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561	Elevated activity and microglial expression of myeloperoxidase in demyelinated cerebral cortex in multiple sclerosis Gray, E., Thomas, T. L., Betmouni, S., Scolding, N., Love, S. January 2008 (has links) No / Recent studies have revealed extensive cortical demyelination in patients with progressive multiple sclerosis (MS). Demyelination in gray matter lesions is associated with activation of microglia. Macrophages and microglia are known to express myeloperoxidase (MPO) and generate reactive oxygen species during myelin phagocytosis in the white matter. In the present study we examined the extent of microglial activation in the cerebral cortex and the relationship of microglial activation and MPO activity to cortical demyelination. Twenty-one cases of neuropathologically confirmed multiple sclerosis, with 34 cortical lesions, were used to assess microglial activation. HLA-DR immunolabeling of activated microglia was significantly higher in demyelinated MS cortex than control cortex and, within the MS cohort, was significantly greater within cortical lesions than in matched non-demyelinated areas of cortex. In homogenates of MS cortex, cortical demyelination was associated with significantly elevated MPO activity. Immunohistochemistry revealed MPO in CD68-positive microglia within cortical plaques, particularly toward the edge of the plaques, but not in microglia in adjacent non-demyelinated cortex. Cortical demyelination in MS is associated with increased activity of MPO, which is expressed by a CD68-positive subset of activated microglia, suggesting that microglial production of reactive oxygen species is likely to be involved in cortical demyelination. Adult Aged Aged 80 and over Antigens CD/immunology Metabolism Antigens Differentiation Myelomonocytic Immunology Biological markers Analysis Cerebral cortex Enzymology Pathology Physiopathology Encephalitis Enzyme activation Female Gliosis HLA-DR antigens Humans Male Microglia Middle aged Multiple Sclerosis Myelin sheath Nerve fibers Myelinated Oxidative stress Peroxidase Reactive oxygen species Up-regulation Wallerian degeneration REF 2014
562	Langzeitkultur von humanen Langerhanszellen Henschke, Cornelia 23 February 2001 (has links) Die Arbeit beschreibt das phänotypische Verhalten von kultivierten Langerhanszellen, antigenpräsentierenden Zellen der Epidermis, sowie die Art und Weise ihrer Elimination. Hierfür wurden Zellkulturen von Langerhanszellen durch Migration aus normaler menschlicher Haut gewonnen. Die Langerhanszellen durchlaufen dabei die gleiche funktionelle Entwicklung, wie nach Antigenpräsentation in situ. Ziel der Untersuchung war es, die funktionellen und zellulären Eigenschaften und die Elimination von Langerhanszellen in der Zellkultur zu ermitteln. Die Anzahl viabler Zellen wurde mittels Trypanblauausschluß zu verschiedenen Zeitpunkten der Kultur ermittelt. Außerdem wurden die Zellen mittels Elektronenmikroskopie und Immuncytochemie untersucht. Die Befunde zeigen, daß die Zellen in der Kultur eine Veränderung ihres Phänotyps sowie funktionelle Änderungen im Sinne einer Ausreifung zu antigenpräsentierenden, T-Zell stimulierenden Zellen erfahren. Das in-vitro-Verhalten entspricht dem von Langerhanszellen in vivo nach Kontaktsensibilisierung. Mit Hilfe von eines für Apoptose spezifischen ELISA (= Enzyme-linked immunosorbent assay: eine Nachweisreaktion für Antigene bzw. Antikörper mithilfe von Enzymen) und Elektronenmikroskopie wurde nachgewiesen, daß die Zellen in unseren Kulturen durch Apoptose starben. Es gibt keinen Anhaltspunkt dafür, daß sich die Zellen nicht auch in vivo apoptotisch eliminieren. Die Verlauf der Funktionsmarker weist darauf hin, daß vorwiegend die maturierten Zellen von Apoptose betroffen waren, und die Apoptose über das CD 95/CD 95 L- System gesteuert wurde. Die Versuche zeigten insgesamt, daß Langerhanszellen durch Apoptose aus der Kultur eliminiert werden. Da sich die Zellen nach Migration in vitro wie Langerhanszellen nach Antigenpräsentation in vivo verhalten, scheint die Apoptose ein biologisches Regulativ für die Elimination von funktionell ausgereiften Langerhanszellen darzustellen. / This work describes the phenotypic behavior of cultivated Langerhans-cells, epidermal cells presenting antigenes and how they are eliminated . Therefore cultures of Langerhans-cells won by migration from normal human skin were used. The migrated Langerhans-cells have the same phenotypic features as Langerhans-cells after presentation of antigenes in situ. The aim of this work was to show the functional and cellular features of Langerhans-cells in culture and the way of their elimination. The cells still alive were count at distinct times using the Trypan-blue-exclusion-method. Additionally the cells were examined by electron microscopy and immuncytochemical methods. The findings show, that the cells in culture have the same characteristics of the phenotype and change of their function in the direction of developing to antigen-presenting, T-cell-stimulating cells. The in vitro behaviour is the same as of Langerhans-cells in vivo after contact-sensitization. With the help of an elisa (=Enzyme-linked immunosorbent assay) specific for apoptosis ( Cell Death Detection Elisa = CDDE) and with electron microscopy was shown, that the cultivated cells died by apoptosis. There is no reference point, that the cells do not do the same in vivo. The process of the functional markers shows, that predominantly the matured cells die by apoptosis and that it was controled by the CD 95/CD 95-L -system The investigations showed, that the Langerhans-cells were eliminated by apoptosis of the culture. The cells after migration in vitro behave in the same manner as after presentation of antigen in vivo. This indicates apoptosis to be the biologic regulation for the elimination of functional matured Langerhans-cells. Apoptose Elektronenmikroskopie Zellkultur APAAP-Färbung Bax Bcl-xl Bcl-2 CD 1a CD 80 CD 86 CD 95 CD 95-L CDDE HLR-DR Langzeitkultur Programmierter Zelltod Electron microscopy Apoptosis Bax Bcl-xl Bcl-2 CD 1a CD 80 CD 86 CD 95 CD 95-L Cellculture Cell Death Detection ELIZA HLA-DR Langerhans cell Long-term culture P Programmed cell death 610 Medizin 33 Medizin WX 6600 ddc:610
