An Investigation of Ode Fourteen of the Septuagint ‘‘ΟΑΑΙ

This paper will pursue a study of. the structure, content, and history of the Gloria in Excelsis, and in this way suggest a possible method for giving meaning to other parts of the public worship service. To do this, we will especially concentrate on the Septuagint Ode Fourteen and on the .English version in the forepart of The Lutheran Hymnal

Demyelinisierung und Axonschaden in der MOG35-55-induzierten experimentellen autoimmunen Enzephalomyelitis der C57BL/6-Maus : eine ultrastrukturelle Studie

Die Multiple Sklerose (MS) gilt als Autoimmunerkrankung des zentralen Nervensystems (ZNS) und ist durch multizentrische Inflammation, Demyelinisierung und Axonschädigung charakterisiert. Trotz großer Forschungsanstrengungen bleiben die zugrunde liegenden Pathomechanismen unverstanden. Die Untersuchung pathogenetischer Mechanismen am Menschen ist mit großen Schwierigkeiten verbunden, daher sind Tiermodelle auch heute noch unerlässlich, um grundlegende Mechanismen der Läsionsentstehung im ZNS verstehen und die Läsionsformation über die Zeit verfolgen zu können. Die experimentelle autoimmune Enzephalomyelitis ist eines der am häufigsten verwendeten Modelle der MS. Insbesondere der C57BL/6 (B6)-Mausstamm ist für mechanistische Studien unabdingbar, da viele genmodifizierte Mäuse auf diesem Hintergrund gezüchtet werden. Eines der traditionellen Modelle der B6-EAE ist die Myelin-Oligodendrozyten-Glykoprotein Peptid 35-55 (MOG35-55)-induzierte EAE. Aufgrund der Ähnlichkeit der histopathologischen Charakteristika der MOG35-55-induzierten EAE mit der menschlichen Erkrankung und aufgrund der einfachen Verfügbarkeit und Herstellbarkeit des MOG35-55 stellt dieses Modell eines der am häufigsten verwendeten MS-Modelle dar. Bevor jedoch die pathogenetische und/oder therapeutische Bedeutung einzelner Effektormechanismen evaluiert werden kann, bedarf es einer eingehenden Charakterisierung des verwendeten Modells. Verschiedene Arbeitsgruppen haben die inflammatorische Komponente der MOG35-55-induzierten EAE untersucht und auch die Rolle neurodegenerativer Prozesse wurde, unter anderem von unserer Arbeitsgruppe, in lichtmikroskopischen und immunhistochemischen Studien bereits evaluiert. Die vorliegende Arbeit ist die erste Studie, die eine Charakterisierung der Myelin- und Axonpathologien in der MOG35-55-induzierten EAE auf ultrastruktureller Ebene vornimmt. Um die Histopathologie der MOG35-55-induzierten EAE der B6-Maus über einen Zeitraum von sechs Monaten untersuchen zu können, wurden eindeutige morphologische Korrelate einer Myelin- und Axonschädigung herangezogen, um zeitabhängige Unterschiede und/oder Ähnlichkeiten zwischen der akuten, chronischen und langzeit-chronischen Phase der EAE zu beurteilen. Für diesen Zweck wurden Querschnitte des lumbalen Rückenmarks MOG35-55-immunisierter Mäuse zum Zeitpunkt der akuten EAE (erstes Auftreten der paralytischen Symptome), drei Monate (chronische EAE) und sechs Monate nach Krankheitsbeginn (langzeit-chronische EAE) angefertigt, in EPON eingebettet und mittels Elektronenmikroskopie untersucht. Das Ausmaß der Myelinpathologie wurde mittels Messung der g-ratio (Axondurchmesser geteilt durch Gesamtdurchmesser der Nervenfaser) evaluiert und nahm zeitlich progredient zu. Eine Schädigung der Axone hingegen konnte bereits früh im Krankheitsverlauf vermehrt nachgewiesen werden und blieb über den beobachteten Zeitraum von sechs Monaten konstant erhöht. Als axonale Pathologien wurden axonaler Verlust, Axolyse, eine Vergrößerung der axonalen Mitochondrien sowie eine Verringerung im Abstand benachbarter Neurofilamente im Axon (NNND) gewertet. In Übereinstimmung mit der Situation beim MS-Patienten zeigt diese Erkenntnis eindrücklich die Bedeutung des axonalen Schadens als morphologisch-strukturelles Korrelat irreversibler klinischer Schäden auf, entsprechend dem chronischen Krankheitsverlauf in diesem Modell. Weiterhin konnten wir bereits früh im Krankheitsverlauf das Auftreten einer isolierten Axonschädigung ohne gleichzeitige Pathologie der Myelinscheide nachweisen. Diese Beobachtung zeigt, dass eine axonale Schädigung, zumindest teilweise, auch in Abwesenheit von Myelinpathologien auftreten kann. Dies bestärkt die Notwendigkeit, auch neuroprotektive Therapiestrategien zu entwickeln und damit die immunmodulierende Basistherapie zu ergänzen. Auch das Auftreten regenerativer Prozesse, d. h. eine Remyelinisierung der zuvor demyelinisierten Myelinscheide, konnte in der vorliegenden Arbeit nachgewiesen und als Charakterisitikum der langzeit-chronischen EAE identifiziert werden. Bei der Auswertung der Myelin- und Axonpathologien wurde zur Evaluation der Traktspezifität stets zwischen Ventrolateral- und Dorsalstrang unterschieden, wobei insgesamt für die beiden untersuchten Bahnsysteme eine völlig unterschiedliche Läsionskinetik gefunden werden konnte. Neben der Untersuchung der Läsionsregion der weißen Substanz wurde in der vorliegenden Studie auch die lichtmikroskopisch normal erscheinende weiße Substanz (normal-appearing white