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  • 1
    Digitale Medien
    Digitale Medien
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 27 (1944), S. 1456-1463 
    ISSN: 0018-019X
    Schlagwort(e): Chemistry ; Organic Chemistry
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 28 (1945), S. 1522-1522 
    ISSN: 0018-019X
    Schlagwort(e): Chemistry ; Organic Chemistry
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 3
    Publikationsdatum: 2009-09-04
    Beschreibung: The Hedgehog (Hh) signaling pathway is inappropriately activated in certain human cancers, including medulloblastoma, an aggressive brain tumor. GDC-0449, a drug that inhibits Hh signaling by targeting the serpentine receptor Smoothened (SMO), has produced promising anti-tumor responses in early clinical studies of cancers driven by mutations in this pathway. To evaluate the mechanism of resistance in a medulloblastoma patient who had relapsed after an initial response to GDC-0449, we determined the mutational status of Hh signaling genes in the tumor after disease progression. We identified an amino acid substitution at a conserved aspartic acid residue of SMO that had no effect on Hh signaling but disrupted the ability of GDC-0449 to bind SMO and suppress this pathway. A mutation altering the same amino acid also arose in a GDC-0449-resistant mouse model of medulloblastoma. These findings show that acquired mutations in a serpentine receptor with features of a G protein-coupled receptor can serve as a mechanism of drug resistance in human cancer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yauch, Robert L -- Dijkgraaf, Gerrit J P -- Alicke, Bruno -- Januario, Thomas -- Ahn, Christina P -- Holcomb, Thomas -- Pujara, Kanan -- Stinson, Jeremy -- Callahan, Christopher A -- Tang, Tracy -- Bazan, J Fernando -- Kan, Zhengyan -- Seshagiri, Somasekar -- Hann, Christine L -- Gould, Stephen E -- Low, Jennifer A -- Rudin, Charles M -- de Sauvage, Frederic J -- New York, N.Y. -- Science. 2009 Oct 23;326(5952):572-4. doi: 10.1126/science.1179386. Epub 2009 Sep 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genentech, South San Francisco, CA 94080, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19726788" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Amino Acid Substitution ; Anilides/metabolism/pharmacology/*therapeutic use ; Animals ; Antineoplastic Agents/metabolism/pharmacology/*therapeutic use ; Brain Neoplasms/*drug therapy/*genetics/pathology ; Cell Line, Tumor ; Cinnamates/pharmacology ; Drug Resistance, Neoplasm ; Hedgehog Proteins/antagonists & inhibitors/genetics/*metabolism ; Humans ; Medulloblastoma/*drug therapy/*genetics/pathology ; Mice ; Molecular Sequence Data ; Mutant Proteins/antagonists & inhibitors/chemistry/metabolism ; Mutation, Missense ; Neoplasm Metastasis ; Protein Conformation ; Pyridines/metabolism/pharmacology/*therapeutic use ; Receptors, Cell Surface/genetics/metabolism ; Receptors, G-Protein-Coupled/antagonists & ; inhibitors/chemistry/*genetics/metabolism ; Signal Transduction ; Veratrum Alkaloids/pharmacology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 4
    Publikationsdatum: 2011-02-08
