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Добірка наукової літератури з теми "Amanitine"

Автор: Grafiati

Опубліковано: 10 березня 2023

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Статті в журналах з теми "Amanitine"

Kubicka, Magdalena, Joanna Wilk, Paweł Dębiec, Krystian Cholewa, Magdalena Makarewicz, and Adrianna Szymańska. "Amanitine poisoning - cases, management, therapy results." Journal of Education, Health and Sport 13, no. 4 (March 1, 2023): 276–80. http://dx.doi.org/10.12775/jehs.2023.13.04.032.

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Mushroom poisoning continues to be a serious clinical problem. The most serious are intoxications with mushrooms containing cytotropic toxins with predominant injury of liver, kidneys and heart. The toxic properties of the phalloides are mainly due to α-amanitin, which is an inhibitor of RNA polymerase II. The clinical course of poisoning can be divided for 4 periods. The asymptomatic period usually lasts 6-24 hours after mushroom consumption. Then the period of the gastrointestinal disorder lasting on average 12-24 hours. The second latency period with apparent improvement of the patient's general condition lasting 12-24 hours is subjected to the stage, during which biochemical markers of hepatocyte activity appear. After a few days (usually on the 4-5th day) from poisoning, kidney function may occur (oliguria or anuria), and circulatory system disorders may also occur. Death usually occurs between 4-16 days after poisoning. The treatment of poisoning with amanita phalloides includes a number of procedures, including rapid removal of toxins, blocking the penetration of amatoxins into the hepatic cell, compensation of systemic metabolic disorders, and extracorporeal support of liver function.

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Mydlík, M. "Haemoperfusion of Alfa Amanitine -- In Vitro Study." Toxicology Letters 78 (August 1995): 59. http://dx.doi.org/10.1016/03784-2749(59)4855b-.

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Gicquel, T., S. Lepage, O. Tribut, B. Duretz та I. Morel. "O44: Dosage des amatoxines (α-amanitine, β-amanitine) et de la phalloidine dans les urines par LC-HR-MS". Toxicologie Analytique et Clinique 26, № 2 (червень 2014): S25—S26. http://dx.doi.org/10.1016/s2352-0078(14)70052-6.

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Vlaskin, D. N., E. T. Gainullina, O. V. Klyuster, I. V. Rybal’chenko, S. B. Ryzhikov, and V. F. Taranchenko. "Express method for detection of Amanita phalloides amanitine toxins." Bulletin of Experimental Biology and Medicine 141, no. 1 (January 2006): 110–11. http://dx.doi.org/10.1007/s10517-006-0107-2.

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Schenk, M., S. Rubitschek, C. Thiel, K. Knubben, M. M. Morgalla, A. Etspüler, and A. Königsrainer. "AMANITINE INTOXICATION IN A PORCINE MODEL: WHEN TRANSPLANT, WHEN WAIT FOR REGENERATION?" Transplantation 86, Supplement (July 2008): 198. http://dx.doi.org/10.1097/01.tp.0000332246.68047.7d.

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Muraoka, Shinjiro, Nobuko Fukamachi, Kiyohisa Mizumoto, and Takao Shinozawa. "Detection and Identification of Amanitins in the Wood-Rotting Fungi Galerina fasciculata andGalerina helvoliceps." Applied and Environmental Microbiology 65, no. 9 (September 1, 1999): 4207–10. http://dx.doi.org/10.1128/aem.65.9.4207-4210.1999.

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ABSTRACT More than 600 strains of wood-rotting fungi were screened for the detection of amanitins. Three strains of Galerina fasciculata and 18 strains of Galerina helvolicepscontained amanitins. These strains contained mainly α- and β-amanitins in the native fruit bodies, while α- and γ-amanitins were found in liquid-cultured mycelia. Purified amanitins were confirmed by their chromatographic profiles, spectra (UV, Fourier transform infrared, and atmospheric ionization mass), cytotoxicity for mammalian cell lines (3T3 and SiHa), and inhibitory effects on RNA polymerase II. The results revealed that the purified amanitin fractions from these species are identical to authentic amanitins and suggest that these two species must be handled as poisonous mushrooms.

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Feigel, Bartłomiej, ariusz Zuba, and Wojciech Lechowicz. "Screening method for the analysis of blood and urine for the presence of naturally occurring toxic compounds from mushrooms (fungi) using the LC-MS method." Problems of Forensic Sciences, no. 126-127 (March 29, 2022): 137–51. http://dx.doi.org/10.4467/12307483pfs.20.008.15448.

