antagonists KW - 0 KW - Protein Sorting Signals KW - Protein Subunits KW - Receptors, N-Methyl-D-Aspartate KW - Recombinant Fusion Proteins KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - Index Medicus KW - Animals KW - Excitatory Amino Acid Antagonists -- metabolism KW - Dizocilpine Maleate -- metabolism KW - Humans KW - Amino Acid Sequence KW - Mice KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Amino Acid Motifs KW - Recombinant Fusion Proteins -- genetics KW - Molecular Sequence Data KW - Protein Structure, Tertiary KW - Cell Line KW - Protein Transport -- physiology KW - Endoplasmic Reticulum -- metabolism KW - Protein Subunits -- genetics KW - Receptors, N-Methyl-D-Aspartate -- metabolism KW - Protein Subunits -- metabolism KW - Receptors, N-Methyl-D-Aspartate -- genetics KW - Receptors, N-Methyl-D-Aspartate -- chemistry KW - Protein Subunits -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66682090?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Export+from+the+endoplasmic+reticulum+of+assembled+N-methyl-d-aspartic+acid+receptors+is+controlled+by+a+motif+in+the+c+terminus+of+the+NR2+subunit.&rft.au=Hawkins%2C+Lynda+M%3BPrybylowski%2C+Kate%3BChang%2C+Kai%3BMoussan%2C+Caroline%3BStephenson%2C+F+Anne%3BWenthold%2C+Robert+J&rft.aulast=Hawkins&rft.aufirst=Lynda&rft.date=2004-07-09&rft.volume=279&rft.issue=28&rft.spage=28903&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 - 2004-08-24 N1 - Date created - 2004-07-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mixed lineage kinase 3 (MLK3)-activated p38 MAP kinase mediates transforming growth factor-beta-induced apoptosis in hepatoma cells. AN - 66679929; 15069087 AB - Although transforming growth factor beta1 (TGF-beta1) acts via the Smad signaling pathway to initiate de novo gene transcription, the TGF-beta1-induced MAPK kinase activation that is involved in the regulation of apoptosis is less well understood. Even though the p38 MAP kinase and c-Jun NH(2)-terminal kinases (JNKs) are involved in TGF-beta1-induced cell death in hepatoma cells, the upstream mediators of these kinases remain to be defined. We show here that the members of the mixed lineage kinase (MLK) family (including MLK1, MLK2, MLK3, and dual leucine zipper-bearing kinase (DLK)) are expressed in FaO rat hepatoma cells and are likely to act between p38 and TGF-beta receptor kinase in death signaling. TGF-beta1 treatment leads to an increase in MLK3 activity. Overexpression of MLK3 enhances TGF-beta1-induced apoptotic death in FaO cells and Hep3B human hepatoma cells, whereas expression of the dominant-negative forms of MLK3 suppresses cell death induced by TGF-beta1. The dominant-negative forms of MLK1 and -2 also suppress TGF-beta1-induced cell death. In MLK3-overexpressing cells, ERK, JNKs, and p38 MAP kinases were further activated in response to TGF-beta1 compared with the control cells. In contrast, overexpression of the dominant-negative MLK3 resulted in suppression of TGF-beta1-induced MAP kinase activation and TGF-beta1-induced caspase-3 activation. We also show that only the inhibition of the p38 pathway suppressed TGF-beta1-induced apoptosis. These observations support a role for MLKs in the TGF-beta1-induced cell death mechanism. JF - The Journal of biological chemistry AU - Kim, Ki-Yong AU - Kim, Byung-Chul AU - Xu, Zhiheng AU - Kim, Seong-Jin AD - Laboratory of Cell Regulation and Carcinogenesis, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2004/07/09/ PY - 2004 DA - 2004 Jul 09 SP - 29478 EP - 29484 VL - 279 IS - 28 SN - 0021-9258, 0021-9258 KW - Enzyme Inhibitors KW - 0 KW - Proteins KW - Recombinant Fusion Proteins KW - TGFB1 protein, human KW - Tgfb1 protein, rat KW - Transforming Growth Factor beta KW - Transforming Growth Factor beta1 KW - Sprk protein, rat KW - EC 2.7.1.- KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - p38 Mitogen-Activated Protein Kinases KW - MAP Kinase Kinase Kinases KW - EC 2.7.11.25 KW - mitogen-activated protein kinase kinase kinase 11 KW - Mitogen-Activated Protein Kinase Kinases KW - EC 2.7.12.2 KW - CASP3 protein, human KW - EC 3.4.22.- KW - Casp3 protein, rat KW - Caspase 3 KW - Caspases KW - Index Medicus KW - Animals KW - Enzyme Activation KW - Humans KW - Transcription, Genetic KW - Cell Line, Tumor KW - Caspases -- metabolism KW - Rats KW - Recombinant Fusion Proteins -- metabolism KW - Signal Transduction -- physiology KW - Phosphorylation KW - Recombinant Fusion Proteins -- genetics KW - Enzyme Inhibitors -- metabolism KW - Liver Neoplasms -- metabolism KW - Carcinoma, Hepatocellular -- metabolism KW - Protein-Serine-Threonine Kinases -- metabolism KW - Mitogen-Activated Protein Kinases -- metabolism KW - Apoptosis -- physiology KW - Protein-Serine-Threonine Kinases -- genetics KW - Transforming Growth Factor beta -- metabolism KW - Proteins -- metabolism KW - Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66679929?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Mixed+lineage+kinase+3+%28MLK3%29-activated+p38+MAP+kinase+mediates+transforming+growth+factor-beta-induced+apoptosis+in+hepatoma+cells.&rft.au=Kim%2C+Ki-Yong%3BKim%2C+Byung-Chul%3BXu%2C+Zhiheng%3BKim%2C+Seong-Jin&rft.aulast=Kim&rft.aufirst=Ki-Yong&rft.date=2004-07-09&rft.volume=279&rft.issue=28&rft.spage=29478&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 - 2004-08-24 N1 - Date created - 2004-07-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A Captured Folding Intermediate Involved in Dimerization and Domain-swapping of GB1 AN - 19806388; 5962010 AB - Immunoglobulin binding domain B1 of streptococcal protein G (GB1), a small (56 residues), stable, single domain protein, is one of the most extensively used model systems in the area of protein folding and design. The recently determined NMR structure of a quadruple mutant (HS#124 super(F26A), L5V/F30V/Y33F/A34F) revealed a domain-swapped dimer that dissociated into a partially folded, monomeric species at low micromolar protein concentrations. Here, we have characterized this monomeric, partially folded species by NMR and show that extensive conformational heterogeneity for a substantial portion of the polypeptide chain exists. Exchange between the conformers within the monomer ensemble on the microsecond to millisecond timescale renders the majority of backbone amide resonances broadened beyond detection. Despite these extensive temporal and spatial fluctuations, the overall architecture of the monomeric mutant protein resembles that of wild-type GB1 and not the monomer unit of the domain-swapped dimer. JF - Journal of Molecular Biology AU - Byeon, IL AU - Louis, J M AU - Gronenborn, A M AD - Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA, gronenborn@nih.gov Y1 - 2004/07/09/ PY - 2004 DA - 2004 Jul 09 SP - 615 EP - 625 PB - Elsevier Ltd VL - 340 IS - 3 SN - 0022-2836, 0022-2836 KW - Microbiology Abstracts B: Bacteriology KW - Streptococcus KW - Monomers KW - Protein folding KW - streptococcal protein G KW - N.M.R. KW - amides KW - Immunoglobulins KW - J 02310:Genetics & Taxonomy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19806388?accountid=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=A+Captured+Folding+Intermediate+Involved+in+Dimerization+and+Domain-swapping+of+GB1&rft.au=Byeon%2C+IL%3BLouis%2C+J+M%3BGronenborn%2C+A+M&rft.aulast=Byeon&rft.aufirst=IL&rft.date=2004-07-09&rft.volume=340&rft.issue=3&rft.spage=615&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Biology&rft.issn=00222836&rft_id=info:doi/10.1016%2Fj.jmb.2004.04.069 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-05-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Monomers; Protein folding; streptococcal protein G; N.M.R.; amides; Immunoglobulins; Streptococcus DO - http://dx.doi.org/10.1016/j.jmb.2004.04.069 ER - TY - JOUR T1 - Increased Susceptibility of Mice Lacking Clara Cell 10-kDa Protein to Lung Tumorigenesis by 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone, a Potent Carcinogen in Cigarette Smoke AN - 17998338; 5944147 AB - Ninety percent of all human lung cancers are related to cigarette smoking. Both tobacco smoke and lung tumorigenesis are associated with drastically reduced levels of Clara cell 10-kDa protein (CC10), a multifunctional secreted protein, naturally produced by the airway epithelia of virtually all mammals. We previously reported that the expression of CC10 is markedly reduced in animals exposed to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, NNK, a potent carcinogen in tobacco smoke. Furthermore, it has been reported that CC10 expression, induced in certain tumor cells, reverses the transformed phenotype. We demonstrate here that NNK exposure of CC10-knock-out (CC10-KO) mice causes a significantly higher incidence of airway epithelial hyperplasia and lung adenomas compared with wild type (WT) littermates (30% CC10-KO versus 5% WT, p = 0.041). We also found that compared with NNK-treated WT mice, CC10-KO mice manifest increased frequency of K-ras mutation, elevated level of Fas ligand (FasL) expression, and increased MAPK/Erk phosphorylation, all of which are considered predisposing events in NNK-induced lung tumorigenesis. We propose that CC10 has a protective role against NNK-induced lung tumorigenesis mediated via down-regulation of the above-mentioned predisposing events. JF - Journal of Biological Chemistry AU - Yang, Y AU - Zhang, Z AU - Mukherjee, AB AU - Linnoila, R I AD - Cell and Cancer Biology Branch, Center for Cancer Research, NCI, National Institutes of Health, Rockville, Maryland, yongpiny@mail.nih.gov Y1 - 2004/07/09/ PY - 2004 DA - 2004 Jul 09 SP - 29336 EP - 29340 PB - American Society for Biochemistry and Molecular Biology, 9650 Rockville Pike Bethesda MD 20814-3996 USA, [mailto:asbmb@asbmb.faseb.org], [URL:http://www.jbc.org] VL - 279 IS - 28 SN - 0021-9258, 0021-9258 KW - Clara cell KW - Clara cells KW - mice KW - Genetics Abstracts; Toxicology Abstracts KW - Transformation KW - Tumorigenesis KW - FasL protein KW - Cigarette smoke KW - Tumor cells KW - Phenotypes KW - Cancer KW - Hyperplasia KW - Phosphorylation KW - Lung KW - Carcinogenesis KW - Tobacco KW - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone KW - Proteins KW - Epithelium KW - Expression KW - CC10 protein KW - Adenoma KW - X 24180:Social poisons & drug abuse KW - G 07221:Specific chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17998338?accountid=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=Increased+Susceptibility+of+Mice+Lacking+Clara+Cell+10-kDa+Protein+to+Lung+Tumorigenesis+by+4-%28Methylnitrosamino%29-1-%283-pyridyl%29-1-butanone%2C+a+Potent+Carcinogen+in+Cigarette+Smoke&rft.au=Yang%2C+Y%3BZhang%2C+Z%3BMukherjee%2C+AB%3BLinnoila%2C+R+I&rft.aulast=Yang&rft.aufirst=Y&rft.date=2004-07-09&rft.volume=279&rft.issue=28&rft.spage=29336&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/10.1074%2Fjbc.C400162200 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Transformation; FasL protein; Tumorigenesis; Cigarette smoke; Phenotypes; Tumor cells; Cancer; Hyperplasia; Phosphorylation; Lung; Carcinogenesis; Tobacco; Proteins; 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone; Expression; Epithelium; CC10 protein; Adenoma DO - http://dx.doi.org/10.1074/jbc.C400162200 ER - TY - JOUR T1 - The challenge of emerging and re-emerging infectious diseases AN - 21292583; 5941597 AB - Infectious diseases have for centuries ranked with wars and famine as major challenges to human progress and survival. They remain among the leading causes of death and disability worldwide. Against a constant background of established infections, epidemics of new and old infectious diseases periodically emerge, greatly magnifying the global burden of infections. Studies of these emerging infections reveal the evolutionary properties of pathogenic microorganisms and the dynamic relationships between microorganisms, their hosts and the environment. JF - Nature AU - Morens, David M AU - Folkers, Gregory K AU - Fauci, Anthony S AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892- 2520, USA, afauciniaid.nih.gov Y1 - 2004/07/08/ PY - 2004 DA - 2004 Jul 08 SP - 242 EP - 249 PB - Nature Publishing Group, The Macmillan Building 4 Crinan Street London N1 9XW UK, [mailto:feedback@nature.com], [URL:http://www.nature.com/] VL - 430 IS - 6996 SN - 0028-0836, 0028-0836 KW - Microbiology Abstracts A: Industrial & Applied Microbiology KW - Famine KW - Epidemics KW - Infectious diseases KW - War KW - Microorganisms KW - Survival KW - Infection KW - Evolution KW - A 01450:Environmental Pollution & Waste Treatment UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21292583?accountid=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=Nature&rft.atitle=The+challenge+of+emerging+and+re-emerging+infectious+diseases&rft.au=Morens%2C+David+M%3BFolkers%2C+Gregory+K%3BFauci%2C+Anthony+S&rft.aulast=Morens&rft.aufirst=David&rft.date=2004-07-08&rft.volume=430&rft.issue=6996&rft.spage=242&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/10.1038%2Fnature02759 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-03-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Famine; Epidemics; Infectious diseases; War; Microorganisms; Survival; Infection; Evolution DO - http://dx.doi.org/10.1038/nature02759 ER - TY - JOUR T1 - A chlamydial type III translocated protein is tyrosine-phosphorylated at the site of entry and associated with recruitment of actin AN - 17823883; 5943511 AB - The obligate intracellular bacterium Chlamydia trachomatis rapidly induces its own entry into host cells. Initial attachment is mediated by electrostatic interactions to heparan sulfate moieties on the host cell, followed by irreversible binding to an unknown secondary receptor. This secondary binding leads to the recruitment of actin to the site of attachment, formation of an actin-rich, pedestallike structure, and finally internalization of the bacteria. How chlamydiae induce this process is unknown. We have identified a high-molecular-mass tyrosine-phosphorylated protein that is rapidly phosphorylated on attachment to the host cell. Immunoelectron microscopy studies revealed that this tyrosine-phosphorylated protein is localized to the cytoplasmic face of the plasma membrane at the site of attachment of surface- associated chlamydiae. The phosphoprotein was isolated by immunoprecipitation with the antiphosphotyrosine antibody 4G10 and identified as the chlamydial protein CT456, a hypothetical protein with unknown function. The chlamydial protein (Tarp) appears to be translocated into the host cell by type III secretion because it is exported in a Yersinia heterologous expression assay. Phosphotyrosine signaling across the plasma membrane preceded the recruitment of actin to the site of chlamydial attachment and may represent the initial signal transduced from pathogen to the host cell. These results suggest that C. trachomatis internalization is mediated by a chlamydial type III- secreted effector protein. JF - Proceedings of the National Academy of Sciences, USA AU - Clifton AU - Fields, KA AU - Grieshaber, S S AU - Dooley, CA AU - Fischer, E R AU - Mead, D J AU - Carabeo, R A AU - Hackstadt, T AD - Host-Parasite Interactions Section, Laboratory of Intracellular Parasites, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT 59840, thackstadt@niaid.nih.gov Y1 - 2004/07/06/ PY - 2004 DA - 2004 Jul 06 SP - 10166 EP - 10171 PB - National Academy of Sciences, 2101 Constitution Ave. Washington DC 20418 USA VL - 101 IS - 27 SN - 0027-8424, 0027-8424 KW - Tarp protein KW - Microbiology Abstracts B: Bacteriology KW - Microbiology KW - Receptor mechanisms KW - Chlamydia trachomatis KW - Pathogens KW - Immunoelectron microscopy KW - Yersinia KW - Heparan sulfate KW - phosphotyrosine KW - Databases KW - Antibodies KW - Plasma membranes KW - Phosphoproteins KW - Actin KW - Signal transduction KW - J 02721:Cell cycle, morphology and motility UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17823883?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=A+chlamydial+type+III+translocated+protein+is+tyrosine-phosphorylated+at+the+site+of+entry+and+associated+with+recruitment+of+actin&rft.au=Clifton%3BFields%2C+KA%3BGrieshaber%2C+S+S%3BDooley%2C+CA%3BFischer%2C+E+R%3BMead%2C+D+J%3BCarabeo%2C+R+A%3BHackstadt%2C+T&rft.aulast=Clifton&rft.aufirst=&rft.date=2004-07-06&rft.volume=101&rft.issue=27&rft.spage=10166&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.0402829101 LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - The sequence reported in this paper has been deposited in the GenBank database (accession no. AY623902). N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Databases; Antibodies; Phosphoproteins; Receptor mechanisms; Plasma membranes; Actin; Immunoelectron microscopy; Pathogens; Heparan sulfate; phosphotyrosine; Signal transduction; Chlamydia trachomatis; Yersinia DO - http://dx.doi.org/10.1073/pnas.0402829101 ER - TY - JOUR T1 - Herp stabilizes neuronal Ca2+ homeostasis and mitochondrial function during endoplasmic reticulum stress. AN - 66661351; 15102845 AB - In response to endoplasmic reticulum (ER) stress, cells launch homeostatic and protective responses, but can also activate cell death cascades. A 54 kDa integral ER membrane protein called Herp was identified as a stress-responsive protein in non-neuronal cells. We report that Herp is present in neurons in the developing and adult brain, and that it is regulated in neurons by ER stress; sublethal levels of ER stress increase Herp levels, whereas higher doses decrease Herp levels and induce apoptosis. The decrease in Herp protein levels following a lethal ER stress occurs prior to mitochondrial dysfunction and cell death, and is mediated by caspases which generate a 30-kDa proteolytic Herp fragment. Mutagenesis of the caspase cleavage site in Herp enhances its neuroprotective function during ER stress. While suppression of Herp induction by RNA interference sensitizes neural cells to apoptosis induced by ER stress, overexpression of Herp promotes survival by a mechanism involving stabilization of ER Ca(2+) levels, preservation of mitochondrial function and suppression of caspase 3 activation. ER stress-induced activation of JNK/c-Jun and caspase 12 are reduced by Herp, whereas induction of major ER chaperones is unaffected. Herp prevents ER Ca(2+) overload under conditions of ER stress and agonist-induced ER Ca(2+) release is attenuated by Herp suggesting a role for Herp in regulating neuronal Ca(2+) signaling. By stabilizing ER Ca(2+) homeostasis and mitochondrial functions, Herp serves a neuroprotective function under conditions of ER stress. JF - The Journal of biological chemistry AU - Chan, Sic L AU - Fu, Weiming AU - Zhang, Peisu AU - Cheng, Aiwu AU - Lee, Jaewon AU - Kokame, Koichi AU - Mattson, Mark P AD - Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Gerontology Research Center, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. chanst@grc.nia.nih.gov Y1 - 2004/07/02/ PY - 2004 DA - 2004 Jul 02 SP - 28733 EP - 28743 VL - 279 IS - 27 SN - 0021-9258, 0021-9258 KW - Amyloid beta-Peptides KW - 0 KW - Membrane Proteins KW - RNA, Small Interfering KW - RNA KW - 63231-63-0 KW - Cytochromes c KW - 9007-43-6 KW - JNK Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinases KW - Casp12 protein, rat KW - EC 3.4.22.- KW - Casp3 protein, rat KW - Caspase 12 KW - Caspase 3 KW - Caspases KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Cytochromes c -- metabolism KW - Apoptosis KW - Brain -- metabolism KW - RNA, Small Interfering -- metabolism KW - Caspases -- metabolism KW - Mutagenesis KW - Rats KW - RNA -- metabolism KW - RNA Interference KW - Time Factors KW - Signal Transduction KW - Plasmids -- metabolism KW - Mitogen-Activated Protein Kinases -- metabolism KW - Enzyme Activation KW - Amyloid beta-Peptides -- chemistry KW - Precipitin Tests KW - Reverse Transcriptase Polymerase Chain Reaction KW - Rats, Sprague-Dawley KW - Transfection KW - Cell Death KW - Subcellular Fractions -- metabolism KW - PC12 Cells KW - Endoplasmic Reticulum -- metabolism KW - Calcium -- metabolism KW - Neurons -- metabolism KW - Membrane Proteins -- chemistry KW - Membrane Proteins -- metabolism KW - Mitochondria -- metabolism KW - Cell Membrane -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66661351?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Herp+stabilizes+neuronal+Ca2%2B+homeostasis+and+mitochondrial+function+during+endoplasmic+reticulum+stress.&rft.au=Chan%2C+Sic+L%3BFu%2C+Weiming%3BZhang%2C+Peisu%3BCheng%2C+Aiwu%3BLee%2C+Jaewon%3BKokame%2C+Koichi%3BMattson%2C+Mark+P&rft.aulast=Chan&rft.aufirst=Sic&rft.date=2004-07-02&rft.volume=279&rft.issue=27&rft.spage=28733&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 - 2004-08-11 N1 - Date created - 2004-06-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activin receptor-like kinase-7 induces apoptosis through activation of MAPKs in a Smad3-dependent mechanism in hepatoma cells. AN - 66658013; 15107418 AB - Activin receptor-like kinase (ALK)7 is a type I serine/threonine kinase receptor of the transforming growth factor (TGF)-beta family of proteins that has similar properties to other type I receptors when activated. To see whether ALK7 can induce apoptosis as can some of the other ALK proteins, we infected the FaO rat hepatoma cell line with adenovirus expressing a constitutively active form of the ALK7. Cells infected with active ALK7 adenovirus showed an apoptotic-positive phenotype, as opposed to those that were infected with a control protein. DNA fragmentation assays and fluorescence-activated cell sorter analysis also indicated that ALK7 infection induced apoptosis in FaO cells. We also confirmed this finding in Hep3B human hepatoma cells by transiently transfecting the constitutively active form of ALK7, ALK7(T194D). Investigation into the downstream targets and mechanisms involved in ALK7-induced apoptosis revealed that the TGF-beta signaling intermediates, Smad2 and -3, were activated, as well as the MAPKs JNK and p38. In addition, caspase-3 and -9 were also activated, and cytochrome c release from the mitochondria was observed. Short interfering RNA-mediated inhibition of Smad3 markedly suppressed ALK7-induced caspase-3 activation. Treatment with protein synthesis inhibitors or the expression of the dominant-negative form of the stress-activated protein/extracellular signal-regulated kinase 1 abolished not only JNK activation but apoptosis as well. Taken together, these results suggest that ALK7 induces apoptosis through activation of the traditional TGF-beta pathway components, thus resulting in new gene transcription and JNK and p38 activation that initiates cross-talk with the cellular stress death pathway and ultimately leads to apoptosis. JF - The Journal of biological chemistry AU - Kim, Byung-Chul AU - van Gelder, Howard AU - Kim, Tae Aug AU - Lee, Ho-Jae AU - Baik, Kim G AU - Chun, Hyun Hye AU - Lee, David A AU - Choi, Kyeong Sook AU - Kim, Seong-Jin AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892-5055, USA. Y1 - 2004/07/02/ PY - 2004 DA - 2004 Jul 02 SP - 28458 EP - 28465 VL - 279 IS - 27 SN - 0021-9258, 0021-9258 KW - DNA-Binding Proteins KW - 0 KW - Madh2 protein, rat KW - Madh3 protein, rat KW - RNA, Small Interfering KW - SMAD2 protein, human KW - SMAD3 protein, human KW - Smad2 Protein KW - Smad3 Protein KW - TGFB1 protein, human KW - Tgfb1 protein, rat KW - Trans-Activators KW - Transforming Growth Factor beta KW - Transforming Growth Factor beta1 KW - Cytochromes c KW - 9007-43-6 KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - p38 Mitogen-Activated Protein Kinases KW - ACVR1C protein, human KW - EC 2.7.11.30 KW - Activin Receptors, Type I KW - Acvr1c protein, rat KW - CASP3 protein, human KW - EC 3.4.22.- KW - CASP9 protein, human KW - Casp3 protein, rat KW - Casp9 protein, rat KW - Caspase 3 KW - Caspase 9 KW - Caspases KW - Index Medicus KW - Animals KW - Cytochromes c -- metabolism KW - Humans KW - Cell Separation KW - RNA, Small Interfering -- metabolism KW - Caspases -- metabolism KW - Cell Survival KW - Rats KW - Genes, Dominant KW - Genetic Vectors KW - Flow Cytometry KW - DNA Fragmentation KW - Adenoviridae -- metabolism KW - Plasmids -- metabolism KW - Dose-Response Relationship, Drug KW - Mitogen-Activated Protein Kinases -- metabolism KW - Cell Line, Tumor KW - Adenoviridae -- genetics KW - Blotting, Western KW - Transfection KW - Transforming Growth Factor beta -- metabolism KW - Cell Line KW - Trans-Activators -- metabolism KW - MAP Kinase Signaling System KW - Carcinoma, Hepatocellular -- metabolism KW - Apoptosis KW - Carcinoma, Hepatocellular -- pathology KW - Activin Receptors, Type I -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66658013?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Activin+receptor-like+kinase-7+induces+apoptosis+through+activation+of+MAPKs+in+a+Smad3-dependent+mechanism+in+hepatoma+cells.&rft.au=Kim%2C+Byung-Chul%3Bvan+Gelder%2C+Howard%3BKim%2C+Tae+Aug%3BLee%2C+Ho-Jae%3BBaik%2C+Kim+G%3BChun%2C+Hyun+Hye%3BLee%2C+David+A%3BChoi%2C+Kyeong+Sook%3BKim%2C+Seong-Jin&rft.aulast=Kim&rft.aufirst=Byung-Chul&rft.date=2004-07-02&rft.volume=279&rft.issue=27&rft.spage=28458&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 - 2004-08-11 N1 - Date created - 2004-06-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gastrointestinally distributed UDP-glucuronosyltransferase 1A10, which metabolizes estrogens and nonsteroidal anti-inflammatory drugs, depends upon phosphorylation. AN - 66657762; 15117964 AB - Among gastrointestinal distributed isozymes encoded at the UGT1 locus, UDP-glucuronosyltransferase 1A10 (UGT1A10) metabolizes a number of important chemicals. Similar to broad conversion of phytoestrogens (Basu, N. K., Ciotti, M., Hwang, M. S., Kole, L., Mitra, P. S., Cho, J. W., and Owens, I. S. (2004) J. Biol. Chem. 279, 1429-1441), UGT1A10 metabolized estrogens and their derivatives, whereas UGT1A1, -1A3, -1A7, and -1A8 differentially exhibited reduced activity toward the same. UGT1A10 compared with UGT1A7, -1A8, and -1A3 generally exhibited high activity toward acidic nonsteroidal anti-inflammatory drugs and natural benzaldehyde derivatives, while UGT1A3 metabolized most efficiently aromatic transcinnamic acids known to be generated from flavonoid glycosides by microflora in the lower gastrointestinal tract. Finally UGT1A10, -1A7, -1A8, and -1A3 converted plant-based salicylic acids; methylsalicylic acid was transformed at high levels, and acetylsalicylic (aspirin) and salicylic acid were transformed at moderate to low levels. Atypically UGT1A10 transformed estrogens between pH 6 and 8 but acidic structures preferentially at pH 6.4. Furthermore evidence indicates UGT1A10 expressed in COS-1 cells depends upon phosphorylation; UGT1A10 versus its single, double, and triple mutants at three predicted protein kinase C phosphorylation sites incorporated [(33)P]-orthophosphate and showed a progressive decrease with no detectable label or activity for the triple T73A/T202A/S432G-1A10 mutant. Single and double mutants revealed either null/full activity or null/additive activity, respectively. Additionally UGT1A10-expressing cultures glucuronidated 17beta-[(14)C]estradiol, whereas cultures containing null mutants at protein kinase C sites showed no estrogen conversion. Importantly UGT1A10 in cells supported 10-fold higher glucuronidation of 17beta-estradiol than UGT1A1. In summary, our results suggest gastrointestinally distributed UGT1A10 is important for detoxifying estrogens/phytoestrogens and aromatic acids with complementary activity by UGT1A7, -1A8, -1A3, and/or -1A1 evidently dependent upon phosphorylation. JF - The Journal of biological chemistry AU - Basu, Nikhil K AU - Kubota, Shigeki AU - Meselhy, Meselhy R AU - Ciotti, Marco AU - Chowdhury, Bhabadeb AU - Hartori, Masao AU - Owens, Ida S AD - Heritable Disorders Branch, National Institute of Child Health & Human Development, National Institutes of Health, Room 9S-21, Building 10, Bethesda, MD 20892, USA. Y1 - 2004/07/02/ PY - 2004 DA - 2004 Jul 02 SP - 28320 EP - 28329 VL - 279 IS - 27 SN - 0021-9258, 0021-9258 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Cinnamates KW - DNA, Complementary KW - Estrogens KW - Salicylates KW - Estradiol KW - 4TI98Z838E KW - UDP-glucuronosyltransferase, UGT1A3 KW - EC 2.4.1.- KW - bilirubin uridine-diphosphoglucuronosyl transferase 1A10 KW - Glucuronosyltransferase KW - EC 2.4.1.17 KW - UDP-glucuronosyltransferase, UGT1A7 KW - UDP-glucuronosyltransferase, UGT1A8 KW - Protein Kinase C KW - EC 2.7.11.13 KW - cinnamic acid KW - U14A832J8D KW - Index Medicus KW - Cinnamates -- chemistry KW - Animals KW - COS Cells KW - Dose-Response Relationship, Drug KW - Humans KW - Hydrogen-Ion Concentration KW - Tissue Distribution KW - Binding Sites KW - Estradiol -- metabolism KW - Protein Kinase C -- metabolism KW - Mutagenesis, Site-Directed KW - Blotting, Western KW - Phosphorylation KW - Transfection KW - Microsomes -- metabolism KW - DNA, Complementary -- metabolism KW - Kinetics KW - Models, Chemical KW - Mutation KW - Salicylates -- metabolism KW - Cell Line KW - Estrogens -- metabolism KW - Glucuronosyltransferase -- metabolism KW - Digestive System -- enzymology KW - Anti-Inflammatory Agents, Non-Steroidal -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66657762?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Gastrointestinally+distributed+UDP-glucuronosyltransferase+1A10%2C+which+metabolizes+estrogens+and+nonsteroidal+anti-inflammatory+drugs%2C+depends+upon+phosphorylation.&rft.au=Basu%2C+Nikhil+K%3BKubota%2C+Shigeki%3BMeselhy%2C+Meselhy+R%3BCiotti%2C+Marco%3BChowdhury%2C+Bhabadeb%3BHartori%2C+Masao%3BOwens%2C+Ida+S&rft.aulast=Basu&rft.aufirst=Nikhil&rft.date=2004-07-02&rft.volume=279&rft.issue=27&rft.spage=28320&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 - 2004-08-11 N1 - Date created - 2004-06-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: J Biol Chem. 2004 Dec 24;279(52):54972 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cross-Linguistic Analysis of Vocabulary in Young Children: Spanish, Dutch, French, Hebrew, Italian, Korean, and American English AN - 85624506; 200504882 AB - The composition of young children's vocabularies in seven contrasting linguistic communities was investigated. Mothers of 269 20-month-olds in Argentina, Belgium, France, Israel, Italy, the Republic of Korea, & the United States completed comparable vocabulary checklists for their children. In each language & vocabulary size grouping (except for children just learning to talk), children's vocabularies contained relatively greater proportions of nouns than other word classes. Each word class was consistently positively correlated with every other class in each language & for children with smaller & larger vocabularies. Noun prevalence in the vocabularies of young children & the merits of several theories that may account for this pattern are discussed. 6 Tables, 1 Appendix, 151 References. Adapted from the source document JF - Child Development AU - Bornstein, Marc H AU - Cote, Linda R AD - National Instit Child Health & Human Development, Bethesda Marc_H_Bornstein@nih.gov Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 1115 EP - 1139 VL - 75 IS - 4 SN - 0009-3920, 0009-3920 KW - Italy (39100) KW - France (25500) KW - Form Classes (25250) KW - Lexicon (47150) KW - Belgium (07990) KW - Nouns (59650) KW - Argentina (03950) KW - Language Acquisition (41600) KW - United States of America (92750) KW - Comparative Linguistics (13850) KW - Korea (40945) KW - Israel (38800) KW - Children (11850) KW - article KW - 4015: psycholinguistics; child language acquisition UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85624506?accountid=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=Child+Development&rft.atitle=Cross-Linguistic+Analysis+of+Vocabulary+in+Young+Children%3A+Spanish%2C+Dutch%2C+French%2C+Hebrew%2C+Italian%2C+Korean%2C+and+American+English&rft.au=Bornstein%2C+Marc+H%3BCote%2C+Linda+R&rft.aulast=Bornstein&rft.aufirst=Marc&rft.date=2004-07-01&rft.volume=75&rft.issue=4&rft.spage=1115&rft.isbn=&rft.btitle=&rft.title=Child+Development&rft.issn=00093920&rft_id=info:doi/ LA - English DB - Linguistics and Language Behavior Abstracts (LLBA) N1 - Date revised - 2005-05-01 N1 - Last updated - 2016-09-27 N1 - CODEN - CHDEAW N1 - SubjectsTermNotLitGenreText - Children (11850); Language Acquisition (41600); Lexicon (47150); Form Classes (25250); Nouns (59650); Comparative Linguistics (13850); Argentina (03950); Belgium (07990); France (25500); Israel (38800); Italy (39100); Korea (40945); United States of America (92750) ER - TY - JOUR T1 - The new-generation positron emission tomography/computed tomography scanners: implications for cardiac imaging AN - 754558334; 13337650 AB - The exceptionally rapid increase in the number of PET/CT scanners (often 3D only) for oncology may well facilitate an increase in cardiac PET imaging. However, there is only limited literature available as to how 3D acquisitions, especially with the new generation of scanners, will affect cardiac imaging. This situation will undoubtedly change very soon. Similarly, several aspects of CT-based attenuation correction for cardiac imaging remain to be investigated. Although, at the moment, 2D imaging with Ge-68 (or Cs-137) attenuation correction may remain the safest alternative for cardiac imaging, the new-generation PET/CT scanners hold great promise for the future of cardiac PET. JF - Journal of Nuclear Cardiology AU - Bacharach, Stephen L AD - Department of Nuclear Medicine, National Institutes of Health, Bldg 10, Room 1C401, 20892, Bethesda, Md., steve-bacharach@nih.gov. Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 388 EP - 392 PB - Mosby, Inc., New York VL - 11 IS - 4 SN - 1071-3581, 1071-3581 KW - Biotechnology and Bioengineering Abstracts KW - Heart KW - Computed tomography KW - Positron emission tomography KW - Oncology KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/754558334?accountid=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+Nuclear+Cardiology&rft.atitle=The+new-generation+positron+emission+tomography%2Fcomputed+tomography+scanners%3A+implications+for+cardiac+imaging&rft.au=Bacharach%2C+Stephen+L&rft.aulast=Bacharach&rft.aufirst=Stephen&rft.date=2004-07-01&rft.volume=11&rft.issue=4&rft.spage=388&rft.isbn=&rft.btitle=&rft.title=Journal+of+Nuclear+Cardiology&rft.issn=10713581&rft_id=info:doi/10.1016%2Fj.nuclcard.2004.04.008 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-08-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Heart; Computed tomography; Positron emission tomography; Oncology DO - http://dx.doi.org/10.1016/j.nuclcard.2004.04.008 ER - TY - JOUR T1 - Noninfectious X4 but not R5 human immunodeficiency virus type 1 virions inhibit humoral immune responses in human lymphoid tissue ex vivo. AN - 72016666; 15194782 AB - Ex vivo human immunodeficiency virus type 1 (HIV-1) infection of human lymphoid tissue recapitulates some aspects of in vivo HIV-1 infection, including a severe depletion of CD4(+) T cells and suppression of humoral immune responses to recall antigens or to polyclonal stimuli. These effects are induced by infection with X4 HIV-1 variants, whereas infection with R5 variants results in only mild depletion of CD4(+) T cells and no suppression of immune responses. To study the mechanisms of suppression of immune responses in this ex vivo system, we used aldrithiol-2 (AT-2)-inactivated virions that have functional envelope glycoproteins but are not infectious and do not deplete CD4(+) T cells in human lymphoid tissues ex vivo. Nevertheless, AT-2-inactivated X4 (but not R5) HIV-1 virions, even with only a brief exposure, inhibit antibody responses in human lymphoid tissue ex vivo, similarly to infectious virus. This phenomenon is mediated by soluble immunosuppressive factor(s) secreted by tissue exposed to virus. JF - Journal of virology AU - Fitzgerald, Wendy AU - Sylwester, Andrew W AU - Grivel, Jean-Charles AU - Lifson, Jeffrey D AU - Margolis, Leonid B AD - Laboratory of Cellular and Molecular Biophysics and NASA/NIH Center for Three-Dimensional Tissue Culture, National Institutes of child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-1855, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 7061 EP - 7068 VL - 78 IS - 13 SN - 0022-538X, 0022-538X KW - Culture Media, Conditioned KW - 0 KW - Disulfides KW - HIV Antibodies KW - Oxidants KW - Receptors, CCR5 KW - Receptors, CXCR4 KW - 2,2'-dipyridyl disulfide KW - 2127-03-9 KW - 2,2'-Dipyridyl KW - 551W113ZEP KW - Index Medicus KW - Culture Media, Conditioned -- pharmacology KW - B-Lymphocytes -- drug effects KW - B-Lymphocytes -- virology KW - Oxidants -- pharmacology KW - HIV Antibodies -- immunology KW - Disulfides -- pharmacology KW - Cells, Cultured KW - Humans KW - B-Lymphocytes -- immunology KW - Culture Media, Conditioned -- metabolism KW - Receptors, CCR5 -- metabolism KW - HIV-1 -- metabolism KW - HIV-1 -- immunology KW - Virion -- pathogenicity KW - HIV-1 -- pathogenicity KW - HIV Infections -- immunology KW - Receptors, CXCR4 -- metabolism KW - Palatine Tonsil -- immunology KW - 2,2'-Dipyridyl -- analogs & derivatives KW - Virion -- immunology KW - HIV-1 -- drug effects KW - 2,2'-Dipyridyl -- pharmacology KW - Virion -- drug effects KW - Palatine Tonsil -- virology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72016666?