14 results on '"Becker MN"'
Search Results
2. Tissue-specific expression of a Drosophila calcium-activated potassium channel
- Author
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Becker, MN, primary, Brenner, R, additional, and Atkinson, NS, additional
- Published
- 1995
- Full Text
- View/download PDF
3. Secondary superheater slagging reduction
- Author
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Benson, R [Northern States Power Co., Becker, MN (US)]
- Published
- 1992
4. Reducing hypoglycemia from overtreatment of type 2 diabetes in older adults: The HypoPrevent study.
- Author
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Koehn DA, Dungan KM, Wallia A, Lucas DO, Lash RW, Becker MN, Dardick LD, and Boord JB
- Subjects
- Humans, Aged, Glycated Hemoglobin, Hypoglycemic Agents adverse effects, Sulfonylurea Compounds adverse effects, Insulin adverse effects, Overtreatment, Blood Glucose, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 epidemiology, Hypoglycemia chemically induced, Hypoglycemia epidemiology
- Abstract
Background: Hypoglycemia from overtreatment is a serious but underrecognized complication among older adults with type 2 diabetes. However, diabetes treatment is seldom deintensified. We assessed the effectiveness of a Clinical Decision Support (CDS) tool and shared decision-making (SDM) in decreasing the number of patients at risk for hypoglycemia and reducing the impact of non-severe hypoglycemic events., Methods: HypoPrevent was a pre-post, single arm study at a five-site primary care practice. We identified at-risk patients (≥65 years-old, with type 2 diabetes, treated with insulin or sulfonylureas, and HbA
1c < 7.0%). During three clinic visits over 6 months, clinicians used the CDS tool and SDM to assess hypoglycemic risk, set individualized HbA1c goals, and adjust use of hypoglycemic agents. We assessed the number of patients setting individualized HbA1c goals or modifying medication use, changes in the population at risk for hypoglycemia, and changes in impact of non-severe hypoglycemic events using a validated patient-reported outcome tool (TRIM-HYPO)., Results: We enrolled 94 patients (mean age-74; mean HbA1c (±SD)-6.36% ± 0.43), of whom 94% set an individualized HbA1c goal at either the baseline or first follow-up visit. Ninety patients completed the study. Insulin or sulfonylurea use was decreased or eliminated in 20%. An HbA1c level before and after goal setting was obtained in 53% (N = 50). Among these patients, the mean HbA1c increased 0.53% (p < 0.0001) and the number of patients at-risk decreased by 46% (p < 0.0001). Statistically significant reductions in the impact of hypoglycemia during daily activities occurred in both the total score and each functional domain of TRIM-HYPO., Conclusions: In a population of older patients at risk for hypoglycemia, the use of a CDS tool and SDM reduced the population at risk and decreased the use of insulin and sulfonylureas. Using a patient-reported outcome tool, we demonstrated significant reductions in the impact of hypoglycemia on daily life., (© 2023 The American Geriatrics Society.)- Published
- 2023
- Full Text
- View/download PDF
5. Affordable Care Act Implementation: Challenges and Opportunities to Impact Patients With Diabetes.
- Author
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Powers AC, Wexler JA, Lash RW, Dyer MC, Becker MN, and Vigersky RA
