84 research outputs found
CD95-independent, caspase- and mitochondria-dependent apoptosis induction, apoptosis independent proliferation
No full text1. Inhaltsverzeichnis
2. Summary/Zusammenfassung
3. Einleitung
4. Zielsetzung
5. Materialien
6. Methoden
7. Ergebnisse
8. Diskussion
9. Abkürzungen und Synonyme
10. Appendix
11. Literatur
12. Erklärung zu eigenen Publikationen
13. Weitere eigene Publikationen
14. Danksagung
15. LebenslaufDreiwertige anorganische Arsenverbindungen wie Arsentrioxid oder Arsensulfid
werden seit über 2400 Jahren in der Medizin verwandt. Nachdem Arsentrioxid
durch die Entdeckung der Röntgenstrahlung und die Entwicklung potenter
Zytostatika bei der Therapie akuter myeloischer Leukämien immer mehr verdrängt
worden war, fanden organische und anorganische dreiwertige Arsenverbindungen
bis Ende des 20. Jahrhunderts bei der Therapie der refraktären oder
rezidivierten akuten Promyelozytenleukämie (APL) Verwendung. Bis vor kurzem
wurde vermutet, daß Arsentrioxid seine therapeutischen Effekte nur in APL-
Zellen entwickeln könne, da die Arsentrioxid-Wirkung an die Anwesenheit des
Fusionsproteins PML-RARalpha gekoppelt sei.
In dieser Arbeit wurde daher die Wirkung von Arsentrioxid auf Apoptose,
Differenzierung und Proliferation an 22 malignen lymphatischen und myeloischen
Zellinien unterschiedlichen Differenzierungsstadiums und Herkunftsgewebes
untersucht. Aufgrund der unterschiedlichen Sensitivität dieser Zellinien
gegenüber Arsentrioxid-Konzentrationen, welche auch bei der APL-Therapie im
Plasma von Patienten zu erzielen sind, konnten drei Sensitivitätsgruppen für
Zellinien definiert werden: Zellinien mit Sensitivität gegenüber 0,1 µM
(Gruppe A), 1 µM (Gruppe B) und 5 µM (Gruppe C) Arsentrioxid. Arsentrioxid-
Behandlung von Zellen führte zu einer Aktivierung der Caspasen-Kaskade, zum
Zusammenbruch des mitochondrialen Membranpotentials und zur Bildung von ROS
(reactive oxygen species). Die Mitochondrien sind als primärer Wirkungsort des
Arsentrioxids anzusehen, da Caspasen-Inhibitoren zwar einen Rückgang des
Prozentsatzes apoptotischer Zellen bewirkten und die Aktivierung von Caspasen
hemmten, aber nur einen geringen Einfluß auf die Bildung von ROS und den
Funktionsverlust der Mitochondrien hatten. NO-Radikale und erhöhte
p53-Expression traten hingegen nur bei einigen Zellinien nach Arsentrioxid-
Behandlung auf.
Im Rahmen der Arsentrioxid-induzierten Apoptose konnte weder eine
CD95-Induktion gemessen noch die Arsentrioxid-induzierte Apoptose durch
Blockierung des CD95-Rezeptors gehemmt werden.
Neben der Apoptose-Induktion zeigte Arsentrioxid eine Apoptose-unabhängige
Proliferationsinhibition. Die Proliferationsinhibition trat bereits bei einer
Arsentrioxid-Konzentration auf, welche entweder keine Apoptose auslöste oder
aber Apoptose nur in einem kleinen Anteil der Gesamtpopulation induzierte.
Aufgrund dieser Arbeit wurde eine Systematik eingeführt, anhand derer
Zellinien gemäß ihrer Sensitivität gegenüber Arsentrioxid-induzierter Apoptose
klassifiziert werden können. Ein für zahlreiche hämatopoetische Zellinien
allgemeingültiger Mechanismus der Apoptose-Induktion wurde beschrieben: die
Caspasen-unabhängige Mitochondrieninaktivierung. Es wurde ferner gezeigt, daß
es im Rahmen der Arsentrioxid-Behandlung hämatopoetischer Zellinien zu einer
Apoptose-unabhängigen Proliferationsinhibition kommen kann.Trivalent anorganic arsenic compounds have been used in medicine for more than
2400 years. However, with the discovery of radiotherapy and high potential
cytostatic drugs in the 20th century, arsenic(III)-oxide disappeared as one of
the cancer standard therapies. Because of its effects in acute promyelocytic
leikemia (APL), the therapeutic use of arsenic(III)-oxide was thought to be
restricted to cells in which the fusion protein PML-RARalpha is present.