    Beschreibung: Geographic atrophy (GA), an untreatable advanced form of age-related macular degeneration, results from retinal pigmented epithelium (RPE) cell degeneration. Here we show that the microRNA (miRNA)-processing enzyme DICER1 is reduced in the RPE of humans with GA, and that conditional ablation of Dicer1, but not seven other miRNA-processing enzymes, induces RPE degeneration in mice. DICER1 knockdown induces accumulation of Alu RNA in human RPE cells and Alu-like B1 and B2 RNAs in mouse RPE. Alu RNA is increased in the RPE of humans with GA, and this pathogenic RNA induces human RPE cytotoxicity and RPE degeneration in mice. Antisense oligonucleotides targeting Alu/B1/B2 RNAs prevent DICER1 depletion-induced RPE degeneration despite global miRNA downregulation. DICER1 degrades Alu RNA, and this digested Alu RNA cannot induce RPE degeneration in mice. These findings reveal a miRNA-independent cell survival function for DICER1 involving retrotransposon transcript degradation, show that Alu RNA can directly cause human pathology, and identify new targets for a major cause of blindness.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3077055/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3077055/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaneko, Hiroki -- Dridi, Sami -- Tarallo, Valeria -- Gelfand, Bradley D -- Fowler, Benjamin J -- Cho, Won Gil -- Kleinman, Mark E -- Ponicsan, Steven L -- Hauswirth, William W -- Chiodo, Vince A -- Kariko, Katalin -- Yoo, Jae Wook -- Lee, Dong-ki -- Hadziahmetovic, Majda -- Song, Ying -- Misra, Smita -- Chaudhuri, Gautam -- Buaas, Frank W -- Braun, Robert E -- Hinton, David R -- Zhang, Qing -- Grossniklaus, Hans E -- Provis, Jan M -- Madigan, Michele C -- Milam, Ann H -- Justice, Nikki L -- Albuquerque, Romulo J C -- Blandford, Alexander D -- Bogdanovich, Sasha -- Hirano, Yoshio -- Witta, Jassir -- Fuchs, Elaine -- Littman, Dan R -- Ambati, Balamurali K -- Rudin, Charles M -- Chong, Mark M W -- Provost, Patrick -- Kugel, Jennifer F -- Goodrich, James A -- Dunaief, Joshua L -- Baffi, Judit Z -- Ambati, Jayakrishna -- NIHU10EY013729/EY/NEI NIH HHS/ -- P30 EY006360/EY/NEI NIH HHS/ -- P30 EY014800/EY/NEI NIH HHS/ -- P30 EY014800-07/EY/NEI NIH HHS/ -- P30 EY021721/EY/NEI NIH HHS/ -- P30EY003040/EY/NEI NIH HHS/ -- P30EY008571/EY/NEI NIH HHS/ -- P30EY06360/EY/NEI NIH HHS/ -- R01 EY018350/EY/NEI NIH HHS/ -- R01 EY018350-05/EY/NEI NIH HHS/ -- R01 EY018836/EY/NEI NIH HHS/ -- R01 EY018836-04/EY/NEI NIH HHS/ -- R01 EY020672/EY/NEI NIH HHS/ -- R01 EY020672-02/EY/NEI NIH HHS/ -- R01 GM068414/GM/NIGMS NIH HHS/ -- R01EY001545/EY/NEI NIH HHS/ -- R01EY011123/EY/NEI NIH HHS/ -- R01EY015240/EY/NEI NIH HHS/ -- R01EY015422/EY/NEI NIH HHS/ -- R01EY017182/EY/NEI NIH HHS/ -- R01EY017950/EY/NEI NIH HHS/ -- R01EY018350/EY/NEI NIH HHS/ -- R01EY018836/EY/NEI NIH HHS/ -- R01EY020672/EY/NEI NIH HHS/ -- R01GM068414/GM/NIGMS NIH HHS/ -- R01HD027215/HD/NICHD NIH HHS/ -- R21 EY019778/EY/NEI NIH HHS/ -- R21 EY019778-02/EY/NEI NIH HHS/ -- R21AI076757/AI/NIAID NIH HHS/ -- R21EY019778/EY/NEI NIH HHS/ -- RC1 EY020442/EY/NEI NIH HHS/ -- RC1 EY020442-02/EY/NEI NIH HHS/ -- RC1EY020442/EY/NEI NIH HHS/ -- T32HL091812/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 Mar 17;471(7338):325-30. doi: 10.1038/nature09830. Epub 2011 Feb 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ophthalmology & Visual Sciences, University of Kentucky, Lexington, Kentucky 40506, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21297615" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Alu Elements/*genetics ; Animals ; Cell Death ; Cell Survival ; Cells, Cultured ; DEAD-box RNA Helicases/*deficiency/genetics/metabolism ; Gene Knockdown Techniques ; Humans ; Macular Degeneration/*genetics/*pathology ; Mice ; MicroRNAs/metabolism ; Molecular Sequence Data ; Oligonucleotides, Antisense ; Phenotype ; RNA/*genetics/*metabolism ; Retinal Pigment Epithelium/enzymology/metabolism/pathology ; Ribonuclease III/*deficiency/genetics/metabolism