- Subjects
- Humans, Diabetes Mellitus therapy, Patient Protection and Affordable Care Act
- Published
- 2016
- Full Text
- View/download PDF
6. The combination of an mTORc1/TORc2 inhibitor with lapatinib is synergistic in bladder cancer in vitro.
- Author
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Becker MN, Wu KJ, Marlow LA, Kreinest PA, Vonroemeling CA, Copland JA, and Williams CR
- Subjects
- Aged, Blotting, Western, Cell Line, Tumor, Cell Proliferation drug effects, Drug Synergism, Female, Humans, Immunohistochemistry, Indoles administration & dosage, Lapatinib, Male, Purines administration & dosage, TOR Serine-Threonine Kinases antagonists & inhibitors, Tissue Array Analysis, Antineoplastic Agents administration & dosage, Imidazoles administration & dosage, Quinazolines administration & dosage, Triazines administration & dosage, Urinary Bladder Neoplasms pathology
- Abstract
Objective: To examine the ability of dual mTORc1/c2 inhibitors in conjunction with lapatinib to function in a synergistic manner to inhibit cell proliferation and anchorage-independent growth in bladder cancer cell lines., Materials and Methods: We examined patient tumor samples for overexpression of pS6, p4EBP1, pAkt, and phosphorylated epidermal growth factor receptor (pEGFR) using a tissue microarray containing 84 cases. Three bladder cancer cell lines, T24, HT1376, and UM-UC-3, were analyzed for cell proliferation after treatment with mTORc1/c2 inhibitors OSI-027 or PP242. Western blots were used to verify that the drugs were inhibiting phosphorylation of target proteins within the mTOR pathway, and they were compared with rapamycin inhibition. We also analyzed cell proliferation and anchorage-independent growth after treatment with OSI-027 and lapatinib in combination. PARP cleavage and autophagic flux were measured by examining levels of LC3B and p62 by western blotting., Results: Tumor samples show increased expression of pEGFR (38% vs. 8%) and HER2 (38% vs. 4%) and decreased expression of pAkt S473 (7.5% vs. 29%) and pAkt T308 (50% vs. 84%) relative to normal tissue. Significant differences between normal and tumor samples for staining with pEGFR (P = 0.0188), HER 2 (P = 0.0017), pATK S473 (P = 0.0128), and pAkt T308 (P = 0.0015) is observed. Expression of proteins within the EGFR/HER2 pathway or within the mTOR pathway is correlated. No correlation was found between staining and tumor stage. OSI-027 and PP242 diminish cell proliferation in all 3 cell lines with IC50 values ranging from 0.63 to 17.95µM. Both drugs inhibit phosphorylation of both mTORc1 and mTORc2 pathway components. OSI-027 and lapatinib inhibit cell proliferation and anchorage-independent growth in a synergistic manner. One cell line exhibited apoptosis in response to combination drug treatment, whereas the other 2 cell lines have increased levels of autophagy indicative of resistance to apoptosis., Conclusions: The combination of OSI-027 and lapatinib results in antitumor synergy and further exploration of this combination should be undertaken., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
7. An Amsacta moorei entomopoxvirus ortholog of the poly(A) polymerase small subunit exhibits methyltransferase activity and is non-essential for virus growth.
- Author
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Becker MN, Todd TM, and Moyer RW
- Subjects
- Amino Acid Sequence, Animals, Cell Line, DNA-Directed RNA Polymerases, Genes, Viral, Larva virology, Molecular Sequence Data, Moths virology, Polynucleotide Adenylyltransferase chemistry, Protein Subunits genetics, Sequence Alignment, Viral Proteins chemistry, Virus Replication, Entomopoxvirinae physiology, Methyltransferases metabolism, Polynucleotide Adenylyltransferase metabolism, Protein Subunits metabolism, Viral Proteins metabolism
- Abstract
Unlike the heterodimeric poly(A) polymerase (PAP) of vaccinia virus (VACV), the PAP from the Amsacta moorei entomopoxvirus, AMEV, is potentially derived from three subunits: a single large and two small subunits (AMV060 and AMV115). The VACV small subunit serves as a 2'-O-methyltransferase, a processivity factor for mRNA polyadenylation, and a transcription elongation factor. We wished to determine the structure-function relationships of the three putative AMEV PAP subunits. We show that AMV060 is expressed as an early gene persisting throughout infection, whereas AMV115 is expressed late. We demonstrate that AMV060 exhibits 2'-O-methyltransferase activity but the gene is not essential for virus growth. Absence of the AMV060 protein has no effect on the length of the poly(A) tails present in mRNA. No physical association was found between any of the putative AMEV PAP subunits. We therefore propose that mRNA polyadenylation does not require interactions between these three proteins.
- Published
- 2008
- Full Text
- View/download PDF
8. Isolation and characterization of cidofovir resistant vaccinia viruses.
- Author
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Becker MN, Obraztsova M, Kern ER, Quenelle DC, Keith KA, Prichard MN, Luo M, and Moyer RW
- Subjects
- Animals, Antiviral Agents pharmacology, Cell Line, Chlorocebus aethiops, Cidofovir, Cytosine pharmacology, DNA-Directed DNA Polymerase chemistry, DNA-Directed DNA Polymerase genetics, DNA-Directed DNA Polymerase metabolism, Female, Humans, Mice, Models, Molecular, Mutation, Vaccinia mortality, Vaccinia virology, Vaccinia virus pathogenicity, Vaccinia virus physiology, Vero Cells, Viral Plaque Assay, Virulence, Cytosine analogs & derivatives, Drug Resistance, Viral, Organophosphonates pharmacology, Vaccinia virus drug effects, Vaccinia virus isolation & purification
- Abstract
Background: The emergence of drug resistant viruses, together with the possibility of increased virulence, is an important concern in the development of new antiviral compounds. Cidofovir (CDV) is a phosphonate nucleotide that is approved for use against cytomegalovirus retinitis and for the emergency treatment of smallpox or complications following vaccination. One mode of action for CDV has been demonstrated to be the inhibition of the viral DNA polymerase., Results: We have isolated several CDV resistant (CDVR) vaccinia viruses through a one step process, two of which have unique single mutations within the DNA polymerase. An additional resistant virus isolate provides evidence of a second site mutation within the genome involved in CDV resistance. The CDVR viruses were 3-7 fold more resistant to the drug than the parental viruses. The virulence of the CDVR viruses was tested in mice inoculated intranasally and all were found to be attenuated., Conclusion: Resistance to CDV in vaccinia virus can be conferred individually by at least two different mutations within the DNA polymerase gene. Additional genes may be involved. This one step approach for isolating resistant viruses without serial passage and in the presence of low doses of drug minimizes unintended secondary mutations and is applicable to other potential antiviral agents.