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Noninfectious+X4+but+not+R5+human+immunodeficiency+virus+type+1+virions+inhibit+humoral+immune+responses+in+human+lymphoid+tissue+ex+vivo.&rft.au=Fitzgerald%2C+Wendy%3BSylwester%2C+Andrew+W%3BGrivel%2C+Jean-Charles%3BLifson%2C+Jeffrey+D%3BMargolis%2C+Leonid+B&rft.aulast=Fitzgerald&rft.aufirst=Wendy&rft.date=2004-07-01&rft.volume=78&rft.issue=13&rft.spage=7061&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 - 2004-07-15 N1 - Date created - 2004-06-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Med Primatol. 2002 Aug;31(4-5):205-16 [12390543] Nat Med. 1999 Mar;5(3):344-6 [10086394] Proc Natl Acad Sci U S A. 2003 May 13;100(10):6057-62 [12730375] J Virol. 2003 Aug;77(15):8280-9 [12857897] J Acquir Immune Defic Syndr. 2003 Sep 1;34(1):7-19 [14501788] J Virol. 2001 Feb;75(3):1152-64 [11152488] Nat Med. 2001 Mar;7(3):344-9 [11231634] AIDS Res Hum Retroviruses. 2001 Jul 20;17(11):1003-8 [11485617] Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10362-7 [11504927] J Immunol Methods. 2002 Feb 1;260(1-2):219-34 [11792391] J Virol. 2002 Mar;76(6):2936-51 [11861860] AIDS. 2002 Jul 5;16(10):1319-29 [12131208] J Infect Dis. 2004 Feb 1;189(3):506-14 [14745709] N Engl J Med. 1983 Aug 25;309(8):453-8 [6224088] J Clin Invest. 1984 Jan;73(1):191-201 [6228564] Ann Intern Med. 1984 Dec;101(6):757-63 [6388451] Proc Natl Acad Sci U S A. 1985 Dec;82(23):8198-202 [2999797] Clin Immunol Immunopathol. 1986 Jun;39(3):359-67 [2938858] J Immunol. 1987 Jun 1;138(11):3720-4 [2953790] Clin Exp Immunol. 1987 Jun;68(3):479-87 [3652522] Clin Immunol Immunopathol. 1988 Jan;46(1):37-54 [3257177] J Clin Invest. 1988 Dec;82(6):1908-14 [2974045] Lancet. 1989 May 6;1(8645):983-5 [2565516] Cell Immunol. 1989 Jul;121(2):336-48 [2786762] Science. 1989 Dec 22;246(4937):1606-8 [2556795] AIDS. 1990 Apr;4(4):307-15 [2190605] N Engl J Med. 1991 Dec 26;325(26):1837-42 [1683682] J Virol. 1992 Mar;66(3):1354-60 [1738194] Eur J Immunol. 1992 Oct;22(10):2729-32 [1396975] AIDS. 1992 Dec;6(12):1465-9 [1492931] J Virol. 1993 Apr;67(4):2182-90 [8445728] Science. 1993 Mar 19;259(5102):1749-54 [8096089] Cell. 1994 Jan 28;76(2):241-51 [7904900] Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6594-8 [7912830] Cell Immunol. 1995 Apr 1;161(2):236-43 [7697734] J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Oct 1;10(2):139-49 [7552477] Nat Med. 1995 Dec;1(12):1320-2 [7489416] Ann Intern Med. 1996 Apr 1;124(7):654-63 [8607594] Immunol Lett. 1995 Nov;48(1):39-44 [8847089] Microbiol Rev. 1996 Jun;60(2):386-406 [8801439] J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Aug 15;12(5):442-50 [8757420] J Biol Regul Homeost Agents. 1995 Jul-Sep;9(3):88-90 [8782013] J Clin Microbiol. 1997 Jan;35(1):41-7 [8968878] AIDS Res Hum Retroviruses. 1997 Apr 10;13(6):461-71 [9100987] J Leukoc Biol. 1997 Jun;61(6):654-66 [9201256] Nature. 1998 Jan 15;391(6664):240 [9440686] Nat Med. 1998 Mar;4(3):346-9 [9500611] Virology. 1998 Feb 15;241(2):181-8 [9499793] J Biol Regul Homeost Agents. 1996 Oct-Dec;10(4):83-91 [9604776] J Exp Med. 1998 Jul 20;188(2):233-45 [9670036] Dev Immunol. 1998;6(1-2):61-70 [9716906] AIDS. 1998 Aug 20;12(12):1437-49 [9727564] J Virol. 1998 Oct;72(10):7992-8001 [9733838] Nature. 1998 Sep 10;395(6698):189-94 [9744279] J Virol. 1998 Nov;72(11):9345-7 [9765486] AIDS Res Hum Retroviruses. 1998 Oct;14 Suppl 3:S311-9 [9814959] J Immunol. 2003 Mar 1;170(5):2449-55 [12594269] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gene expression profiling of rat livers reveals indicators of potential adverse effects. AN - 72003008; 15084756 AB - This study tested the hypothesis that gene expression profiling can reveal indicators of subtle injury to the liver induced by a low dose of a substance that does not cause overt toxicity as defined by conventional criteria of toxicology (e.g., abnormal clinical chemistry and histopathology). For the purpose of this study we defined this low dose as subtoxic, i.e., a dose that elicits effects which are below the detection of conventional toxicological parameters. Acetaminophen (APAP) was selected as a model hepatotoxicant because (1) considerable information exists concerning the mechanism of APAP hepatotoxicity that can occur following high doses, (2) intoxication with APAP is the leading cause of emergency room visits involving acute liver failure within the United States, and (3) conventional clinical markers have poor predictive value. Rats treated with a single dose of 0, 50, 150, or 1500 mg/kg APAP were examined at 6, 24, or 48 h after exposure for conventional toxicological parameters and for gene expression alterations. Patterns of gene expression were found which indicated cellular energy loss as a consequence of APAP toxicity. Elements of these patterns were apparent even after exposure to subtoxic doses. With increasing dose, the magnitude of changes increased and additional members of the same biological pathways were differentially expressed. The energy loss suggested by gene expression changes was confirmed at the 1500 mg/kg dose exposure by measuring ATP levels. Only by ultrastructural examination could any indication of toxicity be identified after exposure to a subtoxic dose of APAP and that was occasional mitochondrial damage. In conclusion, this study provides evidence that supports the hypothesis that gene expression profiling may be a sensitive means of identifying indicators of potential adverse effects in the absence of the occurrence of overt toxicity. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Heinloth, Alexandra N AU - Irwin, Richard D AU - Boorman, Gary A AU - Nettesheim, Paul AU - Fannin, Rickie D AU - Sieber, Stella O AU - Snell, Michael L AU - Tucker, Charles J AU - Li, Leping AU - Travlos, Gregory S AU - Vansant, Gordon AU - Blackshear, Pamela E AU - Tennant, Raymond W AU - Cunningham, Michael L AU - Paules, Richard S AD - National Center for Toxicogenomics, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, North Carolina 27709, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 193 EP - 202 VL - 80 IS - 1 SN - 1096-6080, 1096-6080 KW - Analgesics, Non-Narcotic KW - 0 KW - Acetaminophen KW - 362O9ITL9D KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Index Medicus KW - Rats KW - Administration, Oral KW - Animals KW - Rats, Inbred F344 KW - Dose-Response Relationship, Drug KW - Mitochondria, Liver -- metabolism KW - Mitochondria, Liver -- ultrastructure KW - Adenosine Triphosphate -- metabolism KW - Microarray Analysis KW - Toxicity Tests -- methods KW - Male KW - Gene Expression Profiling KW - Analgesics, Non-Narcotic -- adverse effects KW - Acetaminophen -- administration & dosage KW - Liver -- pathology KW - Chemical and Drug Induced Liver Injury -- etiology KW - Chemical and Drug Induced Liver Injury -- pathology KW - Liver -- drug effects KW - Acetaminophen -- adverse effects KW - Liver -- metabolism KW - Analgesics, Non-Narcotic -- administration & dosage KW - Chemical and Drug Induced Liver Injury -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72003008?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Gene+expression+profiling+of+rat+livers+reveals+indicators+of+potential+adverse+effects.&rft.au=Heinloth%2C+Alexandra+N%3BIrwin%2C+Richard+D%3BBoorman%2C+Gary+A%3BNettesheim%2C+Paul%3BFannin%2C+Rickie+D%3BSieber%2C+Stella+O%3BSnell%2C+Michael+L%3BTucker%2C+Charles+J%3BLi%2C+Leping%3BTravlos%2C+Gregory+S%3BVansant%2C+Gordon%3BBlackshear%2C+Pamela+E%3BTennant%2C+Raymond+W%3BCunningham%2C+Michael+L%3BPaules%2C+Richard+S&rft.aulast=Heinloth&rft.aufirst=Alexandra&rft.date=2004-07-01&rft.volume=80&rft.issue=1&rft.spage=193&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 - 2005-07-25 N1 - Date created - 2004-06-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The schedule-dependent enhanced cytotoxic activity of 7-ethyl-10-hydroxy-camptothecin (SN-38) in combination with Gefitinib (Iressa, ZD1839). AN - 72001641; 15183125 AB - The combination of the topoisomerase I (Topo I) inhibitor CPT-11 with the anti-epidermal growth factor receptor (EGFR) agent Gefitinib (Iressa, ZD1839) represents a promising medical approach for colorectal cancer patients. In this report, we provide pre-clinical evidences for their optimal combination schedule in HT-29 and LoVo human colon cancer cell lines. We analyzed the different effects that three different combination schedules of SN-38 (the active CPT-11 metabolite) and Gefitinib (Gefitinib before; Gefitinib simultaneously; Gefitinib after SN-38) have on cell growth, cell cycle, apoptosis, and expression/phosphorylation of EGFR, Topo I and some steps of the signal transduction pathway. We first determined the IC(50) of each drug choosing the 5 days exposure for Gefitinib (0.6 and 3.8 microM for LoVo and HT-29 cells, respectively) and 1 day exposure for SN-38 (0.31 and 0.5 microM for LoVo and HT-29 cells, respectively). The different drug combination schedules were tested in various concentrations by using equiactive concentrations of the two drugs. The cytotoxicity of Gefitinib and SN-38 combination was schedule- and concentration-dependent but not cell line-specific. The most synergistic schedule was Gefitinib given after SN-38, with combination indexes (CI) of 0.007 and 0.454 in HT-29 and LoVo, respectively. Analysis of bio-molecular targets showed that Gefitinib was able to modulate SN-38 ability to inhibit Topo I, to accumulate cells in S-phase, and to induce apoptosis. Interestingly, SN-38 was able to activate EGFR and its signal transduction pathway. Confirming preliminary clinical experience of Gefitinib with other cytotoxic drugs, it seems that Gefitinib after SN-38 represents the best cytotoxic combination schedule but the biomolecular basis for this synergism remain to be completely elucidated. JF - Biochemical pharmacology AU - Azzariti, Amalia AU - Xu, Jian-Ming AU - Porcelli, Letizia AU - Paradiso, Angelo AD - Clinical Experimental Oncology Laboratory, National Cancer Institute, Bari, Italy. Y1 - 2004/07/01/ PY - 2004 DA - 2004 Jul 01 SP - 135 EP - 144 VL - 68 IS - 1 SN - 0006-2952, 0006-2952 KW - Antineoplastic Agents KW - 0 KW - Quinazolines KW - irinotecan KW - 0H43101T0J KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - gefitinib KW - S65743JHBS KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Signal Transduction -- physiology KW - Receptor, Epidermal Growth Factor -- metabolism KW - Tumor Cells, Cultured KW - Humans KW - Signal Transduction -- drug effects KW - Cell Division -- drug effects KW - HT29 Cells KW - Drug Synergism KW - Colonic Neoplasms -- pathology KW - DNA Topoisomerases, Type I -- metabolism KW - Cell Cycle -- drug effects KW - Quinazolines -- administration & dosage KW - Apoptosis KW - Camptothecin -- pharmacology KW - Antineoplastic Agents -- administration & dosage KW - Camptothecin -- analogs & derivatives KW - Antineoplastic Agents -- pharmacology KW - Quinazolines -- pharmacology KW - Camptothecin -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/72001641?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=The+schedule-dependent+enhanced+cytotoxic+activity+of+7-ethyl-10-hydroxy-camptothecin+%28SN-38%29+in+combination+with+Gefitinib+%28Iressa%2C+ZD1839%29.&rft.au=Azzariti%2C+Amalia%3BXu%2C+Jian-Ming%3BPorcelli%2C+Letizia%3BParadiso%2C+Angelo&rft.aulast=Azzariti&rft.aufirst=Amalia&rft.date=2004-07-01&rft.volume=68&rft.issue=1&rft.spage=135&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=00062952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-19 N1 - Date created - 2004-06-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - L-Carnitine and acetyl-L-carnitine in the treatment of complications associated with HIV infection and antiretroviral therapy. AN - 67303845; 16120381 AB - L-Carnitine (LC) and acetyl-L-carnitine (ALC) play major roles in cell energy and lipid metabolism. Supplementation with these nutrients, which are highly popular in USA, has been associated with favorable effects, including anti-oxidant action, neuro- and cardioprotection, immunomodulation, and cognitive enhancement. Patients with HIV infection and undergoing highly active antiretroviral therapy (HAART) often develop complications, such as polyneuropathy, skeletal myopathy, dyslipidemia and lipodystrophy, which have been linked to mitochondrial dysfunction. Moreover, these patients are often LC-deficient. Thus, they may benefit from LC and ALC supplementation. Indeed, oral, i.v., or i.m. administration of large doses of LC and/or ALC to HIV positive subjects untreated/treated with HAART was shown to: (1) increase the number of CD4 cells and reduce lymphocyte apoptosis; (2) improve symptoms of polyneuropathy; (3) prevent cardiovascular damage from wasting and diarrhea syndromes; (4) decrease serum levels of triglycerides and TNFalpha. No significant toxicities were associated with LC and ALC treatment. Although promising, most of these findings derive from small uncontrolled clinical trials. Further research is warranted to prove the efficacy and safety of LC and ALC supplementation in patients with complications of HIV infection and HAART. JF - Mitochondrion AU - Ilias, Ioannis AU - Manoli, Irini AU - Blackman, Marc R AU - Gold, Philip W AU - Alesci, Salvatore AD - Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 163 EP - 168 VL - 4 IS - 2-3 SN - 1567-7249, 1567-7249 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67303845?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mitochondrion&rft.atitle=L-Carnitine+and+acetyl-L-carnitine+in+the+treatment+of+complications+associated+with+HIV+infection+and+antiretroviral+therapy.&rft.au=Ilias%2C+Ioannis%3BManoli%2C+Irini%3BBlackman%2C+Marc+R%3BGold%2C+Philip+W%3BAlesci%2C+Salvatore&rft.aulast=Ilias&rft.aufirst=Ioannis&rft.date=2004-07-01&rft.volume=4&rft.issue=2-3&rft.spage=163&rft.isbn=&rft.btitle=&rft.title=Mitochondrion&rft.issn=15677249&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-10-24 N1 - Date created - 2005-08-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular insights into NRTI inhibition and mitochondrial toxicity revealed from a structural model of the human mitochondrial DNA polymerase. AN - 67291190; 16120386 AB - NRTI-based therapy used to treat AIDS can cause mitochondrial toxicity resulting from the incorporation of NRTIs into mitochondrial DNA by DNA polymerase gamma (pol gamma). Pol gamma has poor discrimination against many of the currently used NRTIs resulting in aborted DNA synthesis and subsequent depletion of mtDNA. Pol gamma readily incorporates ddCTP, ddITP and D4T-TP with an efficiency similar to the incorporation of normal nucleotides, whereas AZT-TP, CBV-TP, 3TC-TP and PMPApp act as moderate inhibitors to DNA synthesis. We have sought a structural explanation for the unique selection for NRTIs by the human pol gamma. A structural model of the human pol gamma was developed to ascertain the role of active site amino acids. One residue in particular, Y951 in motif B, is primarily responsible for the selection of dideoxynucleotides and D4T-TP. Our structural model of the human pol gamma should assist in rational design of antiviral nucleoside analogs with higher specificity for HIV-RT and minimal selection and incorporation into mitochondrial DNA. JF - Mitochondrion AU - Bienstock, Rachelle J AU - Copeland, Willliam C AD - Scientific Computing Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, NC 27709, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 203 EP - 213 VL - 4 IS - 2-3 SN - 1567-7249, 1567-7249 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67291190?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mitochondrion&rft.atitle=Molecular+insights+into+NRTI+inhibition+and+mitochondrial+toxicity+revealed+from+a+structural+model+of+the+human+mitochondrial+DNA+polymerase.&rft.au=Bienstock%2C+Rachelle+J%3BCopeland%2C+Willliam+C&rft.aulast=Bienstock&rft.aufirst=Rachelle&rft.date=2004-07-01&rft.volume=4&rft.issue=2-3&rft.spage=203&rft.isbn=&rft.btitle=&rft.title=Mitochondrion&rft.issn=15677249&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-10-24 N1 - Date created - 2005-08-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Beyond human papillomavirus: the cervix, exogenous secondary factors, and the development of cervical precancer and cancer. AN - 67278711; 15874868 AB - Human papillomavirus (HPV) is the necessary but probably not sufficient cause of cervical precancer and cancer. Secondary exogenous and endogenous factors, HPV cofactors, may contribute to the probability of a cancer-associated (oncogenic) HPV infection progressing to cervical precancer and cancer. For these cofactors to influence the natural history of HPV infection, they must act on cervical tissue to promote viral persistence, progression to precancer or cancer given viral persistence, or both. The aim of this review was to examine briefly the impact these factors may have on carcinogenesis of the cervix. Specifically, the roles of the cervical transformation zone, cervical immunity, inflammation and coinfection, and exposure to the main HPV cofactors (smoking, oral contraceptive use, and multiparity) are discussed. JF - Journal of lower genital tract disease AU - Castle, Philip E AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. castlep@mail.nih.gov Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 224 EP - 230 VL - 8 IS - 3 SN - 1089-2591, 1089-2591 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67278711?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+lower+genital+tract+disease&rft.atitle=Beyond+human+papillomavirus%3A+the+cervix%2C+exogenous+secondary+factors%2C+and+the+development+of+cervical+precancer+and+cancer.&rft.au=Castle%2C+Philip+E&rft.aulast=Castle&rft.aufirst=Philip&rft.date=2004-07-01&rft.volume=8&rft.issue=3&rft.spage=224&rft.isbn=&rft.btitle=&rft.title=Journal+of+lower+genital+tract+disease&rft.issn=10892591&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-05-19 N1 - Date created - 2005-05-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dynamic balancing of the dual nature of HIF-1alpha for cell survival. AN - 67061539; 15190211 AB - In hypoxic cells, HIF-1alpha escapes from oxygen-dependent proteolysis and binds to the hypoxia-responsive element (HRE) for transcriptional activation of target genes involved in angiogenesis and glycolysis. We recently demonstrated that the G(1) checkpoint gene p21(cip1)is activated by HIF-1alpha with a novel mechanism that involves the HIF-1alpha PAS domains to displace Myc binding from p21(cip1) promoter. This HIF-1alpha-Myc pathway may account for up- and down-regulation of other hypoxia-responsive genes that lack the HRE. Moreover, the role of HIF-1alpha in cell cycle control indicates a dual, yet seemingly conflicting, nature of HIF-1alpha: promoting cell growth and arrest in concomitance. We speculate that a dynamic balance between the two processes is achieved by a "stop-and-go" strategy to maintain cell growth and survival. Tumor cells may adopt such scheme to evade the killing by chemotherapeutic agents. JF - Cell cycle (Georgetown, Tex.) AU - Koshiji, Minori AU - Huang, L Eric AD - Laboratory of Human Carcinogenesis, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 853 EP - 854 VL - 3 IS - 7 KW - Cell Cycle Proteins KW - 0 KW - HIF1A protein, human KW - Hypoxia-Inducible Factor 1, alpha Subunit KW - MYC protein, human KW - Proto-Oncogene Proteins c-myc KW - Index Medicus KW - Animals KW - Adaptation, Physiological -- physiology KW - Humans KW - Cell Division -- physiology KW - Drug Resistance, Neoplasm -- physiology KW - Cell Enlargement -- drug effects KW - Proto-Oncogene Proteins c-myc -- metabolism KW - Hypoxia-Inducible Factor 1, alpha Subunit -- genetics KW - Cell Cycle Proteins -- genetics KW - Cell Hypoxia -- physiology KW - Hypoxia-Inducible Factor 1, alpha Subunit -- metabolism KW - Cell Survival -- physiology KW - Cell Cycle Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67061539?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cycle+%28Georgetown%2C+Tex.%29&rft.atitle=Dynamic+balancing+of+the+dual+nature+of+HIF-1alpha+for+cell+survival.&rft.au=Koshiji%2C+Minori%3BHuang%2C+L+Eric&rft.aulast=Koshiji&rft.aufirst=Minori&rft.date=2004-07-01&rft.volume=3&rft.issue=7&rft.spage=853&rft.isbn=&rft.btitle=&rft.title=Cell+cycle+%28Georgetown%2C+Tex.%29&rft.issn=1551-4005&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-04-14 N1 - Date created - 2004-11-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Applications of magnetic resonance microscopy. AN - 67009411; 15503663 AB - Magnetic resonance imaging (MRI) has enjoyed enormous clinical success since the first demonstration of the method more than 30 years ago. An increasing number of pharmaceutical manufacturers seeking new biomarkers for assessing drug efficacy and toxicity are turning to MRI. A specific application of MRI promises to revolutionize pathology for the basic scientist in the same way MRI has forever altered the standard of care in the clinical domain. More specifically, this application is the use of magnetic resonance microscopy (MRM) in conjunction with new staining methodologies that now make MRM routinely available to the widest range of investigators. JF - Toxicologic pathology AU - Maronpot, Robert R AU - Sills, Robert C AU - Johnson, G Allan AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Maronpot@niehs.nih.gov PY - 2004 SP - 42 EP - 48 VL - 32 Suppl 2 SN - 0192-6233, 0192-6233 KW - Sulfur Oxides KW - 0 KW - carbonyl sulfide KW - 871UI0ET21 KW - Urate Oxidase KW - EC 1.7.3.3 KW - Index Medicus KW - Urate Oxidase -- genetics KW - Imaging, Three-Dimensional KW - Fetus KW - Animals KW - Sulfur Oxides -- metabolism KW - Urate Oxidase -- metabolism KW - Humans KW - Teratology KW - Brain -- metabolism KW - Image Processing, Computer-Assisted KW - Magnetic Resonance Imaging KW - Microscopy -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67009411?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Applications+of+magnetic+resonance+microscopy.&rft.au=Maronpot%2C+Robert+R%3BSills%2C+Robert+C%3BJohnson%2C+G+Allan&rft.aulast=Maronpot&rft.aufirst=Robert&rft.date=2004-07-01&rft.volume=32+Suppl+2&rft.issue=&rft.spage=42&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 - 2005-01-31 N1 - Date created - 2004-10-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacological modulation of GABA(B) receptors affects cocaine-induced seizures in mice. AN - 66933090; 14985936 AB - Previous data have demonstrated that the convulsant effects of cocaine can be modulated by compounds that increase levels of endogenous gamma-aminobutyric acid (GABA) or that directly stimulate GABA(A) receptors. To determine whether the convulsant effects of cocaine can be modulated by ligands selective for GABA(B) receptors in mice. Effects of the GABA(B) receptor agonist ((+/-)-baclofen), antagonist (phaclofen), and their combination were tested against clonic seizures induced by cocaine (75 mg/kg). Enantiomers of baclofen were used to confirm stereospecificity of (+/-)-baclofen's effects. Pharmacological specificity of (+/-)-baclofen's effects was tested by comparison against seizures induced by GBR 12909 (monoamine transporter inhibitor), pentylenetetrazole (GABA(A) antagonist), N-methyl-D-aspartate (NMDA agonist), and aminophylline (A1/A2 adenosine antagonist). Additionally, effects of (+/-)-baclofen on kindled seizures induced by repeated administration of cocaine (60 mg/kg every 24 h for 6 days) were evaluated. The inverted screen test was used to assess behavioral side effects of baclofen. (+/-)-Baclofen dose-dependently inhibited acute (ED50=4.1 mg/kg) and kindled (6.4 mg/kg) seizures induced by cocaine at doses somewhat lower than those producing behavioral side effects (11.5 mg/kg), and these effects were stereospecific. (+/-)-Baclofen suppressed seizures induced by GBR 12909 but not by pentylenetetrazole, NMDA, and aminophylline, suggesting selectivity of its anticonvulsant effects for monoamine-related mechanisms. Finally, phaclofen dose-dependently enhanced the convulsant effects of a threshold dose of cocaine (60 mg/kg). Modulation of GABA(B) receptors can affect seizures induced by cocaine. This molecular mechanism may be involved in seizures induced by cocaine or, alternatively, may function as an independent inhibitory mechanism against seizures arising from blockade of monoamine uptake. JF - Psychopharmacology AU - Gasior, Maciej AU - Kaminski, Rafal AU - Witkin, Jeffrey M AD - Drug Development Group, Behavioral Neuroscience Branch, National Institute on Drug Abuse, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. GasiorM@ninds.nih.gov Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 211 EP - 219 VL - 174 IS - 2 SN - 0033-3158, 0033-3158 KW - Dopamine Uptake Inhibitors KW - 0 KW - GABA-A Receptor Agonists KW - GABA-A Receptor Antagonists KW - GABA-B Receptor Agonists KW - GABA-B Receptor Antagonists KW - Piperazines KW - Receptors, GABA-A KW - Receptors, GABA-B KW - phaclofen KW - 108351-35-5 KW - vanoxerine KW - 90X28IKH43 KW - Baclofen KW - H789N3FKE8 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Piperazines -- antagonists & inhibitors KW - Animals KW - Kindling, Neurologic -- drug effects KW - Mice KW - Piperazines -- toxicity KW - Male KW - Seizures -- chemically induced KW - Dopamine Uptake Inhibitors -- toxicity KW - Dopamine Uptake Inhibitors -- antagonists & inhibitors KW - Cocaine -- toxicity KW - Baclofen -- analogs & derivatives KW - Seizures -- prevention & control KW - Baclofen -- therapeutic use KW - Baclofen -- pharmacology KW - Cocaine -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66933090?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology&rft.atitle=Pharmacological+modulation+of+GABA%28B%29+receptors+affects+cocaine-induced+seizures+in+mice.&rft.au=Gasior%2C+Maciej%3BKaminski%2C+Rafal%3BWitkin%2C+Jeffrey+M&rft.aulast=Gasior&rft.aufirst=Maciej&rft.date=2004-07-01&rft.volume=174&rft.issue=2&rft.spage=211&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-10-19 N1 - Date created - 2004-10-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drugs and driving: the nuances. AN - 66885140; 15372862 JF - Journal of the American Pharmacists Association : JAPhA AU - Wick, Jeannette Y AU - Zanni, Guido R AD - National Cancer Institute, U.S. National Institutes of Health, Bethesda, MD , USA. PY - 2004 SP - 430 EP - 433 VL - 44 IS - 4 SN - 1544-3191, 1544-3191 KW - Index Medicus KW - United States KW - Drug Interactions KW - Patient Education as Topic -- methods KW - Professional Role KW - Humans KW - Automobile Driving -- education KW - Accidents, Traffic -- statistics & numerical data KW - Accidents, Traffic -- mortality KW - Drug Prescriptions -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66885140?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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+Pharmacists+Association+%3A+JAPhA&rft.atitle=Drugs+and+driving%3A+the+nuances.&rft.au=Wick%2C+Jeannette+Y%3BZanni%2C+Guido+R&rft.aulast=Wick&rft.aufirst=Jeannette&rft.date=2004-07-01&rft.volume=44&rft.issue=4&rft.spage=430&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Pharmacists+Association+%3A+JAPhA&rft.issn=15443191&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-06 N1 - Date created - 2004-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Allium vegetables in cancer prevention: an overview. AN - 66883348; 15373701 AB - The Allium genus includes approximately 500 species. Commonly used allium vegetables include garlic, onion, leeks, chives, scallions which are used all over the world in different delicacies. Some allium vegetables have been employed for millenia in the traditional medical practice to treat cardiovascular diseases. They have been shown to have applications as antimicrobial, antithrombotic, antitumor, hypolipidaemic, antiarthritic and hypoglycemic agents. In recent years, extensive research has focused on the anticarcinogenic potential of allium vegetables and their constituents, viz., allylsulfides and flavonoids (particularly quercetin which is present abundantly in onion). Epidemiological studies have shown that higher intake of allium products is associated with reduced risk of several types of cancers. These epidemiological findings are well correlated with laboratory investigations. Organosulfur compounds present in Allium vegetables, are considered to be responsible for the beneficial effects of these herbs. Several mechanisms have been proposed to explain the cancer-preventive effects of Allium vegetables and related organosulfur compounds. These include inhibition of mutagenesis, modulation of enzyme activities, inhibition of DNA adduct formation, free-radical scavenging, and effects on cell proliferation and tumor growth. Although there is a large body of evidence supporting these mechanisms, they are still speculative, and further research is needed to support causality between such properties and cancer-preventive activity in experimental animals. This article reviews current knowledge concerning allium vegetables and cancer prevention. JF - Asian Pacific journal of cancer prevention : APJCP AU - Sengupta, Archana AU - Ghosh, Samit AU - Bhattacharjee, Shamee AD - Dept. of Cancer Chemoprevention, Chittaranjan National Cancer Institute, Kolkata-700026, India. archana_sen@yahoo.com PY - 2004 SP - 237 EP - 245 VL - 5 IS - 3 SN - 1513-7368, 1513-7368 KW - Anticarcinogenic Agents KW - 0 KW - DNA Adducts KW - Free Radical Scavengers KW - Index Medicus KW - Plant Structures KW - Epidemiologic Studies KW - DNA Damage KW - Humans KW - Cell Division KW - Vegetables -- chemistry KW - Anticarcinogenic Agents -- pharmacology KW - Allium -- chemistry KW - Neoplasms -- prevention & control KW - Diet UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66883348?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Allium+vegetables+in+cancer+prevention%3A+an+overview.&rft.au=Sengupta%2C+Archana%3BGhosh%2C+Samit%3BBhattacharjee%2C+Shamee&rft.aulast=Sengupta&rft.aufirst=Archana&rft.date=2004-07-01&rft.volume=5&rft.issue=3&rft.spage=237&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 - 2004-10-26 N1 - Date created - 2004-09-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Asian Pac J Cancer Prev. 2004 Jul-Sep;5(3):229-30 [15373700] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [HCV infection among narcotics/methamphetamine abusers]. AN - 66863509; 15359814 JF - Nihon rinsho. Japanese journal of clinical medicine AU - Wada, Kiyoshi AD - Division of Drug Dependence Research, National Institute of Mental Health, National Center of Neurology and Psychiatry. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 326 EP - 329 VL - 62 Suppl 7 SN - 0047-1852, 0047-1852 KW - Methamphetamine KW - 44RAL3456C KW - Index Medicus KW - Risk KW - Needle Sharing -- statistics & numerical data KW - Needle-Exchange Programs KW - Methamphetamine -- adverse effects KW - Humans KW - Substance-Related Disorders KW - Needle Sharing -- adverse effects KW - Prevalence KW - Hepatitis C -- prevention & control KW - Amphetamine-Related Disorders -- epidemiology KW - Opioid-Related Disorders -- epidemiology KW - Opioid-Related Disorders -- psychology KW - Hepatitis C -- transmission KW - Amphetamine-Related Disorders -- psychology KW - Hepatitis C -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66863509?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nihon+rinsho.+Japanese+journal+of+clinical+medicine&rft.atitle=%5BHCV+infection+among+narcotics%2Fmethamphetamine+abusers%5D.&rft.au=Wada%2C+Kiyoshi&rft.aulast=Wada&rft.aufirst=Kiyoshi&rft.date=2004-07-01&rft.volume=62+Suppl+7&rft.issue=&rft.spage=326&rft.isbn=&rft.btitle=&rft.title=Nihon+rinsho.+Japanese+journal+of+clinical+medicine&rft.issn=00471852&rft_id=info:doi/ LA - Japanese DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-10-18 N1 - Date created - 2004-09-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antidepressant-withdrawal mania:a critical review and synthesis of the literature. AN - 66767618; 15291689 AB - Hypomania or mania have rarely been reported to develop shortly after the discontinuation of an antidepressant drug. The true incidence of this discontinuation syndrome is unknown because it may be underreported as a consequence of underrecognition or misattribution. This article examines the possible etiology, nosology, mechanisms, and other aspects of the syndrome. A PubMed search was conducted in May 2003 and repeated in January 2004 using the search terms antidepressant and mania. Relevant articles containing adequate descriptions for presentation were retrieved, and their reference lists were hand-searched for further pertinent material. Hand-searches of the indexes of leading psychiatry journals were also performed for the years 1998-2003. Twenty-three articles were identified for review. Antidepressant-withdrawal hypomania or mania may occur rarely with almost any antidepressant drug after sudden withdrawal, tapered discontinuation, or even merely a decrease in dose. The syndrome may be self-limiting, may abate with the reinstitution of the antidepressant drug, or may require specific anti-manic treatments; mood stabilizers do not necessarily protect against the syndrome. The true incidence of the syndrome is unknown. Narrow and broad diagnostic criteria are proposed for the syndrome, and a synthesis of literature is provided. JF - The Journal of clinical psychiatry AU - Andrade, Chittaranjan AD - Department of Psychopharmacology, National Institute of Mental Health and Neurosciences, Bangalore, India. andrade@nimhans.kar.nic.in Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 987 EP - 993 VL - 65 IS - 7 SN - 0160-6689, 0160-6689 KW - Antidepressive Agents KW - 0 KW - Antimanic Agents KW - Index Medicus KW - Diagnosis, Differential KW - Syndrome KW - PubMed -- statistics & numerical data KW - Humans KW - Incidence KW - Depressive Disorder -- drug therapy KW - Antimanic Agents -- therapeutic use KW - Bipolar Disorder -- diagnosis KW - Substance Withdrawal Syndrome -- etiology KW - Bipolar Disorder -- epidemiology KW - Antidepressive Agents -- therapeutic use KW - Antidepressive Agents -- adverse effects KW - Bipolar Disorder -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66767618?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Antidepressant-withdrawal+mania%3Aa+critical+review+and+synthesis+of+the+literature.&rft.au=Andrade%2C+Chittaranjan&rft.aulast=Andrade&rft.aufirst=Chittaranjan&rft.date=2004-07-01&rft.volume=65&rft.issue=7&rft.spage=987&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 - 2004-09-13 N1 - Date created - 2004-08-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical proteomics: Applications for prostate cancer biomarker discovery and detection. AN - 66764442; 15283891 AB - The science of proteomics comprises much more than simply generating lists of proteins that change in expression as a cause of or consequence of pathophysiology. The goal of proteomics should be to characterize the information flow through the intercellular protein circuitry that communicates with the extracellular microenvironment and then ultimately to the serum/plasma macroenvironment. Serum proteomic pattern diagnostics is a new type of proteomic concept in which patterns of ion signatures generated from high dimensional mass spectrometry data are used as diagnostic classifiers. This recent approach has exciting potential for clinical utility of diagnostic patterns because low molecular weight metabolites, peptides, and protein fragments may have higher accuracy than traditional biomarkers of cancer detection. Intriguingly, we now have discovered that this diagnostic information exists in a bound state, complexed with circulating highly abundant carrier proteins. These diagnostic fragments may one day be harvested by circulating nanoparticles, designed to absorb, enrich, and amplify the repertoire of diagnostic biomarkers generated-even at the critical, initial stages of carcinogenesis. Copyright 2004 Elsevier Inc. JF - Urologic oncology AU - Petricoin, Emanuel F AU - Ornstein, David K AU - Liotta, Lance A AD - FDA-NCI Clinical Proteomics Program, Office of Cell and Gene Therapies, Center for Biologic Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA. petricoin@cber.fda.gov PY - 2004 SP - 322 EP - 328 VL - 22 IS - 4 SN - 1078-1439, 1078-1439 KW - Biomarkers, Tumor KW - 0 KW - Index Medicus KW - Protein Array Analysis KW - Mass Spectrometry KW - Diagnosis, Differential KW - Humans KW - Male KW - Gene Expression Profiling KW - Prostatic Neoplasms -- diagnosis KW - Proteomics -- trends KW - Biomarkers, Tumor -- analysis KW - Prostatic Neoplasms -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66764442?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Urologic+oncology&rft.atitle=Clinical+proteomics%3A+Applications+for+prostate+cancer+biomarker+discovery+and+detection.