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 5
    Publikationsdatum: 1993-01-01
    Beschreibung: Rat C6 glioma cells express insulin-like growth factor I (IGF-I) and form rapidly growing tumors in syngeneic animals. When transfected with an episome-based vector encoding antisense IGF-I complementary DNA, these cells lost tumorigenicity. Subcutaneous injection of IGF-I antisense-transfected C6 cells into rats prevented formation of both subcutaneous tumors and brain tumors induced by nontransfected C6 cells. The antisense-transfected cells also caused regression of established brain glioblastomas when injected at a point distal to the tumor. These antitumor effects result from a glioma-specific immune response involving CD8+ lymphocytes. Antisense blocking of IGF-I expression may reverse a phenotype that allows C6 glioma cells to evade the immune system.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Trojan, J -- Johnson, T R -- Rudin, S D -- Ilan, J -- Tykocinski, M L -- CA-43703/CA/NCI NIH HHS/ -- HD-18271/HD/NICHD NIH HHS/ -- HD-25004/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 1993 Jan 1;259(5091):94-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉INSERM, Paris.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8418502" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Antigens, CD8/*immunology ; Brain Neoplasms/immunology/pathology/*prevention & control/*therapy ; Cytotoxicity, Immunologic ; DNA, Recombinant ; Glioma/immunology/pathology/*prevention & control/*therapy ; Immunohistochemistry ; Insulin-Like Growth Factor I/*genetics ; RNA, Antisense/pharmacology/*therapeutic use ; Rats ; T-Lymphocyte Subsets/*immunology ; *Transfection ; Tumor Cells, Cultured
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 6
    Digitale Medien
    Digitale Medien
    Weinheim : Wiley-Blackwell
    Angewandte Makromolekulare Chemie 194 (1992), S. 23-33 
    ISSN: 0003-3146
    Schlagwort(e): Chemistry ; Polymer and Materials Science
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie , Physik
    Beschreibung / Inhaltsverzeichnis: Stärke/Styrol- und Stärke/Methylacrylat-Pfropfcopolymere wurden hergestellt und ohne vorherige Abtrennung von homopolymerem Polystyrol (PS) bzw. Poly(methylacrylat) (PMA) extrudiert. Das Extrusionsverhalten ähnelte dem thermoplastischer Schmelzen darin, daß die Copolymeren die Scherung herabsetzen, eine merkliche Strangaufweitung verursachen und Eingangsdruckverluste im Kapillarfließerhalten auftreten. Diese und andere Beobachtungen deuten darauf hin, daß diese Materialien deformierbare, mit dem jeweiligen Polymeren gepfropfte Stärkepartikel in der entsprechenden Homopolymermatrix enthalten. Die Fließeigenschaften können anscheinend eher durch solche „Superpartikel“ als durch das Model1 einer kontinuierlichen, homogenen Schmelze erklärt werden.
    Notizen: Starch-g-polystyrene and starch-g-poly(methyl acrylate) copolymers were synthesized and extruded without separating homopolymer PS or PMA. The extrusion behavior resembled that of thermoplastic melts in that these products were shear thinning and exhibited significant extrudate swelling and entrance pressure losses in capillary flow. These and other observations indicate that the materials comprise deformable polymer-grafted starch particles suspended in the corresponding homopolymer melt. Flow is apparently by superparticle, rather than continuum melt mechanisms.