matter, NAWM) evaluiert. In dieser Region konnten wir im Gegensatz zu Kontrollgewebe vermehrt Myelin- und Axonpathologien nachweisen, das Ausmaß der Pathologie lag zwischen Kontrollgewebe und Läsionsregion. Ingesamt legen die Ergebnisse der vorliegenden Studie nahe, dass die histopathologischen Charakteristika der MOG35-55-induzierten EAE der B6-Maus viele Aspekte der MS Pathologie widerspiegeln und dieses Modell daher besonders gut für mechanistische Studien über den Einfluß sowohl neuroprotektiv als auch neurodegenerativ wirkender Mechanismen in autoimmunen ZNS-Erkrankungen geeignet ist.The human disease multiple sclerosis (MS) is considered to be an autoimmune disorder characterized by multicentric central nervous system (CNS) inflammation, demyelination and axonal pathology. Despite tremendous scientific effort, the underlying pathomechanisms still remain to be elucidated. Since mechanistic studies are difficult to carry out in humans, MS research is still largely dependent on suitable animal models to investigate the patterns and kinetics of lesion formation in the CNS. Experimental autoimmune encephalomyelitis (EAE) has been studied for decades as an animal model for MS. In particular the C57BL/6 (B6) strain is gaining increasing importance since most gene-modified mice are on this background and are needed for mechanism-oriented studies. One of the traditional models in B6 mice is myelin oligodendrocyte glycoprotein peptide 35-55 (MOG35-55)-induced EAE. The histopathological features of MOG35-55-induced EAE closely mirror the hallmarks of the human disease. Along with the easy availability and producibility of MOG35-55, this renders MOG35-55-induced EAE one of the most commonly used animal models of MS. However, an in-depth characterization of the employed model is a prerequisite for such downstream mechanistic studies on the pathogenetic and/or therapeutic impact of single effector pathways and molecules. Various studies have dealt with the inflammatory component of MOG35-55-induced EAE and among others our group has previously investigated the role of neurodegenerative processes in lightmicroscopic and immunhistochemical studies. However, the present study is the first to evaluate the patterns of demyelination and axonal pathology of MOG35-55-induced EAE on the ultrastructural level. Using distinct morphologic correlates of myelin and axonal damage, we assessed the histopathology of MOG35-55-induced EAE in B6 mice over the course of time to determine the stage-dependent differences and/or similarities between acute, chronic and long-term chronic stages of the disease. For this purpose, transverse segments of the lumbar spinal cord of MOG35-55-immunized mice were obtained at the peak of acute EAE, three months after EAE onset (chronic EAE) and six months after the first day of paralytic symptoms (long-term chronic EAE), EPON-embedded and evaluated by electron microscopy. The extent of myelin pathology in CNS lesions was evaluated by measurement of the g-ratio (axon diameter divided by nerve fiber diameter) and increased progressively over the course of time. Conversely, axonal pathology was present already at disease onset and could be observed constantly in the chronic stages of the disease. Features of axonal damage covered axonal loss, axolysis, mitochondrial swelling and decrease in nearest neighbour neurofilament distance (NNND). This renders axonal damage the morphologic-structural correlate of irreversible clinical impairment, strongly supporting the concept that has been proposed for MS patients. Furthermore, we were able to show the occurrence of isolated axonal damage without concurrent myelin damage already early on in the disease course, a finding which demonstrates that axonal pathology can occur, at least partly, independently of myelin pathology. These data clearly point towards the need for alternative therapeutic strageties that are not only immune modulatory, but also neuroprotective. Another finding was the observation that regeneration of the myelin sheath, i.e. remyelination of previously demyelinated nerve fibers, is a consistent feature of the long-term chronic stage of MOG35-55-induced EAE. We also evaluated the tract-specificity of myelin and axonal damage investigating the ventrolateral and dorsal column. Our data demonstrate striking differences in the kinetics of lesion pathology between the two tract systems. Besides the assessment of CNS white matter lesions, we also evaluated the extent of neurodegeneration in the so-called normal-appearing white matter (NAWM). Here, we were able to show an increase in myelin and axonal pathologies compared to control tissue, ranging between the extent of pathology in control tissue and white matter lesions. In sum, our ultrastructural analysis revealed that the histopathologic features of MOG35-55-induced EAE in B6 mice closely mirror many facets of MS pathology and that this model is ideally suited for mechanistic studies on the impact of both neuroprotective and neurodegenerative mechanisms in autoimmune CNS diseases