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Analysis of biological material collected during autopsies and even from living humans for the presence of amanitins and other fungal toxins remains a challenge in forensic toxicology. A qualitative method for the detection of α-amanitin, β-amanitin, γ-amanitin, muscarine, and psilocin in blood and urine has been developed. To achieve this goal, solid phase extraction HLB 3cc 60mg columns were used. Blood and urine samples were purified with water and aqueous methanol solution, and then extracted with acetonitrile. An LC/QTOF system equipped with a C18 column was applied to identify the analytes. Acetonitrile and water with formic acid were utilized as mobile phases. The developed method was validated. The detection limits for α-amanitin, β-amanitin, γ-amanitin, muscarine and psilocin are, respectively, 1.4 ng/ml, 0.3 ng/ml, 1.2 ng/ml, 1.8 ng/ml, and 0.3 ng/ml in blood, and 1.5 ng/ml, 2.1 ng/ml, 1.5 ng/ml, 1.6 ng/ml, and 1.1 ng/ml in urine. The developed method allows for efficient, qualitative identification of all the above-mentioned compounds in a toxicological laboratory.

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Flammer, René, and Katharina M. Schenk-Jäger. "Pilzvergiftungen – die Schattenseiten des Myzetismus." Therapeutische Umschau 66, no. 5 (May 1, 2009): 357–64. http://dx.doi.org/10.1024/0040-5930.66.5.357.

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Die meisten Pilzvergiftungen manifestieren sich innerhalb von 12 Stunden mit Brechdurchfällen. Sie lassen sich grob in Ereignisse mit kurzer (< 4h) und langer Latenz (> 4h) einteilen. In der Regel muss bei langen Latenzzeiten (meistens 8 - 12 - 18h) ein Phalloides-Syndrom erwogen werden, besonders nach Verzehr unkontrollierter Wildpilze. Kürzere Latenzzeiten schließen jedoch eine Amatoxin-Vergiftung nicht aus. Denn üppige Mahlzeiten der auch an Chitin reichen Pilze, Mischgerichte und individuelle Faktoren verkürzen gelegentlich die Latenzzeit und verschleiern eine Amatoxinvergiftung. Deshalb ist jeder Brechdurchfall nach Pilzgenuss bis zum Gegenbeweis verdächtig auf eine Vergiftung durch amanitinhaltige Pilze. Wenn sich die Ursache der Beschwerden nicht innerhalb einer halben Stunde unter Beizug mykologischer Assistenz klären lässt, muss das Phalloides-Programm aktiviert werden. In der Zwischenzeit werden noch vorhandene Pilzfragmente im Abfall, in Mahlzeitenresten und Erbrochenem analysiert (Sporenanalyse) und der Urin auf Amanitine (ELISA) untersucht. Mit dem Grundsatz “Therapie vor Diagnose“ dürfte sich die Mortalität der Knollenblätterpilzvergiftung von aktuell etwa 5% weiter senken lassen. Die aktuellen Therapieprogramme vermittelt das Schweizerische Toxikologische Informationszentrum (Tel. 145), ebenso die Adressen der speziell für Notfälle ausgebildeten Pilzfachleute, die auch unter www.vapko.ch aufgelistet sind. Von den 18 Vergiftungssyndromen stellen wir die in der Schweiz häufigsten und wichtigsten vor. In der Übersicht sind die anderen Syndrome mit aufgeführt. Realtiv häufig sind das Gastrointestinale Frühsyndrom mit Latenz < 4h und die Indigestion mit variabler Latenzzeit von 1–20h. Rauschzustände nach Genuss von Fliegen- und Pantherpilzen sind selten. Hingegen ist Psychodelie nach Genuss von Psilocyben häufig, wobei nur ausnahmsweise ärztliche Hilfe beansprucht wird. Bei Spätmanifestationen nach Tagen wie Nierenversagen oder Rhabdomyolyse empfiehlt sich die Frage nach mykophagen Gewohnheiten. Nur so wird man einem Orellanus- oder Equestre-Syndrom auf die Spur kommen. Pilze im Hausgarten verlocken Kinder oft zum Spielen und kleinen Kostproben. Wie soll man sich verängstigten Eltern gegenüber verhalten? Wie groß ist das toxikologische Potential der Pilze in den Gärten? Wir diskutieren die Optionen.