&rft.au=Petricoin%2C+Emanuel+F%3BOrnstein%2C+David+K%3BLiotta%2C+Lance+A&rft.aulast=Petricoin&rft.aufirst=Emanuel&rft.date=2004-07-01&rft.volume=22&rft.issue=4&rft.spage=322&rft.isbn=&rft.btitle=&rft.title=Urologic+oncology&rft.issn=10781439&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-26 N1 - Date created - 2004-07-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Eradication of HIV in infected patients: some potential approaches. AN - 66746257; 15232518 AB - Although at present, highly active antiretroviral therapy (HAART) has greatly reduced the number of viral copies to an undetectable level and has slowed down the progress of the disease in patients with human immunodeficiency virus (HIV) infection, the HIV-infected cells are not eradicated by this therapy. Virus replication rebounds once the drug therapy is terminated, regardless of duration of the therapy, primarily due to the establishment of a viral reservoir. Therefore, viral suppressive therapy is a lifelong task and may be accompanied by many as yet unidentified serious side effects. In addition, the maximum therapeutic benefits of HAART appear to have been reached recently in the U. S, and the incidences of multi-drug resistant viral strain infections are slowly but steadily increasing. Without an effective vaccine, which has already proved to be very difficult to develop, for the protection of the uninfected population and a feasible eradication strategy to cure infected patients, the number of HIV-infected persons will inevitably continue to rise. While the vast majority of endeavors are focused on developing new drugs that target different steps of HIV replication for suppressive therapy, researchers need to find a therapeutic strategy that directly aims at HIV-infected cells to cure the disease. In this article, I review and discuss some potential approaches to eradicate HIV-infected cells from the patients. JF - Medical science monitor : international medical journal of experimental and clinical research AU - Yang, Quan-en AD - SAIC-Frederick, Inc, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA. yangq@dtpax2.ncifcrf.gov Y1 - 2004/07// PY - 2004 DA - July 2004 SP - RA155 EP - RA165 VL - 10 IS - 7 SN - 1234-1010, 1234-1010 KW - Anti-HIV Agents KW - 0 KW - Immunotoxins KW - RNA, Small Interfering KW - Index Medicus KW - Humans KW - Clinical Trials as Topic KW - Genetic Therapy KW - T-Lymphocytes, Cytotoxic -- immunology KW - Virus Replication -- physiology KW - Transplantation, Homologous KW - RNA, Small Interfering -- therapeutic use KW - Bone Marrow Transplantation -- immunology KW - Virus Latency -- physiology KW - Anti-HIV Agents -- therapeutic use KW - Virus Replication -- drug effects KW - Virus Latency -- drug effects KW - Antiretroviral Therapy, Highly Active KW - Immunotoxins -- therapeutic use KW - RNA, Small Interfering -- pharmacology KW - Immunotoxins -- pharmacology KW - HIV -- physiology KW - HIV Infections -- virology KW - HIV Infections -- therapy KW - HIV Infections -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66746257?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+science+monitor+%3A+international+medical+journal+of+experimental+and+clinical+research&rft.atitle=Eradication+of+HIV+in+infected+patients%3A+some+potential+approaches.&rft.au=Yang%2C+Quan-en&rft.aulast=Yang&rft.aufirst=Quan-en&rft.date=2004-07-01&rft.volume=10&rft.issue=7&rft.spage=RA155&rft.isbn=&rft.btitle=&rft.title=Medical+science+monitor+%3A+international+medical+journal+of+experimental+and+clinical+research&rft.issn=12341010&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-14 N1 - Date created - 2004-07-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Monanchorin, a bicyclic alkaloid from the sponge Monanchora ungiculata. AN - 66741397; 15270573 AB - Monanchorin, a guanidine alkaloid with an unusual bicyclic skeleton, together with the known pentacyclic alkaloid crambescidin acid have been isolated from the aqueous extract of the sponge Monanchoraungiculata. JF - Journal of natural products AU - Meragelman, Karina M AU - McKee, Tawnya C AU - McMahon, James B AD - Molecular Targets Development Program, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702-1201, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 1165 EP - 1167 VL - 67 IS - 7 SN - 0163-3864, 0163-3864 KW - Alkaloids KW - 0 KW - Bridged Bicyclo Compounds, Heterocyclic KW - Guanidines KW - monanchorin KW - Guanidine KW - JU58VJ6Y3B KW - Index Medicus KW - Molecular Structure KW - Animals KW - Nuclear Magnetic Resonance, Biomolecular KW - Pacific Ocean KW - Mice KW - Inhibitory Concentration 50 KW - Mast Cells -- drug effects KW - Bridged Bicyclo Compounds, Heterocyclic -- chemistry KW - Alkaloids -- chemistry KW - Bridged Bicyclo Compounds, Heterocyclic -- pharmacology KW - Porifera -- chemistry KW - Bridged Bicyclo Compounds, Heterocyclic -- isolation & purification KW - Alkaloids -- isolation & purification KW - Guanidines -- isolation & purification KW - Guanidines -- pharmacology KW - Guanidines -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66741397?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+natural+products&rft.atitle=Monanchorin%2C+a+bicyclic+alkaloid+from+the+sponge+Monanchora+ungiculata.&rft.au=Meragelman%2C+Karina+M%3BMcKee%2C+Tawnya+C%3BMcMahon%2C+James+B&rft.aulast=Meragelman&rft.aufirst=Karina&rft.date=2004-07-01&rft.volume=67&rft.issue=7&rft.spage=1165&rft.isbn=&rft.btitle=&rft.title=Journal+of+natural+products&rft.issn=01633864&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-08 N1 - Date created - 2004-07-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Perspectives on familial chronic lymphocytic leukemia: genes and the environment. AN - 66737256; 15269880 AB - Chronic lymphocytic leukemia (CLL) comprises a substantial proportion of leukemias in adults in the western hemisphere. Male gender, increasing age, ethnicity (high in Caucasians, lowest in Asians), and family history are risk factors. Although no specific extrinsic etiologic factors have been established, farming and pesticide exposure are associated with increased risk. Migration studies confirm that ethnic groups retain the risk associated with their origin rather than their new location, favoring a role for heredity. Kindreds with multiple cases of CLL have been well described in the literature and studies in large populations confirm that lymphoproliferative malignancies and especially CLL occur together at a rate that cannot be attributed to chance. Since environmental factors cannot readily explain the familial aggregations, a hereditary factor that affects susceptibility to CLL is likely. The identification of clones that are immunophenotypically identical to CLL in healthy individuals from CLL kindreds (14% to 18%) as well as in the general population (3.5% in age bracket >65 years) suggests a possible precursor condition, but longitudinal studies will be necessary to establish significance in the general population. Family (linkage) and population (candidate gene) studies to date have been too small to identify the specific genes that account for increased susceptibility; larger studies including planned consortia to identify additional high-risk kindreds for genetic studies, as well as the application of advanced technologies such as genomics, cytogenetic, expression, and proteomics, are widely expected to advance understanding over the next few years. JF - Seminars in hematology AU - Caporaso, Neil AU - Marti, Gerald E AU - Goldin, Lynn AD - Genetic Epideimology Branch, Division of Cancer Epideiology and Genetics, National Cancer Institute, Rockville, MD 20892, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 201 EP - 206 VL - 41 IS - 3 SN - 0037-1963, 0037-1963 KW - Index Medicus KW - Genetic Linkage KW - Animals KW - Risk Factors KW - Humans KW - Adult KW - Siblings KW - Male KW - Female KW - Leukemia, Lymphocytic, Chronic, B-Cell -- genetics KW - Leukemia, Lymphocytic, Chronic, B-Cell -- epidemiology KW - Leukemia, Lymphocytic, Chronic, B-Cell -- etiology KW - Environmental Exposure -- adverse effects KW - Family Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66737256?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Seminars+in+hematology&rft.atitle=Perspectives+on+familial+chronic+lymphocytic+leukemia%3A+genes+and+the+environment.&rft.au=Caporaso%2C+Neil%3BMarti%2C+Gerald+E%3BGoldin%2C+Lynn&rft.aulast=Caporaso&rft.aufirst=Neil&rft.date=2004-07-01&rft.volume=41&rft.issue=3&rft.spage=201&rft.isbn=&rft.btitle=&rft.title=Seminars+in+hematology&rft.issn=00371963&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-25 N1 - Date created - 2004-07-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombinant immunotoxins for the treatment of haematological malignancies. AN - 66731057; 15268678 AB - Recombinant immunotoxins are fusion proteins which contain a ligand derived from the immune system fused to a toxin. The protein toxin is truncated to delete its binding domain, allowing selective ligand-directed binding. Growth factor fusion toxins are often considered immunotoxins. One of these molecules, containing the truncated diphtheria toxin and human IL-2 (Ontak), Ligand Pharmaceuticals), has been approved for the treatment of cutaneous T-cell lymphoma. Recombinant immunotoxins have also been produced containing the variable domains (Fv fragment) of monoclonal antibodies fused to toxins. These agents are relatively versatile with respect to the range of antigens possible. Several of these recombinant immunotoxins have showed clinical effectiveness in Phase I testing against haematological malignancies. One of these molecules, BL22, targets CD22 on hairy-cell leukaemia and has enabled patients to achieve complete remissions despite previous treatment and resistance to chemotherapy. JF - Expert opinion on biological therapy AU - Kreitman, Robert J AD - Clinical Immunotherapy Section, Laboratory of Molecular Biology, Centers for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 37, Room 5124b, Bethesda, MD 20892-4255, USA. kreitmar@mail.nih.gov Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 1115 EP - 1128 VL - 4 IS - 7 KW - Antineoplastic Agents KW - 0 KW - Immunoglobulin Fragments KW - Immunotoxins KW - Neoplasm Proteins KW - Recombinant Fusion Proteins KW - Index Medicus KW - Molecular Structure KW - Animals KW - Macaca fascicularis KW - Antineoplastic Agents -- administration & dosage KW - Clinical Trials, Phase II as Topic KW - Combined Modality Therapy KW - Neoplasm Proteins -- immunology KW - Humans KW - Mice KW - Drug Design KW - Immunoglobulin Fragments -- therapeutic use KW - Immunoglobulin Fragments -- administration & dosage KW - Clinical Trials, Phase I as Topic KW - Treatment Outcome KW - Xenograft Model Antitumor Assays KW - Cell Line, Tumor -- drug effects KW - Forecasting KW - Antineoplastic Agents -- therapeutic use KW - Recombinant Fusion Proteins -- therapeutic use KW - Drug Evaluation, Preclinical KW - Remission Induction KW - Immunotoxins -- chemistry KW - Hematologic Neoplasms -- drug therapy KW - Immunotoxins -- therapeutic use KW - Hematologic Neoplasms -- immunology KW - Immunotoxins -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66731057?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+immunotoxins+for+the+treatment+of+haematological+malignancies.&rft.au=Kreitman%2C+Robert+J&rft.aulast=Kreitman&rft.aufirst=Robert&rft.date=2004-07-01&rft.volume=4&rft.issue=7&rft.spage=1115&rft.isbn=&rft.btitle=&rft.title=Expert+opinion+on+biological+therapy&rft.issn=1744-7682&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-05-23 N1 - Date created - 2004-07-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vitamin A toxicity and vitamin E deficiency in a rabbit colony. AN - 66725536; 15264766 AB - Vitamin A toxicosis and vitamin E deficiency was diagnosed in a commercial rabbit-breeding colony and was associated with reproductive abnormalities, abortions, and poor survivability of kits in the breeding colony. Paresis and muscular dystrophy were noted in juvenile rabbits. Another group of New Zealand White rabbits from the same commercial colony was used to assess the effect of vitamin E-based therapy on clinical signs, reproduction, and vitamin A and E serum and liver levels. Blood samples were taken before and after dietary changes and vitamin E therapy. Serum vitamin E remained low after feeding a diet containing the recommended levels of vitamin E. Administration of vitamin E for 2 weeks lowered the serum vitamin A levels and increased the vitamin E serum and liver levels. In conclusion, vitamin E therapy appears to be an effective treatment for hypervitaminosis A. Copyright 2004 American Association for Laboratory Animal Science JF - Contemporary topics in laboratory animal science AU - St Claire, Mark B AU - Kennett, Mary J AU - Besch-Williford, Cynthia L AD - Department of Health and Humane Services, National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland 20892, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 26 EP - 30 VL - 43 IS - 4 SN - 1060-0558, 1060-0558 KW - Vitamin A KW - 11103-57-4 KW - Vitamin E KW - 1406-18-4 KW - Index Medicus KW - Animals KW - Vitamin A -- blood KW - Fetal Death -- etiology KW - Vitamin A -- administration & dosage KW - Liver -- metabolism KW - Rabbits KW - Vitamin E -- blood KW - Pregnancy KW - Animals, Newborn KW - Abortion, Veterinary -- etiology KW - Liver -- drug effects KW - Diet KW - Vitamin E -- administration & dosage KW - Female KW - Male KW - Vitamin E Deficiency -- complications KW - Hypervitaminosis A -- veterinary KW - Vitamin E Deficiency -- diagnosis KW - Hypervitaminosis A -- diagnosis KW - Hypervitaminosis A -- complications KW - Animal Husbandry KW - Vitamin E Deficiency -- veterinary KW - Musculoskeletal Abnormalities -- etiology KW - Animals, Laboratory KW - Musculoskeletal Abnormalities -- veterinary KW - Prenatal Exposure Delayed Effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66725536?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Contemporary+topics+in+laboratory+animal+science&rft.atitle=Vitamin+A+toxicity+and+vitamin+E+deficiency+in+a+rabbit+colony.&rft.au=St+Claire%2C+Mark+B%3BKennett%2C+Mary+J%3BBesch-Williford%2C+Cynthia+L&rft.aulast=St+Claire&rft.aufirst=Mark&rft.date=2004-07-01&rft.volume=43&rft.issue=4&rft.spage=26&rft.isbn=&rft.btitle=&rft.title=Contemporary+topics+in+laboratory+animal+science&rft.issn=10600558&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-24 N1 - Date created - 2004-07-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vitro evaluation of dimethane sulfonate analogues with potential alkylating activity and selective renal cell carcinoma cytotoxicity. AN - 66705096; 15252146 AB - We identified five structurally related dimethane sulfonates with putative selective cytotoxicity in renal cancer cell lines. These compounds have a hydrophobic moiety linked to a predicted alkylating group. A COMPARE analysis with the National Cancer Institute Anticancer Drug Screen standard agent database found significant correlations between the IC50 of the test compounds and the IC50 of alkylating agents (e.g., r = 0.68, P < 0.00001 for chlorambucil). In this report, we examined whether these compounds had activities similar to those of conventional alkylating agents. In cytotoxicity studies, chlorambucil-resistant Walker rat carcinoma cells were 4- to 11-fold cross-resistant to the test compounds compared with 14-fold resistant to chlorambucil. To determine effects on cell cycle progression, renal cell carcinoma (RCC) line 109 was labeled with bromodeoxyuridine prior to drug treatment. Complete cell cycle arrest occurred in cells treated with an IC90 dose of NSC 268965. p53 protein levels increased as much as 5.7-fold in RCC line 109 and as much as 20.4-fold in breast cancer line MCF-7 following an 18-hour drug exposure. Finally, DNA-protein cross-links were found following a 6-hour pretreatment with all compounds. Thus, the dimethane sulfonate analogues have properties expected of some alkylating agents but, unlike conventional alkylating agents, appear to possess activity against RCC. JF - Molecular cancer therapeutics AU - Mertins, Susan D AU - Myers, Timothy G AU - Holbeck, Susan L AU - Medina-Perez, Wilma AU - Wang, Elaine AU - Kohlhagen, Glenda AU - Pommier, Yves AU - Bates, Susan E AD - Cancer Therapeutics Branch, National Cancer Institute, NIH, Bethesda, Maryland, USA. smertins@mail.ncifcrf.gov Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 849 EP - 860 VL - 3 IS - 7 SN - 1535-7163, 1535-7163 KW - Alkylating Agents KW - 0 KW - Mesylates KW - Tumor Suppressor Protein p53 KW - Busulfan KW - G1LN9045DK KW - Bromodeoxyuridine KW - G34N38R2N1 KW - Carmustine KW - U68WG3173Y KW - Index Medicus KW - Animals KW - DNA Damage KW - Humans KW - Tumor Suppressor Protein p53 -- metabolism KW - Rats KW - Tumor Suppressor Protein p53 -- analysis KW - Busulfan -- analogs & derivatives KW - Carmustine -- analogs & derivatives KW - Bromodeoxyuridine -- analysis KW - Inhibitory Concentration 50 KW - Yeasts -- drug effects KW - Drug Evaluation, Preclinical KW - Cell Cycle -- drug effects KW - Drug Resistance, Neoplasm -- drug effects KW - Alkylating Agents -- therapeutic use KW - Kidney Neoplasms -- drug therapy KW - Alkylating Agents -- chemistry KW - Carcinoma, Renal Cell -- drug therapy KW - Alkylating Agents -- toxicity KW - Mesylates -- toxicity KW - Mesylates -- therapeutic use KW - Mesylates -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66705096?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+therapeutics&rft.atitle=In+vitro+evaluation+of+dimethane+sulfonate+analogues+with+potential+alkylating+activity+and+selective+renal+cell+carcinoma+cytotoxicity.&rft.au=Mertins%2C+Susan+D%3BMyers%2C+Timothy+G%3BHolbeck%2C+Susan+L%3BMedina-Perez%2C+Wilma%3BWang%2C+Elaine%3BKohlhagen%2C+Glenda%3BPommier%2C+Yves%3BBates%2C+Susan+E&rft.aulast=Mertins&rft.aufirst=Susan&rft.date=2004-07-01&rft.volume=3&rft.issue=7&rft.spage=849&rft.isbn=&rft.btitle=&rft.title=Molecular+cancer+therapeutics&rft.issn=15357163&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-28 N1 - Date created - 2004-07-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transcriptional signature of flavopiridol-induced tumor cell death. AN - 66705079; 15252147 AB - Flavopiridol has been shown to inhibit the proliferation of a variety of human tumor cells and is currently undergoing clinical evaluation in cancer treatment. Although the antiproliferative effect of flavopiridol has been attributed to the inhibition of cyclin-dependent kinases 2 and 4, recent reports indicate that the mechanism responsible for the cell death induced by this agent is more complex. To provide insight into the molecular processes mediating flavopiridol-induced cytotoxicity and to investigate the availability of markers indicative of its activity, we have applied cDNA microarray technology. Gene expression profiles were determined for four human tumor cell lines (prostate carcinomas PC3 and DU145 and gliomas SF359 and U251) following exposure to selected concentrations of flavopiridol. Treatment of these cell lines with a concentration of flavopiridol sufficient to reduce survival to 10% resulted in the identification of a set of 209 genes, the expression of which were altered in each of the cell lines. This common set of 209 gene expression changes suggested that flavopiridol-induced cell death can be defined in terms of a specific transcriptome. The flavopiridol death transcriptome consisted primarily of down-regulated genes; however, there were also a significant number of genes with increased expression. Whereas causal relationships were not established, these data suggest molecular events/processes that may be associated with flavopiridol-induced tumor cell death. Moreover, the identification of a set of gene expression changes in four human tumor cell lines suggests that such a transcriptome may be applicable to investigations of flavopiridol pharmacodynamics. JF - Molecular cancer therapeutics AU - Lü, Xing AU - Burgan, William E AU - Cerra, Michael A AU - Chuang, Eric Y AU - Tsai, Mong-Hsun AU - Tofilon, Philip J AU - Camphausen, Kevin AD - Molecular Radiation Therapeutics Branch, National Cancer Institute, Bethesda, Maryland 20892-1002, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 861 EP - 872 VL - 3 IS - 7 SN - 1535-7163, 1535-7163 KW - Antineoplastic Agents KW - 0 KW - Flavonoids KW - Piperidines KW - RNA, Messenger KW - RNA, Neoplasm KW - alvocidib KW - 45AD6X575G KW - Index Medicus KW - Gene Expression Profiling KW - RNA, Messenger -- metabolism KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - Cell Death -- genetics KW - Cell Line, Tumor KW - Neoplasms -- genetics KW - Neoplasms -- metabolism KW - Piperidines -- pharmacology KW - Transcription, Genetic -- drug effects KW - Piperidines -- toxicity KW - Antineoplastic Agents -- toxicity KW - Flavonoids -- pharmacology KW - Antineoplastic Agents -- pharmacology KW - RNA, Neoplasm -- metabolism KW - Flavonoids -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66705079?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+therapeutics&rft.atitle=Transcriptional+signature+of+flavopiridol-induced+tumor+cell+death.&rft.au=L%C3%BC%2C+Xing%3BBurgan%2C+William+E%3BCerra%2C+Michael+A%3BChuang%2C+Eric+Y%3BTsai%2C+Mong-Hsun%3BTofilon%2C+Philip+J%3BCamphausen%2C+Kevin&rft.aulast=L%C3%BC&rft.aufirst=Xing&rft.date=2004-07-01&rft.volume=3&rft.issue=7&rft.spage=861&rft.isbn=&rft.btitle=&rft.title=Molecular+cancer+therapeutics&rft.issn=15357163&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-28 N1 - Date created - 2004-07-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Mol Cancer Ther. 2004 Jul;3(7):873-5 [15252148] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytochrome P450 pharmacogenetics as a predictor of toxicity and clinical response to pulse cyclophosphamide in lupus nephritis. AN - 66687703; 15248218 AB - Pulse cyclophosphamide is the treatment of choice for severe lupus nephritis. However, not all patients respond to this therapy, and gonadal toxicity is of particular concern. Cyclophosphamide is a prodrug that requires activation by cytochrome P450 (CYP) enzymes. We conducted a retrospective cohort study to test whether genetic polymorphisms of these enzymes are associated with the toxicity of, and clinical response to, cyclophosphamide in patients with lupus nephritis. Sixty-two patients with proliferative lupus nephritis treated with cyclophosphamide were genotyped for common variant alleles of CYP2B6, 2C19, 2C9, and 3A5. We examined the association between these genotypes and the following clinical end points: development of premature ovarian failure, end-stage renal disease (ESRD), doubling of serum creatinine level, and achievement of complete renal response. The observed frequencies of the variant alleles CYP2B6*5, CYP2C19*2, CYP2C9*2, and CYP3A5*3 were 12.1%, 25.0%, 4.0%, and 75.8%, respectively. Patients who were either heterozygous or homozygous for CYP2C19*2 had a significantly lower risk of developing premature ovarian failure (relative risk 0.10; 95% confidence interval 0.02-0.52), after adjustment for age and total number of cyclophosphamide pulses received. In a survival analysis, patients homozygous for CYP2B6*5 (n = 3) or CYP2C19*2 (n = 4) had a higher probability of reaching ESRD (P = 0.0005) and of doubling the creatinine level (P = 0.0005) as well as a trend toward a lower probability of achieving a complete renal response (P = 0.051). Determination of selected cytochrome P450 enzyme genotypes may be valuable for predicting the risk of premature ovarian failure in lupus nephritis patients treated with cyclophosphamide. The association of these genotypes with renal response needs further validation. JF - Arthritis and rheumatism AU - Takada, Kazuki AU - Arefayene, Million AU - Desta, Zeruesenay AU - Yarboro, Cheryl H AU - Boumpas, Dimitrios T AU - Balow, James E AU - Flockhart, David A AU - Illei, Gabor G AD - National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland 20892, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 2202 EP - 2210 VL - 50 IS - 7 SN - 0004-3591, 0004-3591 KW - Antirheumatic Agents KW - 0 KW - Cyclophosphamide KW - 8N3DW7272P KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Abridged Index Medicus KW - Index Medicus KW - Genetic Variation KW - Homozygote KW - Pulse Therapy, Drug KW - Gene Frequency KW - Humans KW - Retrospective Studies KW - Predictive Value of Tests KW - Kidney Failure, Chronic -- etiology KW - Primary Ovarian Insufficiency -- chemically induced KW - Genotype KW - Alleles KW - Risk Factors KW - Adult KW - Cohort Studies KW - Treatment Outcome KW - Middle Aged KW - Female KW - Male KW - Cyclophosphamide -- administration & dosage KW - Lupus Nephritis -- drug therapy KW - Polymorphism, Genetic KW - Cytochrome P-450 Enzyme System -- genetics KW - Antirheumatic Agents -- administration & dosage KW - Antirheumatic Agents -- adverse effects KW - Lupus Nephritis -- complications KW - Cyclophosphamide -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66687703?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cytochrome+P450+pharmacogenetics+as+a+predictor+of+toxicity+and+clinical+response+to+pulse+cyclophosphamide+in+lupus+nephritis.&rft.au=Takada%2C+Kazuki%3BArefayene%2C+Million%3BDesta%2C+Zeruesenay%3BYarboro%2C+Cheryl+H%3BBoumpas%2C+Dimitrios+T%3BBalow%2C+James+E%3BFlockhart%2C+David+A%3BIllei%2C+Gabor+G&rft.aulast=Takada&rft.aufirst=Kazuki&rft.date=2004-07-01&rft.volume=50&rft.issue=7&rft.spage=2202&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 - 2004-08-13 N1 - Date created - 2004-07-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dog allergen (Can f 1) and cat allergen (Fel d 1) in US homes: results from the National Survey of Lead and Allergens in Housing. AN - 66686314; 15241352 AB - Exposures to dog and cat allergens are believed to play important roles in the etiology of asthma; however, the levels of these allergens have never been assessed in a representative sample of US homes. The objective of this study was to estimate and characterize exposures to Can f 1 (dog allergen) and Fel d 1 (cat allergen) in US homes. Data were obtained from the National Survey of Lead and Allergens in Housing, a nationally representative survey of 831 US homes. Vacuumed-collected dust samples from the bed, bedroom floor, living room floor, and living room sofa were analyzed for concentrations of Can f 1 and Fel d 1 (micrograms of allergen per gram of dust). Although a dog or cat had lived in only 49.1% of homes in the previous 6 months, Can f 1 and Fel d 1 were detected in 100% and 99.9% of homes, respectively. Averaged over the sampled sites, geometric mean concentrations (microg/g) were 4.69 for Can f 1 and 4.73 for Fel d 1. Among homes with an indoor dog and cat, respectively, geometric mean concentrations were 69 for Can f 1 and 200 for Fel d 1. Among homes without the indoor pet, geometric mean concentrations were above 1.0. The independent predictors of elevated concentrations in homes without pets were all demographic variables that were also linked to a higher prevalence of pet ownership. Can f 1 and Fel d 1 are universally present in US homes. Levels that have been associated with an increased risk of allergic sensitization were found even in homes without pets. Because of the transportability of these allergens on clothing, elevated levels in homes without pets, particularly among demographic groups in which pet ownership is more prevalent, implicate the community as an important source of these pet allergens. JF - The Journal of allergy and clinical immunology AU - Arbes, Samuel J AU - Cohn, Richard D AU - Yin, Ming AU - Muilenberg, Michael L AU - Friedman, Warren AU - Zeldin, Darryl C AD - National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 111 EP - 117 VL - 114 IS - 1 SN - 0091-6749, 0091-6749 KW - Allergens KW - 0 KW - Antigens, Plant KW - Glycoproteins KW - allergen Can f I KW - Fel d 1 protein, Felis domesticus KW - G408EE88II KW - Abridged Index Medicus KW - Index Medicus KW - Cross-Sectional Studies KW - Animals KW - Humans KW - Cats KW - Dogs KW - Residence Characteristics -- statistics & numerical data KW - United States -- epidemiology KW - Glycoproteins -- analysis KW - Environmental Exposure -- analysis KW - Allergens -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66686314?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Dog+allergen+%28Can+f+1%29+and+cat+allergen+%28Fel+d+1%29+in+US+homes%3A+results+from+the+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%3BFriedman%2C+Warren%3BZeldin%2C+Darryl+C&rft.aulast=Arbes&rft.aufirst=Samuel&rft.date=2004-07-01&rft.volume=114&rft.issue=1&rft.spage=111&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 - 2004-09-28 N1 - Date created - 2004-07-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antisense protein kinase A RIalpha inhibits 7,12-dimethylbenz(a)anthracene-induction of mammary cancer: blockade at the initial phase of carcinogenesis. AN - 66684482; 15240549 AB - There are two types of cyclic AMP (cAMP)-dependent protein kinase (PKA), type I (PKA-I) and type II (PKA-II), which share a common catalytic (C) subunit but contain distinct regulatory (R) subunits, RI versus RII, respectively. Evidence suggests that increased expression of PKA-I and its regulatory subunit (RIalpha) correlates with tumorigenesis and tumor growth. We investigated the effect of sequence-specific inhibition of RIalpha gene expression at the initial phase of 7,12-dimethylbenz(alphaa)anthracene (DMBA)-induced mammary carcinogenesis. Antisense RIalpha oligodeoxynucleotide (ODN) targeted against PKA RIalpha was administered (0.1 mg/day/rat, i.p.) 1 day before DMBA intubation and during the first 9 days post-DMBA intubation to determine the anticarcinogenic effects. Antisense RIalpha, in a sequence-specific manner, inhibited the tumor production. At 90 days after DMBA intubation, untreated controls and RIalpha-antisense-treated rats exhibited an average mean number of tumors per rat of 4.2 and 1.8, respectively, and 90% of control and 45% of antisense-treated animals had tumors. The antisense also delayed the first tumor appearance. An increase in RIalpha and PKA-I levels in the mammary gland and liver preceded DMBA-induced tumor production, and antisense down-regulation of RIalpha restored normal levels of PKA-I and PKA-II in these tissues. Antisense RIalpha in the liver induced the phase II enzymes, glutathione S-transferase and quinone oxidoreductase, c-fos protein, and activator protein 1 (AP-1)- and cAMP response element (CRE)-directed transcription. In the mammary glands, antisense RIalpha promoted DNA repair processes. In contrast, the CRE transcription-factor decoy could not mimic these effects of antisense RIalpha. The results demonstrate that RIalpha antisense produces dual anticarcinogenic effects: (a) increasing DMBA detoxification in the liver by increasing phase II enzyme activities, increasing CRE-binding-protein phosphorylation and enhancing CRE- and Ap-1-directed transcription; and (b) activating DNA repair processes in the mammary gland by down-regulating PKA-I. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Nesterova, Maria V AU - Cho-Chung, Yoon S AD - Cellular Biochemistry Section, Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA. Y1 - 2004/07/01/ PY - 2004 DA - 2004 Jul 01 SP - 4568 EP - 4577 VL - 10 IS - 13 SN - 1078-0432, 1078-0432 KW - Carcinogens KW - 0 KW - Cyclic AMP-Dependent Protein Kinase RIalpha Subunit KW - Ethanolamines KW - Oligonucleotides, Antisense KW - Prkar1a protein, mouse KW - Prkar1a protein, rat KW - Proto-Oncogene Proteins c-fos KW - Transcription Factor AP-1 KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Cyclic AMP KW - E0399OZS9N KW - NAD(P)H Dehydrogenase (Quinone) KW - EC 1.6.5.2 KW - NADPH Dehydrogenase KW - EC 1.6.99.1 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Cyclic AMP-Dependent Protein Kinase Type II KW - EC 2.7.11.11 KW - Cyclic AMP-Dependent Protein Kinases KW - 2-diethylaminoethanol KW - S6DL4M053U KW - Index Medicus KW - Carcinogens -- pharmacology KW - Animals KW - Proto-Oncogene Proteins c-fos -- metabolism KW - Transcription Factor AP-1 -- metabolism KW - Catalytic Domain KW - Liver -- metabolism KW - Transcription, Genetic KW - NAD(P)H Dehydrogenase (Quinone) -- metabolism KW - Rats KW - NADPH Dehydrogenase -- metabolism KW - Down-Regulation KW - Phosphorylation KW - Time Factors KW - DNA Repair KW - Ethanolamines -- pharmacology KW - Dose-Response Relationship, Drug KW - Glutathione Transferase -- metabolism KW - Immunoprecipitation KW - Mice KW - Protein Binding KW - Rats, Sprague-Dawley KW - Mammary Glands, Animal -- metabolism KW - Cyclic AMP -- metabolism KW - Female KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Mammary Neoplasms, Animal -- pathology KW - Cyclic AMP-Dependent Protein Kinases -- physiology KW - 9,10-Dimethyl-1,2-benzanthracene -- pharmacology KW - Oligonucleotides, Antisense -- pharmacology KW - Mammary Neoplasms, Animal -- metabolism KW - Mammary Neoplasms, Animal -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66684482?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Antisense+protein+kinase+A+RIalpha+inhibits+7%2C12-dimethylbenz%28a%29anthracene-induction+of+mammary+cancer%3A+blockade+at+the+initial+phase+of+carcinogenesis.&rft.au=Nesterova%2C+Maria+V%3BCho-Chung%2C+Yoon+S&rft.aulast=Nesterova&rft.aufirst=Maria&rft.date=2004-07-01&rft.volume=10&rft.issue=13&rft.spage=4568&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 - 2005-01-31 N1 - Date created - 2004-07-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - What is the rationale for new treatment strategies in Alzheimer's disease? AN - 66683434; 15241294 AB - Alzheimer's disease (AD) is characterized by the abnormal extracellular accumulation of amyloid beta-peptide (Abeta) into neuritic plaques and the intraneuronal aggregation of the microtubule-associated protein tau to form neurofibrillary tangles. These molecular events are implicated in the selective damage to neural systems critical for the brain functions that are impaired in AD. Impairment of cholinergic neurotransmission may be an important factor underlying the defects in cognition and memory that characterize AD. Cholinesterase (ChE) inhibitors, such as donepezil, rivastigmine, and galantamine, cause symptomatic improvement by inhibiting the breakdown of the neurotransmitter acetylcholine to increase its synaptic availability and, in the case of galantamine, by also allosterically potentiating nicotinic cholinergic receptors. Other agents, including vitamin E, monoamine oxidase inhibitors, and statins, have shown some benefit in epidemiological studies and clinical trials although compelling evidence of their efficacy is lacking. Memantine, shown to cause cognitive and functional improvement, is not an ChE inhibitor and does not interact with marketed ChE inhibitors. While the mechanism of action of memantine in AD is not known, the principal pharmacologic actions at therapeutic dose are inhibition of ionotropic neurotransmitter receptors, specifically N-methyl-D-aspartate (NMDA), 5-HT3, and nicotinic receptors. Like other NMDA antagonists, memantine causes behavioral activation associated with enhanced cerebral glucose utilization. Studies have shown that memantine can reverse the decreased metabolic activity associated with AD, possibly accounting for its beneficial effects on cognition and global functioning. Memantine also has neuroprotective properties and can inhibit Abeta-induced neurodegeneration. JF - CNS spectrums AU - Rogawski, Michael A AD - Epilepsy Research Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 49 Convent Drive, Bethesda, MD 20892, USA. michael.rogawski@nih.gov Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 6 EP - 12 VL - 9 IS - 7 Suppl 5 SN - 1092-8529, 1092-8529 KW - Cholinesterase Inhibitors KW - 0 KW - Excitatory Amino Acid Antagonists KW - Nootropic Agents KW - Receptors, N-Methyl-D-Aspartate KW - Acetylcholine KW - N9YNS0M02X KW - Memantine KW - W8O17SJF3T KW - Index Medicus KW - Acetylcholine -- physiology KW - Memantine -- therapeutic use KW - Brain -- drug effects KW - Cholinesterase Inhibitors -- therapeutic use KW - Humans KW - Cholinergic Fibers -- physiology KW - Memantine -- adverse effects KW - Brain -- physiopathology KW - Receptors, N-Methyl-D-Aspartate -- physiology KW - Cholinesterase Inhibitors -- adverse effects KW - Excitatory Amino Acid Antagonists -- therapeutic use KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Excitatory Amino Acid Antagonists -- adverse effects KW - Cholinergic Fibers -- drug effects KW - Cognition Disorders -- diagnosis KW - Cognition Disorders -- drug therapy KW - Alzheimer Disease -- physiopathology KW - Alzheimer Disease -- drug therapy KW - Nootropic Agents -- therapeutic use KW - Nootropic Agents -- adverse effects KW - Cognition Disorders -- physiopathology KW - Alzheimer Disease -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66683434?