- Published
- 2008
- Full Text
- View/download PDF
9. Amsacta moorei entomopoxvirus expresses an active superoxide dismutase.
- Author
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Becker MN, Greenleaf WB, Ostrov DA, and Moyer RW
- Subjects
- Amino Acid Sequence, Animals, Blotting, Northern, Blotting, Western, Cell Line, Cloning, Molecular, Copper analysis, Dimerization, Entomopoxvirinae growth & development, Escherichia coli genetics, Escherichia coli metabolism, Gene Deletion, Gene Expression Regulation, Viral, Genes, Viral, Models, Molecular, Molecular Sequence Data, Molecular Weight, RNA, Messenger analysis, RNA, Viral analysis, Recombinant Proteins genetics, Recombinant Proteins isolation & purification, Recombinant Proteins metabolism, Sequence Alignment, Superoxide Dismutase chemistry, Superoxide Dismutase isolation & purification, Viral Proteins metabolism, Zinc analysis, Entomopoxvirinae enzymology, Entomopoxvirinae genetics, Lepidoptera virology, Superoxide Dismutase genetics, Superoxide Dismutase metabolism
- Abstract
The entomopoxvirus from Amsacta moorei serves as the prototype of the group B entomopoxviruses. One of the interesting genes found in Amsacta moorei entomopoxvirus (AmEPV) is a superoxide dismutase (sod) (open reading frame AMV255). Superoxide dismutases (SODs) catalyze the conversion of superoxide radicals to hydrogen peroxide and oxygen. Many vertebrate poxviruses contain a sod gene, but to date, none have been demonstrated to be active. There are three families of SODs, characterized by their metal ion-binding partners, Fe, Mn, or Cu and Zn. Poxvirus enzymes belong to the Cu-Zn SOD family. Unlike inactive vertebrate poxvirus SODs, AMVSOD contains all the amino acids necessary for function. We expressed and purified a 6X-His-tagged version of the AMVSOD in Escherichia coli. The recombinant AMVSOD demonstrates superoxide dismutase activity both in an in situ gel assay and by stopped flow spectrophotometry. The k(cat)/K(m) for AMVSOD is 4 x 10(7) M(-1)s(-1). In infected cells, the AMVSOD protein behaves as a dimer and is catalytically active; however, disruption of the gene in AMEPV has little or no effect on growth of the virus in cell culture. An analysis of mRNA expression indicates that AMVsod is expressed late during infection of Lymantria dispar (Ld652) cells and produces a discrete nonpolydisperse transcript. Characterization of protein expression with a monoclonal antibody generated against AMVSOD confirms that the AMVSOD protein can be classified as a late, postreplicative gene. Therefore, AMVSOD is the first example of an active poxvirus SOD.