    Zusätzliches Material: 3 Ill.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 7
    Digitale Medien
    Digitale Medien
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 67 (1984), S. 2017-2022 
    ISSN: 0018-019X
    Schlagwort(e): Chemistry ; Organic Chemistry
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: Mild Alkaline Hydrolysis of AconitineHydrolysis of aconitine (1) with 0.04N K2CO3 in 90% MeOH at room temperature yields, besides the alkamine aconine 3 considerable amounts of 8-O-methylaconine (6) and smaller quantities of desbenzoyl-pyroaconitine (4) and 16-epi-desbenzoyl-pyroaconitine (5). Better yields of 4 and 5 are obtained when heating a solution of aconitine in 0.04N K2CO3 in 90% EtOH.
    Zusätzliches Material: 2 Tab.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 8
    Digitale Medien
    Digitale Medien
    Stamford, Conn. [u.a.] : Wiley-Blackwell
    Polymer Engineering and Science 33 (1993), S. 377-382 
    ISSN: 0032-3888
    Schlagwort(e): Chemistry ; Chemical Engineering
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie , Maschinenbau , Physik
    Notizen: The viscoelastic responses of some molten polymers, and particularly of low density polyethylene (LDPE), are known to vary with processing history. Reasons for the variations include the effects of shear history on morphological states of the polymer, or on its molecular weight parameters. A typical low density polyethylene has been used to test the shear-history dependence concept following a variety of processing steps. The polymer was sheared in single-screw and twin-screw extruders, and in a high speed melter / mixer (Gelimat). Samples also were precipitated from very dilute solutions in trichlorobenzene and in p-xylene. GPC analyses showed that, in general, these procedures did not affect the various moments of molecular weight. An exception was the Gelimat-mixed sample, for which mild reductions in Mn and Mw were noted. In contrast, melt viscosity and elasticity readings, the former from low shear evaluations and the latter from extrudate swelling, were affected by the various procedures. A drop in melt viscosity and in elasticity was observed, being most pronounced for precipitated and twin-screw extruded versions of the LDPE. Reductions also were observed in the specimen sheared in the Gelimat instrument. Following conditioning at the test extrusion temperature (170°C), viscous and elastic responses tended to revert to those of the unsheared control sample, the exception again being the sample sheared in the Gelimat melter / mixer. Of the various mechanisms proposed in the literature to account for transient property changes such as those reported, temporary changes in the degree of chain entanglement appear the most satisfactory explanation. Irreversible alterations in viscoelastic properties may be associated with changes in molecular weights due to processing at high shear.
    Zusätzliches Material: 2 Ill.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 9
    Digitale Medien
    Digitale Medien
    Stamford, Conn. [u.a.] : Wiley-Blackwell
    Polymer Engineering and Science 33 (1993), S. 1370-1371 
    ISSN: 0032-3888
    Schlagwort(e): Chemistry ; Chemical Engineering
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie , Maschinenbau , Physik
    Zusätzliches Material: 1 Ill.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 10
    Digitale Medien
    Digitale Medien
    Stamford, Conn. [u.a.] : Wiley-Blackwell
    Polymer Engineering and Science 34 (1994), S. 570-579 
    ISSN: 0032-3888
    Schlagwort(e): Chemistry ; Chemical Engineering
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie , Maschinenbau , Physik
    Notizen: In this paper we address the aspects associated with shear modification of low density polyethylene by extrusion. By successive passes of the polymer through an extruder it can be shown that both the melt viscosity and melt elasticity are reduced by shear modification. These reversible variations are not accompanied by significant changes in molecular weight distribution. The major effects of extrusion are to decrease the amount of elastically effecitve material. Study of proton relaxation times at 150°C shows that the melt comprises regions of relatively ordered, entangled, and unentangled polymer. Shearing reduces the proportion of more ordered material. The elastically effective anchors that are reduced by shearing are regions with restricted segmental mobility rather than conventional entanglements or intermolecular knots. Successive extrusions produce a relatively small decrease in the number of such constraints to molecular motion. Repeated shearing has a diminishing effect on the proportion of more ordered material in the polyethlene melt. This parallels observations of the effects of repeated shear modification on the properties of polyethylene films and other extrudates.
    Zusätzliches Material: 14 Ill.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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