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Rėkutė, Skirmantė, Marius Miglinas, and Laurynas Rimševičius. "DAŽNIAUSI APSINUODIJIMO GRYBAIS SINDROMAI IR INKSTŲ PAŽEIDIMAI." Medicinos teorija ir praktika 22, no. 3 (January 2, 2017): 213–17. http://dx.doi.org/10.15591/mtp.2016.033.

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Reikšminiai žodžiai: grybai, apsinuodijimai, amanitinas, orelaninas, inkstai. Apsinuodijimas grybais yra reta ūminių inkstų ir kepenų pažeidimų priežastis, tačiau gali sukelti rimtų sveikatos sutrikimų ir baigtis mirtimi. Lietuvoje dažniausiai apsinuodijama musmirėmis (Amanita genties grybais) ir nuodingaisiais nuosėdžiais (Cortinarius orellanus), kurie atitinkamai sukelia Amanitino ir Orelano sindromus. Užsienyje nustatyta rabdomiolizės sukeltų mirties atvejų apsinuodijus nuodingąja ūmėde (Russula subnigricans). Apsinuodijus grybais, atsiranda ankstyvųjų simptomų – pykinimas, vėmimas, viduriavimas, arba vėlyvųjų – negrįžtamų inkstų ir kepenų pažeidimų, elektrolitų disbalansas, kvėpavimo ir kardiovaskulinės sistemos pokyčių. Intoksikacijos veikimo mechanizmas siejamas su DNR bei RNR sintezės inhibicija, oksidaciniais ląstelės pažeidimais. Lietuvoje diagnozė remiasi klinika ir surinkta anamneze, užsienyje atliekama inkstų biopsija ir ieškoma histologinių pokyčių. Specifinio gydymo nėra. Efektyviausias gydymas – palaikomasis: agresyvus skysčių atstatymas, elektrolitų balanso palaikymas, gyvybiškai svarbių funkcijų stabilizavimas. Sunkiais atvejais atliekama inkstų ar/ ir kepenų transplantacija. Norint apsaugoti save ir aplinkinius nuo apsinuodijimo grybais, svarbu atpažinti valgomus grybus, tinkamai apdoroti prieš valgant bei riboti vartojamų grybų kiekį.

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Bever, Candace S., Kenneth D. Swanson, Elizabeth I. Hamelin, Michael Filigenzi, Robert H. Poppenga, Jennifer Kaae, Luisa W. Cheng, and Larry H. Stanker. "Rapid, Sensitive, and Accurate Point-of-Care Detection of Lethal Amatoxins in Urine." Toxins 12, no. 2 (February 15, 2020): 123. http://dx.doi.org/10.3390/toxins12020123.

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Globally, mushroom poisonings cause about 100 human deaths each year, with thousands of people requiring medical assistance. Dogs are also susceptible to mushroom poisonings and require medical assistance. Cyclopeptides, and more specifically amanitins (or amatoxins, here), are the mushroom poison that causes the majority of these deaths. Current methods (predominantly chromatographic, as well as antibody-based) of detecting amatoxins are time-consuming and require expensive equipment. In this work, we demonstrate the utility of the lateral flow immunoassay (LFIA) for the rapid detection of amatoxins in urine samples. The LFIA detects as little as 10 ng/mL of α-amanitin (α-AMA) or γ-AMA, and 100 ng/mL of β-AMA in urine matrices. To demonstrate application of this LFIA for urine analysis, this study examined fortified human urine samples and urine collected from exposed dogs. Urine is sampled directly without the need for any pretreatment, detection from urine is completed in 10 min, and the results are read by eye, without the need for specialized equipment. Analysis of both fortified human urine samples and urine samples collected from intoxicated dogs using the LFIA correlated well with liquid chromatography–mass spectrometry (LC-MS) methods.

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Більше джерел

Дисертації з теми "Amanitine"

Le, Daré Brendan. "Xénobiotiques hépatotoxiques : études de métabolisme et mécanismes d’action." Thesis, Rennes 1, 2021. http://www.theses.fr/2021REN1B005.