A comparison of Cambro-Ordovician and modern sedimentary prisms in the New England area.

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Earth and Planetary Sciences, 1969.Bibliography: leaves 31-33.M.S

Conventional Housing Conditions Attenuate the Development of Experimental Autoimmune Encephalomyelitis

BACKGROUND: The etiology of multiple sclerosis (MS) has remained unclear, but a causative contribution of factors outside the central nervous system (CNS) is conceivable. It was recently suggested that gut bacteria trigger the activation of CNS-reactive T cells and the development of demyelinative disease. METHODS: C57BL/6 (B6) mice were kept either under specific pathogen free or conventional housing conditions, immunized with the myelin basic protein (MBP)-proteolipid protein (PLP) fusion protein MP4 and the development of EAE was clinically monitored. The germinal center size of the Peyer's patches was determined by immunohistochemistry in addition to the level of total IgG secretion which was assessed by ELISPOT. ELISPOT assays were also used to measure MP4-specific T cell and B cell responses in the Peyer's patches and the spleen. Ear swelling assays were performed to determine the extent of delayed-type hypersensitivity reactions in specific pathogen free and conventionally housed mice. RESULTS: In B6 mice that were actively immunized with MP4 and kept under conventional housing conditions clinical disease was significantly attenuated compared to specific pathogen free mice. Conventionally housed mice displayed increased levels of IgG secretion in the Peyer's patches, while the germinal center formation in the gut and the MP4-specific TH17 response in the spleen were diminished after immunization. Accordingly, these mice displayed an attenuated delayed type hypersensitivity (DTH) reaction in ear swelling assays. CONCLUSIONS: The data corroborate the notion that housing conditions play a substantial role in the induction of murine EAE and suggest that the presence of gut bacteria might be associated with a decreased immune response to antigens of lower affinity. This concept could be of importance for MS and calls for caution when considering the therapeutic approach to treat patients with antibiotics.

Experimental autoimmune encephalomyelitis - achievements and prospective advances

Multiple sclerosis (MS) is an autoimmune disorder of the CNS. Different subtypes of the disease have been noted, and characterized by distinct clinical courses and histopathologic manifestations. The most intensively studied animal model of MS, experimental autoimmune encephalomyelitis (EAE), classically leads to deficits in motor functions, and is mediated by T helper cells. Recently, T(H)17 cells were ascribed an even greater pathogenic impact than T(H)1 cells, but new findings render this view controversial. Although classic EAE has been an invaluable tool, it does not cover the entire pathogenic entity of MS. Especially B-cell contribution and autoantibody-dependence are not mirrored adequately: therefore, new B-cell-dependent models, such as MP4-induced EAE, have been introduced. Furthermore, certain symptoms and the spontaneous onset of MS are not featured in classic EAE. Herein, atypical and spontaneous EAE models can be used for investigation of common symptoms, such as tremor and ataxia, as well as spontaneous disease development. MS displays a marked inter-individual heterogeneity, and no single model will be able to cover all features. Thus, depending on the objective of one's study, the appropriate EAE model has to be carefully chosen. In addition, refined models should be designed to gain a more complete understanding of MS

The extent of ultrastructural spinal cord pathology reflects disease severity in experimental autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) has been studied for decades as an animal model for human multiple sclerosis (MS). Here we performed ultrastructural analysis of corticospinal tract (CST) and motor neuron pathology in myelin oligodendrocyte glycoprotein (MOG) peptide 35-55- and MP4-induced EAE of C57BL/6 mice. Both models were clinically characterized by ascending paralysis. Our data show that CST and motor neuron pathology differentially contributed to the disease. In both MOG peptide- and MP4-induced EAE pathological changes in the CST were evident. While the MP4 model also encompassed severe motor neuron degeneration in terms of rough endoplasmic reticulum alterations, the presence of intracytoplasmic vacuoles and nuclear dissolution, both models showed motor neuron atrophy. Features of axonal damage covered mitochondrial swelling, a decrease in nearest neighbor neurofilament distance (NNND) and an increase of the oligodendroglial cytoplasm inner tongue. The extent of CST and motor neuron pathology was reflective of the severity of clinical EAE in MOG peptide- and MP4-elicited EAE. Differential targeting of CNS gray and white matter are typical features of MS pathology. The MOG peptide and MP4 model may thus be valuable tools for downstream studies of the mechanisms underlying these morphological disease correlate