- Published
- 2004
- Full Text
- View/download PDF
10. Cytokine secretion by cystic fibrosis airway epithelial cells.
- Author
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Becker MN, Sauer MS, Muhlebach MS, Hirsh AJ, Wu Q, Verghese MW, and Randell SH
- Subjects
- Adolescent, Adult, Aged, Cell Culture Techniques methods, Cell Differentiation, Cells, Cultured, Chemokine CCL5 immunology, Chemokine CCL5 metabolism, Child, Child, Preschool, Cystic Fibrosis genetics, Cystic Fibrosis metabolism, Cystic Fibrosis Transmembrane Conductance Regulator genetics, Cytokines immunology, Female, Genotype, Humans, Inflammation, Interleukin-10 immunology, Interleukin-10 metabolism, Interleukin-8 immunology, Interleukin-8 metabolism, Male, Middle Aged, Mutation genetics, NF-kappa B genetics, NF-kappa B immunology, Phenotype, Tumor Necrosis Factor-alpha immunology, Cystic Fibrosis immunology, Cytokines metabolism, Respiratory Mucosa cytology, Respiratory Mucosa immunology, Respiratory Mucosa metabolism
- Abstract
It is controversial whether mutations in cystic fibrosis transmembrane conductance regulator intrinsically dysregulate inflammation. We characterized passage 2 human tracheobronchial epithelial cell cultures morphologically and physiologically and determined whether cytokine production or nuclear factor-kappaB activation was systematically altered in cystic fibrosis (CF) cells. Non-CF and CF cells originating from a total of 33 and 25 lungs, respectively, were available for culture on plastic or at an air-liquid interface until well differentiated. Forskolin-stimulated short-circuit currents were present in representative polarized non-CF cultures and were absent in CF cultures, whereas uridine 5'-triphosphate-stimulated currents were present in both. Constitutive or interleukin (IL)-1beta-induced IL-8 or IL-6 secretion or nuclear factor-kappaB activity was not significantly different between non-CF and CF cells. The cytokines regulated upon activation, normal T cell expressed and secreted (RANTES) and IL-10 were not detectable. Stimulation with tumor necrosis factor-alpha or a synthetic toll-like receptor 2 agonist or variable doses and times of Staphylococcus aureus culture filtrate revealed a single dose- and time-dependent difference in IL-8 production by CF cells. Interestingly, although IL-8 secretion after stimulation with Pseudomonas aeruginosa filtrates was not greater in CF cells in the absence of human serum, it was variably greater in its presence. Thus, although exaggerated responses may develop under certain conditions, our results do not support an overall intrinsically hyperinflammatory phenotype in CF cells.
- Published
- 2004
- Full Text
- View/download PDF
11. CD14-dependent lipopolysaccharide-induced beta-defensin-2 expression in human tracheobronchial epithelium.
- Author
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Becker MN, Diamond G, Verghese MW, and Randell SH
- Subjects
- Bronchi metabolism, Cells, Cultured, Humans, Lipopolysaccharides pharmacology, Defensins physiology, Epithelial Cells physiology, Lipopolysaccharide Receptors physiology, Signal Transduction drug effects
- Abstract
The induction of host antimicrobial molecules following binding of pathogen components to pattern recognition receptors such as CD14 and the Toll-like receptors (TLRs) is a key feature of innate immunity. The human airway epithelium is an important environmental interface, but LPS recognition pathways have not been determined. We hypothesized that LPS would trigger beta-defensin (hBD2) mRNA in human tracheobronchial epithelial (hTBE) cells through a CD14-dependent mechanism, ultimately activating NF-kappa B. An average 3-fold increase in hBD2 mRNA occurs 24 h after LPS challenge of hTBE cells. For the first time, we demonstrate the presence of CD14 mRNA and cell surface protein in hTBE cells and show that CD14 neutralization abolishes LPS induction of hBD2 mRNA. Furthermore, we demonstrate TLR mRNA in hTBE cells and NF-kappa B activation following LPS. Thus, LPS induction of hBD2 in hTBE cells requires CD14, which may complex with a TLR to ultimately activate NF-kappa B.
- Published
- 2000
- Full Text
- View/download PDF
12. Drosophila dumpy is a gigantic extracellular protein required to maintain tension at epidermal-cuticle attachment sites.
- Author
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Wilkin MB, Becker MN, Mulvey D, Phan I, Chao A, Cooper K, Chung HJ, Campbell ID, Baron M, and MacIntyre R
- Subjects
- Amino Acid Sequence, Animals, Chromosome Breakage, Chromosome Mapping, Chromosome Walking, Cloning, Molecular, Drosophila genetics, Epidermis physiology, Extracellular Matrix physiology, Extracellular Matrix Proteins chemistry, Gene Expression Regulation, Developmental, In Situ Hybridization, Insect Proteins chemistry, Magnetic Resonance Spectroscopy, Molecular Sequence Data, Drosophila growth & development, Drosophila Proteins, Extracellular Matrix Proteins genetics, Extracellular Matrix Proteins physiology, Genes, Insect, Insect Proteins genetics, Insect Proteins physiology
- Abstract
Background: Growth and morphogenesis during development depend both on patterning genes, which assign positional information, and on genes that regulate mechanical forces. The dumpy gene of the fruit fly Drosophila melanogaster is an example of the latter class, with mutant phenotypes affecting size and shape of the limbs, thoracic cuticle, trachea and mouthparts., Results: The genetically complex dumpy locus was found to span over 100 kb and encode a gigantic 2.5 MDa extracellular matrix protein. Dumpy represents an extreme form of modular protein evolution, containing 308 epidermal growth factor (EGF) modules, interspersed with a new module class, DPY, and terminating in a crosslinking zona pellucida domain and membrane anchor sequence. We determined the three-dimensional structure of the DPY module by nuclear magnetic resonance (NMR) spectroscopy and found that it forms a disulphide-stabilised beta sheet motif, capable of linking end-to-end with EGF modules to form a fibre. Consistent with its cuticle phenotypes, dumpy is expressed at several sites of cuticle-epidermal cell attachment, including the trachea and the muscle tendon cells, which mediate anchorage of the muscles to the cuticle., Conclusions: The dumpy gene encodes a gigantic extracellular molecule that we predict to be a membrane-anchored fibre of almost a micrometer in length. Insertion and crosslinking of this fibre within the cuticle may provide a strong anchor for the underlying tissue, allowing it to maintain mechanical tension at sites under stress. This would explain its contribution to tissue morphogenesis through its regulation of mechanical properties.
