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  • 1
  • 2
    Keywords: CLONING ; PROTEIN ; SEQUENCE ; ISOFORMS ; IDENTIFICATION ; CHROMATOGRAPHY ; LECTINS ; RIBOSOME-INACTIVATING PROTEINS ; PLANTS ; Riproximin ; A-CHAIN ; Plant lectin ; RICINUS-COMMUNIS AGGLUTININ ; SAMBUCUS ; Type II RIP ; VISCUM-ALBUM L ; Ximenia americana
    Abstract: Highly pure riproximin was isolated from the fruit kernels of Ximenia americana, a defined, seasonally available and potentially unlimited herbal source. The newly established purification procedure included an initial aqueous extraction, removal of lipids with chloroform and subsequent chromatographic purification steps on a strong anion exchange resin and lactosyl-Sepharose. Consistent purity and stable biological properties were shown over several purification batches. The purified, kernel-derived riproximin was characterized in comparison to the African plant material riproximin and revealed highly similar biochemical and biological properties but differences in the electrophoresis pattern and mass spectrometry peptide profile. Our results suggest that although the purified fruit kernel riproximin consists of a mixture of closely related isoforms, it provides a reliable basis for further research and development of this type II ribosome inactivating protein (RIP).
    Type of Publication: Journal article published
    PubMed ID: 22178181
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  • 3
    Keywords: APOPTOSIS ; TOXICITY ; MECHANISM ; IDENTIFICATION ; RAT-LIVER METASTASIS ; RICIN-A-CHAIN ; PLANTS ; TRADITIONAL MEDICINE ; XIMENIA-AMERICANA ; RNA N-GLYCOSIDASE
    Abstract: The development of new anticancer drugs is a salient problem and the traditional use of plants is a potentially rich source of information for detecting new molecules with antineoplastic activity. Riproximin is a recently detected cytotoxic type II ribosome inactivating protein with high selectivity for certain tumor cell lines. Its activity was recognized as the main component in a plant powder used by African healers for treating cancer. By ribulose bisphosphate carboxylase gene sequencing analysis, the powder was identified to be derived from the plant Ximenia americana. The cDNA sequence of riproximin was identified, the protein was modeled to contain one A- and a B-chain, respectively, and a reliable purification procedure from kernels of X. americana was established. Riproximin displays high but differential antiproliferative activity in a panel of human and rodent cancer cell lines, with concentrations inhibiting cell proliferation by 50% (IC50 values) that diverge by a factor of 100. Consistent antineoplastic activity was detected in colorectal and pancreatic cancer liver metastasis models in rats. The cytotoxic mechanism of action was determined to be based on cellular uptake of riproximin followed by its A-chain prompted depurination of the 28S ribosomal RNA and induction of unfolded protein response. Riproximin's specificity depended on its B-chain connected binding to cell surface glycans, the presence of which is crucial for subsequent internalization into cells and cytotoxicity. These N- and O-glycans include bi- and tri-antennary NA structures (NA2/NA3) as well as Tn3 structures (clustered Tn antigen). Riproximin was found to crosslink proteins with N- and O-glycan structure, thus indicating both types of binding sites on its B chain. Due to this crosslinking ability, riproximin is expected to show prominent cytotoxicity towards cells expressing both, NA2/NA3 and clustered Tn structures. Apart from the properties of riproximin, the plant X. americana has been known for some medical uses in traditional African medicine, including various types of infections.
    Type of Publication: Journal article published
    PubMed ID: 24699434
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  • 4
    Abstract: PGC-1alpha is a versatile inducer of mitochondrial biogenesis and responsive to the changing energy demands of the cell. As mitochondrial ATP production requires proteins that derive from translation products of cytosolic ribosomes, we asked whether PGC-1alpha directly takes part in ribosomal biogenesis. Here, we show that a fraction of cellular PGC-1alpha localizes to the nucleolus, the site of ribosomal transcription by RNA polymerase I. Upon activation PGC-1alpha associates with the ribosomal DNA and boosts recruitment of RNA polymerase I and UBF to the rDNA promoter. This induces RNA polymerase I transcription under different stress conditions in cell culture and mouse models as well as in healthy humans and is impaired already in early stages of human Huntington's disease. This novel molecular link between ribosomal and mitochondrial biogenesis helps to explain sarcopenia and cachexia in diseases of neurodegenerative origin.