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La toxicité hépatique des xénobiotiques constitue un sujet extrêmement riche, au vu des multiples mécanismes et acteurs impliqués. Ce travail de toxicologie translationnelle a pour but d’améliorer la compréhension des mécanismes hépatotoxiques de l’éthanol et des amanitines, puissantes toxines de champignons, afin d’apporter de nouveaux éléments permettant d’optimiser les prises en charge thérapeutiques des patients intoxiqués. Dans un premier temps, nous apportons des éléments supplémentaires de compréhension sur les mécanismes de réponse des macrophages à l’éthanol. Ces interactions xénobiotiques – cellules, montrées à travers l’exemple de l’induction des récepteurs P2X7, semblent participer à la sévérité des atteintes hépatiques alcooliques, et témoignent de la plasticité des macrophages en situation pathologique. Ces résultats suggèrent notamment l’intérêt du développement des antagonistes des récepteurs P2X7 dans le traitement des alcoolopathies. Dans un deuxième temps, nous appliquons l’outil de réseau moléculaire, permettant la visualisation de données complexes acquises par LC-MS/MS, à l’étude du métabolisme de xénobiotiques. L’exemple du métabolisme de l’acébutolol dans le cadre d’une intoxication médicamenteuse volontaire d’une part, et l’étude du métabolisme de la quétiapine de manière in vitro d’autre part, ont apporté des preuves consistantes sur l’intérêt du réseau moléculaire dans ce contexte. Dans un troisième et dernier temps, l’application du réseau moléculaire nous a permis d’écarter l’hypothèse d’un métabolisme des amanitines in vivo et in vitro. Par ailleurs, nos résultats montrent que le modèle cellulaire de cellules hépatiques HepaRG différenciés constitue un modèle pertinent dans l’étude des amanitines, et objectivent l’implication de la production des ROS mitochondriaux dans la toxicité de ces substances
Xenobiotic-induced hepatotoxicity is an extremely rich subject, given the multiple mechanisms and actors involved. This translational work aims to improve ethanol and amanitins (powerful fungal toxins) hepatotoxic mechanisms understanding, in order to provide new elements to optimize the therapeutic management of intoxicated patients. In a first step, we provide additional elements of understanding on macrophages response mechanisms to ethanol. These xenobiotic-cell interactions, shown through the P2X7 receptor induction example, seem to contribute in alcoholic liver damage severity, and testify to the macrophages plasticity in pathological situations. These results suggest in particular the interest of P2X7 receptor antagonist’s development in the treatment of alcoholism. In a second step, we are applied molecular networking, which allows the visualization of complex data acquired by LC-MS/MS, to xenobiotic metabolism study. The acebutolol metabolism example, in the context of voluntary drug intoxication on the one hand, and the in vitro quetiapine metabolism study on the other hand, have provided consistent evidence concerning molecular network interest in this context. In a third and final step, the molecular network application allowed us to rule out the hypothesis of an in vivo and in vitro amanitins metabolism. Moreover, our results show that the hepatocyte-like cellular model of differentiated HepaRG is a relevant model in amanitins study, and show the mitochondrial ROS production implication in these substances toxicity

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Nakaya, Helder Takashi Imoto. "Identificação e análise de expressão de RNAs intrônicos não codificadores humanos." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/46/46131/tde-08052007-144816/.