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+spectrums&rft.atitle=What+is+the+rationale+for+new+treatment+strategies+in+Alzheimer%27s+disease%3F&rft.au=Rogawski%2C+Michael+A&rft.aulast=Rogawski&rft.aufirst=Michael&rft.date=2004-07-01&rft.volume=9&rft.issue=7+Suppl+5&rft.spage=6&rft.isbn=&rft.btitle=&rft.title=CNS+spectrums&rft.issn=10928529&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-10-18 N1 - Date created - 2004-07-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antiviral prophylaxis of smallpox. AN - 66681129; 15163655 AB - Proof-of-concept studies suggest that current defences against smallpox could be strengthened by supplementing vaccination with antiviral drug prophylaxis, based on aerosolized or orally available forms of the long-acting medication cidofovir. Delivery of aerosolized cidofovir to mice results in its prolonged retention in respiratory tissues and protection against lethal intranasal or aerosol poxviral challenge. Although cidofovir itself is not orally available, the addition of an alkoxyalkanol ether side-chain allows it to be absorbed from the gastrointestinal tract. This also markedly increases its antiviral activity and lengthens its intracellular half-life from roughly 3 to 8-10 days. Oral treatment also protected mice against lethal poxviral challenge. These results suggest that a single aerosol dose of cidofovir (or an alkoxyalkanol-ether derivative) could provide prolonged protection against initiation of smallpox infection, whereas oral treatment could prevent both initiation of infection and internal dissemination of virus. Both approaches may avoid the nephrotoxicity that occasionally results from intravenous cidofovir therapy. JF - The Journal of antimicrobial chemotherapy AU - Bray, Mike AU - Roy, Chad J AD - Biodefense Clinical Research Branch, Office of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. mbray@niaid.nih.gov Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 1 EP - 5 VL - 54 IS - 1 SN - 0305-7453, 0305-7453 KW - Antiviral Agents KW - 0 KW - Organophosphonates KW - Organophosphorus Compounds KW - Smallpox Vaccine KW - Cytosine KW - 8J337D1HZY KW - cidofovir KW - JIL713Q00N KW - Index Medicus KW - Organophosphorus Compounds -- therapeutic use KW - Combined Modality Therapy KW - Humans KW - Smallpox Vaccine -- therapeutic use KW - Organophosphorus Compounds -- administration & dosage KW - Vaccination KW - Antiviral Agents -- therapeutic use KW - Antiviral Agents -- administration & dosage KW - Cytosine -- therapeutic use KW - Cytosine -- administration & dosage KW - Smallpox -- prevention & control KW - Cytosine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66681129?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+antimicrobial+chemotherapy&rft.atitle=Antiviral+prophylaxis+of+smallpox.&rft.au=Bray%2C+Mike%3BRoy%2C+Chad+J&rft.aulast=Bray&rft.aufirst=Mike&rft.date=2004-07-01&rft.volume=54&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+antimicrobial+chemotherapy&rft.issn=03057453&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-27 N1 - Date created - 2004-07-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hybridization buffer systems impact the quality of filter array data. AN - 66680929; 15233970 AB - cDNA microarray technology has greatly facilitated mechanistic studies in pharmacology and toxicology. A clean hybridization with minimal background is critical for successful microarray analysis and is highly desired. However, clean hybridization alone is not enough; verification is needed. Total RNA was isolated from the livers of acetaminophen-intoxicated mice and was subjected to cDNA microarray analyses using ExpressHyb, ULTRArrayHyb or MicroHyb on nylon membranes. Real-time RT-PCR analyses were performed for verification. We have demonstrated in this paper that hybridization systems can significantly impact the quality of array data. MicroHyb produced very clean hybridizations, but some results could not be confirmed by real-time RT-PCR and in accord with biological responses. The hybridization images from ExpressHyb were not always clean, but were reliable. The sensitivity of ULTRArrayHyb was moderate. This study has indicated the importance of selecting hybridization buffers in membrane arrays and recommended real-time RT-PCR for follow-up analysis. Gene expression changes should also be correlated with biological significance. JF - Journal of pharmacological and toxicological methods AU - Liu, Jie AU - Walker, Nigel AU - Waalkes, Michael P AD - Inorganic Carcinogenesis Section, LCC, NCI at NIEHS, 111 Alexander Drive, RTP, NC 27709, USA. Liu6@niehs.nih.gov PY - 2004 SP - 67 EP - 71 VL - 50 IS - 1 SN - 1056-8719, 1056-8719 KW - Analgesics, Non-Narcotic KW - 0 KW - Buffers KW - DNA Primers KW - RNA, Messenger KW - Acetaminophen KW - 362O9ITL9D KW - Index Medicus KW - Animals KW - RNA, Messenger -- metabolism KW - Analgesics, Non-Narcotic -- toxicity KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - Male KW - Acetaminophen -- toxicity KW - Liver -- drug effects KW - Nucleic Acid Hybridization -- methods KW - Oligonucleotide Array Sequence Analysis -- methods KW - Liver -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66680929?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+pharmacological+and+toxicological+methods&rft.atitle=Hybridization+buffer+systems+impact+the+quality+of+filter+array+data.&rft.au=Liu%2C+Jie%3BWalker%2C+Nigel%3BWaalkes%2C+Michael+P&rft.aulast=Liu&rft.aufirst=Jie&rft.date=2004-07-01&rft.volume=50&rft.issue=1&rft.spage=67&rft.isbn=&rft.btitle=&rft.title=Journal+of+pharmacological+and+toxicological+methods&rft.issn=10568719&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-25 N1 - Date created - 2004-07-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A pilot study of antiangiogenic therapy with bevacizumab and thalidomide in patients with metastatic renal cell carcinoma. AN - 66679439; 15235386 AB - The use of antiangiogenic agents represents a promising strategy for the treatment of patients with metastatic renal cell carcinoma. Objective responses to single-agent thalidomide have been described, and a randomized study showed that bevacizumab (a neutralizing antibody against vascular endothelial growth factor) delayed time to progression of metastatic renal cancer. A pilot study combining these two agents was performed. Sequential cohorts of 10 and 12 patients (crossing over from placebo therapy in the aforementioned randomized bevacizuamab trial) were treated with low-dose bevacizumab alone or bevacizumab plus the maximum tolerated dose of thalidomide as determined by intrapatient escalation. Toxicity, objective responses, and time to progression were the endpoints of this study. Patients tolerated thalidomide and bevacizumab well, with more than 50% of patients escalating to at least 500 mg/d thalidomide. Grades 1 and 2 sensory neuropathy limited thalidomide dose escalation in 3 of 12 patients. The incidence of grades 3 and 4 toxicity was not different between patients treated with bevacizumab alone versus bevacizumab plus thalidomide. There were no objective responses and no difference in progression-free survival between the groups (2.4 months for bevacizumab alone, 3.0 months for bevacizumab plus thalidomide). Combination antiangiogenic therapy with bevacizumab plus thalidomide in patients with renal cell carcinoma is associated with similar toxicity and progression-free survival compared with bevacizumab alone. This study illustrates a clinical trial design for rapidly testing the feasibility and safety of combining antiangiogenic agents, an approach that will be necessary for rapidly evaluating the many potential combinations of antiangiogenic agents. JF - Journal of immunotherapy (Hagerstown, Md. : 1997) AU - Elaraj, Dina M AU - White, Donald E AU - Steinberg, Seth M AU - Haworth, Leah AU - Rosenberg, Steven A AU - Yang, James C AD - Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 2004 SP - 259 EP - 264 VL - 27 IS - 4 SN - 1524-9557, 1524-9557 KW - Angiogenesis Inhibitors KW - 0 KW - Antibodies, Monoclonal KW - Antibodies, Monoclonal, Humanized KW - Bevacizumab KW - 2S9ZZM9Q9V KW - Thalidomide KW - 4Z8R6ORS6L KW - Index Medicus KW - Survival Rate KW - Humans KW - Adult KW - Neoplasm Metastasis KW - Aged KW - Pilot Projects KW - Middle Aged KW - Male KW - Female KW - Carcinoma, Renal Cell -- pathology KW - Angiogenesis Inhibitors -- therapeutic use KW - Antineoplastic Combined Chemotherapy Protocols KW - Thalidomide -- administration & dosage KW - Carcinoma, Renal Cell -- drug therapy KW - Thalidomide -- therapeutic use KW - Antibodies, Monoclonal -- administration & dosage KW - Antibodies, Monoclonal -- therapeutic use KW - Angiogenesis Inhibitors -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66679439?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunotherapy+%28Hagerstown%2C+Md.+%3A+1997%29&rft.atitle=A+pilot+study+of+antiangiogenic+therapy+with+bevacizumab+and+thalidomide+in+patients+with+metastatic+renal+cell+carcinoma.&rft.au=Elaraj%2C+Dina+M%3BWhite%2C+Donald+E%3BSteinberg%2C+Seth+M%3BHaworth%2C+Leah%3BRosenberg%2C+Steven+A%3BYang%2C+James+C&rft.aulast=Elaraj&rft.aufirst=Dina&rft.date=2004-07-01&rft.volume=27&rft.issue=4&rft.spage=259&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunotherapy+%28Hagerstown%2C+Md.+%3A+1997%29&rft.issn=15249557&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-04 N1 - Date created - 2004-07-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: N Engl J Med. 1999 Nov 18;341(21):1565-71 [10564685] Ann Surg. 1998 Sep;228(3):307-19 [9742914] Br J Cancer. 2000 Feb;82(4):812-7 [10732751] Oncology (Williston Park). 2000 Dec;14(12 Suppl 13):33-6 [11204672] J Clin Oncol. 2001 Feb 1;19(3):843-50 [11157038] J Clin Oncol. 2002 Jan 1;20(1):302-6 [11773183] J Clin Oncol. 2002 Mar 1;20(5):1368-74 [11870181] Ann Oncol. 2002 Jul;13(7):1029-35 [12176780] Invest New Drugs. 2002 Nov;20(4):389-93 [12448656] CA Cancer J Clin. 2003 Jan-Feb;53(1):5-26 [12568441] Ann Intern Med. 1988 Apr;108(4):518-23 [3258138] Cancer Res. 1988 Dec 15;48(24 Pt 1):7310-3 [3056613] Urology. 1989 Oct;34(4 Suppl):80-3; discussion 87-96 [2678687] Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):4082-5 [7513432] Nat Genet. 1994 May;7(1):85-90 [7915601] Graefes Arch Clin Exp Ophthalmol. 1998 Jun;236(6):461-6 [9646092] J Clin Oncol. 1999 Aug;17(8):2530-40 [10561319] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Associations between plasma DDE levels and immunologic measures in African-American farmers in North Carolina. AN - 66676891; 15238281 AB - Experimental studies in rodents demonstrate evidence of immunosuppressive effects of dietary exposure to DDT [2,2-bis((italic)p(/italic)-chlorophenyl)-1,1,1-trichloroethane], but human data pertaining to immunomodulating effects of DDT exposure are limited. In this study we examined the association between the persistent organochlorine breakdown product 1,1-dichloro-2,2,bis(p-chlorophenyl)ethylene p,p'-DDE) and immunologic measures using blood samples in a relatively highly exposed population of farmers in the United States. Levels of serum immunoglobulin A (IgA) and IgG and the prevalence of antinuclear antibodies in relation to plasma p,p'-DDE levels were evaluated in samples from 137 African-American male farmers (30-88 years of age; median, 64 years). Participants were recruited through black churches in four rural counties in eastern North Carolina. Data collection included a telephone interview pertaining to farming practices and health history, and one blood sample was collected from each participant. Linear and logistic regression, adjusting for age, cholesterol, triglycerides, smoking status, and years of any kind of pesticide use, was used to assess the association between immunologic parameters and plasma levels of p,p'-DDE. The median plasma p,p'-DDE concentration was 7.7 microg/L (range, 0.6-77.4 microg/L). There was no association between p,p'-DDE and IgA in any of the models. IgG levels decreased with increasing p,p'-DDE levels, with a statistically significant decrease of approximately 50% in the highest two categories of exposure (greater than or equal to 6.0 microg/L) compared with values of or = 12.0 microg/L compared with < 3.0 microg/L p,p'-DDE), but this difference was not statistically significant. These analyses provide evidence that p,p'-DDE modulates immune responses in humans. JF - Environmental health perspectives AU - Cooper, Glinda S AU - Martin, Stephen A AU - Longnecker, Matthew P AU - Sandler, Dale P AU - Germolec, Dori R AD - Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 1080 EP - 1084 VL - 112 IS - 10 SN - 0091-6765, 0091-6765 KW - Immunoglobulin A KW - 0 KW - Immunoglobulin G KW - Insecticides KW - Dichlorodiphenyl Dichloroethylene KW - 4M7FS82U08 KW - Index Medicus KW - Agriculture KW - Aged, 80 and over KW - Humans KW - North Carolina KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Occupational Exposure KW - Insecticides -- poisoning KW - Immunoglobulin G -- analysis KW - Dichlorodiphenyl Dichloroethylene -- poisoning KW - Immunoglobulin A -- analysis KW - African Americans KW - Dichlorodiphenyl Dichloroethylene -- blood KW - Antibody Formation -- drug effects KW - Insecticides -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66676891?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Associations+between+plasma+DDE+levels+and+immunologic+measures+in+African-American+farmers+in+North+Carolina.&rft.au=Cooper%2C+Glinda+S%3BMartin%2C+Stephen+A%3BLongnecker%2C+Matthew+P%3BSandler%2C+Dale+P%3BGermolec%2C+Dori+R&rft.aulast=Cooper&rft.aufirst=Glinda&rft.date=2004-07-01&rft.volume=112&rft.issue=10&rft.spage=1080&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 - 2004-09-21 N1 - Date created - 2004-07-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Immunol Res. 1999;20(1):67-78 [10467984] Am J Epidemiol. 2001 Jan 1;153(1):53-63 [11159147] Lancet. 2001 Jul 14;358(9276):110-4 [11463412] Toxicology. 2002 Jun 5;174(3):201-10 [12007859] Epidemiology. 2002 Jul;13(4):454-8 [12094101] Ann Clin Biochem. 2002 Jul;39(Pt 4):374-7 [12117441] Environ Health Perspect. 2002 Jul;110(7):617-24 [12117636] Environ Health Perspect. 2003 Aug;111(10):1273-7 [12896845] Pediatrics. 1966 May;37(5):715-27 [4956666] N Engl J Med. 1970 Sep 17;283(12):631-4 [4194865] Arch Environ Health. 1975 Feb;30(2):81-4 [234722] Infect Immun. 1978 Apr;20(1):30-5 [97225] Int Arch Occup Environ Health. 1982;50(4):329-40 [7174118] Clin Immunol Immunopathol. 1984 Oct;33(1):13-22 [6478653] Am J Public Health. 1987 Oct;77(10):1294-7 [3115123] Bull Environ Contam Toxicol. 1987 Nov;39(5):822-6 [3318960] Bull Environ Contam Toxicol. 1987 Nov;39(5):827-34 [3690008] Arch Environ Health. 1991 Jul-Aug;46(4):249-53 [2069434] Arch Environ Health. 1992 Jul-Aug;47(4):295-301 [1497384] Arch Environ Health. 1993 Mar-Apr;48(2):81-8 [8476309] Arch Environ Health. 1993 Mar-Apr;48(2):89-93 [7682805] Toxicol Appl Pharmacol. 1993 Oct;122(2):233-43 [8212005] Am J Public Health. 1995 Apr;85(4):504-8 [7702113] Nature. 1995 Jun 15;375(6532):581-5 [7791873] J AOAC Int. 1995 Nov-Dec;78(6):1353-63 [8664570] Environ Health Perspect. 1996 Apr;104(4):362-9 [8732939] Int J Lepr Other Mycobact Dis. 1997 Mar;65(1):97-9 [9207760] Clin Invest Med. 1998 Feb;21(1):4-11 [9512879] Arthritis Rheum. 1998 Oct;41(10):1714-24 [9778212] Arch Environ Contam Toxicol. 1999 May;36(4):504 [10227872] J Toxicol Environ Health A. 1999 Jun 25;57(4):225-36 [10406347] Environ Health Perspect. 1999 Oct;107 Suppl 5:783-92 [10502545] Bull Environ Contam Toxicol. 1992 Apr;48(4):535-40 [1504498] Environ Health Perspect. 2000 Mar;108(3):205-11 [10706525] Environ Health Perspect. 2001 Jan;109(1):27-33 [11171521] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparing questionnaire-based methods to assess occupational silica exposure. AN - 66674669; 15232404 AB - Epidemiologic assessment of occupational exposure to silica is typically limited to long-term work in the dusty trades, primarily in jobs held by men. We compared alternative questionnaire-based methods to assess silica exposure in a recent case-control study of 265 patients with systemic lupus erythematosus (mostly women) and 355 controls randomly selected from state driver's license registries and frequency-matched by age and sex. In-person interviews included a job history (all jobs held at least 12 months) and checklist of silica-related jobs and tasks (work of at least 2 weeks). Three industrial hygienists reviewed job descriptions without knowing case-control status. Potential high- or moderate-intensity exposures were confirmed or revised based on follow-up telephone interviews. In the full assessment including all work of at least 2 weeks, 9% of cases and 4% of controls were classified as medium or high silica exposure (odds ratio of disease = 2.9; 95% confidence interval = 1.3-6.4). In contrast, only 4% of cases and 9% of controls were identified by the standardized code groups index as having worked in silica-related industries or occupations for at least 12 months, providing a much lower risk estimate for disease (0.4; 0.2-0.9). Specific task-based questions must be included to assess the full potential of occupational silica exposure. These findings highlight the limitations of using standardized code groups to define exposure or to select jobs for industrial hygienist review. Copyright 2004 Lippincott Williams and Wilkins JF - Epidemiology (Cambridge, Mass.) AU - Parks, Christine G AU - Cooper, Glinda S AU - Nylander-French, Leena A AU - Hoppin, Jane A AU - Sanderson, Wayne T AU - Dement, John M AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. Cqp8@cdc.gov Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 433 EP - 441 VL - 15 IS - 4 SN - 1044-3983, 1044-3983 KW - Air Pollutants, Occupational KW - 0 KW - Silicon Dioxide KW - 7631-86-9 KW - Index Medicus KW - Registries KW - Humans KW - Adult KW - Case-Control Studies KW - Task Performance and Analysis KW - Interviews as Topic KW - Middle Aged KW - North Carolina -- epidemiology KW - Male KW - Female KW - South Carolina -- epidemiology KW - Silicon Dioxide -- analysis KW - Air Pollutants, Occupational -- analysis KW - Surveys and Questionnaires KW - Silicon Dioxide -- toxicity KW - Occupational Exposure -- adverse effects KW - Lupus Erythematosus, Systemic -- chemically induced KW - Air Pollutants, Occupational -- toxicity KW - Risk Assessment -- methods KW - Occupations -- classification KW - Lupus Erythematosus, Systemic -- epidemiology KW - Occupational Exposure -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66674669?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Comparing+questionnaire-based+methods+to+assess+occupational+silica+exposure.&rft.au=Parks%2C+Christine+G%3BCooper%2C+Glinda+S%3BNylander-French%2C+Leena+A%3BHoppin%2C+Jane+A%3BSanderson%2C+Wayne+T%3BDement%2C+John+M&rft.aulast=Parks&rft.aufirst=Christine&rft.date=2004-07-01&rft.volume=15&rft.issue=4&rft.spage=433&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 - 2004-09-09 N1 - Date created - 2004-07-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High-throughput retroviral tagging for identification of genes involved in initiation and progression of mouse splenic marginal zone lymphomas. AN - 66674028; 15231650 AB - Human B-cell lymphomas are frequently associated with specific genetic changes caused by chromosomal translocations that activate proto-oncogenes. For lymphomas of mice expressing murine leukemia virus, mutagenic proviral insertions are thought to play a similar role. Here we report studies designed to determine whether specific retroviral integration sites might be associated with a specific subset of mouse B-cell lymphomas and if the genes associated with these sites are regularly altered in expression. We studied splenic marginal zone lymphomas (MZL) of NFS.V(+) mice that are unusual in exhibiting frequent progression from low to high grade, potentially allowing assignment of cancer genes to processes of initiation and progression. We used inverse PCR to clone and analyze 212 retroviral integration sites from 43 MZL at different stages of progression. Sixty-two marked common integration sites and included 31 that had been marked previously. Among the new common integration sites, seven were unique to MZL. Using microarrays and real-time quantitative PCR analysis, we defined differential patterns of gene expression in association with disease progression for Gfi1, Sox4, Brca2, Snf1lk, Nfkb1, Pou2af1, Prdm1, Stat6, and Blnk. Heightened expression of Gfi1 distinguishes MZL from other lymphoma types. The combined use of proviral tagging and analyses of gene expression thus provides a powerful approach to understanding of genes that collaborate in tumorigenesis. JF - Cancer research AU - Shin, Min Sun AU - Fredrickson, Torgny N AU - Hartley, Janet W AU - Suzuki, Takeshi AU - Akagi, Keiko AU - Agaki, Keiko AU - Morse, Herbert C AD - Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, Rockville, Maryland 20852, USA. Y1 - 2004/07/01/ PY - 2004 DA - 2004 Jul 01 SP - 4419 EP - 4427 VL - 64 IS - 13 SN - 0008-5472, 0008-5472 KW - Index Medicus KW - Hematologic Neoplasms -- pathology KW - Animals KW - Oligonucleotide Array Sequence Analysis KW - Polymerase Chain Reaction -- methods KW - Hematologic Neoplasms -- genetics KW - Mice, Inbred C57BL KW - Gene Expression KW - Disease Progression KW - Mice, Nude KW - Mice KW - Virus Integration -- genetics KW - Splenic Neoplasms -- genetics KW - Splenic Neoplasms -- pathology KW - Lymphoma, B-Cell -- pathology KW - Lymphoma, B-Cell -- genetics KW - Retroviridae -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66674028?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=High-throughput+retroviral+tagging+for+identification+of+genes+involved+in+initiation+and+progression+of+mouse+splenic+marginal+zone+lymphomas.&rft.au=Shin%2C+Min+Sun%3BFredrickson%2C+Torgny+N%3BHartley%2C+Janet+W%3BSuzuki%2C+Takeshi%3BAkagi%2C+Keiko%3BAgaki%2C+Keiko%3BMorse%2C+Herbert+C&rft.aulast=Shin&rft.aufirst=Min&rft.date=2004-07-01&rft.volume=64&rft.issue=13&rft.spage=4419&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 - 2004-08-26 N1 - Date created - 2004-07-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Cancer Res. 2006 Mar 15;66(6):3345 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fish intake during pregnancy and early cognitive development of offspring. AN - 66672651; 15232398 AB - Fish is a source of many nutrients that can be beneficial during pregnancy, as well as a source of neurotoxicant contaminants such as methylmercury. Previous investigations of fish intake in relation to neurodevelopment have focused on possible damage from contaminants, whereas potential benefits of fish consumption have been relatively unexplored We evaluated the association between maternal fish intake during pregnancy and offspring's early development of language and communication skills in a cohort of 7421 British children born in 1991-1992. Fish intake by the mother and child was measured by questionnaire. The child's cognitive development was assessed using adaptations of the MacArthur Communicative Development Inventory at 15 months of age and the Denver Developmental Screening Test at 18 months of age. Mercury was measured in umbilical cord tissue for a subset of 1054 children Total mercury concentrations were low and were not associated with neurodevelopment. Fish intake by the mother during pregnancy, and by the infant postnatally, was associated with higher mean developmental scores. For example, the adjusted mean MacArthur comprehension score for children whose mothers consumed fish 4 or more times per week was 72 (95% confidence interval = 71-74), compared with 68 (66-71) among those whose mothers did not consume fish. When fish is not contaminated, moderate fish intake during pregnancy and infancy may benefit development. Copyright 2004 Lippincott Williams and Wilkins JF - Epidemiology (Cambridge, Mass.) AU - Daniels, Julie L AU - Longnecker, Matthew P AU - Rowland, Andrew S AU - Golding, Jean AU - ALSPAC Study Team. University of Bristol Institute of Child Health AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. juliedanielsunc.edu ; ALSPAC Study Team. University of Bristol Institute of Child Health Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 394 EP - 402 VL - 15 IS - 4 SN - 1044-3983, 1044-3983 KW - Mercury KW - FXS1BY2PGL KW - Index Medicus KW - Fetal Blood -- chemistry KW - Mercury -- blood KW - Breast Feeding KW - Humans KW - Linear Models KW - Feeding Behavior KW - Longitudinal Studies KW - Pregnancy KW - Maternal-Fetal Exchange -- physiology KW - Infant KW - United Kingdom -- epidemiology KW - Risk Factors KW - Adult KW - Surveys and Questionnaires KW - Female KW - Male KW - Prenatal Exposure Delayed Effects KW - Cognition -- drug effects KW - Infant Nutritional Physiological Phenomena KW - Seafood -- adverse effects KW - Nervous System -- drug effects KW - Child Development -- drug effects KW - Child Development -- physiology KW - Maternal Nutritional Physiological Phenomena UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66672651?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Fish+intake+during+pregnancy+and+early+cognitive+development+of+offspring.&rft.au=Daniels%2C+Julie+L%3BLongnecker%2C+Matthew+P%3BRowland%2C+Andrew+S%3BGolding%2C+Jean%3BALSPAC+Study+Team.+University+of+Bristol+Institute+of+Child+Health&rft.aulast=Daniels&rft.aufirst=Julie&rft.date=2004-07-01&rft.volume=15&rft.issue=4&rft.spage=394&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 - 2004-09-09 N1 - Date created - 2004-07-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Epidemiology. 2004 Jul;15(4):383-4 [15232396] Epidemiology. 2005 Jan;16(1):133 [15613962] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The insertional history of an active family of L1 retrotransposons in humans. AN - 66671220; 15197167 AB - As humans contain a currently active L1 (LINE-1) non-LTR retrotransposon family (Ta-1), the human genome database likely provides only a partial picture of Ta-1-generated diversity. We used a non-biased method to clone Ta-1 retrotransposon-containing loci from representatives of four ethnic populations. We obtained 277 distinct Ta-1 loci and identified an additional 67 loci in the human genome database. This collection represents approximately 90% of the Ta-1 population in the individuals examined and is thus more representative of the insertional history of Ta-1 than the human genome database, which lacked approximately 40% of our cloned Ta-1 elements. As both polymorphic and fixed Ta-1 elements are as abundant in the GC-poor genomic regions as in ancestral L1 elements, the enrichment of L1 elements in GC-poor areas is likely due to insertional bias rather than selection. Although the chromosomal distribution of Ta-1 inserts is generally a function of chromosomal length and gene density, chromosome 4 significantly deviates from this pattern and has been much more hospitable to Ta-1 insertions than any other chromosome. Also, the intra-chromosomal distribution of Ta-1 elements is not uniform. Ta-1 elements tend to cluster, and the maximal gaps between Ta-1 inserts are larger than would be expected from a model of uniform random insertion. Copyright 2004 Cold Spring Harbor Laboratory Press ISSN JF - Genome research AU - Boissinot, Stéphane AU - Entezam, Ali AU - Young, Lynn AU - Munson, Peter J AU - Furano, Anthony V AD - Section on Genomic Structure and Function, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 1221 EP - 1231 VL - 14 IS - 7 SN - 1088-9051, 1088-9051 KW - Retroelements KW - 0 KW - Index Medicus KW - Genome, Human KW - Consensus Sequence -- genetics KW - Polymorphism, Genetic -- genetics KW - Humans KW - GC Rich Sequence -- genetics KW - Genetic Variation -- genetics KW - Chromosome Mapping -- statistics & numerical data KW - Databases, Genetic KW - Sequence Alignment -- methods KW - Male KW - Ethnic Groups -- genetics KW - Chromosomes, Human -- genetics KW - Statistical Distributions KW - Retroelements -- genetics KW - Mutagenesis, Insertional -- genetics KW - Evolution, Molecular KW - Long Interspersed Nucleotide Elements -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66671220?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+insertional+history+of+an+active+family+of+L1+retrotransposons+in+humans.&rft.au=Boissinot%2C+St%C3%A9phane%3BEntezam%2C+Ali%3BYoung%2C+Lynn%3BMunson%2C+Peter+J%3BFurano%2C+Anthony+V&rft.aulast=Boissinot&rft.aufirst=St%C3%A9phane&rft.date=2004-07-01&rft.volume=14&rft.issue=7&rft.spage=1221&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 - 2004-09-03 N1 - Date created - 2004-07-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Biol Evol. 2000 Jun;17(6):915-28 [10833198] Nat Genet. 2000 Apr;24(4):363-7 [10742098] 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] Annu Rev Genet. 2001;35:501-38 [11700292] Mol Biol Evol. 2001 Dec;18(12):2186-94 [11719568] Genome Res. 2001 Dec;11(12):2050-8 [11731495] RNA. 2002 Mar;8(3):345-56 [12003494] Nat Genet. 2002 Jul;31(3):241-7 [12053178] Am J Hum Genet. 2002 Aug;71(2):312-26 [12070800] Genomics. 2002 Oct;80(4):402-6 [12376094] Nat Genet. 2002 Dec;32(4):655-60 [12415270] Nature. 2002 Dec 5;420(6915):520-62 [12466850] Am J Hum Genet. 2003 Apr;72(4):823-38 [12632328] Hum Genet. 2003 May;112(5-6):527-33 [12601470] Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5280-5 [12682288] Nucleic Acids Res. 2003 Aug 1;31(15):4385-90 [12888497] Nat Genet. 2003 Sep;35(1):41-8 [12897783] Proc Natl Acad Sci U S A. 1990 Apr;87(7):2531-5 [2157203] J Mol Biol. 1990 Oct 5;215(3):403-10 [2231712] J Mol Biol. 1995 Feb 24;246(3):401-417 [7877164] Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1872-7 [9050872] J Mol Evol. 1998 Sep;47(3):292-301 [9732456] Biochemistry. 1998 Dec 22;37(51):18081-93 [9922177] Hum Mol Genet. 1999 Aug;8(8):1557-60 [10401005] Nat Genet. 2003 Nov;35(3):221-8 [14517553] Nat Genet. 2003 Dec;35(4):363-6 [14625551] J Mol Biol. 1986 Jan 20;187(2):291-304 [3009828] Mol Cell Biol. 1988 Apr;8(4):1385-97 [2454389] Nucleic Acids Res. 1989 Jan 11;17(1):452 [2911481] Prog Nucleic Acid Res Mol Biol. 2000;64:255-94 [10697412] Genome Res. 2000 Oct;10(10):1496-508 [11042149] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Endotoxin-induced uveitis in cyclooxygenase-2-deficient mice. AN - 66669784; 15223810 AB - Endotoxin-induced uveitis (EIU) is a model that mimics human acute anterior uveitis. Cyclooxygenase (COX)-2 is an enzyme that initiates the conversion of arachidonic acid (AA) into prostaglandins (PGs), whereas 5-lipoxygenase (5-LO) generates leukotrienes (LT). The purpose of this study was to delineate the role of COX-2 in acute ocular inflammation. EIU was induced in wild-type (WT), heterozygotic (COX-2(+/-)) and COX-2 null (COX-2(-/-)) mice by injection of lipopolysaccharide (LPS). Other mice were coinjected with LPS and IFN gamma. Ocular histology, serum cytokines, and AA products determined by ELISA, and relevant ocular messengers determined by RT-PCR were compared among the different groups. Histology showed that the EIU score was significantly enhanced in COX-2(-/-) mice in comparison to WT and COX-2(+/-). PGE(2) was increased in WT and COX-2(+/-) EIU but not in COX-2(-/-) EIU. LTB(4) in serum and ocular 5-LO transcripts were increased in COX-2(-/-) EIU mice in comparison with WT and COX-2(+/-) EIU mice. IL-6 increased, whereas IFN gamma decreased both in serum and ocular transcripts in COX-2(-/-) EIU mice in comparison with WT and COX-2(+/-). Furthermore, EIU was suppressed in mice treated with recombinant IFN gamma, as shown by the decreased EIU scores, the presence of serum LTB(4) and IL-6 and ocular 5-LO and IL-6 mRNA, and the increases in serum IFN gamma and ocular IFN gamma, particularly in COX-2(-/-) mice. These data suggest that disturbance of the AA pathway exacerbates EIU in COX-2-deficient mice. IFN gamma moderately reverses this exacerbation and protects against EIU. JF - Investigative ophthalmology & visual science AU - Tuo, Jingsheng AU - Tuaillon, Nadine AU - Shen, DeFen AU - Chan, Chi-Chao AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 2306 EP - 2313 VL - 45 IS - 7 SN - 0146-0404, 0146-0404 KW - Interleukin-6 KW - 0 KW - Isoenzymes KW - Lipopolysaccharides KW - Recombinant Proteins KW - Leukotriene B4 KW - 1HGW4DR56D KW - Arachidonic Acid KW - 27YG812J1I KW - Interferon-gamma KW - 82115-62-6 KW - Arachidonate 5-Lipoxygenase KW - EC 1.13.11.34 KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - Prostaglandin-Endoperoxide Synthases KW - Dinoprostone KW - K7Q1JQR04M KW - Index Medicus KW - Animals KW - Interferon-gamma -- genetics KW - Leukotriene B4 -- blood KW - Dinoprostone -- metabolism KW - Interleukin-6 -- metabolism KW - Interleukin-6 -- genetics KW - Interferon-gamma -- metabolism KW - Interferon-gamma -- pharmacology KW - Enzyme-Linked Immunosorbent Assay KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - Arachidonate 5-Lipoxygenase -- genetics KW - Arachidonic Acid -- metabolism KW - Mice, Knockout KW - Uveitis, Anterior -- enzymology KW - Prostaglandin-Endoperoxide Synthases -- deficiency KW - Uveitis, Anterior -- prevention & control KW - Uveitis, Anterior -- chemically induced KW - Isoenzymes -- deficiency KW - Uveitis, Anterior -- pathology KW - Lipopolysaccharides -- toxicity KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - Salmonella typhimurium KW - Isoenzymes -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66669784?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Endotoxin-induced+uveitis+in+cyclooxygenase-2-deficient+mice.&rft.au=Tuo%2C+Jingsheng%3BTuaillon%2C+Nadine%3BShen%2C+DeFen%3BChan%2C+Chi-Chao&rft.aulast=Tuo&rft.aufirst=Jingsheng&rft.date=2004-07-01&rft.volume=45&rft.issue=7&rft.spage=2306&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 - 2004-07-27 N1 - Date created - 2004-06-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Smad-binding defective mutant of transforming growth factor beta type I receptor enhances tumorigenesis but suppresses metastasis of breast cancer cell lines. AN - 66669058; 15231662 AB - The role of transforming growth factor beta (TGF-beta) in carcinogenesis is complex, with tumor suppressor and pro-oncogenic activities depending on the particular tumor cell and its stage in malignant progression. We previously have demonstrated in breast cancer cell lines that Smad2/3 signaling played a dominant role in mediating tumor suppressor effects on well-differentiated breast cancer cell lines grown as xenografts and prometastatic effects on a more invasive, metastatic cell line. Our present data based on selective interference with activation of endogenous Smad2 and Smad3 by stable expression of a mutant form of the TGF-beta type I receptor (RImL45) unable to bind Smad2/3 but with a functional kinase again show that reduction in Smad2/3 signaling by expression of RImL45 enhanced the malignancy of xenografted tumors of the well-differentiated MCF10A-derived tumor cell line MCF10CA1h, resulting in formation of larger tumors with a higher proliferative index and more malignant histologic features. In contrast, expression of RImL45 in the more aggressive MCF10CA1a cell line strongly suppressed formation of lung metastases following tail vein injection. These results suggest a causal, dominant role for the endogenous Smad2/3 signaling pathway in the tumor suppressor and prometastatic activities of TGF-beta in these cells. Using an in vitro assay, we further show that non-Smad signaling pathways, including p38 and c-Jun NH(2)-terminal kinase, cooperate with TGF-beta/Smads in enhancing migration of metastatic MCF10CA1a cells, but that, although necessary for migration, these other pathways are not sufficient for metastasis. JF - Cancer research AU - Tian, Fang AU - Byfield, Stacey DaCosta AU - Parks, W Tony AU - Stuelten, Christina H AU - Nemani, Deepa AU - Zhang, Ying E AU - Roberts, Anita B AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892-5055, USA. Y1 - 2004/07/01/ PY - 2004 DA - 2004 Jul 01 SP - 4523 EP - 4530 VL - 64 IS - 13 SN - 0008-5472, 0008-5472 KW - DNA-Binding Proteins KW - 0 KW - Receptors, Transforming Growth Factor beta KW - SMAD2 protein, human KW - SMAD3 protein, human KW - Smad2 Protein KW - Smad2 protein, mouse KW - Smad3 Protein KW - Smad3 protein, mouse KW - Trans-Activators KW - Transforming Growth Factor beta KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - transforming growth factor-beta type II receptor KW - EC 2.7.11.30 KW - Index Medicus KW - Animals KW - Humans KW - Cell Line, Tumor KW - Mice KW - Mice, Nude KW - Transcriptional Activation KW - Transforming Growth Factor beta -- antagonists & inhibitors KW - Transforming Growth Factor beta -- physiology KW - Phosphorylation KW - Neoplasm Metastasis KW - Mutation KW - Breast Neoplasms -- genetics KW - Trans-Activators -- metabolism KW - Receptors, Transforming Growth Factor beta -- genetics KW - Breast Neoplasms -- pathology KW - Trans-Activators -- genetics KW - Receptors, Transforming Growth Factor beta -- metabolism KW - DNA-Binding Proteins -- genetics KW - Breast Neoplasms -- metabolism KW - Receptors, Transforming Growth Factor beta -- biosynthesis KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66669058?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Smad-binding+defective+mutant+of+transforming+growth+factor+beta+type+I+receptor+enhances+tumorigenesis+but+suppresses+metastasis+of+breast+cancer+cell+lines.