    Type of Publication: Journal article published
    PubMed ID: 28819135
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  • 5
    Keywords: carcinoma ; glycosylation ; SERUM ; BREAST-CANCER PATIENTS ; prostate-specific antigen ; RIBOSOME-INACTIVATING PROTEINS ; HUMAN COLON ; XIMENIA-AMERICANA ; BOVINE SUBMAXILLARY MUCIN ; SEMINAL PLASMA
    Abstract: Riproximin is a cytotoxic type II ribosome-inactivating protein showing high selectivity for tumor cell lines. Its binding to cell surface glycans is crucial for subsequent internalization and cytotoxicity. In this paper, we describe a unique mechanism of interaction and discuss its implications for the cellular targeting and cytotoxicity of riproximin. On a carbohydrate microarray, riproximin specifically bound to two types of asialo-glycans, namely to bi- and triantennary complex N-glycan structures (NA2/NA3) and to repetitive N-acetyl-d-galactosamine (GalNAc), the so-called clustered Tn antigen, a cancer-specific O-glycan on mucins. Two glycoproteins showing high riproximin binding, the NA3-presenting asialofetuin and the clustered Tn-rich asialo-bovine submaxillary mucin, were subsequently chosen as model glycoproteins to mimic the binding interactions of riproximin with the two types of glycans. ELISA analyses were used to relate the two binding specificities of riproximin to its two sugar binding sites. The ability of riproximin to cross-link the two model proteins revealed that binding of the two types of glycoconjugates occurs within different binding sites. The biological implications of these binding properties were analyzed in cellular assays. The cytotoxicity of riproximin was found to depend on its specific and concomitant interaction with the two glycoconjugates as well as on dynamic avidity effects typical for lectins binding to multivalent glycoproteins. The presence of definite, cancer-related structures on the cells to be targeted determines the therapeutic potency of riproximin. Due to its cross-linking ability, riproximin is expected to show a high degree of specificity for cells exposing both NA2/NA3 and clustered Tn structures.
    Type of Publication: Journal article published
    PubMed ID: 22872642
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  • 6
    ISSN: 0044-2313
    Keywords: Chemistry ; Inorganic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: Preparation and Some Properties of Silyl Derivatives of Hyponitrous Acid and of its AmidesBis(trimethylsilyl)hyponitrite Me3SiO—N=N—OSiMe3 (1) is formed by reaction of Ag2N2O2 with Me3SiCl and of (Me3Si)2NOLi with SO2Cl2. Tris(trimethylsilyl)-1-hydroxytriazen (2) is formed by reaction of (Me3Si)3N2Li and i-amyl nitrite. The thermolysis of 1 leads to nitrogen, trimethylsilanol, and hexamethyldisiloxane, the thermolysis of 2 leads to hexamethyldisiloxane and trimethylsilylazide. HO—N=N—NH2 could not be isolated as a product of protolysis of 2. 2 is converted into LiO—N=N—N(SiMe3)2 (4) by LiNR2 (R = Me, SiMe3), 4 is converted into MeO—N=N—N(SiMe3)2 (5) by Me2SO4. The thermolysis of 4 leads to LiN3 and (Me3Si)2O, the thermolysis of 5 leads to Me3SiN3 and Me3SiOMe.
    Notes: Bis(trimethylsilyl)hyponitrit Me3SiO—N=N—OSiMe3 (1) entsteht durch Reaktion von Ag2N2O2 mit Me3SiCl sowie von (Me3Si)2NOLi mit SO2Cl2. Tris(trimethylsilyl)-1-hydroxytriazen Me3SiO—N=N—N(SiMe3)2 (2) bildet sich aus (Me3Si)3N2Li und i-Amylnitrit. Die Thermolyse von 1 führt zu Stickstoff, Trimethylsilanol und Hexamethyldisiloxan, die Thermolyse von 2 zu Hexamethyldisiloxan und Trimethylsilylazid. HO—N=N—NH2 ließ sich nicht als Produkt der 2-Protolyse isolieren. 2 wird durch LiNR2 (R = Me, Me3Si) in LiO—N=N—N(SiMe3)2 (4), 4 durch Me2SO4 in MeO—N=N—N(SiMe3)2 (5) übergeführt. Die Thermolyse von 4 führt zu LiN3 und (Me3Si)2O, von 5 zu Me3SiN3 und Me3SiOMe.
