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Author (up) Allen, S.L.; Lundberg, A.S. file  url
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  Title Amonafide: a potential role in treating acute myeloid leukemia Type Journal Article
  Year 2011 Publication Expert Opinion on Investigational Drugs Abbreviated Journal Expert Opin Investig Drugs  
  Volume 20 Issue 7 Pages 995-1003  
  Keywords Animals; Antineoplastic Agents--pharmacokinetics, therapeutic use; Clinical Trials as Topic--methods; DNA Topoisomerases, Type II--metabolism; Drug Resistance, Neoplasm; Enzyme Inhibitors--pharmacokinetics, therapeutic use; Humans; Leukemia, Myeloid, Acute--drug therapy, enzymology, mortality; Naphthalimides--pharmacokinetics, therapeutic use; Survival Rate--trends; Treatment Outcome  
  Abstract INTRODUCTION: Amonafide is a novel topoisomerase II (Topo II) inhibitor and DNA intercalator that induces apoptotic signaling by blocking the binding of Topo II to DNA. Amonafide retains cytotoxic activity even in the presence of P-glycoprotein (Pgp)-mediated multi-drug resistance (MDR), a major contributor to clinical treatment failure. AREAS COVERED: In vitro, Pgp-mediated transport (efflux) of amonafide from myeloblasts obtained from patients with secondary acute myeloid leukemia (sAML) was significantly less than efflux of daunorubicin. Amonafide has shown efficacy in patients with sAML, as well as in patients with poor prognostic characteristics such as older age and unfavorable cytogenetics, all associated with MDR. Improved antileukemic activity is observed when amonafide is given together with cytarabine, rather than as monotherapy, with a complete remission rate of approximately 40% in a recent Phase II trial in sAML. The efficacy of amonafide was maintained among poor-risk subsets of patients, including older patients and patients who had previous myelodysplastic syndrome or previous leukemogenic therapy. The safety profile was acceptable and manageable. EXPERT OPINION: Amonafide plus cytarabine may have clinical utility in patients with sAML and in other poor-risk subgroups of acute myeloid leukemia (AML). Ongoing trials will help define the role for amonafide in the treatment of poor-risk AML.  
  Call Number Serial 199  
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Author (up) Burlina, A.P.; Skaper, S.D.; Mazza, M.R.; Ferrari, V.; Leon, A.; Burlina, A.B. file  url
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  Title N-acetylaspartylglutamate selectively inhibits neuronal responses to N-methyl-D-aspartic acid in vitro Type Journal Article
  Year 1994 Publication Journal of Neurochemistry Abbreviated Journal J Neurochem  
  Volume 63 Issue 3 Pages 1174-1177  
  Keywords Animals; Aspartic Acid/analogs & derivatives/pharmacology; Canavan Disease; Cell Survival/drug effects; Cells, Cultured; Cerebellum/cytology/drug effects; Culture Media; Dipeptides/*pharmacology; Kainic Acid/pharmacology; Mice; Mice, Inbred BALB C; N-Methylaspartate/*pharmacology; Neurons/*drug effects/physiology  
  Abstract Canavan's disease is an autosomal recessive disorder characterized by a deficiency of aspartoacylase and accumulation of N-acetylaspartic acid (NAA), leading to a severe leukodystrophy and spongy degeneration of the brain. N-Acetylaspartylglutamate (NAAG), the presumed product of NAA, also accumulates in this disease. The endogenous dipeptide NAAG has been suggested to have low potency at NMDA receptors. Here we have tested the actions of NAAG and NAA on NMDA-evoked responses in cultured cerebellar granule cells. In differentiating granule cells grown in low-K+ medium, NAAG negated the survival-promoting effects of NMDA but not K+ depolarization. Neither NAAG nor NAA alone promoted cell survival in low-K+ medium. The modest trophic action of 50 microM kainic acid in low-K+ medium was reinforced by the NMDA receptor antagonist dizocilpine maleate and by NAAG. In K(+)-differentiated granule cells, NAAG raised the threshold of NMDA neurotoxicity but not that of kainate. The observed activities of NAAG were overcome by excess NMDA and were not mimicked by NAA. These data raise the possibility that disruption of NMDA receptor processes by NAAG may be of pathophysiological relevance.  
  Call Number Serial 103  
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Author (up) Buttke, T.M.; McCubrey, J.A.; Owen, T.C. file  url
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  Title Use of an aqueous soluble tetrazolium/formazan assay to measure viability and proliferation of lymphokine-dependent cell lines Type Journal Article
  Year 1993 Publication Journal of Immunological Methods Abbreviated Journal J Immunol Methods  
  Volume 157 Issue 1-2 Pages 233-240  
  Keywords Animals; *Cell Division; Cell Line; *Cell Survival; Colorimetry; Formazans/*analysis; Interleukin-2/analysis/*physiology; Interleukin-3/analysis/*physiology; Mice; Tetrazolium Salts/*pharmacology; Thiazoles/pharmacology  
  Abstract A new tetrazolium compound, MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3- carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt), has recently been described which in the presence of phenazine methosulfate (PMS) is reduced by living cells to yield a formazan product that can be assayed colorimetrically. An important advantage of MTS/PMS over other tetrazolium dyes (e.g., MTT) is the aqueous solubility of the reduced formazan product which eliminates the need for detergent solubilization or organic solvent extraction steps. Its advantages over XTT/PMS, another tetrazolium which yields a water-soluble formazan product, include the absorbance range of color produced (515-580 nm as opposed to 450 nm), the rapidity of color development, and the storage stability of the MTS/PMS reagent solution. In the present study, MTS/PMS was used to assay viability and proliferation of the IL-2-dependent HT-2 and CTLL-2 cell lines and the IL-3-dependent FDC-P1 and FL5.12 cell lines. With each cell line, the amount of formazan product was time-dependent and proportional to the number of viable cells. Furthermore, with both HT-2 and CTLL-2 cells it was found that cultures could be simultaneously labeled with MTS/PMS and [3H]thymidine, with relatively little effect of the dye on uptake of the latter. This feature was further capitalized upon in studies with FDC-P1 cells, in which the co-addition of MTS/PMS and [3H]thymidine was used to distinguish between cell viability and proliferation.  