&rft.au=Tian%2C+Fang%3BByfield%2C+Stacey+DaCosta%3BParks%2C+W+Tony%3BStuelten%2C+Christina+H%3BNemani%2C+Deepa%3BZhang%2C+Ying+E%3BRoberts%2C+Anita+B&rft.aulast=Tian&rft.aufirst=Fang&rft.date=2004-07-01&rft.volume=64&rft.issue=13&rft.spage=4523&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 - 2004-08-26 N1 - Date created - 2004-07-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Encapsulated cell-based intraocular delivery of ciliary neurotrophic factor in normal rabbit: dose-dependent effects on ERG and retinal histology. AN - 66666351; 15223826 AB - ERG and histologic changes were investigated in normal rabbits after intravitreal implantation of encapsulated cell technology (ECT) devices releasing ciliary neurotrophic factor (CNTF). Fifteen adult New Zealand White albino rabbits had ECT devices secreting CNTF at 22, 5, or 0 ng/d implanted in the superior temporal quadrant of the left eye. The low dose has been shown to produce substantial rescue of photoreceptors in the rcd1 canine model of retinal degeneration. Right eyes were untreated. Ganzfeld dark- and light-adapted ERGs and clinical observations were performed at 5, 15, and 25 days after implantation. Rod a-waves and rod and cone b-waves and outer nuclear layer (ONL) morphology were evaluated at 25 days. Clinical examination showed minimal changes in a few CNTF-treated eyes, including vitreous membranes and engorgement of iris vessels at day 25. Retinas appeared normal. CNTF did not significantly affect the rod a- or b-waves, although the b-wave amplitude tended to be larger in CNTF-treated retinas at low flash intensities. The cone b-wave amplitude was significantly reduced in high-dose eyes at some flash intensities. The ONL area in high-dose eyes was significantly greater because of increased thickness than in fellow retinas. ONL cell size was significantly increased, and staining density decreased in CNTF-treated retinas. CNTF, given by intravitreal ECT device at doses that protect photoreceptors in a canine model of retinal degeneration (5 ng/d), did not adversely affect either rod or cone ERG function of normal rabbit retina. The cone ERG was more sensitive to suppression being reduced, at low flash intensities, by 22 ng/d. Dose-related changes in the ONL and photoreceptor cell nuclei did not represent a toxic effect, because they were not associated with deficits in the rod ERG over a broad range of intensities. JF - Investigative ophthalmology & visual science AU - Bush, Ronald A AU - Lei, Bo AU - Tao, Weng AU - Raz, Dorit AU - Chan, Chi-Chao AU - Cox, Terry A AU - Santos-Muffley, Maria AU - Sieving, Paul A AD - Department of Ophthalmology and Visual Science, Kellogg Eye Center, University of Michigan, Ann Arbor, USA. bushr@nidcd.nih.gov Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 2420 EP - 2430 VL - 45 IS - 7 SN - 0146-0404, 0146-0404 KW - Ciliary Neurotrophic Factor KW - 0 KW - Drug Implants KW - Index Medicus KW - Vitreous Body KW - Animals KW - Photic Stimulation KW - Dark Adaptation KW - Dose-Response Relationship, Drug KW - Rabbits KW - Drug Delivery Systems KW - Ciliary Neurotrophic Factor -- administration & dosage KW - Retina -- physiology KW - Retina -- drug effects KW - Retina -- pathology KW - Electroretinography -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66666351?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Encapsulated+cell-based+intraocular+delivery+of+ciliary+neurotrophic+factor+in+normal+rabbit%3A+dose-dependent+effects+on+ERG+and+retinal+histology.&rft.au=Bush%2C+Ronald+A%3BLei%2C+Bo%3BTao%2C+Weng%3BRaz%2C+Dorit%3BChan%2C+Chi-Chao%3BCox%2C+Terry+A%3BSantos-Muffley%2C+Maria%3BSieving%2C+Paul+A&rft.aulast=Bush&rft.aufirst=Ronald&rft.date=2004-07-01&rft.volume=45&rft.issue=7&rft.spage=2420&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 - 2004-07-27 N1 - Date created - 2004-06-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cell-autonomous and cell non-autonomous signaling through endothelin receptor B during melanocyte development. AN - 66663775; 15201217 AB - The endothelin receptor B gene (Ednrb) encodes a G-protein-coupled receptor that is expressed in a variety of cell types and is specifically required for the development of neural crest-derived melanocytes and enteric ganglia. In humans, mutations in this gene are associated with Waardenburg-Shah syndrome, a disorder characterized by pigmentation defects, deafness and megacolon. To address the question of whether melanocyte development depends entirely on a cell-autonomous action of Ednrb, we performed a series of tissue recombination experiments in vitro, using neural crest cell cultures from mouse embryos carrying a novel Ednrb-null allele characterized by the insertion of a lacZ marker gene. The results show that Ednrb is not required for the generation of early neural crest-derived melanoblasts but is required for the expression of the differentiation marker tyrosinase. Tyrosinase expression can be rescued, however, by the addition of Ednrb wild-type neural tubes. These Ednrb wild-type neural tubes need not be capable of generating melanocytes themselves, but must be capable of providing KIT ligand, the cognate ligand for the tyrosine kinase receptor KIT. In fact, soluble KIT ligand is sufficient to induce tyrosinase expression in Ednrb-deficient cultures. Nevertheless, these tyrosinase-expressing, Ednrb-deficient cells do not develop to terminally differentiated, pigmented melanocytes. Pigmentation can be induced, however, by treatment with tetradecanoyl phorbol acetate, which mimics EDNRB signaling, but not by treatment with endothelin 1, which stimulates the paralogous receptor EDNRA. The results suggest that Ednrb plays a significant role during melanocyte differentiation and effects melanocyte development by both cell non-autonomous and cell-autonomous signaling mechanisms. JF - Development (Cambridge, England) AU - Hou, Ling AU - Pavan, William J AU - Shin, Myung K AU - Arnheiter, Heinz AD - Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-4472, USA. lhou@mail.nih.gov Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 3239 EP - 3247 VL - 131 IS - 14 SN - 0950-1991, 0950-1991 KW - DNA-Binding Proteins KW - 0 KW - Genetic Markers KW - Microphthalmia-Associated Transcription Factor KW - Mitf protein, mouse KW - Phorbol Esters KW - Receptor, Endothelin B KW - Receptors, G-Protein-Coupled KW - Stem Cell Factor KW - Transcription Factors KW - Monophenol Monooxygenase KW - EC 1.14.18.1 KW - beta-Galactosidase KW - EC 3.2.1.23 KW - Index Medicus KW - Pigmentation KW - Monophenol Monooxygenase -- metabolism KW - Animals KW - Stem Cell Factor -- metabolism KW - Phorbol Esters -- metabolism KW - Cell Lineage KW - Transcription Factors -- metabolism KW - Cell Differentiation KW - Mice KW - Models, Biological KW - Genotype KW - Alleles KW - beta-Galactosidase -- metabolism KW - Receptors, G-Protein-Coupled -- metabolism KW - Mice, Inbred C3H KW - Mice, Inbred C57BL KW - Time Factors KW - Mutation KW - Lac Operon KW - Neural Crest -- cytology KW - Cell Division KW - DNA-Binding Proteins -- metabolism KW - Melanocytes -- metabolism KW - Melanocytes -- cytology KW - Receptor, Endothelin B -- metabolism KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66663775?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Development+%28Cambridge%2C+England%29&rft.atitle=Cell-autonomous+and+cell+non-autonomous+signaling+through+endothelin+receptor+B+during+melanocyte+development.&rft.au=Hou%2C+Ling%3BPavan%2C+William+J%3BShin%2C+Myung+K%3BArnheiter%2C+Heinz&rft.aulast=Hou&rft.aufirst=Ling&rft.date=2004-07-01&rft.volume=131&rft.issue=14&rft.spage=3239&rft.isbn=&rft.btitle=&rft.title=Development+%28Cambridge%2C+England%29&rft.issn=09501991&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-30 N1 - Date created - 2004-06-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Exploration of low-dose estrogen effects: identification of No Observed Transcriptional Effect Level (NOTEL). AN - 66663208; 15223774 AB - Identifying a minimal dose capable of eliciting a biological response is a fundamental issue in a number of scientific fields, including: drug development, signal transduction research, and environmental toxicology. Frequently, proliferation, viability, and other assays based on the cellular response to a treatment are used to assess the threshold dose for minimal activity. Here we propose a novel approach for identifying the effects of low dose treatments and pinpointing the threshold dose. Using microarrays, we examined the transcriptional response of a hormone responsive breast cancer cell line (MCF-7) stimulated with various concentrations of estrogen. Previous studies have focused on transcriptional responses to physiologically relevant concentrations of estrogen. However, relatively few studies have examined the transcriptional effects of concentrations below normal physiologic levels. These doses may not stimulate the expression of any genes or, alternatively, may regulate a different subset of genes that had not been previously characterized as estrogen responsive. We used gene expression profiling, coupled with a detailed analysis of replicates, to measure estrogen effects on many transcriptional targets and found that only physiologically relevant doses of estrogen (1 x 10(-10) M and higher) were capable of inducing a transcriptional response. This study demonstrates the utility of gene expression profiling as a means to identify concentrations that do not elicit a change in gene expression, or simply a No Observed Transcriptional Effect Level (NOTEL). The identification of a NOTEL for a given compound may be beneficial in several different scientific disciplines. For example, in the development of therapeutic drugs, a NOTEL could be used to identify doses of pharmaceutical compounds that are no longer effective at modulating the expression of biomarkers of efficacy. JF - Toxicologic pathology AU - Lobenhofer, Edward K AU - Cui, Xiangqin AU - Bennett, Lee AU - Cable, P LouAnn AU - Merrick, B Alex AU - Churchill, Gary A AU - Afshari, Cynthia A AD - National Center for Toxicogenomics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. elobenhofer@paragen.com PY - 2004 SP - 482 EP - 492 VL - 32 IS - 4 SN - 0192-6233, 0192-6233 KW - Estrogens KW - 0 KW - Index Medicus KW - Cell Proliferation -- drug effects KW - Breast Neoplasms -- genetics KW - Analysis of Variance KW - No-Observed-Adverse-Effect Level KW - Oligonucleotide Array Sequence Analysis KW - Breast Neoplasms -- pathology KW - Dose-Response Relationship, Drug KW - Humans KW - Cell Line, Tumor KW - Reverse Transcriptase Polymerase Chain Reaction KW - Female KW - Gene Expression Regulation, Neoplastic KW - Estrogens -- genetics KW - Transcription, Genetic -- drug effects KW - Epithelial Cells -- drug effects KW - Estrogens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66663208?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Exploration+of+low-dose+estrogen+effects%3A+identification+of+No+Observed+Transcriptional+Effect+Level+%28NOTEL%29.&rft.au=Lobenhofer%2C+Edward+K%3BCui%2C+Xiangqin%3BBennett%2C+Lee%3BCable%2C+P+LouAnn%3BMerrick%2C+B+Alex%3BChurchill%2C+Gary+A%3BAfshari%2C+Cynthia+A&rft.aulast=Lobenhofer&rft.aufirst=Edward&rft.date=2004-07-01&rft.volume=32&rft.issue=4&rft.spage=482&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 - 2005-02-15 N1 - Date created - 2004-06-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evidence for the involvement of SDF-1 and CXCR4 in the disruption of endothelial cell-branching morphogenesis and angiogenesis by TNF-alpha and IFN-gamma. AN - 66663052; 15075355 AB - Vigorous inflammatory responses are associated with tissue damage, particularly when toxic levels of inflammatory cytokines are produced. Despite proangiogenic factors being present early at sites of inflammation, vascular repair occurs toward the end of the inflammatory response, suggesting modulation of the proangiogenic response. Endogenous inhibitors of angiogenesis induced during acute inflammation are poorly characterized. Here, we looked for endothelial cell-derived modulators of angiogenesis that may account for delayed neovascularization during inflammation. Gene profiling of endothelial cells showed that the inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interferon-gamma (IFN-gamma) selectively promote expression of the antiangiogenic molecules, IFN-inducible protein-10, monokine induced by IFN-gamma, tryptophanyl-tRNA synthetase, and tissue inhibitor of metalmetalloproteinase-1, and inhibit expression of the proangiogenic molecules, platelet-endothelial cell adhesion molecule-1, vascular endothelial growth factor receptor-2, stromal cell-derived factor-1 (SDF-1), collagen type IV, endothelial cell growth factor-1, and carcinoembryonic antigen-related cell adhesion molecule-1. Reduced endothelial cell expression of SDF-1 protein by TNF-alpha and IFN-gamma disrupts extracellular matrix-dependent endothelial cell tube formation, an in vitro morphogenic process that recapitulates critical steps in angiogenesis. Replacement of SDF-1 onto the endothelial cell surface reconstitutes this morphogenic process. In vivo, TNF-alpha and IFN-gamma inhibit growth factor-induced angiogenesis and SDF-1 expression in endothelial cells. These results demonstrate that SDF-1/CXC chemokine receptor-4 constitutes a TNF-alpha- and IFN-gamma-regulated signaling system that plays a critical role in mediating angiogenesis inhibition by these inflammatory cytokines. JF - Journal of leukocyte biology AU - Salvucci, Ombretta AU - Basik, Mark AU - Yao, Lei AU - Bianchi, Rossella AU - Tosato, Giovanna AD - Center for Cancer Research, National Cancer Institute, Building 10, Room 12N226, MSC 1907, Bethesda, MD 20892, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 217 EP - 226 VL - 76 IS - 1 SN - 0741-5400, 0741-5400 KW - CXCL12 protein, human KW - 0 KW - Chemokine CXCL12 KW - Chemokines, CXC KW - Receptors, CXCR4 KW - Tumor Necrosis Factor-alpha KW - Interferon-gamma KW - 82115-62-6 KW - Index Medicus KW - Signal Transduction -- physiology KW - Gene Expression Profiling KW - Blotting, Western KW - Oligonucleotide Array Sequence Analysis KW - Cells, Cultured KW - Humans KW - Signal Transduction -- drug effects KW - Neovascularization, Pathologic -- metabolism KW - Up-Regulation KW - Reverse Transcriptase Polymerase Chain Reaction KW - Immunohistochemistry KW - Image Processing, Computer-Assisted KW - Endothelial Cells -- drug effects KW - Endothelial Cells -- physiology KW - Receptors, CXCR4 -- biosynthesis KW - Chemokines, CXC -- biosynthesis KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Receptors, CXCR4 -- drug effects KW - Interferon-gamma -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66663052?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Evidence+for+the+involvement+of+SDF-1+and+CXCR4+in+the+disruption+of+endothelial+cell-branching+morphogenesis+and+angiogenesis+by+TNF-alpha+and+IFN-gamma.&rft.au=Salvucci%2C+Ombretta%3BBasik%2C+Mark%3BYao%2C+Lei%3BBianchi%2C+Rossella%3BTosato%2C+Giovanna&rft.aulast=Salvucci&rft.aufirst=Ombretta&rft.date=2004-07-01&rft.volume=76&rft.issue=1&rft.spage=217&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 - 2004-08-03 N1 - Date created - 2004-06-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Targeted disruption of the IA-2beta gene causes glucose intolerance and impairs insulin secretion but does not prevent the development of diabetes in NOD mice. AN - 66661580; 15220191 AB - Insulinoma-associated protein (IA)-2beta, also known as phogrin, is an enzymatically inactive member of the transmembrane protein tyrosine phosphatase family and is located in dense-core secretory vesicles. In patients with type 1 diabetes, autoantibodies to IA-2beta appear years before the development of clinical disease. The genomic structure and function of IA-2beta, however, is not known. In the present study, we determined the genomic structure of IA-2beta and found that both human and mouse IA-2beta consist of 23 exons and span approximately 1,000 and 800 kb, respectively. With this information, we prepared a targeting construct and inactivated the mouse IA-2beta gene as demonstrated by lack of IA-2beta mRNA and protein expression. The IA-2beta(-/-) mice, in contrast to wild-type controls, showed mild glucose intolerance and impaired glucose-stimulated insulin secretion. Knockout of the IA-2beta gene in NOD mice, the most widely studied animal model for human type 1 diabetes, failed to prevent the development of cyclophosphamide-induced diabetes. We conclude that IA-2beta is involved in insulin secretion, but despite its importance as a major autoantigen in human type 1 diabetes, it is not required for the development of diabetes in NOD mice. JF - Diabetes AU - Kubosaki, Atsutaka AU - Gross, Steffen AU - Miura, Junnosuke AU - Saeki, Keiichi AU - Zhu, Min AU - Nakamura, Shinichiro AU - Hendriks, Wiljan AU - Notkins, Abner Louis AD - Experimental Medicine Section, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892-4322, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 1684 EP - 1691 VL - 53 IS - 7 SN - 0012-1797, 0012-1797 KW - Autoantigens KW - 0 KW - Immunosuppressive Agents KW - Insulin KW - Membrane Proteins KW - Cyclophosphamide KW - 8N3DW7272P KW - PTPRN2 protein, human KW - EC 3.1.3.48 KW - Protein Tyrosine Phosphatase, Non-Receptor Type 1 KW - Protein Tyrosine Phosphatases KW - Receptor-Like Protein Tyrosine Phosphatases, Class 8 KW - Glucose KW - IY9XDZ35W2 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Genome, Human KW - Exons KW - Mice, Inbred NOD KW - Diabetes Mellitus -- chemically induced KW - Humans KW - Autoantigens -- genetics KW - Diabetes Mellitus -- genetics KW - Mice KW - Genome KW - Mice, Knockout KW - Glucose -- pharmacology KW - Molecular Sequence Data KW - Male KW - Female KW - Protein Tyrosine Phosphatases -- genetics KW - Glucose Intolerance -- genetics KW - Diabetes Mellitus, Type 1 -- genetics KW - Insulin -- secretion KW - Membrane Proteins -- genetics KW - Gene Deletion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66661580?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Diabetes&rft.atitle=Targeted+disruption+of+the+IA-2beta+gene+causes+glucose+intolerance+and+impairs+insulin+secretion+but+does+not+prevent+the+development+of+diabetes+in+NOD+mice.&rft.au=Kubosaki%2C+Atsutaka%3BGross%2C+Steffen%3BMiura%2C+Junnosuke%3BSaeki%2C+Keiichi%3BZhu%2C+Min%3BNakamura%2C+Shinichiro%3BHendriks%2C+Wiljan%3BNotkins%2C+Abner+Louis&rft.aulast=Kubosaki&rft.aufirst=Atsutaka&rft.date=2004-07-01&rft.volume=53&rft.issue=7&rft.spage=1684&rft.isbn=&rft.btitle=&rft.title=Diabetes&rft.issn=00121797&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-16 N1 - Date created - 2004-06-28 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AJ583055; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Randomized phase II trial of docetaxel plus thalidomide in androgen-independent prostate cancer. AN - 66661578; 15226321 AB - Both docetaxel and thalidomide have demonstrated activity in androgen-independent prostate cancer (AIPC). We compared the efficacy of docetaxel to docetaxel plus thalidomide in patients with AIPC. Seventy-five patients with chemotherapy-naïve metastatic AIPC were randomly assigned to receive either docetaxel 30 mg/m(2) intravenously every week for 3 consecutive weeks, followed by a 1-week rest period (n = 25); or docetaxel at the same dose and schedule, plus thalidomide 200 mg orally each day (n = 50). Prostate-specific antigen (PSA) consensus criteria and radiographic scans were used to determine the proportion of patients with a PSA decline, and time to progression. After a median potential follow-up time of 26.4 months, the proportion of patients with a greater than 50% decline in PSA was higher in the docetaxel/thalidomide group (53% in the combined group, 37% in docetaxel-alone arm). The median progression-free survival in the docetaxel group was 3.7 months and 5.9 months in the combined group (P =.32). At 18 months, overall survival in the docetaxel group was 42.9% and 68.2% in the combined group. Toxicities in both groups were manageable after administration of prophylactic low-molecular-weight heparin in the combination group. In this randomized phase II trial, the addition of thalidomide to docetaxel resulted in an encouraging PSA decline rate and overall median survival rate in patients with metastatic AIPC. After the prophylactic low-molecular-weight heparin was instituted to prevent venous thromboses, the combination regimen was well tolerated. Larger randomized trials are warranted to assess the impact of this combination. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Dahut, William L AU - Gulley, James L AU - Arlen, Philip M AU - Liu, Yinong AU - Fedenko, Katherine M AU - Steinberg, Seth M AU - Wright, John J AU - Parnes, Howard AU - Chen, Clara C AU - Jones, Elizabeth AU - Parker, Catherine E AU - Linehan, W Marston AU - Figg, William D AD - Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/07/01/ PY - 2004 DA - 2004 Jul 01 SP - 2532 EP - 2539 VL - 22 IS - 13 SN - 0732-183X, 0732-183X KW - Taxoids KW - 0 KW - docetaxel KW - 15H5577CQD KW - Thalidomide KW - 4Z8R6ORS6L KW - Prostate-Specific Antigen KW - EC 3.4.21.77 KW - Index Medicus KW - Prostate-Specific Antigen -- analysis KW - Administration, Oral KW - Disease-Free Survival KW - Infusions, Intravenous KW - Aged, 80 and over KW - Humans KW - Adult KW - Treatment Outcome KW - Aged KW - Thalidomide -- administration & dosage KW - Middle Aged KW - Male KW - Taxoids -- administration & dosage 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/66661578?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Randomized+phase+II+trial+of+docetaxel+plus+thalidomide+in+androgen-independent+prostate+cancer.&rft.au=Dahut%2C+William+L%3BGulley%2C+James+L%3BArlen%2C+Philip+M%3BLiu%2C+Yinong%3BFedenko%2C+Katherine+M%3BSteinberg%2C+Seth+M%3BWright%2C+John+J%3BParnes%2C+Howard%3BChen%2C+Clara+C%3BJones%2C+Elizabeth%3BParker%2C+Catherine+E%3BLinehan%2C+W+Marston%3BFigg%2C+William+D&rft.aulast=Dahut&rft.aufirst=William&rft.date=2004-07-01&rft.volume=22&rft.issue=13&rft.spage=2532&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 - 2004-09-03 N1 - Date created - 2004-06-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Clin Oncol. 2005 Mar 20;23(9):2113; author reply 2113-4 [15774812] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Whole-body biodistribution and radiation dosimetry estimates for the PET dopamine transporter probe 18F-FECNT in non-human primates. AN - 66659851; 15208503 AB - 2 beta-Carbomethoxy-3-(4-chlorophenyl)-8-(2-[18F]fluoroethyl)nortropane (18F-FECNT) is a selective radioligand for the in vivo quantification of dopamine transporters by using positron emission tomography. The aim of the current study was to quantify the distribution of radioactivity in three rhesus monkeys after the injection of approximately 185 MBq (5 mCi) of 18F-FECNT. Whole-body images were acquired at 23-30 time points for a total of 220 min following injection of the radioligand. Source organs were identified at each time point from planar images. The peak activities in planar images in the six identified source organs (expressed as per cent injected dose (%ID)) were lungs (16.5%ID at 2 min), kidneys (12.5%ID at 3 min), brain (9.5%ID at 6 min), liver (7.5%ID at 3 min), red bone marrow (3.5%ID at 12 min), and urinary bladder (2%ID at 98 min). Radiation absorbed doses were calculated using the gastrointestinal tract model in two ways: (1) assuming no urine voiding, and (2) using a dynamic bladder model with voiding intervals of 2.4 and 4.8 h. Using the gastrointestinal tract model and dynamic bladder model with a voiding interval 4.8 h, the three organs with highest exposure (in mu Gy.MBq(-1) (mrad.mCi(-1)) were kidneys 75.68 (280), lungs 44.86 (166) and urinary bladder 58.38 (216). Effective doses estimated with and without urine voiding were in the range 21.35-22.70 mu Gy.MBq(-1) (79-84 mrad.mCi(-1)). The estimated radiation burden of 18F-FECNT is relatively modest and would allow multiple scans per research subject per year. JF - Nuclear medicine communications AU - Tipre, Dnyanesh N AU - Fujita, Masahiro AU - Chin, Frederick T AU - Seneca, Nicholas AU - Vines, Douglas AU - Liow, Jeih-San AU - Pike, Victor W AU - Innis, Robert B AD - Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bldg 1 Rm. B3-10, 1 Center Drive, Bethesda, MD 20892-0135, USA. TipreD@intra.nimh.nih.gov Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 737 EP - 742 VL - 25 IS - 7 SN - 0143-3636, 0143-3636 KW - 2-carbomethoxy-3-(4-chlorophenyl)-8-(2-fluoroethyl)nortropane KW - 0 KW - Dopamine Plasma Membrane Transport Proteins KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Nortropanes KW - Radiopharmaceuticals KW - Index Medicus KW - Radiopharmaceuticals -- pharmacokinetics KW - Radiation Dosage KW - Animals KW - Relative Biological Effectiveness KW - Positron-Emission Tomography -- methods KW - Humans KW - Body Burden KW - Metabolic Clearance Rate KW - Organ Specificity KW - Macaca mulatta KW - Tissue Distribution KW - Drug Evaluation, Preclinical KW - Male KW - Whole-Body Counting -- methods KW - Nortropanes -- pharmacokinetics KW - Nerve Tissue Proteins -- metabolism KW - Brain -- metabolism KW - Radiometry -- methods KW - Membrane Transport Proteins -- metabolism KW - Brain -- diagnostic imaging KW - Membrane Glycoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66659851?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+communications&rft.atitle=Whole-body+biodistribution+and+radiation+dosimetry+estimates+for+the+PET+dopamine+transporter+probe+18F-FECNT+in+non-human+primates.&rft.au=Tipre%2C+Dnyanesh+N%3BFujita%2C+Masahiro%3BChin%2C+Frederick+T%3BSeneca%2C+Nicholas%3BVines%2C+Douglas%3BLiow%2C+Jeih-San%3BPike%2C+Victor+W%3BInnis%2C+Robert+B&rft.aulast=Tipre&rft.aufirst=Dnyanesh&rft.date=2004-07-01&rft.volume=25&rft.issue=7&rft.spage=737&rft.isbn=&rft.btitle=&rft.title=Nuclear+medicine+communications&rft.issn=01433636&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-07 N1 - Date created - 2004-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bleeding patterns after vaginal misoprostol for treatment of early pregnancy failure. AN - 66657743; 15178656 AB - Dilatation and curettage (D&C) has been the usual treatment for early pregnancy failure (EPF). Medical management with misoprostol may be an effective alternative. Bleeding patterns during and after medical management of EPF are unknown. A prospective cohort study was conducted at University-based clinics and physician offices. Eighty women <11 weeks estimated gestational age with a diagnosis of missed abortion or fetal demise were enrolled. Treatment consisted of either 800 micro g of moistened (2 ml of saline) or dry vaginal misoprostol. Self-reported bleeding and sanitary product usage were recorded in a daily 2 week diary. Haemoglobin was assessed at enrollment and 2 weeks later. After misoprostol treatment, patients reported bleeding or spotting every day for the 14 days observed. Self-assessed heavy bleeding days were few (median 3) and usually occurred immediately after treatment. Sanitary pad use was highly variable (mean 30.5, range 2-125 pads over the 2 week period) and not related to changes in haemoglobin. The mean decrease in haemoglobin was 0.5 g/dl (SD 1.2). Complete expulsion without D&C occurred in 85% of subjects. Bleeding for at least 2 weeks after vaginal misoprostol for EPF is common. Heavy bleeding is usually limited to a few days after treatment. Clinically important changes in haemoglobin are rare. JF - Human reproduction (Oxford, England) AU - Davis, A R AU - Robilotto, C M AU - Westhoff, C L AU - Forman, S AU - Zhang, J AU - NICHD Management of Early Pregnancy Failure Trial group AD - Department of Obstetrics and Gynecology, Columbia University, New York, NY 10032, USA. ard4@columbia.edu ; NICHD Management of Early Pregnancy Failure Trial group Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 1655 EP - 1658 VL - 19 IS - 7 SN - 0268-1161, 0268-1161 KW - Abortifacient Agents, Nonsteroidal KW - 0 KW - Hemoglobins KW - Misoprostol KW - 0E43V0BB57 KW - Index Medicus KW - Medical Records KW - Pregnancy Trimester, First KW - Hemoglobins -- metabolism KW - Humans KW - Adult KW - Administration, Intravaginal KW - Time Factors KW - Female KW - Pregnancy KW - Uterine Hemorrhage -- physiopathology KW - Uterine Hemorrhage -- blood KW - Misoprostol -- adverse effects KW - Abortifacient Agents, Nonsteroidal -- adverse effects KW - Pregnancy Complications -- drug therapy KW - Abortion, Incomplete -- drug therapy KW - Uterine Hemorrhage -- chemically induced KW - Misoprostol -- administration & dosage KW - Abortifacient Agents, Nonsteroidal -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66657743?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+reproduction+%28Oxford%2C+England%29&rft.atitle=Bleeding+patterns+after+vaginal+misoprostol+for+treatment+of+early+pregnancy+failure.&rft.au=Davis%2C+A+R%3BRobilotto%2C+C+M%3BWesthoff%2C+C+L%3BForman%2C+S%3BZhang%2C+J%3BNICHD+Management+of+Early+Pregnancy+Failure+Trial+group&rft.aulast=Davis&rft.aufirst=A&rft.date=2004-07-01&rft.volume=19&rft.issue=7&rft.spage=1655&rft.isbn=&rft.btitle=&rft.title=Human+reproduction+%28Oxford%2C+England%29&rft.issn=02681161&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-13 N1 - Date created - 2004-06-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pilot study of celecoxib and infusional 5-fluorouracil as second-line treatment for advanced pancreatic carcinoma. AN - 66656590; 15221998 AB - Cyclooxygenase-2 (COX-2) is up-regulated frequently and may constitute a promising therapeutic target in patients with pancreatic ductal adenocarcinoma (PDAC). Patients with advanced PDAC who had progressive disease after gemcitabine-based chemotherapy were eligible for this pilot study. Treatment was comprised of oral celecoxib (400 mg twice daily) and protracted intravenous (i.v.) infusion 5-fluorouracil (5-FU) (200 mg/m(2) per day), both given continuously for a maximum of 9 treatment months, in the absence of disease progression or unacceptable toxicity. Patients were examined weekly for toxicity and were restaged every 6-8 weeks for tumor assessment. Seventeen patients entered the study. Asymptomatic transaminase elevation was the most common toxicity and reached NCI-CTC (version 3.0) Grade 3-4 in 4 of 133 treatment weeks. No other hematologic or nonhematologic toxicity > Grade 2 was observed. Four patients discontinued celecoxib due to upper gastrointestinal tract toxicity. Two confirmed partial responses (durations of 23 weeks and 68 weeks, respectively) and 2 patients with stable disease (durations of 10 weeks and 13 weeks, respectively) were observed for an overall response rate of 12% (95% confidence interval, 0-27%) in the intent-to-treat population. A significant decrease (> or = 50%) in serum CA 19.9 levels was observed in 3 of 9 evaluable patients. The median time to disease progression was 8 weeks, and the median overall survival was 15 weeks. The combination of oral celecoxib and 5-FU by protracted i.v. infusion was found to be feasible and well tolerated, and was capable of inducing durable objective responses, even in patients with far advanced, gemcitabine-resistant/refractory PDAC. Further exploration of COX-2 inhibitor/fluropyrimidine combinations is warranted. Copyright 2004 American Cancer Society. JF - Cancer AU - Milella, Michele AU - Gelibter, Alain AU - Di Cosimo, Serena AU - Bria, Emilio AU - Ruggeri, Enzo Maria AU - Carlini, Paolo AU - Malaguti, Paola AU - Pellicciotta, Mario AU - Terzoli, Edmondo AU - Cognetti, Francesco AD - Divisions of Medical Oncology "A" and "C", Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy. milella@ifo.it Y1 - 2004/07/01/ PY - 2004 DA - 2004 Jul 01 SP - 133 EP - 138 VL - 101 IS - 1 SN - 0008-543X, 0008-543X KW - Carcinoembryonic Antigen KW - 0 KW - Pyrazoles KW - Sulfonamides KW - Celecoxib KW - JCX84Q7J1L KW - Fluorouracil KW - U3P01618RT KW - Abridged Index Medicus KW - Index Medicus KW - Infusions, Intravenous KW - Humans KW - Disease Progression KW - Aged KW - Pilot Projects KW - Sulfonamides -- administration & dosage KW - Fluorouracil -- administration & dosage KW - Fluorouracil -- adverse effects KW - Sulfonamides -- adverse effects KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Carcinoembryonic Antigen -- blood KW - Carcinoembryonic Antigen -- drug effects KW - Female KW - Male KW - Pancreatic Neoplasms -- pathology KW - Pancreatic Neoplasms -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Adenocarcinoma -- drug therapy KW - Adenocarcinoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66656590?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Pilot+study+of+celecoxib+and+infusional+5-fluorouracil+as+second-line+treatment+for+advanced+pancreatic+carcinoma.&rft.au=Milella%2C+Michele%3BGelibter%2C+Alain%3BDi+Cosimo%2C+Serena%3BBria%2C+Emilio%3BRuggeri%2C+Enzo+Maria%3BCarlini%2C+Paolo%3BMalaguti%2C+Paola%3BPellicciotta%2C+Mario%3BTerzoli%2C+Edmondo%3BCognetti%2C+Francesco&rft.aulast=Milella&rft.aufirst=Michele&rft.date=2004-07-01&rft.volume=101&rft.issue=1&rft.spage=133&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-16 N1 - Date created - 2004-06-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A potential cholinergic mechanism of procaine's limbic activation. AN - 66654808; 14997171 AB - The local anesthetic procaine, when administered to humans intravenously (i.v.), yields brief intense emotional and sensory experiences, and concomitant increases in anterior paralimbic cerebral blood flow, as measured by positron emission tomography (PET). Procaine's high muscarinic affinity, together with the distribution of muscarinic receptors that overlaps with brain regions activated by procaine, suggests a muscarinic contribution to procaine's emotional and sensory effects. This study evaluates the effects of procaine on cerebral muscarinic cholinergic receptors in the anesthetized rhesus monkey. Whole brain and regional muscarinic receptor binding was measured before and after procaine administration on the same day in three anesthetized rhesus monkeys with PET and the radiotracer 3-(3-(3[18F]fluoropropylthio)-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine ([18F]FP-TZTP), a cholinergic ligand that has preferential binding to muscarinic (M(2)) receptors. On separate days each animal received six different doses of i.v. procaine in a randomized fashion. Procaine blocked up to approximately 90% of [18F]FP-TZTP specific binding globally in a dose-related manner. There were no regional differences in procaine's inhibitory concentration for 50% blockade (IC50) for [18F]FP-TZTP. Tracer delivery, which was highly correlated to cerebral blood flow in previous monkey studies, was significantly increased at all doses of procaine with the greatest increases occurring near procaine's IC50 for average cortex. Furthermore, anterior limbic regions showed greater increases in tracer delivery than nonlimbic regions. Procaine has high affinity to muscarinic M2 receptors in vivo in the rhesus monkey. This, as well as a preferential increase of tracer delivery to paralimbic regions, suggests that action at these receptors could contribute to i.v. procaine's emotional and sensory effects in man. These findings are consistent with other evidence of cholinergic modulation of mood and emotion. Copyright 2004 Nature Publishing Group JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Benson, Brenda E AU - Carson, Richard E AU - Kiesewetter, Dale O AU - Herscovitch, Peter AU - Eckelman, William C AU - Post, Robert M AU - Ketter, Terence A AD - Biological Psychiatry Branch, NIMH, NIH, Bethesda, MD 20892-1272, USA. bbenson@mail.nih.gov Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 1239 EP - 1250 VL - 29 IS - 7 SN - 0893-133X, 0893-133X KW - Anesthetics, Local KW - 0 KW - FP-TZTP KW - Fluorine Radioisotopes KW - Pyridines KW - Receptors, Muscarinic KW - Thiazoles KW - Procaine KW - 4Z8Y51M438 KW - Index Medicus KW - Animals KW - Fluorine Radioisotopes -- pharmacokinetics KW - Anesthetics, Local -- pharmacology KW - Dose-Response Relationship, Drug KW - Pyridines -- pharmacokinetics KW - Thiazoles -- pharmacokinetics KW - Anesthetics, Local -- administration & dosage KW - Brain Mapping KW - Macaca mulatta KW - Inhibitory Concentration 50 KW - Autoradiography -- methods KW - Radioligand Assay -- methods KW - Male KW - Tomography, Emission-Computed -- methods KW - Limbic System -- drug effects KW - Limbic System -- metabolism KW - Cerebrovascular Circulation -- drug effects KW - Procaine -- pharmacology KW - Procaine -- administration & dosage KW - Receptors, Muscarinic -- physiology KW - Limbic System -- blood supply UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66654808?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.atitle=A+potential+cholinergic+mechanism+of+procaine%27s+limbic+activation.