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Neste trabalho, nós mostramos estudos em larga-escala de RNAs não codificadores antisenso que são transcritos em regiões intrônicas de genes humanos. Alguns destes transcritos intrônicos possuem níveis de expressão correlacionados ao grau de diferenciação tumoral de câncer de próstata, apontando para uma relevância biológica destas mensagens em doenças complexas como o câncer. Nós também avaliamos a existência de um mecanismo comum de regulação de transcrição, compartilhado por mRNAs codificadores de proteína e RNAs intrônicos, através de análises de perfis de expressão de uma linhagem tumoral de próstata estimulada por andrógeno. A análise de ESTs e mRNAs depositados em bancos públicos de seqüências revelou mais de 55 mil RNAs Totalmente Intrônicos Não-codificadores (TIN), transcritos dos íntrons de 74% de todos os genes RefSeq únicos. Guiados por esta informação, nós desenhamos uma plataforma de oligonucleotídeos contendo sondas senso e antisenso para cada um de 7.520 transcritos TIN selecionados aleatoriamente, além de sondas para os genes codificadores de proteína correspondentes. Nós identificamos assinaturas intrônicas e exônicas de expressão tecido-específicas em fígado, próstata e rim. Os RNAs TIN antisenso mais altamente expressos eram transcritos de íntrons de genes codificadores de proteína enriquecidos na categoria ?Regulação da transcrição?. A inibição da RNA Polimerase II resultou num aumento de expressão de uma fração dos RNAs intrônicos em células em cultura, sugerindo que outras RNA Polimerases possam estar envolvidas em sua biossíntese. Um subconjunto das assinaturas intrônicas e exônicas localizadas nos mesmos loci genômicos possuíram padrões de expressão correlacionados, sugerindo que RNAs intrônicos regulem a abundância ou o padrão de uso de éxons de mensagens codificadoras de proteína. Nós identificamos diversos padrões de expressão de RNAs intrônicos, indicando que eles possam ter papéis regulatórios. Esta estratégia orientada pelo gene, que combina um microarray intrônico/exônico deve permitir análises comparativas futuras de transcrição intrônica sob várias condições fisiológicas e patológicas, avançando assim em nosso conhecimento sobre as funções biológicas destes RNAs não codificadores.
In this work, we show large-scale studies of antisense noncoding RNAs transcribed from intronic regions of human genes. The correlation of expression levels of some intronic transcripts to the degree of tumor differentiation in prostate cancer points to the biological relevance of these messages in complex diseases such as cancer. We also evaluated the existence of a common mechanism of regulation of transcription shared by protein-coding mRNAs and intronic RNAs by measuring the effect of androgen on the transcriptional profile of a prostate cancer cell line. Survey of mRNA and EST public databases revealed more than 55,000 Totally Intronic Noncoding (TIN) RNAs transcribed from the introns of 74% of all unique RefSeq genes. Guided by this information, we designed an oligoarray platform containing sense and antisense probes for each of 7,520 randomly-selected TIN transcripts plus probes for the corresponding protein-coding genes. We identified exonic and intronic tissue-specific expression signatures for human liver, prostate and kidney. The most highly expressed antisense TIN RNAs were transcribed from introns of proteincoding genes enriched in the \"Regulation of transcription\" class. RNA Polymerase II inhibition resulted in increased expression of a fraction of the intronic RNAs in cell cultures, suggesting that other RNA polymerases may be involved in their biosynthesis. A subset of intronic and protein-coding signatures transcribed from the same genomic loci has correlated expression patterns, suggesting that intronic RNAs regulate the abundance or the pattern of exon usage in protein-coding messages. We have identified diverse intronic RNA expression patterns, indicating that they may have regulatory roles. This gene-oriented approach, using a combined intronic/exonic microarray should permit further comparative analysis of intronic transcription under various physiological and pathological conditions, thus advancing current knowledge about the biological functions of these noncoding RNAs.

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Amaral, Paulo de Paiva Rosa. "Estudo da biossíntese e regulação de RNAs não-codificadores intrônicos em células humanas." Universidade de São Paulo, 2006. http://www.teses.usp.br/teses/disponiveis/46/46131/tde-03012007-000256/.