563	A Pragmatic Standard of Legal Validity Tyler, John 2012 May 1900 (has links) American jurisprudence currently applies two incompatible validity standards to determine which laws are enforceable. The natural law tradition evaluates validity by an uncertain standard of divine law, and its methodology relies on contradictory views of human reason. Legal positivism, on the other hand, relies on a methodology that commits the analytic fallacy, separates law from its application, and produces an incomplete model of law. These incompatible standards have created a schism in American jurisprudence that impairs the delivery of justice. This dissertation therefore formulates a new standard for legal validity. This new standard rejects the uncertainties and inconsistencies inherent in natural law theory. It also rejects the narrow linguistic methodology of legal positivism. In their stead, this dissertation adopts a pragmatic methodology that develops a standard for legal validity based on actual legal experience. This approach focuses on the operations of law and its effects upon ongoing human activities, and it evaluates legal principles by applying the experimental method to the social consequences they produce. Because legal history provides a long record of past experimentation with legal principles, legal history is an essential feature of this method. This new validity standard contains three principles. The principle of reason requires legal systems to respect every subject as a rational creature with a free will. The principle of reason also requires procedural due process to protect against the punishment of the innocent and the tyranny of the majority. Legal systems that respect their subjects' status as rational creatures with free wills permit their subjects to orient their own behavior. The principle of reason therefore requires substantive due process to ensure that laws provide dependable guideposts to individuals in orienting their behavior. The principle of consent recognizes that the legitimacy of law derives from the consent of those subject to its power. Common law custom, the doctrine of stare decisis, and legislation sanctioned by the subjects' legitimate representatives all evidence consent. The principle of autonomy establishes the authority of law. Laws must wield supremacy over political rulers, and political rulers must be subject to the same laws as other citizens. Political rulers may not arbitrarily alter the law to accord to their will. Legal history demonstrates that, in the absence of a validity standard based on these principles, legal systems will not treat their subjects as ends in themselves. They will inevitably treat their subjects as mere means to other ends. Once laws do this, men have no rest from evil. natural law theory legal positivism HLA Hart William Blackstone John Locke Jeremy Bentham John Austin Galileo Socrates Trotsky Athens Soviet law Stuart dynasty John Dewey Dewey Commission Sidney Hook Congregation of the Holy Office Galileo Affair trial of Socrates Moscow Trials trial of Galileo heresy trial of Trotsky reason autonomy consent philosophy of law pragmatism Kant Inquisition ostracism Anaxagoras Protagoras Alcibiades Arginusae Pericles Peloponnesian War Solon Ephialtes Apology Plato Herodotus Xenophon Plutarch Roscoe Pound common law Oliver Wendell Holmes, Jr. The Common Law The Path of the Law Learned Hand Christopher Columbus Langdell Ronald Dworkin Lon Fuller Lenin Stalin King Rex Sergei Kirov Permanent Revolution Socialism in One Country Great Terror Dekulakization Holomodor Terror Famine Italian positivist school Harold J. Berman Gustav Radbruch Ramon Mercader Trotsky assassination Marteman Ryutin Old Bolsheviks Genrikh Yagoda Pope Urban VIII Walter Duranty Harold Denny New York Times Joseph E. Davies Mission to Moscow New Republic John F. Finerty Lev Sedov Military Collegium Vasili Ulrikh Gaspare Borgia Cardinal Robert Bellarmine Pericles Father Commissary Michelangelo Segizzi Cardinal Francesco Barberini Cardinal Maffeo Barberini Siderius Nuncius Starry Messenger Accademia dei Lincei Letters on Sunspots Friar Tommaso Caccini Niccolo Lorini Commentaries on the Laws of England Second Treatise on Civil Government Henry de Bracton Sir Edward Coke Sir John Fortescue Matthew Hale Ranulf de Glanvil James I Charles I James II Charles II ship money forest fines distraint of knighthood impositions dispensing power royal prerogative Duke of Buckingham Oliver Cromwell Bishops Wars William Prynne Great Migration Declaration of Indulgence Settlement Act Test Act Protectorate Clarendon Code Quaker Act William and Mary English Civil War Puritan Revolution Glorious Revolution Thirty Years' War Earl of Shaftesbuty William Laud Historiomatrix Long Parliament Rump Parliament Barebones Parliament sociological jurisprudence Red Terror war communism New Economic Policy 1926 Criminal Code Kirov Amendments judicial discretion semantic sting The Concept of Law Fragments on Government The Province of Jurisprudence Determined A Fragment on Government Anarchical Fallacies primary rules secondary rules rule of recognition legal validity internal point of view external point of view law as prediction the bad man perspective on law life of the law page of history Basilikon Doron Trew Law of Free Monarchies

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