&rft.au=Benson%2C+Brenda+E%3BCarson%2C+Richard+E%3BKiesewetter%2C+Dale+O%3BHerscovitch%2C+Peter%3BEckelman%2C+William+C%3BPost%2C+Robert+M%3BKetter%2C+Terence+A&rft.aulast=Benson&rft.aufirst=Brenda&rft.date=2004-07-01&rft.volume=29&rft.issue=7&rft.spage=1239&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 - 2004-08-02 N1 - Date created - 2004-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The nitric oxide donor, O2-vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (V-PYRRO/NO), protects against cadmium-induced hepatotoxicity in mice. AN - 66653956; 15010501 AB - The nitric oxide (NO) donor, O2-vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (V-PYRRO/NO), is metabolized by P450 enzymes to release NO within the liver and is effective in protecting against hepatotoxicity of endotoxin and acetaminophen. This study examined the effects of V-PYRRO/NO on cadmium (Cd) hepatotoxicity in mice. Mice were given multiple injections of V-PYRRO/NO (10 mg/kg, s.c. at 2-h intervals) before and after a hepatotoxic dose of Cd (3.7 mg/kg Cd as CdCl2, i.p.). V-PYRRO/NO administration reduced Cd-induced hepatotoxicity as evidenced by reduced serum alanine aminotransferase activity, improved pathology, and reduced hepatic lipid peroxidation. The protection by V-PYRRO/NO was not mediated by altered Cd distribution to the liver or within hepatic subcellular fractions. Similar inductions of metallothionein, a metal-binding protein, were observed in mice receiving Cd alone or Cd plus V-PYRRO/NO. Real-time reverse transcription-polymerase chain reaction analysis revealed that V-PYRRO/NO administration suppressed the expression of inflammation-related genes such as macrophage inflammatory protein-2, CXC chemokine, thrombospondin-1, intracellular adhesion molecular-1, and interleukin-6. V-PYRRO/NO also suppressed the expression of acute phase protein genes and genes related to cell-death pathways, such as c-jun/AP-1, nuclear factor-kappaB, early response growth factor-1, heme oxygenase-1, caspase-3, growth arrest, and DNA-damaging protein-153. In summary, the liver-selective NO donor, V-PYRRO/NO, protects against Cd hepatotoxicity in mice. This protection is not mediated through altered distribution of Cd but may be related to reduced hepatic inflammation, reduced acute phase responses, and the suppression of cell-death-related components. JF - The Journal of pharmacology and experimental therapeutics AU - Liu, Jie AU - Qu, Wei AU - Saavedra, Joseph E AU - Waalkes, Michael P AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at the National Instititue of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 18 EP - 24 VL - 310 IS - 1 SN - 0022-3565, 0022-3565 KW - Nitric Oxide Donors KW - 0 KW - O(2)-vinyl-1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate KW - Pyrrolidines KW - Cadmium KW - 00BH33GNGH KW - Metallothionein KW - 9038-94-2 KW - Index Medicus KW - Gene Expression -- drug effects KW - Animals KW - Subcellular Fractions KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - Metallothionein -- metabolism KW - Male KW - Chemical and Drug Induced Liver Injury -- prevention & control KW - Pyrrolidines -- therapeutic use KW - Nitric Oxide Donors -- therapeutic use KW - Chemical and Drug Induced Liver Injury -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66653956?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=The+nitric+oxide+donor%2C+O2-vinyl+1-%28pyrrolidin-1-yl%29diazen-1-ium-1%2C2-diolate+%28V-PYRRO%2FNO%29%2C+protects+against+cadmium-induced+hepatotoxicity+in+mice.&rft.au=Liu%2C+Jie%3BQu%2C+Wei%3BSaavedra%2C+Joseph+E%3BWaalkes%2C+Michael+P&rft.aulast=Liu&rft.aufirst=Jie&rft.date=2004-07-01&rft.volume=310&rft.issue=1&rft.spage=18&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 - 2004-09-07 N1 - Date created - 2004-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhanced cytotoxicity of allogeneic NK cells with killer immunoglobulin-like receptor ligand incompatibility against melanoma and renal cell carcinoma cells. AN - 66653646; 15016654 AB - Cellular inactivation through killer immunoglobulin-like receptors (KIRs) may allow neoplastic cells to evade host natural killer (NK) cell-mediated immunity. Recently, alloreactive NK cells were shown to mediate antileukemic effects against acute myelogenous leukemia (AML) after mismatched transplantation, when KIR ligand incompatibility existed in the direction of graft-versus-host disease (GVHD). Therefore, we investigated whether solid tumor cells would have similar enhanced susceptibility to allogeneic KIR-incompatible NK cells compared with their KIR-matched autologous or allogeneic counterparts. NK populations enriched and cloned from the blood of cancer patients or healthy donors homozygous for HLA-C alleles in group 1 (C-G1) or group 2 (C-G2) were tested in vitro for cytotoxicity against Epstein-Barr virus-transformed lymphoblastic cell lines (EBV-LCLs), renal cell carcinoma (RCC), and melanoma (MEL) cells with or without a matching KIR-inhibitory HLA-C ligand. Allogeneic NK cells were more cytotoxic to tumor targets mismatched for KIR ligands than their KIR ligand-matched counterparts. Bulk NK populations (CD3(-)/CD2(+)/CD56(+)) expanded 10(4)-fold from patients homozygous for C-G1 or C-G2 had enhanced cytotoxicity against KIR ligand-mismatched tumor cells but only minimal cytotoxicity against KIR ligand-matched targets. Further, NK cell lines from C-G1 or C-G2 homozygous cancer patients or healthy donors expanded but failed to kill autologous or KIR-matched MEL and RCC cells yet had significant cytotoxicity (more than 50% lysis at 20:1 effector-target [E/T] ratio) against allogeneic KIR-mismatched tumor lines. These data suggest immunotherapeutic strategies that use KIR-incompatible allogeneic NK cells might have superior antineoplastic effects against solid tumors compared with approaches using autologous NK cells. JF - Blood AU - Igarashi, Takehito AU - Wynberg, Jason AU - Srinivasan, Ramprasad AU - Becknell, Brian AU - McCoy, J Phillip AU - Takahashi, Yoshiyuki AU - Suffredini, Dante A AU - Linehan, W Marston AU - Caligiuri, Michael A AU - Childs, Richard W AD - Hematology Branch, Flow Cytometry Core Facility, National Heart, Lund, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1652, USA. Y1 - 2004/07/01/ PY - 2004 DA - 2004 Jul 01 SP - 170 EP - 177 VL - 104 IS - 1 SN - 0006-4971, 0006-4971 KW - Antigens, CD KW - 0 KW - Histocompatibility Antigens Class I KW - Ligands KW - Receptors, Immunologic KW - Receptors, KIR KW - Abridged Index Medicus KW - Index Medicus KW - Clone Cells KW - Gamma Rays -- adverse effects KW - Homozygote KW - Humans KW - Histocompatibility Antigens Class I -- immunology KW - B-Lymphocytes -- immunology KW - Cell Line, Tumor KW - Histocompatibility Antigens Class I -- genetics KW - Cytotoxicity, Immunologic -- immunology KW - Histocompatibility Testing KW - Antigens, CD -- metabolism KW - Cytotoxicity Tests, Immunologic KW - Herpesvirus 4, Human -- immunology KW - Antigens, CD -- immunology KW - Histocompatibility -- immunology KW - Receptors, Immunologic -- immunology KW - Killer Cells, Natural -- transplantation KW - Histocompatibility -- genetics KW - Immunotherapy, Adoptive -- methods KW - Melanoma -- immunology KW - Killer Cells, Natural -- radiation effects KW - Carcinoma, Renal Cell -- immunology KW - Killer Cells, Natural -- immunology KW - Kidney Neoplasms -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66653646?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Enhanced+cytotoxicity+of+allogeneic+NK+cells+with+killer+immunoglobulin-like+receptor+ligand+incompatibility+against+melanoma+and+renal+cell+carcinoma+cells.&rft.au=Igarashi%2C+Takehito%3BWynberg%2C+Jason%3BSrinivasan%2C+Ramprasad%3BBecknell%2C+Brian%3BMcCoy%2C+J+Phillip%3BTakahashi%2C+Yoshiyuki%3BSuffredini%2C+Dante+A%3BLinehan%2C+W+Marston%3BCaligiuri%2C+Michael+A%3BChilds%2C+Richard+W&rft.aulast=Igarashi&rft.aufirst=Takehito&rft.date=2004-07-01&rft.volume=104&rft.issue=1&rft.spage=170&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-27 N1 - Date created - 2004-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Laulimalide and paclitaxel: a comparison of their effects on tubulin assembly and their synergistic action when present simultaneously. AN - 66649420; 15213302 AB - Previous work has shown that laulimalide, a sponge-derived natural product, resembles paclitaxel in enhancing tubulin assembly and in its effects on cellular microtubules. The two compounds, however, seem to have distinct binding sites on tubulin polymer. Nearly equimolar amounts of tubulin, laulimalide, and paclitaxel are recovered from microtubules formed with both drugs. In the present study, we searched for differences between laulimalide and paclitaxel in their interactions with tubulin polymer. Laulimalide was compared with paclitaxel and epothilone A, a natural product that competes with paclitaxel in binding to microtubules, for assembly properties at different temperatures and for effects of GTP and microtubule-associated proteins on assembly. Although minor differences were observed among the three drugs, their overall effects were highly similar, except that aberrant assembly products were observed more frequently with paclitaxel and that the polymers formed with laulimalide and epothilone A were more stable at 0 degrees C. The most dramatic difference observed between laulimalide and epothilone A was that only laulimalide was able to enhance assembly synergistically with paclitaxel, as would be predicted if the two drugs bound at different sites in polymer. Because stoichiometric amounts of laulimalide and paclitaxel can cause extensive tubulin assembly, maximum synergy was observed at lower temperatures under reaction conditions in which each drug alone is relatively inactive. Laulimalide-induced assembly, like paclitaxel-induced assembly, was inhibited by drugs that inhibit tubulin assembly by binding at either the colchicine- or vinblastine-binding site. When radiolabeled GTP is present in a reaction mixture with either laulimalide or paclitaxel, nucleotide hydrolysis occurs with incorporation of radiolabeled GDP into polymer. JF - Molecular pharmacology AU - Gapud, Eric J AU - Bai, Ruoli AU - Ghosh, Arun K AU - Hamel, Ernest AD - Screening Technologies Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnostics, National Cancer Institute at Frederick, Frederick, MD 21702, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 113 EP - 121 VL - 66 IS - 1 SN - 0026-895X, 0026-895X KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Biopolymers KW - Macrolides KW - Microtubule-Associated Proteins KW - Taxoids KW - Tubulin KW - Tubulin Modulators KW - laulimalide KW - Guanosine Triphosphate KW - 86-01-1 KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Animals KW - Cattle KW - Antineoplastic Agents, Phytogenic -- pharmacology KW - Drug Synergism KW - Hydrolysis KW - Guanosine Triphosphate -- metabolism KW - Microtubule-Associated Proteins -- metabolism KW - Microtubules -- metabolism KW - Tubulin -- metabolism KW - Paclitaxel -- pharmacology KW - Microtubules -- drug effects KW - Taxoids -- pharmacology KW - Taxoids -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66649420?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmacology&rft.atitle=Laulimalide+and+paclitaxel%3A+a+comparison+of+their+effects+on+tubulin+assembly+and+their+synergistic+action+when+present+simultaneously.&rft.au=Gapud%2C+Eric+J%3BBai%2C+Ruoli%3BGhosh%2C+Arun+K%3BHamel%2C+Ernest&rft.aulast=Gapud&rft.aufirst=Eric&rft.date=2004-07-01&rft.volume=66&rft.issue=1&rft.spage=113&rft.isbn=&rft.btitle=&rft.title=Molecular+pharmacology&rft.issn=0026895X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-15 N1 - Date created - 2004-06-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tumor spectrum in the p53 heterozygous zeta globin-promoted Tg.AC (v-Ha-ras) bitransgenic mouse model. AN - 66648782; 15204965 AB - The use of a bitransgenic mouse model for cancer is an effective approach for studying the impact of specific carcinogens and the occurrence of tissue-specific lesions. We studied the novel p53 heterozygous zeta globin-promoted Tg.AC (v-Ha-ras) mouse model because these mice contain a carcinogen-inducible ras oncogene and one functional p53 tumor suppressor allele, both of which occur frequently in human cancers. Our aim was to characterize the short-term control and chemically induced tumor spectrum in this novel model. Mice were placed on basal semipurified diet containing 20% soy protein for 2 weeks prior to random allocation to groups. Subsequently, 15 male and 15 female mice were administered corn oil vehicle alone or containing benzo(a)pyrene (20 mg/kg body weight) via oral gavage 2 times per week for 10 weeks with subsequent observation for 18 weeks. Mice exhibited lesions characteristic of FVB/N, p53 heterozygous and Tg.AC mouse models. However, an array of unique, novel lesions were observed including uterine leiomyosarcomas, mammary gland carcinomas, mammary squamous cell carcinomas, and parotid salivary gland carcinomas suggesting tissue-specific interactions of the 2 genotypes. Thus, this bitransgenic model may provide further insight into the mechanistic interaction of 2 genes commonly mutated in neoplasia. JF - Toxicologic pathology AU - Martin, Keith R AU - Jokinen, Michael P AU - Honeycutt, Hayden P AU - Quinn, Anita AU - Kari, Frank W AU - Barrett, J Carl AU - French, John E AD - Laboratory of Environmental Carcinogenesis & Mutagenesis, NIEHS, Research Triangle Park, North Carolina, USA. krm12@psu.edu PY - 2004 SP - 418 EP - 425 VL - 32 IS - 4 SN - 0192-6233, 0192-6233 KW - Carcinogens KW - 0 KW - Benzo(a)pyrene KW - 3417WMA06D KW - Globins KW - 9004-22-2 KW - Index Medicus KW - Drug Administration Schedule -- veterinary KW - Animals KW - Alleles KW - Carcinogens -- administration & dosage KW - Gene Silencing KW - Heterozygote KW - Carcinogens -- toxicity KW - Mice KW - Male KW - Female KW - Neoplasms -- veterinary KW - Genes, ras KW - Benzo(a)pyrene -- administration & dosage KW - Neoplasms -- pathology KW - Neoplasms -- classification KW - Genes, p53 KW - Neoplasms -- chemically induced KW - Globins -- genetics KW - Benzo(a)pyrene -- toxicity KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66648782?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Tumor+spectrum+in+the+p53+heterozygous+zeta+globin-promoted+Tg.AC+%28v-Ha-ras%29+bitransgenic+mouse+model.&rft.au=Martin%2C+Keith+R%3BJokinen%2C+Michael+P%3BHoneycutt%2C+Hayden+P%3BQuinn%2C+Anita%3BKari%2C+Frank+W%3BBarrett%2C+J+Carl%3BFrench%2C+John+E&rft.aulast=Martin&rft.aufirst=Keith&rft.date=2004-07-01&rft.volume=32&rft.issue=4&rft.spage=418&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 - 2005-02-15 N1 - Date created - 2004-06-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The development of phosphatidylinositol ether lipid analogues as inhibitors of the serine/threonine kinase, Akt. AN - 66647618; 15212619 AB - The serine/threonine kinase Akt is a component of the phosphatidylinositol 3'-kinase/Akt signal transduction pathway that is activated by receptor tyrosine kinases, activated Ras and integrins. As Akt regulates many processes crucial to carcinogenesis, and Akt activation has been observed in human cancers, intense efforts are underway to develop Akt inhibitors as cancer therapeutics. Towards this aim, phosphatidylinositol ether lipid analogues (PIAs), which are structurally similar to the products of phosphatidylinositol 3'-kinase, have been synthesised. PIAs inhibit Akt translocation, phosphorylation and kinase activity. Furthermore, they selectively induce apoptosis in cancer cell lines that depend on Akt for survival. This review will trace the development of PIAs, cover the biological activities of PIAs and discuss future steps and challenges in their development. JF - Expert opinion on investigational drugs AU - Gills, Joell J AU - Dennis, Phillip A AD - Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20889, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 787 EP - 797 VL - 13 IS - 7 KW - Enzyme Inhibitors KW - 0 KW - Phosphatidylinositols KW - Phospholipid Ethers KW - Proto-Oncogene Proteins KW - AKT1 protein, human KW - EC 2.7.11.1 KW - Protein-Serine-Threonine Kinases KW - Proto-Oncogene Proteins c-akt KW - Index Medicus KW - Animals KW - Humans KW - Enzyme Inhibitors -- pharmacology KW - Phospholipid Ethers -- pharmacology KW - Proto-Oncogene Proteins -- antagonists & inhibitors KW - Phosphatidylinositols -- pharmacology KW - Protein-Serine-Threonine Kinases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66647618?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+investigational+drugs&rft.atitle=The+development+of+phosphatidylinositol+ether+lipid+analogues+as+inhibitors+of+the+serine%2Fthreonine+kinase%2C+Akt.&rft.au=Gills%2C+Joell+J%3BDennis%2C+Phillip+A&rft.aulast=Gills&rft.aufirst=Joell&rft.date=2004-07-01&rft.volume=13&rft.issue=7&rft.spage=787&rft.isbn=&rft.btitle=&rft.title=Expert+opinion+on+investigational+drugs&rft.issn=1744-7658&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-07-21 N1 - Date created - 2004-06-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Susceptibility of rats to mammary gland carcinogenesis by the food-derived carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) varies with age and is associated with the induction of differential gene expression. AN - 66646997; 15215175 AB - 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a heterocyclic amine found in cooked meat, induces mammary gland cancer when administered to adolescent female rats (43-day-old). In contrast, mature virgin rats (150-day-old) were resistant to mammary carcinogenesis by PhIP. To explore the possible mechanisms for the age-related differences in susceptibility, PhIP-DNA adduct levels, mutations, and gene expression were examined in glands from 43-day and 150-day-old PhIP-treated rats. In rats of different ages, PhIP-DNA adduct levels detected by the (32)P-post-labeling assay and mutant frequency measured in the lacI reporter gene of Big Blue rats were not statistically different. PhIP-DNA adduct levels, adduct removal, and mutation burden did not appear to account for the variation in carcinogen susceptibility with age. However, cDNA microarray analysis indicated that PhIP treatment differentially altered the profile of gene expression in glands from 43-day-old and 150-day-old rats. In 150-day-old rats, PhIP enhanced the expression of genes associated with differentiation (eg, beta-casein, kappa-casein, whey acidic protein) and induced morphological differentiation. In contrast, in 43-day-old rats, PhIP inhibited the expression of differentiation genes and enhanced cellular proliferation. From 3 hours to 6 weeks after PhIP dosing, the number of clones showing altered expression declined more than 50% in 150-day-old rats but increased fourfold in 43-day-old rats (29 clones versus 194, respectively) suggesting that PhIP induced a cascade of gene expression alterations only in susceptible rats. Genes showing altered expression specifically in 43-day-old rats included the Ras superfamily genes and genes associated with protein synthesis/degradation (lysosomal proteins, heat shock proteins, and proteasomes). The microarray data support the notion that the mechanism of age-dependent susceptibility to mammary gland cancer is largely associated with differential responses in expression of genes involved in cellular differentiation, proliferation, and protein homeostasis. JF - The American journal of pathology AU - Shan, Liang AU - Yu, Minshu AU - Schut, Herman A J AU - Snyderwine, Elizabeth G AD - Chemical Carcinogenesis Section, Laboratory of Experimental Carcinogenesis, Center for Cancer Research, Building 37, National Cancer Institute/NIH, Bethesda, MD 20892-4262, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 191 EP - 202 VL - 165 IS - 1 SN - 0002-9440, 0002-9440 KW - Carcinogens KW - 0 KW - DNA Adducts KW - Imidazoles KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Disease Susceptibility KW - Oligonucleotide Array Sequence Analysis KW - Aging KW - Cell Division -- drug effects KW - Reverse Transcriptase Polymerase Chain Reaction KW - Rats KW - Gene Expression Profiling KW - Rats, Sprague-Dawley KW - DNA Adducts -- analysis KW - Cell Differentiation -- drug effects KW - Time Factors KW - Cluster Analysis KW - Female KW - Mammary Neoplasms, Experimental -- chemically induced KW - Imidazoles -- toxicity KW - Food KW - Carcinogens -- toxicity KW - Mammary Neoplasms, Experimental -- genetics KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Mammary Neoplasms, Experimental -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66646997?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+rats+to+mammary+gland+carcinogenesis+by+the+food-derived+carcinogen+2-amino-1-methyl-6-phenylimidazo%5B4%2C5-b%5Dpyridine+%28PhIP%29+varies+with+age+and+is+associated+with+the+induction+of+differential+gene+expression.&rft.au=Shan%2C+Liang%3BYu%2C+Minshu%3BSchut%2C+Herman+A+J%3BSnyderwine%2C+Elizabeth+G&rft.aulast=Shan&rft.aufirst=Liang&rft.date=2004-07-01&rft.volume=165&rft.issue=1&rft.spage=191&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 - 2004-09-03 N1 - Date created - 2004-06-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biochim Biophys Acta. 1995 May 17;1262(1):64-8 [7772601] Int Rev Immunol. 1999;18(5-6):429-48 [10672495] J Natl Cancer Inst. 2000 Aug 16;92(16):1352-4 [10944558] Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11391-6 [11005832] Carcinogenesis. 1995 Nov;16(11):2725-31 [7586192] J Cell Biol. 1996 Jul;134(1):25-35 [8698819] Br J Cancer. 1996 Sep;74(5):717-21 [8795573] Biochem Soc Symp. 1998;63:101-13 [9513715] Carcinogenesis. 1998 Jul;19(7):1209-15 [9683179] Carcinogenesis. 1998 Sep;19(9):1573-81 [9771927] Nutr Cancer. 1998;31(3):160-7 [9795967] Carcinogenesis. 1998 Dec;19(12):2181-5 [9886576] Carcinogenesis. 1999 Mar;20(3):353-68 [10190547] Cancer Res. 1999 Apr 1;59(7 Suppl):1765-1771s; discussion 1771s-1772s [10197594] J Cell Sci. 1999 May;112 ( Pt 10):1477-86 [10212142] Science. 1969 Aug 22;165(3895):810-1 [5796556] J Natl Cancer Inst. 1974 Feb;52(2):609-10 [4816015] Biochemistry. 1975 Jul;14(13):2895-903 [1148182] Br J Cancer. 1975 Feb;31(2):189-96 [809048] J Natl Cancer Inst. 1978 Jan;60(1):173-7 [415147] J Natl Cancer Inst. 1978 Dec;61(6):1439-49 [102856] J Natl Cancer Inst. 1978 Dec;61(6):1451-9 [102857] J Mammary Gland Biol Neoplasia. 2000 Apr;5(2):165-85 [11149571] Microsc Res Tech. 2001 Jan 15;52(2):204-23 [11169868] J Mammary Gland Biol Neoplasia. 2001 Jan;6(1):101-13 [11467446] Mol Endocrinol. 2001 Nov;15(11):1993-2009 [11682629] Cell Growth Differ. 2001 Dec;12(12):649-56 [11751460] Ann N Y Acad Sci. 2001 Dec;952:23-35 [11795441] Anal Biochem. 2002 Feb 15;301(2):314-24 [11814302] Eur J Biochem. 2002 Feb;269(4):1209-18 [11856354] Environ Mol Mutagen. 2002;39(2-3):165-70 [11921185] Mol Cell Biochem. 2002 Jan;229(1-2):35-44 [11936845] J Cell Mol Med. 2002 Jan-Mar;6(1):25-48 [12003667] Carcinogenesis. 2002 May;23(5):877-84 [12016163] Surg Oncol. 2002 May;10(4):183-92 [12020673] Bioinformatics. 2002 May;18(5):774-5 [12050079] Proteomics. 2002 Jul;2(7):850-6 [12124930] Cancer Res. 2002 Aug 15;62(16):4540-4 [12183401] Environ Med. 1999 Dec;43(2):79-87 [12296368] Mutat Res. 2002 Sep 30;506-507:145-52 [12351154] Cancer Lett. 2003 Jan 28;189(2):117-28 [12490304] Carcinogenesis. 2002 Dec;23(12):2123-8 [12507937] Endocr Relat Cancer. 2002 Dec;9(4):207-20 [12542399] Curr Med Chem. 2003 Mar;10(6):479-503 [12570694] Nat Rev Cancer. 2003 Mar;3(3):179-92 [12612653] Biochem Biophys Res Commun. 2003 May 9;304(3):505-12 [12729585] Eur J Surg Oncol. 2003 Jun;29(5):475-9 [12798754] Metabolism. 2003 Jul;52(7):810-4 [12870152] J Endocrinol. 1966 Aug;35(4):331-40 [5923706] Am J Pathol. 1979 Sep;96(3):721-36 [112872] Cancer Res. 1980 Aug;40(8 Pt 1):2677-87 [7388818] J Natl Cancer Inst. 1981 Jul;67(1):155-61 [6788991] Carcinogenesis. 1981;2(12):1327-33 [6799218] J Natl Cancer Inst. 1983 Jan;70(1):209-12 [6571916] Int J Cancer. 1983 Mar 15;31(3):321-7 [6402455] Carcinogenesis. 1983;4(6):733-8 [6407772] Chem Biol Interact. 1985 Oct;55(1-2):13-21 [3933840] Lab Invest. 1990 Mar;62(3):244-78 [2107367] Mol Cell Biol. 1991 Aug;11(8):3842-9 [1712897] Cancer Res. 1992 Mar 15;52(6):1477-80 [1540955] Carcinogenesis. 1992 Sep;13(9):1535-9 [1394836] J Natl Cancer Inst. 1993 Jan 6;85(1):25-31 [8416252] Cancer Lett. 1992 Dec 24;67(2-3):117-24 [1483260] Epidemiol Rev. 1993;15(1):7-16 [8405214] Carcinogenesis. 1994 Nov;15(11):2429-33 [7955086] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Candida glabrata erg1 mutant with increased sensitivity to azoles and to low oxygen tension. AN - 66642713; 15215098 AB - A Candida glabrata erg1 (Cgerg1) mutant, CgTn201S, was identified by transposon mutagenesis and by increased fluconazole susceptibility. CgERG1 encodes a 489-amino-acid protein which, on the basis of its homology with Saccharomyces cerevisiae ERG1, is a squalene epoxidase essential for ergosterol synthesis. Interruption following codon 475 of CgErg1p decreased the ergosterol content by 50%; caused accumulation of the squalene precursor; increased the levels of susceptibility to fluconazole, itraconazole, and terbinafine; increased the level of resistance to amphotericin B; increased the levels of rhodamine 6G and [(3)H]-fluconazole uptake; reduced the level of growth; and blocked growth under conditions of low oxygen tension. In addition, CgTn201S efficiently took up exogenous cholesterol from cholesterol-containing serum. Cholesterol constituted 34% of the extractable sterols in CgTn201S when it was grown aerobically on serum-containing medium. Under the same conditions, C. albicans contained only 0.1 to 1.2% cholesterol. Exogenous sterols also restored growth under conditions of low oxygen tension. Finally, complementation of the Cgerg1 mutation restored the levels of [(3)H]fluconazole uptake and drug susceptibility to wild-type levels. JF - Antimicrobial agents and chemotherapy AU - Tsai, Huei-Fung AU - Bard, Martin AU - Izumikawa, Koichi AU - Krol, Anna A AU - Sturm, Aaron M AU - Culbertson, Nicholas T AU - Pierson, Charles A AU - Bennett, John E AD - Clinical Mycology Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, Clinical Center NIH, Bethesda, MD 20892, USA. Y1 - 2004/07// PY - 2004 DA - July 2004 SP - 2483 EP - 2489 VL - 48 IS - 7 SN - 0066-4804, 0066-4804 KW - Antifungal Agents KW - 0 KW - Azoles KW - DNA Transposable Elements KW - ERG1 Potassium Channel KW - Ether-A-Go-Go Potassium Channels KW - Fluorescent Dyes KW - Potassium Channels KW - Potassium Channels, Voltage-Gated KW - Rhodamines KW - Sterols KW - rhodamine 6G KW - 037VRW83CF KW - Squalene KW - 7QWM220FJH KW - Fluconazole KW - 8VZV102JFY KW - Cholesterol KW - 97C5T2UQ7J KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Squalene -- metabolism KW - Plasmids -- genetics KW - Fluconazole -- pharmacology KW - Fluconazole -- metabolism KW - Cloning, Molecular KW - Phenotype KW - Cholesterol -- metabolism KW - Sterols -- metabolism KW - Drug Resistance, Fungal KW - Genetic Complementation Test KW - DNA Transposable Elements -- genetics KW - Microbial Sensitivity Tests KW - Candida glabrata -- metabolism KW - Candida glabrata -- genetics KW - Antifungal Agents -- pharmacology KW - Azoles -- pharmacology KW - Antifungal Agents -- metabolism KW - Potassium Channels -- genetics KW - Oxygen -- pharmacology KW - Mutation -- genetics KW - Candida glabrata -- drug effects KW - Azoles -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66642713?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Candida+glabrata+erg1+mutant+with+increased+sensitivity+to+azoles+and+to+low+oxygen+tension.&rft.au=Tsai%2C+Huei-Fung%3BBard%2C+Martin%3BIzumikawa%2C+Koichi%3BKrol%2C+Anna+A%3BSturm%2C+Aaron+M%3BCulbertson%2C+Nicholas+T%3BPierson%2C+Charles+A%3BBennett%2C+John+E&rft.aulast=Tsai&rft.aufirst=Huei-Fung&rft.date=2004-07-01&rft.volume=48&rft.issue=7&rft.spage=2483&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 - 2004-09-07 N1 - Date created - 2004-06-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Yeast. 2003 Feb;20(3):249-61 [12557277] Genetics. 1993 Jul;134(3):717-28 [8349105] Biochem Biophys Res Commun. 2003 Sep 26;309(3):666-71 [12963042] Antimicrob Agents Chemother. 2000 Sep;44(9):2411-8 [10952588] Antimicrob Agents Chemother. 2001 Nov;45(11):3037-45 [11600353] Antimicrob Agents Chemother. 2002 Jun;46(6):1723-7 [12019081] EMBO J. 2002 Aug 1;21(15):4114-24 [12145211] Antimicrob Agents Chemother. 2003 Dec;47(12):3890-900 [14638499] Antimicrob Agents Chemother. 2004 May;48(5):1773-7 [15105134] J Gen Microbiol. 1972 Sep;72(2):339-48 [4562308] Gene. 1979 Dec;8(1):17-24 [395030] Antimicrob Agents Chemother. 1995 Aug;39(8):1696-9 [7486903] Antimicrob Agents Chemother. 1995 Dec;39(12):2708-17 [8593007] Yeast. 1996 May;12(6):609-13 [8771716] Gene. 1996 Oct 10;175(1-2):105-8 [8917084] J Bacteriol. 1999 Mar;181(6):1868-74 [10074081] J Antimicrob Chemother. 1999 Jul;44(1):27-31 [10459807] Genome Res. 2003 May;13(5):905-15 [12695329] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modulation of phagocyte apoptosis by bacterial pathogens AN - 20191161; 6024536 AB - Phagocytic leukocytes such as neutrophils and macrophages are essential for the innate immune response against invading bacteria. Binding and ingestion of bacteria by these host cells triggers potent anti-microbial activity, including production of reactive oxygen species. Although phagocytes are highly adept at destroying bacteria, modulation of leukocyte apoptosis or cell death by bacteria has emerged as a mechanism of pathogenesis. Whereas induction of macrophage apoptosis by pathogens may adversely affect the host immune response to infection, acceleration of neutrophil apoptosis following phagocytic interaction with bacteria appears essential for the resolution of infection. This idea is supported by the finding that some bacterial pathogens alter normal phagocytosis-induced neutrophil apoptosis to survive and cause disease. This review summarizes what is currently known about modulation of phagocyte apoptosis by bacteria and describes a paradigm whereby bacteria-induced neutrophil apoptosis plays a role in the resolution of infection. JF - Apoptosis AU - DeLeo AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA., fdeleo@niaid.nih.gov Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 399 EP - 413 PB - Kluwer Academic Publishers VL - 9 IS - 4 SN - 1360-8185, 1360-8185 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Macrophages KW - Bacteria KW - Apoptosis KW - Reactive oxygen species KW - Phagocytes KW - Reviews KW - Leukocytes (neutrophilic) KW - Pathogens KW - Immune response KW - Infection KW - A 01490:Miscellaneous KW - F 06910:Microorganisms & Parasites KW - J 02340:Antibiotics & Antimicrobials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20191161?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Apoptosis&rft.atitle=Modulation+of+phagocyte+apoptosis+by+bacterial+pathogens&rft.au=DeLeo&rft.aulast=DeLeo&rft.aufirst=&rft.date=2004-07-01&rft.volume=9&rft.issue=4&rft.spage=399&rft.isbn=&rft.btitle=&rft.title=Apoptosis&rft.issn=13608185&rft_id=info:doi/10.1023%2FB%3AAPPT.0000031448.64969.fa LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-08-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Macrophages; Apoptosis; Reactive oxygen species; Phagocytes; Reviews; Leukocytes (neutrophilic); Immune response; Pathogens; Infection; Bacteria DO - http://dx.doi.org/10.1023/B:APPT.0000031448.64969.fa ER - TY - JOUR T1 - Hyaluronic Acid Facilitates the Recovery of Hematopoiesis following 5- Fluorouracil Administration AN - 19941986; 5965494 AB - The fate of hematopoietic stem cells (HSCs) is determined by microenvironmental niches, but the molecular structure of these local networks is not yet completely characterized. Our recent observation that glycosaminoglycan hyaluronic acid (HA), a major component of the bone marrow extracellular matrix, is required for in vitro hematopoiesis led us to suggest a role for HA in structuring the hematopoietic niche. Accordingly, HA deprivation induced by various treatments might lead to an imbalance of normal HSC homeostasis. Since 5-fluorouracil (5-FU) administration sharply decreases the amount of cell surface-associated HA in bone marrow, we examined whether the administration of exogenous HA enhances suppressed hematopoiesis in 5-FU-treated mice. HA administered to mice following 5-FU infusion facilitated the recovery of leukocytes and thrombocytes in the peripheral blood. Intravenously infused HA was found in the bone marrow, where it bound endothelial cells and resident macrophages and increased expression of the hematopoiesis-supportive cytokines interleukin-1 and interleukin-6. In agreement with these observations, enhanced hematopoietic activity was detected in the bone marrow, as measured by elevated counts of long-term culture-initiating cells (LTC-ICs), committed progenitors, and the total number of mature bone marrow cells. Overall, our results suggest that HA is required for regulation of the hematopoiesis-supportive function of bone marrow accessory cells and, therefore, participates in hematopoietic niche assembly. JF - Stem Cells AU - Matrosova, Vera Y AU - Orlovskaya, Irina A AU - Serobyan, Naira AU - Khaldoyanidi, Sophia K AD - National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland. Institute for Clinical Immunology, Novosibirsk, Russia Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 544 EP - 555 VL - 22 IS - 4 SN - 1066-5099, 1066-5099 KW - Biotechnology and Bioengineering Abstracts KW - Macrophages KW - Interleukin 6 KW - Hyaluronic acid KW - Accessory cells KW - Interleukin 1 KW - Leukocytes KW - Bone marrow KW - Peripheral blood KW - Homeostasis KW - Endothelial cells KW - Stem cells KW - 5-Fluorouracil KW - Glycosaminoglycans KW - Extracellular matrix KW - Platelets KW - Hemopoiesis KW - W 30920:Tissue Engineering UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19941986?accountid=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=Stem+Cells&rft.atitle=Hyaluronic+Acid+Facilitates+the+Recovery+of+Hematopoiesis+following+5-+Fluorouracil+Administration&rft.au=Matrosova%2C+Vera+Y%3BOrlovskaya%2C+Irina+A%3BSerobyan%2C+Naira%3BKhaldoyanidi%2C+Sophia+K&rft.aulast=Matrosova&rft.aufirst=Vera&rft.date=2004-07-01&rft.volume=22&rft.issue=4&rft.spage=544&rft.isbn=&rft.btitle=&rft.title=Stem+Cells&rft.issn=10665099&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-07-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Interleukin 6; Macrophages; Hyaluronic acid; Leukocytes; Interleukin 1; Accessory cells; Bone marrow; Peripheral blood; Homeostasis; Endothelial cells; Stem cells; Glycosaminoglycans; 5-Fluorouracil; Extracellular matrix; Platelets; Hemopoiesis ER - TY - JOUR T1 - Characterizing polychlorinated dibenzo-p-dioxins and dibenzofurans in the surrounding environment and workplace of a secondary aluminum smelter AN - 19815352; 5929599 AB - This study aims to characterize polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) in the surrounding environment and workplace of a secondary aluminum smelter (secondary ALS). The mean I-TEQ concentrations in the stack flue gases and PCDD/F emission factor of the secondary ALS is 9.02 ng I-TEQ N m super(-3) and 50.1 mu g I-TEQ ton-feedstock super(- 1), respectively. The PCDD/F concentrations of outdoor (site O1, O2 and O3) and workplace air (site W1) during operation period are 0.670, 0.284, 0.141 and 0.571 pg I-TEQ N m super(-3), which are 3.3-, 2.1-, 1.8- and 2.5-fold higher than that during no operation period. The highest PCDD/F air concentrations (2.26 pg I-TEQ N-m super(-3)) were measured at site W2 during furnace maintenance. The elevated PCDD/F air concentration (2.26 pg I-TEQ N m super(-3)) caused by the fugitive particle during furnace maintenance implies that the PCDD/F concentration of air in the furnace that worker breathe could be extremely high. It reveals that PCDD/F exposure of furnace maintenance workers may be serious and further research on occupational exposure needs to be conducted. JF - Atmospheric Environment AU - Chen, S-J AU - Lee, W-S AU - Chang-Chien, G-P AU - Wang, L-C AU - Lee, W-J AU - Kao, J-H AU - Hu, M-TM-T AD - Department of Environmental Engineering and Science, National Pingtung University of Science and Technology, Nei Pu 91207, Ping Tung, Taiwan, ROC, guoping@csu.edu.tw Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 3729 EP - 3732 PB - Elsevier Science B.V., P.O. Box 211 Amsterdam 1000 AE Netherlands, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl/] VL - 38 IS - 22 SN - 1352-2310, 1352-2310 KW - Toxicology Abstracts; Meteorological & Geoastrophysical Abstracts; Pollution Abstracts; Health & Safety Science Abstracts KW - Dioxin KW - Secondary aluminum smelter KW - Workplace KW - Furnace maintenance KW - Polychlorinated dibenzofurans in atmosphere KW - Atmospheric pollution effects on health KW - Aluminum deposition KW - Flue gas KW - Polychlorinated dibenzofurans KW - Stack emissions KW - Smelters KW - Air pollution KW - Workers KW - Amyotrophic lateral sclerosis KW - Gases KW - Dibenzofuran KW - Aluminum KW - PCDF KW - Emission measurements KW - Dibenzo-p-dioxin KW - Polychlorinated dibenzo-p-dioxins in atmosphere KW - PCDD KW - Occupational exposure KW - H 3000:Environment and Ecology KW - M2 551.510.42:Air Pollution (551.510.42) KW - P 0000:AIR POLLUTION KW - X 24360:Metals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19815352?accountid=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=Atmospheric+Environment&rft.atitle=Characterizing+polychlorinated+dibenzo-p-dioxins+and+dibenzofurans+in+the+surrounding+environment+and+workplace+of+a+secondary+aluminum+smelter&rft.au=Chen%2C+S-J%3BLee%2C+W-S%3BChang-Chien%2C+G-P%3BWang%2C+L-C%3BLee%2C+W-J%3BKao%2C+J-H%3BHu%2C+M-TM-T&rft.aulast=Chen&rft.aufirst=S-J&rft.date=2004-07-01&rft.volume=38&rft.issue=22&rft.spage=3729&rft.isbn=&rft.btitle=&rft.title=Atmospheric+Environment&rft.issn=13522310&rft_id=info:doi/10.1016%2Fj.atmosenv.2004.02.051 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2004-08-01 N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Workers; Gases; Amyotrophic lateral sclerosis; Dibenzofuran; Aluminum; Dibenzo-p-dioxin; Polychlorinated dibenzofurans; Smelters; Occupational exposure; Polychlorinated dibenzofurans in atmosphere; Atmospheric pollution effects on health; Aluminum deposition; Polychlorinated dibenzo-p-dioxins in atmosphere; Air pollution; Emission measurements; PCDF; Flue gas; Stack emissions; PCDD DO - http://dx.doi.org/10.1016/j.atmosenv.2004.02.051 ER - TY - JOUR T1 - Development of a Multispecies Oral Bacterial Community in a Saliva-Conditioned Flow Cell AN - 18050885; 5963425 AB - Microbial communities within the human oral cavity are dynamic associations of more than 500 bacterial species that form biofilms on the soft and hard tissues of the mouth. Understanding the development and spatial organization of oral biofilms has been facilitated by the use of in vitro models. We used a saliva-conditioned flow cell, with saliva as the sole nutritional source, as a model to examine the development of multispecies biofilm communities from an inoculum containing the coaggregation partners Streptococcus gordonii, Actinomyces naeslundii, Veillonella atypica, and Fusobacterium nucleatum. Biofilms inoculated with individual species in a sequential order were compared with biofilms inoculated with coaggregates of the four species. Our results indicated that flow cells inoculated sequentially produced biofilms with larger biovolumes compared to those biofilms inoculated with coaggregates. Individual- species biovolumes within the four-species communities also differed between the two modes of inoculation. Fluorescence in situ hybridization with genus- and species-specific probes revealed that the majority of cells in both sequentially and coaggregate-inoculated biofilms were S. gordonii, regardless of the inoculation order. However, the representation of A. naeslundii and V. atypica was significantly higher in biofilms inoculated with coaggregates compared to sequentially inoculated biofilms. Thus, these results indicate that the development of multispecies biofilm communities is influenced by coaggregations preformed in planktonic phase. Coaggregating bacteria such as certain streptococci are especially adapted to primary colonization of saliva- conditioned surfaces independent of the mode of inoculation and order of addition in the multispecies inoculum. Preformed coaggregations favor other bacterial strains and may facilitate symbiotic relationships. JF - Applied and Environmental Microbiology AU - Foster, Jamie S AU - Kolenbrander, Paul E AD - Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 4340 EP - 4348 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 70 IS - 7 SN - 0099-2240, 0099-2240 KW - streptococci KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Ecology Abstracts KW - Colonization KW - Veillonella atypica KW - Community composition KW - Symbiosis KW - Streptococcus gordonii KW - Biofilms KW - Saliva KW - Actinomyces naeslundii KW - Fusobacterium nucleatum KW - Plankton KW - Oral cavity KW - A 01116:Bacteria KW - D 04620:Microorganisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18050885?accountid=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=Applied+and+Environmental+Microbiology&rft.atitle=Development+of+a+Multispecies+Oral+Bacterial+Community+in+a+Saliva-Conditioned+Flow+Cell&rft.au=Foster%2C+Jamie+S%3BKolenbrander%2C+Paul+E&rft.aulast=Foster&rft.aufirst=Jamie&rft.date=2004-07-01&rft.volume=70&rft.issue=7&rft.spage=4340&rft.isbn=&rft.btitle=&rft.title=Applied+and+Environmental+Microbiology&rft.issn=00992240&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-05-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Colonization; Community composition; Symbiosis; Saliva; Biofilms; Oral cavity; Plankton; Veillonella atypica; Streptococcus gordonii; Actinomyces naeslundii; Fusobacterium nucleatum ER - TY - JOUR T1 - Evaluation of the Safety, Immunogenicity, and Protective Efficacy of Whole Inactivated Simian Immunodeficiency Virus (SIV) Vaccines with Conformationally and Functionally Intact Envelope Glycoproteins AN - 18046694; 6016301 AB - A novel, general approach to chemical inactivation of retroviruses was used to produce inactivated simian immunodeficiency virus (SIV) particles with functional envelope glycoproteins. Inactivated virions of three different virus isolates (SIVmne E11S, SIVmac239, and SIVmac239 g4,5), prepared by treatment with 2,2'dithiodipyridine (aldrithol-2, AT-2), were not detectably infectious, in vitro or in vivo. Immunization of pigtailed macaques with inactivated SIVmne E11S particles, without adjuvant, induced both humoral and cellular immune responses. Four of six animals immunized with the inactivated particles did not show measurable SIV RNA in plasma (<100 copy Eq/ml) following intravenous challenge with pathogenic, homologous virus (SIVmne E11S), compared to peak values of greater than or equal to 10 super(6) copy Eq/ml in challenged SIV-naive control animals (p = 0.0001). Despite the absence of measurable viral RNA in plasma in these animals, culturable virus and viral DNA were initially detectable in blood and lymph node specimens; in contrast to control animals, SIV DNA could no longer be detected in PBMC by 10 weeks postchallenge in five of six SIV-immunized animals (p = 0.0001). However, vaccines did not resist a sequential rechallenge with the heterologous pathogenic virus SIVsm E660. AT-2-inactivated virus with functional envelope glycoproteins is a novel class of vaccine immunogen and was noninfectious, under conditions of rigorous in vivo challenge, and induced both binding and neutralizing antibody responses, along with cellular immune responses. Results suggest that immunization facilitated effective containment of pathogenic homologous challenge virus. With further optimization, AT-2-inactivated viral particles may be a useful class of immunogen in the development of a vaccine to prevent AIDS. JF - AIDS Research and Human Retroviruses AU - Lifson, J D AU - Rossio, J L AU - Piatak, M Jr AU - Bess, J Jr AU - Chertova, E AU - Schneider, D K AU - Coalter, V J AU - Poore, B AU - Kiser, R F AU - Imming, R J AU - Scarzello, A J AU - Henderson, LE AU - Alvord, W G AU - Hirsch, V M AD - AIDS Vaccine Program, SAIC Frederick, National Cancer Institute-Frederick, Building 535, Fifth Floor, Frederick, MD 21702, USA, lifson@ncifcrf.gov Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 772 EP - 787 VL - 20 IS - 7 SN - 0889-2229, 0889-2229 KW - immunogenicity KW - aldrithol-2 KW - SIV KW - Pigtail Macaque KW - 2,2'dithiodipyridine KW - Health & Safety Science Abstracts; Immunology Abstracts; Virology & AIDS Abstracts KW - Virions KW - Acquired immune deficiency syndrome KW - vaccines KW - Macaca nemestrina KW - Adjuvants KW - immunization KW - Envelopes KW - Glycoproteins KW - Immune response (humoral) KW - Plasma KW - Lymph nodes KW - Immunization KW - Antibodies KW - Immune response (cell-mediated) KW - Immunogenicity KW - Immune response KW - Vaccines KW - Side effects KW - Simian immunodeficiency virus KW - F 06807:Active immunization KW - V 22003:AIDS: Immunological aspects KW - F 06856:Animal KW - H 4000:Food and Drugs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18046694?accountid=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=AIDS+Research+and+Human+Retroviruses&rft.atitle=Evaluation+of+the+Safety%2C+Immunogenicity%2C+and+Protective+Efficacy+of+Whole+Inactivated+Simian+Immunodeficiency+Virus+%28SIV%29+Vaccines+with+Conformationally+and+Functionally+Intact+Envelope+Glycoproteins&rft.au=Lifson%2C+J+D%3BRossio%2C+J+L%3BPiatak%2C+M+Jr%3BBess%2C+J+Jr%3BChertova%2C+E%3BSchneider%2C+D+K%3BCoalter%2C+V+J%3BPoore%2C+B%3BKiser%2C+R+F%3BImming%2C+R+J%3BScarzello%2C+A+J%3BHenderson%2C+LE%3BAlvord%2C+W+G%3BHirsch%2C+V+M&rft.aulast=Lifson&rft.aufirst=J&rft.date=2004-07-01&rft.volume=20&rft.issue=7&rft.spage=772&rft.isbn=&rft.btitle=&rft.title=AIDS+Research+and+Human+Retroviruses&rft.issn=08892229&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Simian immunodeficiency virus; Macaca nemestrina; Side effects; vaccines; immunization; Acquired immune deficiency syndrome; Vaccines; Immune response (cell-mediated); Immune response (humoral); Glycoproteins; Envelopes; Immune response; Immunization; Plasma; Immunogenicity; Lymph nodes; Adjuvants; Antibodies; Virions ER - TY - JOUR T1 - Another Look at Heavy Episodic Drinking and Alcohol Use Disorders among College and Noncollege Youth AN - 18046249; 6020569 AB - To estimate rates of heavy episodic drinking, alcohol abuse and alcohol dependence among U.S. adults 18-29 years of age and determine the relationship of these rates to student status and residence. The analysis is based on data from a subsample of U.S. adults 18-29 years of age (N = 8,666; 4,849 female) who were interviewed as part of the 2001-02 National Epidemiologic Survey on Alcohol and Related Conditions (N = 43,093). Data were collected in personal interviews from a representative sample of adults 18 and older, living in households and selected group quarters in the United States, including Alaska, Hawaii and the District of Columbia. Of all adults 18-29 years of age, 73.1% reported any drinking in the past year, 39.6% reported any heavy episodic drinking, 21.1% reported heavy drinking more than once a month and 11.0% reported heavy drinking more than once a week. Among past-year drinkers, these correspond to rates of 54.3% for any heavy episodic drinking, 28.9% for heavy drinking more than once a month and 15.0% for heavy drinking more than once a week. Although rates of heavy episodic drinking were slightly higher for college students than for noncollege students (p < .01), differences according to place of residence were greater than differences according to student status. Overall, 7.0% of adults ages 18-29 met the DSM-IV criteria for alcohol abuse in the past year, and 9.2% met the criteria for alcohol dependence. The prevalence of abuse was highest among students living off campus (p < .01), and rates of dependence were highest among students living on campus (p < .01). Heavy episodic drinking and alcohol use disorders are youth as well as college phenomena. Prevention campaigns targeted at all youth are needed to supplement interventions conducted at the campus level. JF - Journal of Studies on Alcohol AU - Dawson, DA AU - Grant, B F AU - Stinson, F S AU - Chou, P S AD - NIAAA/LEB, 5635 Fishers Lane, Room 3083, MSC 9304, Bethesda, MD 20892-9304, USA, ddawson@willco.niaaa.nih.gov Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 477 EP - 488 VL - 65 IS - 4 SN - 0096-882X, 0096-882X KW - Physical Education Index KW - Alcohol KW - College students KW - Interviews KW - Youth KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18046249?accountid=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+Studies+on+Alcohol&rft.atitle=Another+Look+at+Heavy+Episodic+Drinking+and+Alcohol+Use+Disorders+among+College+and+Noncollege+Youth&rft.au=Dawson%2C+DA%3BGrant%2C+B+F%3BStinson%2C+F+S%3BChou%2C+P+S&rft.aulast=Dawson&rft.aufirst=DA&rft.date=2004-07-01&rft.volume=65&rft.issue=4&rft.spage=477&rft.isbn=&rft.btitle=&rft.title=Journal+of+Studies+on+Alcohol&rft.issn=0096882X&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Alcohol; Youth; College students; Interviews ER - TY - JOUR T1 - Irreversible Ototoxicity Associated with Difluoromethylornithine AN - 18020213; 5968840 AB - Difluoromethylornithine (DFMO) is a potent, irreversible inhibitor of ornithine decarboxylase, the rate-limiting enzyme in the synthesis of polyamines that promote cellular proliferation. DFMO has been tested as a potential cancer therapeutic and chemopreventive agent in clinical trials. Reversible hearing loss is a recognized toxicity of DFMO that usually occurs at doses above 2 g/m super(2)/d, and generally when the cumulative dose exceeds 250 g/m super(2). In a recently completed Barrett's esophagus chemoprevention trial, a participant developed a 15-dB decrease in hearing at frequencies of 250, 2,000, and 3,000 Hz in the right ear and a =>20-dB decrease in hearing at 4,000 to 6,000 Hz in the left ear after taking 0.5 g/m super(2)/d DFMO for approximately 13 weeks (cumulative dose of 45 g/m super(2)). The threshold shifts persisted 7 months after DFMO was discontinued. There was no obvious impact on the participant's clinical hearing, but these findings were consistent with irreversible hearing loss. This is the first case reported of irreversible ototoxicity in a clinical trial participant receiving DFMO and, thus, trial participants should be made aware of this small but important risk. JF - Cancer Epidemiology, Biomarkers & Prevention AU - Lao, Christopher D AU - Backoff, Patricia AU - Shotland, Lawrence I AU - Mccarty, Deborah AU - Eaton, Tracy AU - Ondrey, Frank G AU - Viner, Jaye L AU - Spechler, Stuart Jon AU - Hawk, Ernest T AU - Brenner, Dean E AD - Departments of Internal Medicine and Pharmacology, University of Michigan Medical Center, Ann Arbor, Michigan. Ann Arbor VA Medical Center, Ann Arbor, Michigan. James H. Quillen VA Medical Center, Mountain Home, Tennessee. Dallas VA Medical Center, Dallas, Texas. Department of Otolaryngology, University of Minnesota, Minneapolis, Minnesota. Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 1250 EP - 1252 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 USA, [URL:http://www.aacr.org/] VL - 13 IS - 7 SN - 1055-9965, 1055-9965 KW - Toxicology Abstracts KW - polyamines KW - Ototoxicity KW - Ornithine decarboxylase KW - Barrett's esophagus KW - chemopreventive agents KW - Ear KW - Hearing loss KW - biomarkers KW - Clinical trials KW - Cancer KW - X 24113:Side effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18020213?accountid=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+Epidemiology%2C+Biomarkers+%26+Prevention&rft.atitle=Irreversible+Ototoxicity+Associated+with+Difluoromethylornithine&rft.au=Lao%2C+Christopher+D%3BBackoff%2C+Patricia%3BShotland%2C+Lawrence+I%3BMccarty%2C+Deborah%3BEaton%2C+Tracy%3BOndrey%2C+Frank+G%3BViner%2C+Jaye+L%3BSpechler%2C+Stuart+Jon%3BHawk%2C+Ernest+T%3BBrenner%2C+Dean+E&rft.aulast=Lao&rft.aufirst=Christopher&rft.date=2004-07-01&rft.volume=13&rft.issue=7&rft.spage=1250&rft.isbn=&rft.btitle=&rft.title=Cancer+Epidemiology%2C+Biomarkers+%26+Prevention&rft.issn=10559965&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 - Clinical trials; Cancer; Ear; Ototoxicity; Hearing loss; chemopreventive agents; biomarkers; Barrett's esophagus; polyamines; Ornithine decarboxylase ER - TY - JOUR T1 - The role of Par proteins in the active segregation of the P1 plasmid AN - 18014511; 5966454 AB - The parS centromere-like site promotes active P1 plasmid segregation in the presence of P1 ParA and ParB proteins. At the modest growth rate used here, time-lapse and still photomicroscopy shows that the plasmid copies are clustered as a focus at the Escherichia coli cell centre. Just before cell division, the focus is actively divided and ejects bidirectionally into opposite halves of the dividing cell. In the absence of the wild-type parS binding protein ParB, a focus was formed, but generally did not go to the cell centre. The randomly placed focus did not divide and was inherited by one daughter cell only. In the absence of ParA, foci formed and frequently fixed to the cell centre. However, they failed to divide or eject and were left at the new cell pole of one cell at division. Thus, ParB appears to be required for recognition of the plasmid and its attachment to the cell centre, and ParA is required for focus division and energetic ejection from the cell centre. The ATPase active site mutation, parAK122E, blocked ejection. Mutant parAM314I ejected weakly, and the daughter foci took two generations to reach a new cell centre. This explains the novel alternation of segregation and missegregation in successive generations seen in time-lapse images of this mutant. JF - Molecular Microbiology AU - Li, Y AU - Dabrazhynetskaya, A AU - Youngren, B AU - Austin, S AD - Gene Regulation and Chromosome Biology Laboratory, National Cancer Institute, CCR, NCI-Frederick, Frederick, MD 21702-1201, USA., austin@ncifcrf.gov Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 93 EP - 102 PB - Blackwell Science Ltd VL - 53 IS - 1 SN - 0950-382X, 0950-382X KW - parS gene KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - DNA-binding protein KW - ParB protein KW - Plasmids KW - ParA protein KW - Cell division KW - Segregation KW - Escherichia coli KW - J 02760:Plasmids KW - G 07203:Plasmids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18014511?accountid=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+role+of+Par+proteins+in+the+active+segregation+of+the+P1+plasmid&rft.au=Li%2C+Y%3BDabrazhynetskaya%2C+A%3BYoungren%2C+B%3BAustin%2C+S&rft.aulast=Li&rft.aufirst=Y&rft.date=2004-07-01&rft.volume=53&rft.issue=1&rft.spage=93&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1111%2Fj.1365-2958.2004.04111.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Plasmids; Segregation; ParB protein; DNA-binding protein; Cell division; ParA protein DO - http://dx.doi.org/10.1111/j.1365-2958.2004.04111.x ER - TY - JOUR T1 - Transcriptional and translational regulation of the marRAB multiple antibiotic resistance operon in Escherichia coli AN - 18013166; 5966432 AB - The marRAB multiple antibiotic resistance operon of Escherichia coli is autorepressed by MarR. MarR binds to two palindromic sequences in vitro: site I lies between and overlaps the -35 and -10 hexamers for RNA polymerase binding; site II lies between the transcription start site and the GTG initiation codon of marR. To assess the importance of these sites in vivo, the effects of mutant sites on transcription were analysed using fusions to lacZ in the presence and absence of wild-type MarR. When both sites were wild type, transcription in the derepressed marR-deleted strain was 19-fold that of the wild-type strain; when only site I or site II was wild type, this ratio was reduced to 4.3- and 2.6-fold, respectively, showing that full repression requires both sites, but some repression can occur at one site independently of the other. Translational fusions of the wild-type promoter to lacZ demonstrated that marR translation proceeds at only 4.5% of the transcription rate. Analysis of translational fusions with mutant leader sequences demonstrated that the principal reason for inefficient translation is a weak Shine-Dalgarno (SD) sequence, AGG(G). Although the SD sequence is located within the potential stem-loop structure of site II, no evidence for occlusion of the SD sequence was found in the wild-type strain. However, a single basepair mutation that strengthens the stem-loop structure drastically reduced the translational efficiency. Substitution of ATG for GTG as the initiation codon increased translational efficiency by 50%. Increasing the 5 bp spacing between the SD sequence and the GTG codon by one to four bases reduced the translational efficiency by 50-75%. Inefficient translation of marR may help to sensitize the cell to environmental signals. JF - Molecular Microbiology AU - Martin, R G AU - Rosner, J L AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bldg. 5, Rm 333, National Institutes of Health, Bethesda, MD 20892-0560, USA., rgmartin@helix.nih.gov Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 183 EP - 191 PB - Blackwell Science Ltd VL - 53 IS - 1 SN - 0950-382X, 0950-382X KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - MarR protein KW - Escherichia coli KW - Antibiotic resistance KW - lacZ gene KW - N 14400:General KW - N 14550:General KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18013166?accountid=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=Transcriptional+and+translational+regulation+of+the+marRAB+multiple+antibiotic+resistance+operon+in+Escherichia+coli&rft.au=Martin%2C+R+G%3BRosner%2C+J+L&rft.aulast=Martin&rft.aufirst=R&rft.date=2004-07-01&rft.volume=53&rft.issue=1&rft.spage=183&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1111%2Fj.1365-2958.2004.04080.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Antibiotic resistance; MarR protein; lacZ gene DO - http://dx.doi.org/10.1111/j.1365-2958.2004.04080.x ER - TY - JOUR T1 - Hepatic Effects in Workers Exposed to 2-Methoxy Ethanol AN - 18012169; 5983882 AB - The objective of this study was to investigate the effects of 2-ME on hepatic function in exposed workers. Fifty-three impregnation workers from two copper-clad laminate-manufacturing factories using 2-ME as a solvent were recruited as the exposed group. Another group of 121 lamination workers with indirect exposure to 2-ME was recruited as the comparison group. Environmental monitoring of air 2-ME concentrations and biological monitoring of urine 2-methoxy acetic acid concentrations were performed. Venous blood was collected for blood biochemistry analyses. Liver function examination results showed that the aspartate amino transferase, alanine amino transferase, and gamma -glutamyl transferase in the 2-ME-exposed workers were not significantly different from those in the comparison workers. After adjustment for hepatitis carrier status, gender, body mass index, and duration of employment, no difference were found between exposed and comparison groups. We conclude that 2-ME was not a hepatotoxin. JF - Journal of Occupational and Environmental Medicine AU - Loh, Ching-Hui AU - Shih, Tung-Sheng AU - Hsieh, An-Tsz AU - Chen, Yeong-Hwang AU - Liao, Guo-Dong AU - Liou, Saou-Hsing AD - Department of Public Health, National Defense Medical Center, P.O. Box 90048-509, Nei-Hu, Taipei, Taiwan, 114, Republic of China, shliou@ndmctsgh.edu.tw Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 707 EP - 713 VL - 46 IS - 7 SN - 1076-2752, 1076-2752 KW - 2-methoxy acetic acid KW - 2-methoxy ethanol KW - hepatotoxin KW - man KW - Toxicology Abstracts; Health & Safety Science Abstracts KW - Biochemistry KW - Solvents KW - Alanine transaminase KW - Blood levels KW - Hepatitis KW - gamma -Glutamyltransferase KW - Factories KW - Blood KW - Urine KW - Liver KW - Occupational exposure KW - X 24156:Environmental impact KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18012169?accountid=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+Occupational+and+Environmental+Medicine&rft.atitle=Hepatic+Effects+in+Workers+Exposed+to+2-Methoxy+Ethanol&rft.au=Loh%2C+Ching-Hui%3BShih%2C+Tung-Sheng%3BHsieh%2C+An-Tsz%3BChen%2C+Yeong-Hwang%3BLiao%2C+Guo-Dong%3BLiou%2C+Saou-Hsing&rft.aulast=Loh&rft.aufirst=Ching-Hui&rft.date=2004-07-01&rft.volume=46&rft.issue=7&rft.spage=707&rft.isbn=&rft.btitle=&rft.title=Journal+of+Occupational+and+Environmental+Medicine&rft.issn=10762752&rft_id=info:doi/10.1097%2F01.jom.0000131785.15184.c5 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - gamma -Glutamyltransferase; Hepatitis; Blood; Biochemistry; Liver; Alanine transaminase; Occupational exposure; Factories; Urine; Solvents; Blood levels DO - http://dx.doi.org/10.1097/01.jom.0000131785.15184.c5 ER - TY - JOUR T1 - Replication of a unit-copy plasmid F in the bacterial cell cycle: a replication rate function analysis AN - 18009530; 5960796 AB - For stability, the replication of unit-copy plasmids ought to occur by a highly controlled process. We have characterized the replication dynamics of a unit-copy plasmid F by a replication rate function defined as the probability per unit age interval of the cell cycle that a plasmid will initiate replication. Analysis of baby-machine data by stochastics that make no detailed reference to underlying mechanism revealed that this rate function increased monotonically over the cell cycle with rapid increase near cell division. This feature is highly suggestive of a replication control mechanism that is designed to force most plasmids to replicate before cells undergo division. The replication rate function is developed anew from a mechanistic model incorporating the hypotheses that initiators are limiting and that steric hindrance of origins by handcuffing control initiation of replication. The model is based on correctly folded initiator protein monomers arising from an inactive dimer pool via chaperones in limiting amounts, their random distribution to high affinity sites (iterons) at the origin (ori) and an outside locus (incC), the statistical mechanics of bound monomer participation in pairing the two loci (cis-handcuffing), and initiation probability as proportional to the number of non-handcuffed ori-saturated plasmids. Provided cis-handcuffing is present, this model closely accounts for the shape of the replication rate function derived from experiment, and reproduces the observation that replication occurs throughout the cell cycle. Present concepts of iteron-based molecular mechanisms thus appear capable of yielding a quantitative description of unit-copy-number plasmid replication dynamics. JF - Plasmid AU - Morrison, P F AU - Chattoraj, D K AD - Division of Bioengineering and Physical Science, ORS, National Institutes of Health, Bethesda, MD 20892-5766, USA, chattord@dc37a.nci.nih.gov Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 13 EP - 30 VL - 52 IS - 1 SN - 0147-619X, 0147-619X KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - Replication KW - Cell cycle KW - Plasmids KW - Copy number control KW - J 02760:Plasmids KW - G 07203:Plasmids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18009530?accountid=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=Replication+of+a+unit-copy+plasmid+F+in+the+bacterial+cell+cycle%3A+a+replication+rate+function+analysis&rft.au=Morrison%2C+P+F%3BChattoraj%2C+D+K&rft.aulast=Morrison&rft.aufirst=P&rft.date=2004-07-01&rft.volume=52&rft.issue=1&rft.spage=13&rft.isbn=&rft.btitle=&rft.title=Plasmid&rft.issn=0147619X&rft_id=info:doi/10.1016%2Fj.plasmid.2004.04.001 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Plasmids; Replication; Copy number control; Cell cycle DO - http://dx.doi.org/10.1016/j.plasmid.2004.04.001 ER - TY - JOUR T1 - Small RNAs Shed Some Light AN - 18005869; 5978657 AB - Small regulatory RNAs can act by pairing with their target messages, targeting themselves and the mRNA for degradation; Lenz et al. (this issue of Cell) now report that multiple small RNAs are essential regulators of the quorum-sensing systems of Vibrio species, including the regulation of virulence in V. cholerae. JF - Cell AU - Gottesman, S AD - Laboratory of Molecular Biology, National Cancer Institute, Bethesda, MD 20892, USA, susang@helix.nih.gov Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 1 EP - 2 PB - Cell Press, 1100 Massachusetts Avenue Cambridge MA 02138 USA, [mailto:subs@cell.com], [URL:http://www.cellpress.com] VL - 118 IS - 1 SN - 0092-8674, 0092-8674 KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Virulence KW - Vibrio cholerae KW - quorum sensing KW - mRNA KW - J 02726:RNA and ribosomes KW - N 14540:Structure, sequence & physical properties UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18005869?accountid=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=Cell&rft.atitle=Small+RNAs+Shed+Some+Light&rft.au=Gottesman%2C+S&rft.aulast=Gottesman&rft.aufirst=S&rft.date=2004-07-01&rft.volume=118&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Cell&rft.issn=00928674&rft_id=info:doi/10.1016%2Fj.cell.2004.06.024 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Vibrio cholerae; mRNA; quorum sensing; Virulence DO - http://dx.doi.org/10.1016/j.cell.2004.06.024 ER - TY - JOUR T1 - Brain hyperthermia induced by MDMA ('ecstasy'): modulation by environmental conditions AN - 17995684; 5966543 AB - Drugs of abuse, such as 3,4-methylenedioxymethamphetamine (MDMA), often have more powerful effects during states of increased activation and under specific environmental conditions. Because hyperthermia is a major complication of MDMA use and a factor potentiating neurotoxicity, we examined the effects of this drug (9 mg/kg, sc; approximately one-fifth of the known LD sub(50) in rats) on brain [nucleus accumbens (Nacc) and hippocampus (Hippo)] and muscle (musculus temporalis) temperatures in male rats under conditions that either model human drug use (social interaction with female, warm temperature) or restrict heat dissipation from the brain (chronic occlusion of jugular veins). Under quiet resting conditions at 23 degree C, MDMA induced a moderate but prolonged hyperthermia. Both NAcc and Hippo showed more rapid and stronger temperature increases than muscle, suggesting metabolic neural activation as a primary cause of brain hyperthermia. During social interaction with a female, brain hyperthermia induced by MDMA was significantly potentiated (+89%). Brain hyperthermia induced by MDMA was also strongly potentiated (+188%) in animals with chronically occluded jugular veins, suggesting impaired cerebral outflow enhances intrabrain heat accumulation. At 29 degree C, MDMA pushed temperatures in the brain to its biological limits (>41 degree C; +268%), resulting in fatalities in most (83%) tested animals. Therefore, by inducing metabolic brain activation and restricting heat dissipation, MDMA use under 'party' conditions may be much more dangerous than under standard laboratory conditions. JF - European Journal of Neuroscience AU - Brown, P L AU - Kiyatkin, E A AD - Behavioural Neuroscience Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Department of Health and Human Services, 5500 Nathan Shock Drive, Baltimore, Maryland 21224, USA, ekiyatki@intra.nida.nih.gov Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 51 EP - 58 PB - Blackwell Science Ltd VL - 20 IS - 1 SN - 0953-816X, 0953-816X KW - rats KW - Toxicology Abstracts KW - Temperature effects KW - Nucleus accumbens KW - Hyperthermia KW - Environments KW - Hippocampus KW - Neurotoxicity KW - Muscles KW - Brain KW - MDMA KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17995684?accountid=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=European+Journal+of+Neuroscience&rft.atitle=Brain+hyperthermia+induced+by+MDMA+%28%27ecstasy%27%29%3A+modulation+by+environmental+conditions&rft.au=Brown%2C+P+L%3BKiyatkin%2C+E+A&rft.aulast=Brown&rft.aufirst=P&rft.date=2004-07-01&rft.volume=20&rft.issue=1&rft.spage=51&rft.isbn=&rft.btitle=&rft.title=European+Journal+of+Neuroscience&rft.issn=0953816X&rft_id=info:doi/10.1111%2Fj.0953-816X.2004.03453.x LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Temperature effects; Nucleus accumbens; Hyperthermia; Environments; Hippocampus; Neurotoxicity; Brain; Muscles; MDMA DO - http://dx.doi.org/10.1111/j.0953-816X.2004.03453.x ER - TY - JOUR T1 - Conformational stability and domain coupling in D-glucose/D-galactose-binding protein from Escherichia coli AN - 17850753; 6091457 AB - The monomeric D-glucose/D-galactose-binding protein (GGBP) from Escherichia coli (M sub(r) 33000) is a periplasmic protein that serves as a high-affinity receptor for the active transport and chemotaxis towards both sugars. The effect of D-glucose binding on the thermal unfolding of the GGBP protein at pH 7.0 has been measured by differential scanning calorimetry (DSC), far-UV CD and intrinsic tryptophanyl residue fluorescence (Trp fluorescence). All three techniques reveal reversible, thermal transitions and a midpoint temperature (T sub(m)) increase from 50 to 63 degree C produced by 10 mM D-glucose. Both in the absence and presence of D-glucose a single asymmetric endotherm for GGBP is observed in DSC, although each endotherm consists of two transitions about 4 degree C apart in T sub(m) values. In the absence of D-glucose, the protein unfolding is best described by two non-ideal transitions, suggesting the presence of unfolding intermediates. In the presence of D-glucose protein, unfolding is more co-operative than in the absence of the ligand, and the experimental data are best fitted to a model that assumes two ideal (two-state) sequential transitions. Thus D-glucose binding changes the character of the GGBP protein folding/unfolding by linking the two domains such that protein unfolding becomes a cooperative, two two-state process. A K sub(A) value of 5.6x10 super(6) M super(-1) at 63 degree C for D-glucose binding is estimated from DSC results. The domain with the lower stability in DSC measurements has been identified as the C-terminal domain of GGBP from thermally induced Trp fluorescence changes. JF - Biochemical Journal AU - Piszczek, G AU - D'Auria, S AU - Staiano, M AU - Rossi, M AU - Ginsburg, A AD - Section on Protein Chemistry, Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-8012, USA, grzegorz_piszczek@nih.gov Y1 - 2004/07/01/ PY - 2004 DA - 2004 Jul 01 SP - 97 EP - 103 VL - 381 IS - 1 SN - 0264-6021, 0264-6021 KW - Microbiology Abstracts B: Bacteriology KW - Temperature effects KW - Sugar KW - Fluorescence KW - Protein folding KW - Glucose KW - Escherichia coli KW - Active transport KW - Chemotaxis KW - Differential scanning calorimetry KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17850753?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+Journal&rft.atitle=Conformational+stability+and+domain+coupling+in+D-glucose%2FD-galactose-binding+protein+from+Escherichia+coli&rft.au=Piszczek%2C+G%3BD%27Auria%2C+S%3BStaiano%2C+M%3BRossi%2C+M%3BGinsburg%2C+A&rft.aulast=Piszczek&rft.aufirst=G&rft.date=2004-07-01&rft.volume=381&rft.issue=1&rft.spage=97&rft.isbn=&rft.btitle=&rft.title=Biochemical+Journal&rft.issn=02646021&rft_id=info:doi/10.1042%2FBJ20040232 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Glucose; Protein folding; Fluorescence; Differential scanning calorimetry; Active transport; Temperature effects; Chemotaxis; Sugar DO - http://dx.doi.org/10.1042/BJ20040232 ER - TY - JOUR T1 - Potential use of procalcitonin as a diagnostic criterion in febrile neutropenia: experience from a multicentre study AN - 17788197; 5966871 AB - In order to assess the diagnostic value of procalcitonin, 158 patients with febrile neutropenia from centres across Europe were studied. Patients with fever were diagnosed on the basis of either: (1) clinical, radiological and microbiological criteria; or (2) the procalcitonin value. In the latter case, concentrations of 0.5-1.0 ng/mL were considered diagnostic of localised infection, concentrations of 1.0-5.0 ng/mL of bacteraemia, and concentrations of > 5.0 ng/mL of severe sepsis. Procalcitonin and C-reactive protein were estimated daily in serum by immunochemiluminescence and nephelometry, respectively. Overall, the sensitivity (specificity) of procalcitonin for bacteraemia was 44.2% (64.3%) at concentrations of 1.0-5.0 ng/mL, and 83.3% (100%) for severe sepsis at concentrations of > 5.0 ng/mL. It was concluded that procalcitonin is a marker strongly suggestive of severe sepsis at concentrations of > 5.0 ng/mL. Estimated concentrations of < 0.5 ng /mL indicate that infection is unlikely, but it was observed that bacteraemia associated with coagulase-negative staphylococci may fail to elevate serum procalcitonin levels. JF - Clinical Microbiology and Infection AU - Giamarellou, H AU - Giamarellos-Bourboulis, E J AU - Repoussis, P AU - Galani, L AU - Anagnostopoulos, N AU - Grecka, P AU - Lubos, D AU - Aoun, M AU - Athanassiou, K AU - Bouza, E AU - Devigili, E AU - Krcmery, V AU - Menichetti, F AU - Panaretou, E AU - Papageorgiou, E AU - Plachouras, D AD - 4th Department of Internal Medicine, Athens Medical School, Department of Haematology, Pireas Metaxa Hospital, Department of Haematology, Athens General Hospital G. Gennimatas, Athens, Greece, Department of Internal Medicine, National Cancer Institute, Bratislava, Slovakia, Department of Infectious Diseases, Institut J. Bordet, Bruxelles, Belgium, Hospital 'Gregorio Maranon', Madrid, Spain, Ospedale Generale Regionale, Centro Trapianti Di Midollo Osseo, Bolzano, Azienda Ospedaliera Pisana, UO Malattie Cisanelo, Pisa, Italy and Department of Haematology, Athens Hospital Evangelismos, Athens, Greece, giamarel@internet.gr Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 628 EP - 633 PB - Blackwell Science Ltd VL - 10 IS - 7 SN - 1198-743X, 1198-743X KW - Microbiology Abstracts B: Bacteriology KW - Fever KW - Nephelometry KW - Neutropenia KW - Sepsis KW - Bacteremia KW - procalcitonin KW - Infection KW - C-reactive protein KW - J 02855:Human Bacteriology: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17788197?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Microbiology+and+Infection&rft.atitle=Potential+use+of+procalcitonin+as+a+diagnostic+criterion+in+febrile+neutropenia%3A+experience+from+a+multicentre+study&rft.au=Giamarellou%2C+H%3BGiamarellos-Bourboulis%2C+E+J%3BRepoussis%2C+P%3BGalani%2C+L%3BAnagnostopoulos%2C+N%3BGrecka%2C+P%3BLubos%2C+D%3BAoun%2C+M%3BAthanassiou%2C+K%3BBouza%2C+E%3BDevigili%2C+E%3BKrcmery%2C+V%3BMenichetti%2C+F%3BPanaretou%2C+E%3BPapageorgiou%2C+E%3BPlachouras%2C+D&rft.aulast=Giamarellou&rft.aufirst=H&rft.date=2004-07-01&rft.volume=10&rft.issue=7&rft.spage=628&rft.isbn=&rft.btitle=&rft.title=Clinical+Microbiology+and+Infection&rft.issn=1198743X&rft_id=info:doi/10.1111%2Fj.1469-0691.2004.00883.