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Recentemente, tem sido demonstrado que a maioria dos RNAs transcritos em células humanas são RNAs não-codificadores de proteínas (ncRNAs) originados de íntrons ou regiões intergênicas. Em trabalhos anteriores realizados por nosso grupo, foram descritos longos ncRNAs transcritos de regiões intrônicas de genes codificadores e cuja expressão foi correlacionada ao grau de diferenciação de tumores de próstata, apontando para a relevância fisiológica desta classe de transcritos. Apesar de sua abundância, as propriedades, funções e regulação da grande maioria dos ncRNAs ainda não foram elucidadas. O objetivo do presente trabalho foi investigar a biossíntese de ncRNAs intrônicos em células humanas, primordialmente a contribuição da RNA Polimerase II (RNAP II), bem como aspectos de sua regulação. Primeiramente, o modelo de regulação da expressão gênica por hormônio andrógeno foi utilizado para avaliação da participação direta de um fator de transcrição de RNAP II, o Receptor de Andrógeno (AR), na modulação da transcrição de ncRNAs intrônicos. Utilizando-se a técnica de imunoprecipitação da cromatina, foi detectada a ligação do AR ao elemento de resposta a andrógeno (ARE) presente em um possível promotor de um transcrito intrônico antisenso (derivado do locus Myo5A), cuja expressão é aumentada em células da linhagem LNCaP tratadas com o hormônio. A ligação ao ARE foi induzida pelo tratamento, sugerindo que o efeito do andrógeno na expressão do ncRNA é mediado pelo AR. Em uma segunda abordagem, o efeito da inibição da transcrição por RNAP II com α-amanitina por 24 h em células LNCaP foi avaliado com o uso de microarranjos de oligonucleotídeos representando transcritos total ou parcialmente intrônicos, além de éxons de genes codificadores. A expressão de menos de 20 % dos transcritos intrônicos foi afetada, fração significativamente menor que a observada para os transcritos exônicos (40 %). Ainda que a maioria dos ncRNAs intrônicos diferencialmente expressos tenha sua abundância diminuída, interessantemente, 13 a 16 % foram aumentados, contrastando com aproximadamente 2 a 3 % de exônicos que aumentaram. Os resultados obtidos neste trabalho indicam que a RNAP II atua na transcrição de ncRNAs intrônicos, mas que uma fração considerável pode ser transcrita por outra RNA Polimerase.
It has been recently shown that the bulk of the transcription in human cells is comprised of non-protein-coding RNAs (or noncoding RNAs - ncRNAs) transcribed from introns and intergenic regions of the genome. Previous work from our group has demonstrated that expression of long intronic ncRNAs can be correlated to the degree of prostate tumor differentiation, underscoring the physiological relevance of these transcripts. However, the properties, functions, and regulation of this huge population of ncRNAs remain largely unknown. The present work aimed to investigate the biosynthesis of intronic ncRNAs and aspects of its regulation in human cells, focusing on the contribution of RNA Polymerase II (RNAP II). Initially, the model of regulation of gene expression by androgen hormone was used in order to evaluate the participation of the RNAP II transcription factor Androgen Receptor (AR) in the transcriptional regulation of intronic ncRNAs. Chromatin immunoprecipitation experiments revealed the binding of the AR in an androgen response element (ARE) present in a putative promoter driving the expression of an antisense intronic transcript in Myo5A locus in LNCaP cells. The interaction occurred in an androgen-inducible fashion, along with the up-regulation of the transcript, suggesting that hormone activation occurred in a direct manner mediated by the AR. In a different approach, the effect of RNAP II inhibition with α-amanitin for 24 h in LNCaP cells was analyzed using an oligoarray representing totally and partially intronic transcripts, as well as exons of proteincoding genes. The expression of less than 20 % of the intronic transcripts was affected by the treatment, contrasting to a significantly higher fraction observed for exonic messages (40 %). Moreover, most differentially expressed intronic transcripts were down-regulated, but strikingly 13 to 16 % were up-regulated in cells with blocked RNAP II, while this fraction for exonic transcripts was about 2 %. The results described here demonstrate that RNAP II in fact plays a role in intronic transcription in human cells, but also highlight that another transcriptional system may account for the biogenesis of a fraction of intronic ncRNAs.

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Brückner, Florian. "Molecular basis of translocation, alpha-amanitin inhibition, and CPD damage recognition by RNA polymerase II." Diss., lmu, 2008. http://nbn-resolving.de/urn:nbn:de:bvb:19-86461.

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Brückner, Florian. "Molecular basis of translocation, alpha-amanitin inhibition, and CPD damage recognition by RNA polymerase II." kostenfrei, 2008. http://edoc.ub.uni-muenchen.de/8646/.

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CHAUD, JEAN-PAUL. "L'intoxication phalloidienne : a propos de quatre observations recensees dans le departement des alpes-maritimes." Nice, 1988. http://www.theses.fr/1988NICE6539.

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BENVENUTO, VINCENT. "Intoxication phalloidienne : aspect botanique, toxicologique, clinique, therapeutique et preventif." Saint-Etienne, 1989. http://www.theses.fr/1989STET6215.

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Dietrich, David John. "Synthesis and evaluation of probes of RNA polymerase II : adaptation of the bicyclic scaffold of the octapeptide amanitin." Thesis, University of British Columbia, 2010. http://hdl.handle.net/2429/27427.