In this work, the effects of arsenic(III)-oxide on apoptosis and
differentiation was analyzed in 22 cell. These cell lines represented various
stages of lympho-haematopoietic differentiation. According to their
sensitivity towards apoptosis induction a classification system was
introduced: induction of apoptosis with concentrations 0,1 µM, 1 µM or 5 µM
arsenic(III)-oxide was classified as sensitivity group A, group B or group C,
respectively.
The potential mechanisms responsible for apoptosis induction were analysed in
representative cell lines of all three sensitivity groups. Arsenic(III)-oxide
induced activity of caspases, breakdown of the mitochondrial membrane
potential and synthesis of reactive oxygen species (ROS), whereas an increase
of NO-radicals and p53-protein level could be measured only for some cell
lines. Mitochondria can be regarded as the primary target of action for
arsenic(III)-oxide, as caspases specific inhibitors could reduce the
percentage of apoptotic (i. e. Annexin V-FITC and 7-amino-actinomycin
(7?AAD)-positive) cells and caspase activity (measured by FITC-VAD-FMK-
binding) but had no effect on the breakdown of mitochondrial membrane
potential.
The treatment of cell lines with arsenic(III)-oxide had no regulatory effect
on CD95, and no inhibition of arsenic(III)-oxide-induced apoptosis could be
detected by blocking the CD95 pathway.
Beside the effect of apoptosis induction, treatment of cell lines with
arsenic(III)-oxide also lead to an apoptosis independent inhibition of
proliferation. Proliferation inhibition could already be observed for
concentrations of arsenic(III)-oxide that themselves were not able to induce
apoptosis or induced apoptosis only in a low percentage of the cell
population.
A classification system of sensitivity for haematopoietic cell lines to
arsenic(III)-oxide was introduced by this work. This system is based on the
sensitivity of cell lines towards arsenic(III)-oxide induced apoptosis. This
work clearly shows that a common mechanism is responsible for
arsenic(III)-oxide effects on a variety of haematopoeitic cell lines: the
caspase-independent breakdown of mitochondrial membrane potential.
Furthermore, this work clearly shows that an apoptosis-independent inhibition
of cell proliferation can occur during arsenic(III)-oxide treatment of
haematopoietic cell lines
Assessment of insurance risks in the compulsory crop insurance
No full textThis article is an analysis of the issue insurance risks from the point of view of the subjective scope, and of the mandatory crop insurance in the Polish legal system. The issues raised as an element of introduced within the framework of the Common Agricultural Policy for the years 2014-2020 of the system of risk management in agriculture determine the direction of the development of crop insurance as a tool for securing not only the interests of agricultural producers, but also entities in any way dependent on the economic situation of agriculture as a sector of economy. At the same time, the author points to the issues specific to individual insurance risks, as well as to questions of interpretation arising under these regulations. The author also draws attention to the achievements of home insurance legislation in the matter, reaching the beginning of the reborn Polish State, as well as the development trends in the market of compulsory insurance of agricultural crops in Poland, from the perspective of its functioning after Poland’s accession to the European Union.Uniwersytet ŚląskiFendler Z., Prywatne prawo ubezpieczeniowe wraz z komentarzem i orzecznictwem sądów polskich, Kraków 1934.Fuchs D., Zakres obowiązku prewencji w prawie ubezpieczeń gospodarczych. Uwagi na tle art. 826 k.c., „Prawo Asekuracyjne” 2004, nr 2.Kamiński T., Likwidacja szkód w uprawach, [w:] Ubezpieczenia produkcji roślinnej w Polsce, M. Kaczała, K. Rojewski (red.), Warszawa 2015.Kowalewski E., Prawo ubezpieczeń gospodarczych, Bydgoszcz – Toruń 2002.Łyskawa K., Rojewski K., Kategorie zagrożeń i ryzyko w działalności rolniczej – szczególnie w produkcji rolnej, [w:] Ubezpieczenia produkcji roślinnej w Polsce, M. Kaczała, K. Rojewski (red.), Warszawa 2015.Nawracała J., [w:] Prawo ubezpieczeń gospodarczych, Komentarz tom I, Z. Brodecki, M. Serwach, M. Glicz (red.), Warszawa 2010.Orlicki M., Ubezpieczenia Obowiązkowe, Warszawa 2011.Serwach M., [w:] Ryzyko ubezpieczeniowe, Wybrane zagadnienia teorii i praktyki, M. Serwach (red.), Łódź 2013.Wąsiewicz A., Umowa ubezpieczenia, [w:] A. Wąsiewicz (red.), Ubezpieczenia w gospodarce rynkowej t. 3, Bydgoszcz 1997.373-3881437338
The Role of Computerisation in the Development of an Efficient Judiciary and Administration on the Example of the National Court Register and Land and Mortgage Registers
No full textAutor przedstawia znaczącą rolę informatyzacji w rozwoju sprawnego sądownictwa i administracji na przykładzie Krajowego Rejestru Sądowego i ksiąg wieczystych. W Polsce to jedno z największych osiągnięć wymiaru sprawiedliwości XXI wieku. Autor wskazuje zasady prowadzenia ksiąg wieczystych: zasadę jawności formalnej ksiąg wieczystych, zasadę domniemania zgodności ze stanem prawnym, zasadę przyrzeczenia wiary publicznej oraz zasadę pierwszeństwa praw. W związku z tym autor koncentruje się na księgach wieczystych w systemie informatycznym. Rozwiązanie to umożliwia bezpośredni dostęp do ksiąg wieczystych osobom zainteresowanym wydaniem odpisów. Co więcej, dostęp do ksiąg wieczystych jest możliwy za pośrednictwem Internetu (odpowiednia strona internetowa). Przedstawiono również funkcjonowanie Krajowego Rejestru Sądowego w systemie informatycznym.The author presents the