Time-Dependent Progression of Demyelination and Axonal Pathology in MP4-Induced Experimental Autoimmune Encephalomyelitis.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by inflammation, demyelination and axonal pathology. Myelin basic protein/proteolipid protein (MBP-PLP) fusion protein MP4 is capable of inducing chronic experimental autoimmune encephalomyelitis (EAE) in susceptible mouse strains mirroring diverse histopathological and immunological hallmarks of MS. Lack of human tissue underscores the importance of animal models to study the pathology of MS.Twenty-two female C57BL/6 (B6) mice were immunized with MP4 and the clinical development of experimental autoimmune encephalomyelitis (EAE) was observed. Methylene blue-stained semi-thin and ultra-thin sections of the lumbar spinal cord were assessed at the peak of acute EAE, three months (chronic EAE) and six months after onset of EAE (long-term EAE). The extent of lesional area and inflammation were analyzed in semi-thin sections on a light microscopic level. The magnitude of demyelination and axonal damage were determined using electron microscopy. Emphasis was put on the ventrolateral tract (VLT) of the spinal cord.B6 mice demonstrated increasing demyelination and severe axonal pathology in the course of MP4-induced EAE. Additionally, mitochondrial swelling and a decrease in the nearest neighbor neurofilament distance (NNND) as early signs of axonal damage were evident with the onset of EAE. In semi-thin sections we observed the maximum of lesional area in the chronic state of EAE while inflammation was found to a similar extent in acute and chronic EAE. In contrast to the well-established myelin oligodendrocyte glycoprotein (MOG) model, disease stages of MP4-induced EAE could not be distinguished by assessing the extent of parenchymal edema or the grade of inflammation.Our results complement our previous ultrastructural studies of B6 EAE models and suggest that B6 mice immunized with different antigens constitute useful instruments to study the diverse histopathological aspects of MS

Blockade of tumour necrosis factor-α in experimental autoimmune encephalomyelitis reveals differential effects on the antigen-specific immune response and central nervous system histopathology.

In various autoimmune diseases, anti-tumour necrosis factor (TNF)-α treatment has been shown to reduce both clinical disease severity and T helper type 1 (Th1)1/Th17 responses. In experimental autoimmune encephalomyelitis (EAE), however, the role of TNF-α has remained unclear. Here, C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 and treated with anti-TNF-α, control antibody or vehicle. The clinical disease course, incidence and severity were assessed. On day 20 after immunization the antigen-specific Th1/Th17 response was evaluated by enzyme-linked immunospot (ELISPOT) in spleen and central nervous system (CNS). Also, the extent of spinal cord histopathology was analysed on semi- and ultrathin sections. Our results demonstrate that anti-TNF-α treatment reduced the incidence and delayed the onset of EAE, but had no effect on disease severity once EAE had been established. Whereas anti-TNF-α treatment induced an increase in splenic Th1/Th17 responses, there was no effect on the number of antigen-specific Th1/Th17 cells in the spinal cord. Accordingly, the degree of CNS histopathology was comparable in control and anti-TNF-α-treated mice. In conclusion, while the anti-TNF-α treatment had neither immunosuppressive effects on the Th1/Th17 response in the CNS nor histoprotective properties in EAE, it enhanced the myelin-specific T cell response in the immune periphery

Early axonal damage and progressive myelin pathology define the kinetics of CNS histopathology in a mouse model of multiple sclerosis

Studies of MS histopathology are largely dependent on suitable animal models. While light microscopic analysis gives an overview of tissue pathology, it falls short in evaluating detailed changes in nerve fiber morphology. The ultrastructurat data presented here and obtained from studies of myelin oligodendrocyte glycoprotein (MOG):35-55-induced experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice delineate that axonal damage and myelin pathology follow different kinetics in the disease course. While myelin pathology accumulated with disease progression, axonal damage coincided with the initial clinical disease symptoms and remained stable over time. This pattern applied both to irreversible axolysis and early axonal pathology. Notably, these histopathotogical patterns were reflected by the normal-appearing white matter (NAWM), suggesting that the NAWM is also in an active neurodegenerative state. The data underline the need for neuroprotection in MS and suggest the MOG model as a highly valuable toot for the assessment of different therapeutic strategies. (C) 2013 Elsevier Inc. All rights reserved