  Call Number Serial 1376  
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Author (up) Buu, M.M.C.; Sanders, L.M.; Mayo, J.A.; Milla, C.E.; Wise, P.H. file  url
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  Title Assessing Differences in Mortality Rates and Risk Factors Between Hispanic and Non-Hispanic Patients With Cystic Fibrosis in California Type Journal Article
  Year 2016 Publication Chest Abbreviated Journal Chest  
  Volume 149 Issue 2 Pages 380-389  
  Keywords Adolescent; California/epidemiology; Child; Child, Preschool; Cystic Fibrosis/*mortality; *European Continental Ancestry Group; Female; Follow-Up Studies; *Hispanic Americans; Humans; Infant; Male; Outcome Assessment (Health Care)/*methods; Prevalence; Registries; Retrospective Studies; Risk Factors; Socioeconomic Factors; Survival Rate/trends; cystic fibrosis; ethnicity; health disparities; pediatric pulmonology  
  Abstract BACKGROUND: Over the past 30 years, therapeutic advances have extended the median lifespan of patients with cystic fibrosis (CF). Hispanic patients are a vulnerable subpopulation with a high prevalence of risk factors for worse health outcomes. The consequences of these differences on health outcomes have not been well described. The objective of this study was to characterize the difference in health outcomes, including mortality rate, between Hispanic and non-Hispanic patients with CF. METHODS: This study is a retrospective analysis of CF Foundation Patient Registry data of California residents with CF, diagnosed during or after 1991, from 1991 to 2010. Ethnicity was self-reported. The primary outcome was mortality. Hazard ratios were estimated from a Cox regression model, stratified by sex, and adjusted for socioeconomic status, clinical risk factors, and year of diagnosis. RESULTS: Of 1,719 patients, 485 (28.2%) self-identified as Hispanic. Eighty-five deaths occurred, with an overall mortality rate of 4.9%. The unadjusted mortality rate was higher among Hispanic patients than among non-Hispanic patients (9.1% vs 3.3%, P < .0001). Compared with non-Hispanic patients, Hispanic patients had a lower survival rate 18 years after diagnosis (75.9% vs 91.5%, P < .0001). Adjusted for socioeconomic status and clinical risk factors, Hispanic patients had an increased rate of death compared with non-Hispanic patients (hazard ratio, 2.81; 95% CI, 1.70-4.63). CONCLUSIONS: Hispanic patients with CF have a higher mortality rate than do non-Hispanic patients, even after adjusting for socioeconomic status and clinical severity. Further investigation into the mechanism for the measured difference in lung function will help inform interventions and improve the health of all patients with CF.  
  Call Number Serial 1377  
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Author (up) Campbell, L.L.; Tyson, J.A.; Stackpole, E.E.; Hokenson, K.E.; Sherrill, H.; McKeon, J.E.; Kim, S.A.; Edmands, S.D.; Suarez, C.; Hall, A.C. file  url
openurl 
  Title Assessment of general anaesthetic cytotoxicity in murine cortical neurones in dissociated culture Type Journal Article
  Year 2011 Publication Toxicology Abbreviated Journal Toxicology  
  Volume 283 Issue 1 Pages 1-7  
  Keywords Anesthetics, General/*toxicity; Animals; Animals, Newborn; Cell Survival/drug effects; Cerebral Cortex/cytology/*drug effects/metabolism; Isoflurane/*toxicity; Ketamine/*toxicity; L-Lactate Dehydrogenase/metabolism; Mice; Mice, Inbred C57BL; Microscopy, Fluorescence; Microtubule-Associated Proteins/metabolism; N-Methylaspartate/metabolism; Neurons/cytology/*drug effects/metabolism; Nitrous Oxide/*toxicity; gamma-Aminobutyric Acid/metabolism  
  Abstract General anaesthetics are proposed to cause unconsciousness by modulating neuronal excitability in the mammalian brain through mechanisms that include enhancement of inhibitory GABA(A) receptor currents and suppression of excitatory glutamate receptor responses. Both intravenous and volatile agents may produce neurotoxic effects during early postnatal rodent brain development through similar mechanisms. In the following study, we investigated anaesthetic cytotoxicity in primary cortical neurones and glia from postnatal day 2-8 mice. Cultures at 4-20 days in vitro were exposed to combinations of ketamine (100 muM to 3 mM), nitrous oxide (75%, v/v) and/or isoflurane (1.5-5%, v/v) for 6-12 h. Neuronal survival and cell death were measured via microtubule associated protein 2 immunoassay and lactate dehydrogenase release assays, respectively. Clinically relevant anaesthetic concentrations of ketamine, nitrous oxide and isoflurane had no significant neurotoxic effects individually or when given as anaesthetic cocktails, even with up to 12 h exposure. This lack of neurotoxicity was observed regardless of whether cultures were prepared from postnatal day 0-2 or day 8 mice, and was also unaffected by number of days in vitro (DIV 4-20). Significant neurotoxic effects were only observed at supraclinical concentrations (e.g. 1-3 mM ketamine). Our study suggests that neurotoxicity previously reported in vivo is not due to direct cytotoxicity of anaesthetic agents, but results from other impacts of the anaesthetised state during early brain development.  
  Call Number Serial 510  
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