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - procalcitonin; Bacteremia; Sepsis; Infection; Neutropenia; Nephelometry; Fever; C-reactive protein DO - http://dx.doi.org/10.1111/j.1469-0691.2004.00883.x ER - TY - JOUR T1 - Comparison of methods to assess change in children's body composition AN - 17704277; 5956508 AB - Background: Little is known about how simpler and more available methods to measure change in body fatness compare with criterion methods such as dual-energy X-ray absorptiometry (DXA) in children. Objective: Our objective was to determine the ability of air-displacement plethysmography (ADP) and formulas based on triceps skinfold thickness (TSF) and bioelectrical impedance analysis (BIA) to estimate changes in body fat over time in children. Design: Eighty-six nonoverweight and overweight boys (n = 34) and girls (n = 52) with an average age of 11.0 plus or minus 2.4 y underwent ADP, TSF measurement, BIA, and DXA to estimate body fatness at baseline and 1 plus or minus 0.3 y later. Recent equations were used to estimate percentage body fat by TSF measurement (Dezenberg equation) and by BIA (Suprasongsin and Lewy equations). Percentage body fat estimates by ADP, TSF measurement, and BIA were compared with those by DXA. Results: All methods were highly correlated with DXA (P < 0.001). No mean bias for estimates of percentage body fat change was found for ADP (Siri equation) compared with DXA for all subjects examined together, and agreement between body fat estimation by ADP and DXA did not vary with race or sex. Magnitude bias was present for ADP relative to DXA (P < 0.01). Estimates of change in percentage body fat were systematically overestimated by BIA equations (1.37 plus or minus 6.98%; P < 0.001). TSF accounted for only 13% of the variance in percentage body fat change. Conclusion: Compared with DXA, there appears to be no noninvasive and simple method to measure changes in children's percentage body fat accurately and precisely, but ADP performed better than did TSF or BIA. ADP could prove useful for measuring changes in adiposity in children. JF - American Journal of Clinical Nutrition AU - Elberg, J AU - McDuffie, J R AU - Sebring, NG AU - Salaita, C AU - Keil, M AU - Robotham, D AU - Reynolds, J C AU - Yanovski, JA AD - Unit on Growth and Obesity, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, and the Nutrition Department and the Department of Nuclear Medicine, Warren Magnuson Clinical Center, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 64 EP - 69 VL - 80 IS - 1 SN - 0002-9165, 0002-9165 KW - Physical Education Index KW - Obesity KW - Scanning KW - Nutrition (effects) KW - Body composition KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17704277?accountid=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+Clinical+Nutrition&rft.atitle=Comparison+of+methods+to+assess+change+in+children%27s+body+composition&rft.au=Elberg%2C+J%3BMcDuffie%2C+J+R%3BSebring%2C+NG%3BSalaita%2C+C%3BKeil%2C+M%3BRobotham%2C+D%3BReynolds%2C+J+C%3BYanovski%2C+JA&rft.aulast=Elberg&rft.aufirst=J&rft.date=2004-07-01&rft.volume=80&rft.issue=1&rft.spage=64&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Clinical+Nutrition&rft.issn=00029165&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Nutrition (effects); Body composition; Scanning; Obesity ER - TY - JOUR T1 - Inhibition of Mycobacterium tuberculosis AhpD, an Element of the Peroxiredoxin Defense against Oxidative Stress AN - 17700637; 5949423 AB - The resistance of Mycobacterium tuberculosis to isoniazid (INH) is largely linked to suppression of a catalase-peroxidase enzyme (KatG) that activates INH. In the absence of KatG, antioxidant protection is provided by enhanced expression of the peroxiredoxin AhpC, which is itself reduced by AhpD, a protein with low alkylhydroperoxidase activity of its own. Inhibition of AhpD might therefore impair the antioxidant protection afforded by AhpC and make KatG- negative strains more sensitive to oxidative stress. We report here that the 3(E),17-dioxime of testosterone is a potent competitive AhpD inhibitor, with a K sub(i) of 50 +/- 2 nM. The inhibitor is stereospecific, in that the 3(E) but not 3(Z) isomer is active. Computational studies provide support for a proposed AhpD substrate binding site. However, the inhibitor does not completely suppress the in vitro activity of AhpC/AhpD, because a low titer of AhpD suffices to maintain AhpC activity. This finding, and the low solubility of the inhibitor, explains its inability to suppress the growth of INH-resistant M. tuberculosis in infected mouse lungs. JF - Antimicrobial Agents & Chemotherapy AU - Koshkin, Aleksey AU - Zhou, Xiao-Ti AU - Kraus, Carl N AU - Brenner, Jason M AU - Bandyopadhyay, Pradipta AU - Kuntz, Irwin D AU - Barry, Clifton E AU - Ortiz De Montellano, Paul R AD - Department of Pharmaceutical Chemistry, University of California-San Francisco, San Francisco, California 94143-2280. Tuberculosis Research Section, National Institute of Allergy and Infectious Diseases, Rockville, Maryland 20852 Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 2424 EP - 2430 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 48 IS - 7 SN - 0066-4804, 0066-4804 KW - Microbiology Abstracts B: Bacteriology KW - Testosterone KW - Antioxidants KW - Solubility KW - Oxidative stress KW - Lung KW - Peroxiredoxin KW - Tuberculosis KW - Computer applications KW - Mycobacterium tuberculosis KW - Isomers KW - Isoniazid KW - J 02845:Ear, nose and respiratory tract UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17700637?accountid=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=Antimicrobial+Agents+%26+Chemotherapy&rft.atitle=Inhibition+of+Mycobacterium+tuberculosis+AhpD%2C+an+Element+of+the+Peroxiredoxin+Defense+against+Oxidative+Stress&rft.au=Koshkin%2C+Aleksey%3BZhou%2C+Xiao-Ti%3BKraus%2C+Carl+N%3BBrenner%2C+Jason+M%3BBandyopadhyay%2C+Pradipta%3BKuntz%2C+Irwin+D%3BBarry%2C+Clifton+E%3BOrtiz+De+Montellano%2C+Paul+R&rft.aulast=Koshkin&rft.aufirst=Aleksey&rft.date=2004-07-01&rft.volume=48&rft.issue=7&rft.spage=2424&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+Agents+%26+Chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Testosterone; Solubility; Antioxidants; Lung; Oxidative stress; Peroxiredoxin; Tuberculosis; Computer applications; Isoniazid; Isomers; Mycobacterium tuberculosis ER - TY - JOUR T1 - NMR Structural Studies of Domain 1 of Receptor-associated Protein AN - 17688636; 6024344 AB - The 39 kDa receptor-associated protein (RAP) is an endoplasmic reticulum resident protein that binds tightly to the low-density lipoprotein receptor-related protein (LRP) as well as to other members of the low-density lipoprotein receptor superfamily. The association of RAP with LRP prevents this receptor from interacting with ligands. RAP is a three-domain protein that contains two independent LRP binding sites; one located within domains 1 and 2, and one located within domain 3. As the first step toward defining the structure of the full-length protein and understanding the interaction between RAP and this family of receptors, we have determined the 3D structure of domain 1 using constraints derived from heteronuclear multi-dimensional NMR spectra, including NOEs, dihedral angles, J-couplings and chemical shifts, as well as two sets of non-correlated residual dipolar couplings measured from the protein solutions in anisotropic media of Pf1 and 6% polyacrylamide gel. The backbone C sub( alpha ) rmsd between the current structure and a homo-nuclear NOE-based structure is about 2 Aa. The large rmsd mainly reflects the significant differences in helical orientation and in the structural details of the long helix (helix 2) between the two structures. JF - Journal of Biomolecular NMR AU - Wu, Y AU - Migliorini, M AU - Walsh, J AU - Yu, P AU - Strickland, D K AU - Wang, Y AD - Protein-Nucleic Acid Interaction Section, Structural Biophysics Laboratory, National Cancer Institute at Frederick, National Institutes of Health, Frederick, MD 21702, U.S.A. Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 271 EP - 279 PB - Kluwer Academic Publishers VL - 29 IS - 3 SN - 0925-2738, 0925-2738 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/17688636?accountid=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+Biomolecular+NMR&rft.atitle=NMR+Structural+Studies+of+Domain+1+of+Receptor-associated+Protein&rft.au=Wu%2C+Y%3BMigliorini%2C+M%3BWalsh%2C+J%3BYu%2C+P%3BStrickland%2C+D+K%3BWang%2C+Y&rft.aulast=Wu&rft.aufirst=Y&rft.date=2004-07-01&rft.volume=29&rft.issue=3&rft.spage=271&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biomolecular+NMR&rft.issn=09252738&rft_id=info:doi/10.1023%2FB%3AJNMR.0000032507.96325.6d LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-04-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1023/B:JNMR.0000032507.96325.6d ER - TY - JOUR T1 - Measurement and automatic correction of high-order B sub(0) inhomogeneity in the rat brain at 11.7 Tesla AN - 17680198; 5970351 AB - In vivo B sub(0) inhomogeneity in the rat brain at 11.7 Tesla was measured and decomposed up to the fourth-order spherical harmonic terms using an automatic slice shimming routine derived from the FLATNESS method. In vivo shimming of horizontal slices showed that significant improvement in the T sub(2)-weighted echo-planar imaging was achieved after correction of all first-, second- and third-order in-slice shims. For localized proton spectroscopy, reproducible, high quality data were obtained after correcting all first- and second-order shims. The measured high-order in vivo B sub(0) inhomogeneity in terms of spherical harmonic terms should provide a useful guide for designing shims to meet in vivo requirements. JF - Magnetic Resonance Imaging AU - Chen, Z AU - Li, S S AU - Yang, J AU - Letizia, D AU - Shen, J AD - Molecular Imaging Branch, NIMH, National Institute of Health, Bethesda, MD 20892, USA, shenj@intra.nimh.nih.gov Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 835 EP - 842 PB - Elsevier Science Ltd., The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:usinfo-f@elsevier.com], [URL:http://www.elsevier.nl] VL - 22 IS - 6 SN - 0730-725X, 0730-725X KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; CSA Neurosciences Abstracts KW - N3 11021:Neuroimaging techniques KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17680198?accountid=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+Imaging&rft.atitle=Measurement+and+automatic+correction+of+high-order+B+sub%280%29+inhomogeneity+in+the+rat+brain+at+11.7+Tesla&rft.au=Chen%2C+Z%3BLi%2C+S+S%3BYang%2C+J%3BLetizia%2C+D%3BShen%2C+J&rft.aulast=Chen&rft.aufirst=Z&rft.date=2004-07-01&rft.volume=22&rft.issue=6&rft.spage=835&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+Imaging&rft.issn=0730725X&rft_id=info:doi/10.1016%2Fj.mri.2004.01.062 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-06-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/j.mri.2004.01.062 ER - TY - JOUR T1 - Application of the GA/KNN method to SELDI proteomics data AN - 17601247; 5946090 AB - SUMMARY: Proteomics technology has shown promise in identifying biomarkers for disease, toxicant exposure and stress. We show by example that the genetic algorithm/k-nearest neighbors method, developed for mining high-dimensional microarray gene expression data, is also capable of mining surface enhanced laser desorption/ionization-time-of-flight proteomics data. AVAILABILITY: The source code of the program and documentation on how to use it are freely available to non-commercial users at http://dir.niehs.nih.gov/dirbb/lifiles/softlic.htm JF - Bioinformatics AU - Li, Leping AU - Umbach, David M AU - Terry, Paul AU - Taylor, Jack A AD - Biostatistics Branch, Epidemiology Branch and Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA Y1 - 2004/07/01/ PY - 2004 DA - 2004 Jul 01 SP - 1638 EP - 1640 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 - 20 IS - 10 SN - 1367-4803, 1367-4803 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Gene expression KW - Desorption KW - Data processing KW - Toxicants KW - Algorithms KW - Stress KW - Lasers KW - Bioinformatics KW - proteomics KW - biomarkers KW - DNA microarrays 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/17601247?accountid=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+the+GA%2FKNN+method+to+SELDI+proteomics+data&rft.au=Li%2C+Leping%3BUmbach%2C+David+M%3BTerry%2C+Paul%3BTaylor%2C+Jack+A&rft.aulast=Li&rft.aufirst=Leping&rft.date=2004-07-01&rft.volume=20&rft.issue=10&rft.spage=1638&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 - Data processing; proteomics; DNA microarrays; Bioinformatics; biomarkers; Lasers; Toxicants; Gene expression; Algorithms; Desorption; Stress ER - TY - JOUR T1 - The basolateral complex of the amygdala mediates the modulation of intracranial self-stimulation threshold by drug-associated cues AN - 17592217; 5966535 AB - Learning and memory appear to be critical aspects of drug abuse; presumably playing an especially important role in craving and relapse. Thus, understanding the interaction of learning- and memory-related brain areas with the classical reward circuitry is of importance. Toward this goal, the effect of drug-associated contextual cues on intracranial self-stimulation (ICSS) behaviour was assessed in rats. We used a method that allows the establishment of baseline behaviour, the pairing of drug exposure with unique cues, and testing the effect of cue exposure within the same apparatus. ICSS thresholds were decreased by morphine (5 mg /kg, i.p.) or cocaine (10 mg/kg, i.p.) during five days of paired drug-cue training sessions. Subsequent presentation of the drug-associated cues decreased thresholds in the absence of drug. Cues associated with saline had no effect. These results suggest a Pavlovian conditioning phenomenon in which the functioning of brain reward circuitry is modulated by drug-associated cues. In a second experiment, we tested the hypothesis that the mechanism by which conditioning affects ICSS thresholds may include the basolateral complex of the amygdala (BLC) due to its known role in conditioning and anatomical linkage with classical reward circuitry. Lesions of the BLC abolished the ability of cocaine-associated cues to lower ICSS threshold. Lesions did not alter response capability or the unconditioned effect of cocaine. We conclude that the BLC is necessary for cues associated with previous drug exposure to modulate activity within or downstream from the classical reward circuitry of the medial forebrain bundle. JF - European Journal of Neuroscience AU - Hayes, R J AU - Gardner, EL AD - Neuroimaging Research Branch, Intramural Research Program, National Institute on Drug Abuse, 5500 Nathan Shock Dr, Baltimore, Maryland 21224, USA, rhayes@intra.nida.nih.gov Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 273 EP - 280 PB - Blackwell Science Ltd VL - 20 IS - 1 SN - 0953-816X, 0953-816X KW - CSA Neurosciences Abstracts; Toxicology Abstracts KW - X 24180:Social poisons & drug abuse KW - N3 11139:Toxicological and psychoactive drug correlates UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17592217?accountid=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=European+Journal+of+Neuroscience&rft.atitle=The+basolateral+complex+of+the+amygdala+mediates+the+modulation+of+intracranial+self-stimulation+threshold+by+drug-associated+cues&rft.au=Hayes%2C+R+J%3BGardner%2C+EL&rft.aulast=Hayes&rft.aufirst=R&rft.date=2004-07-01&rft.volume=20&rft.issue=1&rft.spage=273&rft.isbn=&rft.btitle=&rft.title=European+Journal+of+Neuroscience&rft.issn=0953816X&rft_id=info:doi/10.1111%2Fj.1460-9568.2004.03463.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2005-08-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1111/j.1460-9568.2004.03463.x ER - TY - JOUR T1 - Physical Activity, Exercise, and Inflammatory Markers in Older Adults: Findings from The Health, Aging and Body Composition Study AN - 17591500; 5965568 AB - To examine the association between physical activity and inflammatory markers, with consideration for body fatness and antioxidant use. Cross-sectional study, using baseline data from the Health, Aging and Body Composition Study. Metropolitan areas surrounding Pittsburgh, Pennsylvania, and Memphis, Tennessee. Black and white, well-functioning men and women (N=3,075), aged 70 to 79. Interviewer-administered questionnaires of previous-week household, walking, exercise, and occupational/volunteer physical activities. Analysis of covariance was used to examine the association between activity level and serum C-reactive protein (CRP), interleukin-6 (IL-6), and plasma tumor necrosis factor alpha (TNF alpha ) with covariate adjustment. Antioxidant supplement use (multivitamin, vitamins E or C, beta carotene) was evaluated as an effect modifier of the association. Higher levels of exercise were associated with lower levels of CRP (P180 min/wk). Adjustment for body fatness attenuated the associations somewhat. Use of antioxidant supplements modified the CRP (P sub(interaction)=.01) and IL-6 (P sub(interaction)=.08) associations such that concentrations were low in those taking supplements (e.g., CRP=1.79-1.84 across exercise levels) and higher in nonsupplement users who did no exercise (2.03) than in those who did the most (1.72). Among nonexercisers, higher levels of other physical activity were related to lower levels of CRP (P<.01) and IL-6 (P=.02) but not TNF alpha (P=.36), even after accounting for body fat. Inflammatory markers are lower in older adults with higher levels of exercise and nonexercise activity and in antioxidant supplement users regardless of exercise level. JF - Journal of the American Geriatrics Society AU - Colbert, L H AU - Visser, M AU - Simonsick, E M AU - Tracy, R P AU - Newman, AB AU - Kritchevsky, S B AU - Pahor, M AU - Taaffe AU - Brach, J AU - Rubin, S AU - Harris, T B AD - From the Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, Maryland; , lhcolbert@education.wisc.edu Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 1098 EP - 1104 PB - Blackwell Science Ltd VL - 52 IS - 7 SN - 0002-8614, 0002-8614 KW - Physical Education Index KW - Antioxidants KW - Blacks KW - Gerontology KW - Surveys KW - Walking KW - Health KW - Analysis KW - Vitamins KW - Dietary supplements KW - Proteins KW - Exercise (effects) KW - Body composition KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17591500?accountid=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+the+American+Geriatrics+Society&rft.atitle=Physical+Activity%2C+Exercise%2C+and+Inflammatory+Markers+in+Older+Adults%3A+Findings+from+The+Health%2C+Aging+and+Body+Composition+Study&rft.au=Colbert%2C+L+H%3BVisser%2C+M%3BSimonsick%2C+E+M%3BTracy%2C+R+P%3BNewman%2C+AB%3BKritchevsky%2C+S+B%3BPahor%2C+M%3BTaaffe%3BBrach%2C+J%3BRubin%2C+S%3BHarris%2C+T+B&rft.aulast=Colbert&rft.aufirst=L&rft.date=2004-07-01&rft.volume=52&rft.issue=7&rft.spage=1098&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Geriatrics+Society&rft.issn=00028614&rft_id=info:doi/10.1111%2Fj.1532-5415.2004.52307.x LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Antioxidants; Dietary supplements; Exercise (effects); Health; Gerontology; Body composition; Vitamins; Walking; Blacks; Analysis; Surveys; Proteins DO - http://dx.doi.org/10.1111/j.1532-5415.2004.52307.x ER - TY - CONF T1 - The LIFE study: A randomized clinical trial of exercise to prevent disability in high-risk older persons AN - 17328250; 6249852 AB - Sarcopenia and frailty in the oldest old population can be self-perpetuating syndromes rapidly leading to the loss of independence, increased falls risk, hospitalization and, ultimately, death. In the past 3 years, results from several randomized controlled trials across the world have demonstrated the feasibility of regular exercise training for the frail older adults, and most of these studies offer convincing evidence that exercise training is effective in reducing the negative correlates of frailty. Despite this positive message, it is still not clear what the most appropriate exercise regime is for the frail older adult, if the beneficial effects of exercise depend on initial levels of frailty, or if an active lifestyle is effective in delaying or preventing the onset of frailty. Exercise studies usually don't address frailty per se, rather the assumption is made that improvements in such variables as strength, endurance and agility will transfer to improved performance of functional tasks associated with daily living. There is good evidence that this transfer does in fact occur, and that a reduction in the incidence of falls can also be expected. A key question though is what happens after a research intervention is over? From the limited literature on detraining effects in the older population, it appears that any gains in physical function attained through a progressive exercise program will be gradually lost if the participants stop exercising. Therefore, researchers and geriatric professionals now need to focus on such things as exercise compliance, and which factors might "motivate" frail older adults to continue to exercise regularly. Nursing homes will need guidance not only on the specifics of the exercise program they should be offering to their frail population, but also on motivational strategies to ensure that regular exercise becomes integrated into the daily lifestyle of the oldest segment of our population. JF - Journal of Aging and Physical Activity AU - Guralnik, J Y1 - 2004/07// PY - 2004 DA - Jul 2004 PB - Human Kinetics Publishers, P.O. Box 5076 Champaign IL 61825-5076 USA VL - 12 IS - 3 KW - Physical Education Index KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17328250?accountid=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+Aging+and+Physical+Activity&rft.atitle=The+LIFE+study%3A+A+randomized+clinical+trial+of+exercise+to+prevent+disability+in+high-risk+older+persons&rft.au=Guralnik%2C+J&rft.aulast=Guralnik&rft.aufirst=J&rft.date=2004-07-01&rft.volume=12&rft.issue=3&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Journal+of+Aging+and+Physical+Activity&rft.issn=10638652&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-02-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Production of Hydroxyl Radicals from the Decomposition of Hydrogen Peroxide Catalyzed by Various Iron Oxides at pH 7 AN - 17282840; 5956021 AB - The hydroxyl radical, generated from the Fenton-like catalysis of hydrogen peroxide (H sub(2)O sub(2)), is the major reactant involved in the oxidation of toxic organic contaminants. This study evaluated the effects of H sub(2)O sub(2) doses and types of iron oxides on the yields and production rates of hydroxyl radicals at molar ratio of H sub(2)O sub(2)/total iron oxide = 0.2-9.7 and pH = 7. The results showed that for both ferrihydrite and goethite, the yields and production rates were in the order of 10 super(-12) mM and 1-5 X 10 super(-14) mM/S, respectively, and irrelevant to the initial H sub(2)O sub(2) dose. However, a higher H sub(2)O sub(2) dose was required in aquifer sand to produce the same level of radicals. JF - Practice Periodical of Hazardous, Toxic, and Radioactive Waste Management AU - Yeh, CK-J AU - Chen, W-S AU - Chen, W-Y AD - Dept. of Environmental Science and Engineering, National Pingtung Univ. of Science and Technology, 1 Hseuh Fu Rd., Nei Pu 91207, Pingtung, Taiwan, ROC, kjyeh@mail.npust.edu.tw Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 161 EP - 165 VL - 8 IS - 3 SN - 1090-025X, 1090-025X KW - Pollution Abstracts KW - Aquifers KW - Radioactive wastes KW - Hydrogen KW - Iron KW - Hazardous wastes KW - pH KW - Hydroxyl radicals KW - Waste management KW - Catalysis KW - P 4000:WASTE MANAGEMENT UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17282840?accountid=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=Practice+Periodical+of+Hazardous%2C+Toxic%2C+and+Radioactive+Waste+Management&rft.atitle=Production+of+Hydroxyl+Radicals+from+the+Decomposition+of+Hydrogen+Peroxide+Catalyzed+by+Various+Iron+Oxides+at+pH+7&rft.au=Yeh%2C+CK-J%3BChen%2C+W-S%3BChen%2C+W-Y&rft.aulast=Yeh&rft.aufirst=CK-J&rft.date=2004-07-01&rft.volume=8&rft.issue=3&rft.spage=161&rft.isbn=&rft.btitle=&rft.title=Practice+Periodical+of+Hazardous%2C+Toxic%2C+and+Radioactive+Waste+Management&rft.issn=1090025X&rft_id=info:doi/10.1061%2F%28ASCE%291090-025X%282004%298%3A3%28161%29 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-06-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Aquifers; Radioactive wastes; Hydrogen; Iron; pH; Hazardous wastes; Catalysis; Waste management; Hydroxyl radicals DO - http://dx.doi.org/10.1061/(ASCE)1090-025X(2004)8:3(161) ER - TY - JOUR T1 - Protein microarray detection strategies: focus on direct detection technologies AN - 17275743; 6045675 AB - Protein microarrays are being utilized for functional proteomic analysis, providing information not obtainable by gene arrays. Microarray technology is applicable for studying protein-protein, protein-ligand, kinase activity and posttranslational modifications of proteins. A precise and sensitive protein microarray, the direct detection or reverse-phase microarray, has been applied to ongoing clinical trials at the National Cancer Institute for studying phosphorylation events in EGF-receptor-mediated cell signaling pathways. The variety of microarray applications allows for multiple, creative microarray designs and detection strategies. Herein, we discuss detection strategies and challenges for protein microarray technology, focusing on direct detection of protein microarrays. JF - Journal of Immunological Methods AU - Espina, V AU - Woodhouse, E C AU - Wulfkuhle, J AU - Asmussen, H D AU - Petricoin, EF III AU - Liotta, LA AD - FDA-NCI Clinical Proteomics Program, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Room B1B53, Bldg. 10, 9000 Rockville Pike, Bethesda, MD 20892, USA, espinav@mail.nih.gov Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 121 EP - 133 VL - 290 IS - 1-2 SN - 0022-1759, 0022-1759 KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Phosphorylation KW - Protein arrays KW - Protein kinase KW - Epidermal growth factor receptors KW - F 06713:Physicochemical methods KW - W3 33243:Molecular methods KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17275743?accountid=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=Protein+microarray+detection+strategies%3A+focus+on+direct+detection+technologies&rft.au=Espina%2C+V%3BWoodhouse%2C+E+C%3BWulfkuhle%2C+J%3BAsmussen%2C+H+D%3BPetricoin%2C+EF+III%3BLiotta%2C+LA&rft.aulast=Espina&rft.aufirst=V&rft.date=2004-07-01&rft.volume=290&rft.issue=1-2&rft.spage=121&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunological+Methods&rft.issn=00221759&rft_id=info:doi/10.1016%2Fj.jim.2004.04.013 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Protein arrays; Protein kinase; Phosphorylation; Epidermal growth factor receptors DO - http://dx.doi.org/10.1016/j.jim.2004.04.013 ER - TY - JOUR T1 - Influenza and pneumococcal vaccination of the elderly in Taiwan AN - 1500774039; 19046149 AB - In 1998, Taiwan became the first country in Asia to provide free influenza vaccination to high-risk groups, mainly the elderly. The purpose of this study is to determine: (1) the annual mortality rate from influenza and pneumococcal-related illnesses such as pneumonia, chronic bronchitis, pulmonary emphysema and asthma and (2) the effectiveness of and adverse events associated with the influenza vaccination. In the elderly, influenza vaccination caused the annual death rate due chronic bronchitis, pulmonary emphysema, and asthma to decline steadily but had no effect on the annual pneumonia death rate. The only adverse effect of concern was vertigo (in approximately 2-3%). JF - Vaccine AU - Chen, Yeong-Hwang AU - Liou, Saou-Hsing AU - Chou, Chih-Chieh AU - Su, Wen-Lin AU - Loh, Ching-Hui AU - Lin, Shih-Ha AD - Department of Family Medicine, Tri-Service General Hospital, No. 325, Section 2, Chen-Kung Road, Nei-Hu, Taipei, Taiwan, ROC Y1 - 2004/07// PY - 2004 DA - Jul 2004 SP - 2806 EP - 2811 PB - Elsevier B.V., The Boulevard Kidlington Oxford OX5 1GB United Kingdom VL - 22 IS - 21 SN - 0264-410X, 0264-410X KW - Risk Abstracts; Health & Safety Science Abstracts; Virology & AIDS Abstracts; Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Emphysema KW - Mortality KW - Taiwan KW - Elderly KW - Asthma KW - Respiratory diseases KW - Vaccination KW - vertigo KW - Influenza KW - Streptococcus pneumoniae KW - Lung KW - Geriatrics KW - Risk groups KW - Bronchitis KW - Vaccines KW - Asia KW - Pneumonia KW - Side effects KW - F 06925:Hypersensitivity KW - R2 23060:Medical and environmental health KW - J 02350:Immunology KW - H 4000:Food and Drugs KW - V 22400:Human Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1500774039?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Vaccine&rft.atitle=Influenza+and+pneumococcal+vaccination+of+the+elderly+in+Taiwan&rft.au=Chen%2C+Yeong-Hwang%3BLiou%2C+Saou-Hsing%3BChou%2C+Chih-Chieh%3BSu%2C+Wen-Lin%3BLoh%2C+Ching-Hui%3BLin%2C+Shih-Ha&rft.aulast=Chen&rft.aufirst=Yeong-Hwang&rft.date=2004-07-01&rft.volume=22&rft.issue=21&rft.spage=2806&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/10.1016%2Fj.vaccine.2004.01.003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2014-02-01 N1 - Last updated - 2014-08-21 N1 - SubjectsTermNotLitGenreText - Influenza; Mortality; Emphysema; Lung; Geriatrics; Risk groups; Asthma; Bronchitis; Vaccination; Side effects; Pneumonia; vertigo; Elderly; Vaccines; Respiratory diseases; Streptococcus pneumoniae; Taiwan; Asia DO - http://dx.doi.org/10.1016/j.vaccine.2004.01.003 ER - TY - JOUR T1 - Chlormethiazole potentiates the discriminative stimulus effects of methamphetamine in rats. AN - 66646661; 15212973 AB - Chlormethiazole is a positive modulator of gamma-aminobutyric acid (GABA)(A) receptors used in the treatment of alcohol withdrawal seizures. It recently has been reported to attenuate seizures engendered by acute and repeated exposure to cocaine in mice and neurotoxic effects of methamphetamine in rats. The aim of the present study was to determine whether chlormethiazole could also attenuate the discriminative stimulus effects of methamphetamine, a behavior predictive of the subjective effects of methamphetamine in humans. In Sprague-Dawley rats trained to discriminate 1.0 mg/kg methamphetamine [intraperitoneally (i.p.)] from saline under a fixed-ratio schedule of food delivery, the ability of chlormethiazole (i.p.) to (1) substitute for methamphetamine, (2) antagonize effects of methamphetamine and to (3) shift the methamphetamine dose-effect function was investigated. Chlormethiazole (18 and 30 mg/kg, i.p.) partially substituted for the discriminative stimulus effects of methamphetamine when administered alone (maximum group average, 60% responses on the methamphetamine-appropriate lever). Chlormethiazole did not attenuate effects of methamphetamine when coadministered with the training dose of methamphetamine. Instead, chlormethiazole potentiated the discriminative stimulus effects of methamphetamine as demonstrated by a significant (about 2.5-fold) leftward and upward shift in the methamphetamine dose-effect function in the presence of chlormethiazole (10 mg/kg). In conclusion, the present findings suggest that there is a behavioral interaction between methamphetamine and chlormethiazole. The profile of this interaction is qualitatively different from that of methamphetamine and classical GABAergic drugs (i.e., benzodiazepines and barbiturates), suggesting the involvement of non-GABAergic mechanisms in the effects produced by chlormethiazole. JF - European journal of pharmacology AU - Gasior, Maciej AU - Witkin, Jeffrey M AU - Goldberg, Steven R AU - Munzar, Patrik AD - Epilepsy Research Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Drive, MSC: 1408, Building 10, Room 5N250, Bethesda, MD 20892-1408, USA. gasiorm@ninds.nih.gov Y1 - 2004/06/28/ PY - 2004 DA - 2004 Jun 28 SP - 183 EP - 189 VL - 494 IS - 2-3 SN - 0014-2999, 0014-2999 KW - Central Nervous System Stimulants KW - 0 KW - GABA Modulators KW - Chlormethiazole KW - 0C5DBZ19HV KW - Methamphetamine KW - 44RAL3456C KW - Index Medicus KW - Seizures -- chemically induced KW - Rats KW - Generalization (Psychology) -- drug effects KW - Discrimination Learning -- drug effects KW - Conditioning, Operant -- drug effects KW - Behavior, Animal -- drug effects KW - Animals KW - Rats, Sprague-Dawley KW - Dose-Response Relationship, Drug KW - Neurotoxicity Syndromes -- physiopathology KW - Drug Synergism KW - Male KW - Discrimination (Psychology) -- drug effects KW - Central Nervous System Stimulants -- pharmacology KW - Central Nervous System Stimulants -- toxicity KW - GABA Modulators -- pharmacology KW - Chlormethiazole -- pharmacology KW - Methamphetamine -- pharmacology KW - Methamphetamine -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66646661?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+pharmacology&rft.atitle=Chlormethiazole+potentiates+the+discriminative+stimulus+effects+of+methamphetamine+in+rats.&rft.au=Gasior%2C+Maciej%3BWitkin%2C+Jeffrey+M%3BGoldberg%2C+Steven+R%3BMunzar%2C+Patrik&rft.aulast=Gasior&rft.aufirst=Maciej&rft.date=2004-06-28&rft.volume=494&rft.issue=2-3&rft.spage=183&rft.isbn=&rft.btitle=&rft.title=European+journal+of+pharmacology&rft.issn=00142999&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-14 N1 - Date created - 2004-06-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High urea and NaCl carbonylate proteins in renal cells in culture and in vivo, and high urea causes 8-oxoguanine lesions in their DNA. AN - 66643313; 15190183 AB - Urea and NaCl are elevated in the renal inner medulla. We now find that a high concentration of urea or NaCl increases reactive oxygen species (ROS) in mouse renal inner medullary (mIMCD3) cells in culture. Previously, high NaCl, but not high urea, was found to cause DNA double-strand breaks. We now tested whether high urea or NaCl causes oxidative damage to DNA or cellular proteins. We find that high urea increases mIMCD3 cell DNA single-strand breaks and 8-oxoguanine lesions. High NaCl does not cause detectable 8-oxoguanine lesions. High urea or NaCl also greatly increases carbonylation of proteins in mIMCD3 cells. Carbonylation occurs within 5 min and with as little as 5 mM urea, a normal plasma level. It increases as urea is raised over the range in uremia. A high raffinose level increases ROS and carbonylation. High sorbitol and glycerol levels do not increase ROS or carbonylation. Carbonyl content is high in mouse renal inner medullas where interstitial NaCl and urea concentrations are normally high. There, numerous proteins are carbonylated, and carbonylation occurs in both collecting ducts and thin limbs. (i) Oxidative stress, associated with high urea, causes 8-oxoguanine DNA lesions in mIMCD3 cell DNA. (ii) High urea or NaCl carbonylates proteins in mIMCD3 cells and in renal inner medullary cells in vivo. (iii) In mIMCD3 cells a normal plasma concentration of urea causes carbonylation, and carbonylation increases over the uremic range of urea concentration, indicating that urea can contribute directly to the carbonylation found in uremia. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Zhang, Zheng AU - Dmitrieva, Natalia I AU - Park, Jong-Hwan AU - Levine, Rodney L AU - Burg, Maurice B AD - Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA. zhangz@nhlbi.nih.gov Y1 - 2004/06/22/ PY - 2004 DA - 2004 Jun 22 SP - 9491 EP - 9496 VL - 101 IS - 25 SN - 0027-8424, 0027-8424 KW - Reactive Oxygen Species KW - 0 KW - Sodium Chloride KW - 451W47IQ8X KW - Sorbitol KW - 506T60A25R KW - 8-hydroxyguanine KW - 5614-64-2 KW - Guanine KW - 5Z93L87A1R KW - Urea KW - 8W8T17847W KW - Glycerol KW - PDC6A3C0OX KW - Index Medicus KW - Reactive Oxygen Species -- metabolism KW - Comet Assay KW - Animals KW - Cells, Cultured KW - Sorbitol -- pharmacology KW - Mice KW - Glycerol -- pharmacology KW - Kidney -- metabolism KW - Kidney Medulla -- metabolism KW - Kidney Medulla -- drug effects KW - Kidney -- cytology KW - Guanine -- analysis KW - Kidney Medulla -- cytology KW - Guanine -- analogs & derivatives KW - Urea -- pharmacology KW - Sodium Chloride -- pharmacology KW - DNA Damage -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66643313?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=High+urea+and+NaCl+carbonylate+proteins+in+renal+cells+in+culture+and+in+vivo%2C+and+high+urea+causes+8-oxoguanine+lesions+in+their+DNA.&rft.au=Zhang%2C+Zheng%3BDmitrieva%2C+Natalia+I%3BPark%2C+Jong-Hwan%3BLevine%2C+Rodney+L%3BBurg%2C+Maurice+B&rft.aulast=Zhang&rft.aufirst=Zheng&rft.date=2004-06-22&rft.volume=101&rft.issue=25&rft.spage=9491&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 - 2004-08-23 N1 - Date created - 2004-06-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Physiol. 1985 Apr;248(4 Pt 2):F522-6 [3985159] Science. 1982 Sep 24;217(4566):1214-22 [7112124] Arch Biochem Biophys. 1991 Sep;289(2):371-5 [1680314] Am J Physiol. 1993 Sep;265(3 Pt 2):F416-24 [8214101] Methods Enzymol. 1994;233:346-57 [8015469] J Biol Chem. 1994 Oct 14;269(41):25865-70 [7929290] Mutat Res. 1995 Feb;339(1):37-59 [7877644] J Clin Invest. 1996 Apr 15;97(8):1884-9 [8621772] Free Radic Res. 1996 Jan;24(1):1-7 [8747887] Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):11242-7 [8855340] J Histochem Cytochem. 1998 Jun;46(6):731-5 [9603784] J Biol Chem. 1998 Aug 28;273(35):22165-8 [9712826] Clin Exp Pharmacol Physiol. 1999 Jan;26(1):69-73 [10027073] Am J Physiol. 1999 May;276(5 Pt 2):F786-93 [10330061] Am J Physiol. 1990 Jan;258(1 Pt 2):F154-61 [2105661] Ann N Y Acad Sci. 2000;899:191-208 [10863540] Methods Mol Biol. 2000;99:15-24 [10909073] Nat Cell Biol. 2000 Sep;2(9):E163-5 [10980714] Am J Physiol Lung Cell Mol Physiol. 2000 Dec;279(6):L1005-28 [11076791] Kidney Int. 2000 Dec;58(6):2571-8 [11115093] Kidney Int Suppl. 2001 Feb;78:S102-7 [11168993] Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1999-2004 [11172065] Free Radic Biol Med. 2002 May 1;32(9):790-6 [11978480] Am J Physiol Renal Physiol. 2002 Oct;283(4):F792-8 [12217871] Pflugers Arch. 2002 Oct;445(1):67-73 [12397389] DNA Repair (Amst). 2003 Feb 3;2(2):211-29 [12531391] Trends Mol Med. 2003 Apr;9(4):169-76 [12727143] Proc Natl Acad Sci U S A. 2004 Feb 24;101(8):2317-22 [14983007] Comment In: Proc Natl Acad Sci U S A. 2004 Jun 22;101(25):9177-8 [15199186] N1 - Last updated - 2017-01-18 ER - TY - JOUR