significant role of computerisation in the development of an efficient judiciary and administration on the example of the National Court Register and land and mortgage registers. In Poland, it is one of the biggest achievements of justice in the XXI century. The author indicates the principles of land and mortgage registers: the principle of openness of the formal land and mortgage registers, the principle of presumption of conformity with the legal status, the principle of pledge of public faith and the principle of priority rule rights enshrined. Consequently, the author focuses on the land and mortgage registers in the computer system. This solution enables direct access to the land and mortgage registers for those interested in issuing copies. What is more, access to the land and mortgage registers is possible by using the Internet (proper website). There is also presented functioning of the National Court Register in the computer system.
“Quien será un gran pintor...” Análisis de las condicionantes y de las capacidades necesarias para ser artista según Durero
No full textResumen: La historiografía artística de la Edad Moderna, plasmada en tratados, paragonae, discursos y correspondencias entre humanistas, permite a los historiadores del arte reconstruir y analizar distintos aspectos de la producción artística italiana de esa época. En el caso de los territorios del Norte de Europa, la ausencia de esta documentación no permite precisar con claridad de detalle fenómenos análogos para los pintores flamencos o acerca de la llamada escuela alemana hasta las primeras décadas del siglo XVI. La poca documentación conservada imposibilita una definición profunda de los aspectos teóricos y estéticos ligados a la producción de los artistas. Además, la estructura gremial del Norte disuadía el proceso de individualización de los artistas. Alberto Durero, artista vinculado a la corte de Maximliano I y posteriormente a la corte de Carlos V, se considera el primer autor de tratados teóricos sobre la creación artística al Norte de los Alpes. Gracias a sus viajes a Italia, Durero entró en contacto con las corrientes de pensamiento acerca de la teoría del arte, que le llevaron a redactar varias publicaciones: Proyecto para el tratado sobre la pintura(1508-1513), Los cuatro libros sobre medidas. Instrucciones de medir con compás y regla(1525) y Cuatro libros sobre las proporciones humanas (1528). El objetivo de este estudio es analizar los tres tratados mencionados con una atención especial a las recomendaciones del autor respecto a la formación del artista. A partir del corpus dureriano, traducido por Bialostocki en 1954 ,este estudio permitirá revisar la difusión y aplicación de las sugerencias en el ámbito de los artistas durante las primeras décadas del siglo XVI.Abstract: The artistic historiography of the Modern Age, formed by theoretical treatises, paragonae, speeches and correspondence between humanists, permit the Historians of art to reconstruct and to analyse various aspects of Italian artistic production. In the case of Northern Europe, the absence of that kind of documentation does not allow to precise clear analogous phenomena for Flemish painters or for German school, until the early decades of the sixteenth century. Not much preserved documentation makes impossible to define well theoretical and aesthetic aspects relate to the artistic production. Besides, the guild structure on the Northern Europe dissuades the process of artists individualization. Albrecht Durer, connected to the court of Maximlian I and to the Charles V court artist, is considered as the first author of artistic theoretical treaties on the North of the Alps. Thanks for the trip to Italy, Dürer came into contact with modern art theory, which resulted in writing several treaties: Project for the Treatise on Painting (1508-1513), Four Books on Measurement. Instructions for Measuring with Compass and Ruler (1525) and Four Books on Human Proportion (1528). The aim of this study is to analyse the three mentioned treaties with special attention on the author's recommendations for appropriated formation of the artist. The base is the Durer´s corpus, translated by Bialostocki in 1954. This study will review the dissemination and implementation of Durer´s suggestions for artists during the first decades of the sixteenth century
Arsenic trioxide therapy in acute promyelocytic leukemia and beyond: from bench to bedside
No full textNumerical investigation of endplates influence on the wing in ground effect lift force
No full textThe article presents a comparison of the wing in ground effect magnitude of conceptual WIG craft model main
characteristics for a wing with and without endplates which are also known as winglets in regular aircraft. In article,
the author describes WIG effect with and WIG craft, which operates on low altitude, smaller than the length of wing
chord, mostly above the water reservoir. WIG effect phenomenon is simple. The first aircraft needs to fly at adequate
altitude, with a smaller distance between lower airfoil surface and ground static pressure rises, leading to rising of lift
force. The main advantage of the wing in ground effect craft on regular aircraft is a much higher lift to drag ratio,
also this phenomenon provides to drop in specific fuel consumption of aircraft and allows flying with heavier cargo
due to higher lift force. Characteristics present in the article were designated from simulations, which were conducted
in Ansys Fluent software. Results obtained for a wing with endplate in numerical analysis shows the superiority of this