    Additional Material: 2 Tab.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1435-2451
    Keywords: Biliary tract ; Endoscopic sphincterotomy ; Relaparotomy ; Gallenwegssystem ; Endoskopische Sphincterotomie ; Relaparotomie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Vom 1.1.1973 bis 28.2.1980 wurden 2593 Primäreingriffe an den Gallenwegen durchgeführt. Dem stehen 162 Relaparotomien und 285 endoskopische Sphincterotomien nach vorausgegangener Cholecystektomie gegenüber. Der Reeingriff erfolgte in 36 Fällen wegen Frühkomplikationen und in 126 Fällen wegen Spätkomplikationen. Die Gesamtmortalität betrug 1,8%. Beim alten und beim Risikopatienten kann die endoskopische Sphincterotomie die Relaparotomie ersparen.
    Notes: Summary In the time from 1.1.1973 until 28.2.1980 2593 primary surgical interventions at the biliary tract had been performed. In the same period 162 reinterventions on the biliary system and 285 endoscopic sphincterotomies were done in cholecystectomized patients. Relaparotomy was indicated for early complications in 36 and for late complications in 126 cases. The overall mortality rate was 1.8%. In the aged and high-risk patient endoscopic sphincterotomy instead of relaparotomy is preferred.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1435-2451
    Keywords: Injury, abdominal, blunt ; Liver damage ; Delayed effects ; Stumpfes Bauchtrauma ; Leberverletzungen ; Spätergebnisse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Diagnose eines kompensierten Leberparenchymschaden ist trotz unzähliger Funktionsprüfungen schwierig. Ist der Gewebeuntergang und die reparative Phase noch nicht zum Stillstand gekommen, bieten die Patienten Krankheitszeichen, die in Korrelation mit dem Operationsbefund und den Labortests oft unglaubwürdig erscheinen. Wann mit dem Auftreten von Schädigungszeichen zu rechnen ist und inwieweit sie Folge des Traumas sind, konnte anhand der geringen Zahl der Nachuntersuchten nicht sicher festgestellt werden. Völlige Sorglosigkeit scheint nicht gerechtfertigt.
    Notes: Summary The diagnosis of compensated liver parenchyma damage is difficult in spite of numerous function tests. If the destruction of the tissue and the reparative phase are not complete, the patients often exhibit symptoms that do not correlate with the findings at operation or with the results of laboratory tests. It has not been possible to determine with certainty when symptoms of damage can be expected or to what extent they are the result of trauma, because the number of patients that have been followed up is too small. Complete lack of concern, however, does not appear to be justified.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1437-1596
    Keywords: Bariumsulfat, Verteilung im Organismus ; Kontrastmittelzwischenfall
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Law
    Description / Table of Contents: Zusammenfassung Bei einer nach einem Kontrastmittelzwischenfall in einem protrahierten Schock verstorbenen Frau wurde mit morphologischen und chemischen Methoden das Organspektrum von auf vorwiegend hämatogenem Wege verteiltem Bariumsulfat untersucht. Das Kontrastmittel konnte beinahe diffus im Bereiche des Gehirns, des Herzens, der Milz, der Leber, der Lunge und der Nieren in der Capillarstrombahn, vorzugsweise an Makrophagen gebunden, nachgewiesen werden. Cytotoxische, insbesondere auch anaphylaktische Reaktionen waren nicht nachweisbar. Die pathologische Leistung bei einem unbeabsichtigten Eintritt von BaSO4 in die Blutbahn ist vorwiegend in den „mechanischen“ Embolieeigenschaften des inkorporierten Kontrastmittels zu sehen.
    Notes: Summary The spread of barium sulfate through the organs various of a woman who died during a protracted state of shock following the installation of an opaque medium was investigated by morphological and chemical methods. The opaque medium was seen diffusely through most of the brain, heart, spleen, liver, lungs and the capillary bed of the kidneys, chiefly attached to macrophages. There were no cytotoxic, anaphylactic or anaphylactoid reactions. The pathological effects are due more to the purely mechanical, embolic properties of the compound BaSO4.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Langenbeck's archives of surgery 264 (1950), S. 96-98 
    ISSN: 1435-2451
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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