- Published
- 2000
- Full Text
- View/download PDF
13. Alteration of brainstem auditory evoked potentials in diethylbenzene and diacetylbenzene-treated rats.
- Author
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Gagnaire F, Becker MN, and De Ceaurriz J
- Subjects
- Administration, Oral, Animals, Central Nervous System Diseases chemically induced, Central Nervous System Diseases physiopathology, Dose-Response Relationship, Drug, Injections, Intraperitoneal, Male, Rats, Rats, Sprague-Dawley, Time Factors, Acetophenones toxicity, Benzene Derivatives toxicity, Evoked Potentials, Auditory, Brain Stem drug effects
- Abstract
Male Sprague-Dawley rats were treated either with 1,2-diethylbenzene (1,2-DEB) or its putative active metabolite, 1,2-diacetylbenzene (1,2-DAB). Experimental rats and appropriate controls were examined electrophysiologically for brainstem auditory evoked potentials (BAEP). Oral administration of 1,2-DEB (75 or 100 mg kg-1 once a day, 4 days a week, for 8 weeks) and intraperitoneal injection of 1,2-DAB (10 or 15 mg kg-1 once a day, 4 days a week, for 8 weeks) produced time- and dose-dependent increases in the peak latencies of all BAEP components as well as in interpeak (I-V) differences, and a decrease in the amplitudes of all the components. The absolute and interpeak latencies recovered partially during an 8-week (1,2-DEB) or a 10-week (1,2-DAB) recovery period, whereas there were long-lasting decreases in peak amplitudes.
- Published
- 1992
- Full Text
- View/download PDF
14. Diethylbenzene inhalation-induced electrophysiological deficits in peripheral nerves and changes in brainstem auditory evoked potentials in rats.
- Author
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Gagnaire F, Becker MN, Marignac B, Bonnet P, and De Ceaurriz J
- Subjects
- Action Potentials drug effects, Action Potentials physiology, Administration, Inhalation, Animals, Central Nervous System Diseases chemically induced, Central Nervous System Diseases physiopathology, Dose-Response Relationship, Drug, Electrophysiology, Male, Motor Neurons drug effects, Motor Neurons physiology, Neurons, Afferent drug effects, Neurons, Afferent physiology, Peripheral Nervous System Diseases physiopathology, Psychomotor Performance drug effects, Psychomotor Performance physiology, Rats, Rats, Sprague-Dawley, Synaptic Transmission drug effects, Synaptic Transmission physiology, Benzene Derivatives toxicity, Evoked Potentials, Auditory, Brain Stem drug effects, Peripheral Nervous System Diseases chemically induced
- Abstract
Motor and sensory conduction velocities (MCV and SCV), amplitude of the sensory action potential (ASAP) of the tail nerve and parameters of brainstem auditory evoked potentials (BAEP) were studied in male Sprague-Dawley rats after prolonged inhalation exposure to a commercial isomer mixture of diethylbenzene (DEB mixture) containing 6% 1,2-DEB. The MCV, SCV and ASAP were studied in one control group (10 rats) and three groups of 12 rats exposed to 500, 700 or 900 ppm DEB mixture for 6 h daily, 5 days per week, for 18 weeks. Rats used for recording BAEP (one control group and two other groups of 15 rats) were exposed to 600 and 800 ppm DEB mixture. The exposure time was the same. Rats exposed to DEB mixture exhibited a time- and concentration-dependent decrease in MCV, SCV and ASAP and a time- and concentration-dependent increase of both the peak latencies of all BAEP components and the interpeak (I-V) differences.
- Published
- 1992
- Full Text
- View/download PDF
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