approach. Endplates provide to increase WIG effect by a decrease in induced drag through the move out vertices from
the wing tips, which are made by differential pressure above and under the wing. As winglets in regular aircraft,
endplates provide to save fuel. WIG craft does not need airports so it could be a cheap alternative for modern aircraft
Paroxysmal nocturnal hemoglobinuria (PNH): higher sensitivity and validity in diagnosis and serial monitoring by flow cytometric analysis of reticulocytes
No full textAn investigation of the post high school outcomes of individuals with disabilities, and teacher and parent perceptions of transition services provided in a western Wisconsin school district
No full textPlan BThe purpose of this study was to evaluate the outcome of students with disabilities after leaving high school. Secondly, this research explores teacher and parent attitudes about transition services provided by the school to students with disabilities. A historical framework was based on the research of significant legislative acts that have shaped the implementation of transition services. Data was collected to research the areas of independent living, postsecondary education, and the employment of former graduates and dropouts who exited high school between May 2000 and May 2001. These former students received services from the special education program while in high school. Furthermore, the perceptions of teachers and parents of former students who received special education services were assessed to supplement student feedback. Data analysis was constructed by the use of numbers and individual student, teacher, and parent suggestions. Results from this study indicate that there is a blend of positive and negative former student outcomes within the school district. One to 2 years after exiting high school, the majority of the students were employed and working full-time. Most of the students were earning less than $10 per hour and living with a parent or relative; however, nearly ½ were attending postsecondary education and working. Teachers and parents indicated that the school district has offered several beneficial services to students in past years including extracurricular activities, the school-to-work program, and the summer youth work program. As students evolve and individual’s needs change there continues to be a need to evaluate and improve transition programming. Students, teachers, and parents agreed that additional classes or curriculum were needed to allow students to practice monetary management, independent living, and job attainment skills. Further study is recommended to determine the post high school outcomes, and parent and teacher suggestions within the same district in 2 years to assess transition program progress
Flow cytometric analysis of T cell subsets in paired samples of cerebrospinal fluid and peripheral blood from patients with neurological and psychiatric disorders
No full textValidation of Microbiological Testing of Cellular Medicinal Products Containing Antibiotics
No full textS.144-151Background: The risk of microbial contamination of cellular products can be reduced when cultured in the presence of antibiotics. This however, may impact the sensitivity of microbiological tests. Given that the addition of antibiotics to cell/tissue products does not guarantee sterility but may just reduce the proliferation rate of microorganisms, microbiological testing of medicinal products remains obligatory. Thus, an appropriate method to test for microbial contamination of antibiotic-containing products has to be validated. Objectives: In the context of microbiological testing of a cellular advance therapy medicinal product, the method was validated and approved by German competent authorities for four different matrices with three matrices containing antibiotics. The paper shall provide help for establishing test methods for other investigational medicinal products which contain antibiotics. Methods: Matrices were spiked individually with Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Streptococcus pyogenes, Escherichia coli, Clostridium sporogenes, Propionibacterium acnes, Candida albicans, and Aspergillus brasiliensis. Samples were pretreated with penicillinase for 1 h before inoculation and incubation in BacT/ALERT iFA Plus and iFN Plus culture bottles using 3D BacT/ALERT automates. Microorganisms within positive BacT/ALERT bottles were specified. The procedure was performed in two different laboratories to prove robustness of test. Results: All nine tested microorganisms were detected within 14 days of incubation in accordance with requirements of the European Pharmacopoiea in terms of sensitivity, specificity and robustness of the test. Penicillin and streptomycin did not have any influence on specifications defined within the investigational medicinal product dossier. Conclusions: Culturing cellular products in the presence of antibiotics can serve as an effective method to reduce contamination risk but only if the chosen antibiotics neither have any influence on specifications of the investigational medicinal product nor interfere with microbiological tests. Consequently, cells and tissues primarily contaminated with microorganisms, like placenta, may be considered as a source of cellular therapeutics when cultured for a sufficient time with antibiotics and tested with a validated method. The choice of microorganisms for the validation of the microbiological test should always consider all conceivable scenarios and should not be reduced to minimal criteria defined in European Pharmacopoiea, wrongfully believing to thus save time and effort.47Nr.
- …