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This thesis covers the synthesis and evaluation of bicyclic octapeptides as intracellular probes of RNAP polymerase II. In Chapter 2, the synthetic methodology used to achieve the rigid bicyclic octapeptide and the introduction of modifications to gain spatio-temporal control and visualization is presented. This includes the synthesis of a nitrorveratryl protected derivative of hydroxyproline, and a diethylaminocoumarin labeled asparagine residue. These amino acids were incorporated into amatoxins through solid-phase peptide synthesis. The synthesis and properties of these amatoxins, including their photolability and fluorescent properties is discussed. Chapter 3 describes the initial evaluation of the amatoxin probes in various eukaryotic cell lines. The cytotoxicity of α-amanitin in a variety of cell lines was investigated, where Chinese hamster ovary cells proved to be most sensitive to the toxin. These cytotoxic effects were observed at ~1 μM, which is much higher than the reported binding constant (~ 3 nM). The cytotoxicity was slow, requiring 60-72 hours to achieve 100% cell death. This diminished activity was attributed to cell uptake. Cell permeabilizing agents digitonin and saponin were applied to improve α-amanitin uptake and toxicity. All synthetic amatoxins were shown to have minimal cytotoxic effects. Confocal microscopy demonstrated no cell uptake of a fluorescent amatoxin unless the cells were treated with detergent, pointing to critical issues of cell permeability. The optimization of amatoxin synthesis is presented in Chapter 4. It is shown that up to 20% water can inhibit epimerization during macrolactamization of amatoxins. A convergent synthetic approach to the bicyclic octapeptide was also developed. This allowed for the incorporation of a variety of amino acids at position three. This new synthetic approach was applied to the synthesis of tryptathionine-containing analogs of the opioid receptor agonist enkephalin. The attempted synthesis of the unnatural amino acid (2S),(3R),(4R)-dihydroxyisoleucine is described in Chapter 5. This was achieved through the use of a diastereoselective [3,3] sigmatropic rearrangement followed by Sharpless asymmetric dihydroxylation (AD). Surprising selectivity was noted during the AD reaction using phthalazine-based ligands, but this selectivity was reversed using pyrimidine-based ligands.

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Korsak, Barbara [Verfasser]. "DUPA α-Amanitin Conjugates for Targeted Prostate Cancer Therapy - Optimization and Evaluation of In Vivo Potency / Barbara Korsak". Bielefeld : Universitätsbibliothek Bielefeld, 2021. http://d-nb.info/1237815606/34.

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SEITZ, ISABELLE. "Pharmacologie et toxicologie de l'amanite tue-mouche : ses aspects historiques et modernes." Strasbourg 1, 1991. http://www.theses.fr/1991STR15023.

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Книги з теми "Amanitine"

Mullersman, Jerald Eric. Chemical modification of alpha-amanitin to yield derivatives suitable for conjugation to proteins via reductive alkylation. 1986.

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Tamin, Azaibi. Molecular genetic analysis of vaccinia virus genes which confer resistance to alpha-amanitin. 1989.

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Частини книг з теми "Amanitine"

Vidal, C., and W. R. Külpmann. "Amanitine." In Lexikon der Medizinischen Laboratoriumsdiagnostik, 1–2. Berlin, Heidelberg: Springer Berlin Heidelberg, 2018. http://dx.doi.org/10.1007/978-3-662-49054-9_159-1.

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Vidal, C., and W. R. Külpmann. "Amanitine." In Springer Reference Medizin, 83–84. Berlin, Heidelberg: Springer Berlin Heidelberg, 2019. http://dx.doi.org/10.1007/978-3-662-48986-4_159.

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Faulstich, Heinz, and Theodor Wieland. "New Aspects of Amanitin and Phalloidin Poisoning." In Advances in Experimental Medicine and Biology, 309–14. Boston, MA: Springer US, 1996. http://dx.doi.org/10.1007/978-1-4613-0361-9_24.

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Fenoil, R., R. Alfieri, and G. Weisz. "A Rapid and Sensitive HPLC Method for Determination of Alpha Amanitin in Urine." In Developments in Analytical Methods in Pharmaceutical, Biomedical, and Forensic Sciences, 143–46. Boston, MA: Springer US, 1987. http://dx.doi.org/10.1007/978-1-4899-3526-7_16.

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"Amanitin (C39H54N10O13S)." In Encyclopedia of Genetics, Genomics, Proteomics and Informatics, 74. Dordrecht: Springer Netherlands, 2008. http://dx.doi.org/10.1007/978-1-4020-6754-9_599.

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"Amanitin Toxicosis." In Clinical Veterinary Advisor, 21–22. Elsevier, 2012. http://dx.doi.org/10.1016/b978-1-4160-9979-6.00014-3.

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"A-I (Abscisic acid to Amanitins)." In RÖMPP Encyclopedia Natural Products, edited by Wolfgang Steglich, Burkhard Fugmann, and Susanne Lang-Fugmann. Stuttgart: Georg Thieme Verlag, 2000. http://dx.doi.org/10.1055/b-0036-133798.

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Arici, M. Aylin, and Yesim Tuncok. "Mushroom-related toxins, alpha amanitin, and usage of antioxidants: Directions toward antioxidant capacity." In Toxicology, 447–56. Elsevier, 2021. http://dx.doi.org/10.1016/b978-0-12-819092-0.00044-3.

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"Raise of a Monoclonal Antibody Against et-Amanitin and Studies on its Molecular Interaction with Amatoxin Peptides." In Proceedings of the Fifth USSR-FRG Symposium on Chemistry of Peptides and Proteins, Odessa, USSR, May 16–20, 1985, 331–38. De Gruyter, 1986. http://dx.doi.org/10.1515/9783110858846-031.

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Тези доповідей конференцій з теми "Amanitine"

Kulke, Michael, Anikó Pálfi, Christoph Müller, Werner Simon, Susanne Werner-Simon, Christian Lutz, Torsten Hechler, and Andreas Pahl. "Abstract 735: SAR of amanitin and optimization of linker-amanitin derivatives for solid tumors." In Proceedings: AACR Annual Meeting 2018; April 14-18, 2018; Chicago, IL. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/1538-7445.am2018-735.

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Hechler, Torsten, Aniko Palfi, Christoph Müller, Christian Lutz, Andreas Pahl, and Michael Kulke. "Abstract 62: CD19 - a potential target for Amanitin-based ADCs." In Proceedings: AACR Annual Meeting 2017; April 1-5, 2017; Washington, DC. American Association for Cancer Research, 2017. http://dx.doi.org/10.1158/1538-7445.am2017-62.

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Palfi, Aniko, Torsten Hechler, Christoph Mueller, Andreas Pahl, and Michael Kulke. "Abstract 2973: CD269 - A promising target for amanitin based ADCs." In Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-2973.

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Hechler, Torsten, Christoph Müller, Andreas Pahl, and Jan Anderl. "Abstract 633: Amanitin-based ADCs with an improved therapeutic index." In Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.am2015-633.

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Bai, Xueke, Peixi Jiang та Yuyou Wu. "Toxic Mechanisms of α-Amanitin and Its Potential to Fight Cancer". У The International Conference on Biomedical Engineering and Bioinformatics. SCITEPRESS - Science and Technology Publications, 2022. http://dx.doi.org/10.5220/0011378000003443.

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Anderl, Jan, Christoph Müller, Brigitte Heckl-Östreicher, and Roland Wehr. "Abstract 3616: Highly potent antibody-amanitin conjugates cause tumor-selective apoptosis." In Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-3616.

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Hechler, Torsten, Michael Kulke, Christoph Mueller, Andreas Pahl, and Jan Anderl. "Abstract 664: Amanitin-based antibody-drug conjugates targeting the prostate-specific membrane antigen." In Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA. American Association for Cancer Research, 2014. http://dx.doi.org/10.1158/1538-7445.am2014-664.

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Pálfi, Anikó, Christian Breunig, Torsten Hechler, Christoph Müller, Christian Lutz, Andreas Pahl, and Michael Kulke. "Abstract 740: Preclinical evaluation of an anti-PSMA antibody-targeted amanitin conjugate (ATAC)." In Proceedings: AACR Annual Meeting 2018; April 14-18, 2018; Chicago, IL. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/1538-7445.am2018-740.

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Braun, Alexandra, Aniko Palfi, Christoph Mueller, Torsten Hechler, Andreas Pahl, and Michael Kulke. "Abstract 910: Amanitin-based ADCs targeting PSMA as novel therapeutic modality for prostate cancer therapy." In Proceedings: AACR Annual Meeting 2021; April 10-15, 2021 and May 17-21, 2021; Philadelphia, PA. American Association for Cancer Research, 2021. http://dx.doi.org/10.1158/1538-7445.am2021-910.

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Voss, Stephanie, Aniko Palfi, Christoph Mueller, Andreas Pahl, Torsten Hechler, and Michael Kulke. "Abstract 915: Preclinical evaluation of anti-CD37 antibody-targeted amanitin conjugates (ATAC) in B-cell malignancies." In Proceedings: AACR Annual Meeting 2021; April 10-15, 2021 and May 17-21, 2021; Philadelphia, PA. American Association for Cancer Research, 2021. http://dx.doi.org/10.1158/1538-7445.am2021-915.

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