Intramedulläre Tumoren – Management- und Outcome-Analyse

In der Therapie intramedullärer Tumoren herrschen noch Unsicherheiten über den Zeitpunkt und das Ausmaß der Tumorresektion sowie über die damit verbundenen funktionellen Ergebnisse. Die vorliegende Arbeit stellt eine retrospektive Analyse der Krankengeschichte von 70 Patienten mit intramedullären Tumoren dar, die zwischen 1987 und 2007 in der Neuro-chirurgischen Universitätsklinik Bonn operiert wurden. Die Krankenakten wurden hin-sichtlich des progressionsfreien Überlebens und des neurologischen Status sowie des Einflusses der o.g. Faktoren analysiert. Des Weiteren wurde die Durchführung eines intraoperativen Monitorings sowie adjuvanter Therapiemaßnahmen erfasst. Das progressionsfreie Überleben für Patienten mit einer vollständigen Tumorresektion war mit durchschnittlich 66 Monaten signifikant länger als für Patienten mit einer Tumorbiopsie, deren progressionsfreies Überleben im Mittel 2,7 Monate betrug (p=0,014). Keinen statistisch signifikanten Einfluss auf das progressionsfreie Überleben zeigten in unserer Studie der WHO-Grad, die Höhenausbreitung sowie die Lokalisation der Tumore. Das neurologische Outcome der Patienten war maßgeblich vom präoperativen neurologischen Zustand der Patienten abhängig (p=0,001). So konnten unter den Patienten, die sich präoperativ in einem guten neurologischen Status entsprechend dem Mc-Cormick-Grad I oder II befanden, postoperativ 82,6 % bzw. zum Zeitpunkt des letzten Follow-up 73,3 % diesem zugeordnet werden, während nur 8,3 % bzw. 13,1 % der Patienten mit einem präoperativen McCormick-Grad III oder IV diesem entsprachen. Dabei beeinflussten weder die Geschlechtszugehörigkeit noch das Alter noch die Tumorlokalisation noch die Anzahl der Wirbelkörperhöhen oder die Dauer der präoperativ bestehenden Symptomatik das neurologische Outcome signifikant. Unseren Ergebnissen zufolge profitieren von einer Operation insbesondere Patienten, die frühzeitig, bei noch gering ausgeprägten neurologischen Defiziten, operiert wurden und jene, bei denen eine komplette Tumorresektion erreicht werden konnte. Der Einsatz eines intraoperativen Monitorings scheint dabei das Erreichen einer kompletten Tumorresektion zu begünstigen. Eine adjuvante Therapie bleibt malignen Tumoren und Metastasen vorbehalten

Host–microbe interactions in the developing zebrafish

The amenability of the zebrafish to in vivo imaging and genetic analysis has fueled expanded use of this vertebrate model to investigate the molecular and cellular foundations of host-microbe relationships. Study of microbial encounters in zebrafish hosts has concentrated on developing embryonic and larval stages, when the advantages of the zebrafish model are maximized. A comprehensive understanding of these host-microbe interactions requires appreciation of the developmental context into which a microbe is introduced, as well as the effects of that microbial challenge on host ontogeny. In this review, we discuss how in vivo imaging and genetic analysis in zebrafish has advanced our knowledge of host-microbe interactions in the context of a developing vertebrate host. We focus on recent insights into immune cell ontogeny and function, commensal microbial relationships in the intestine, and microbial pathogenesis in zebrafish hosts

La influencia de la cultura sobre la búsqueda de información. El caso de la vivienda para 'turismo residencial' en la Costa Blanca.

The influence of culture in the buying decision process is analyzed by focusing on the information seeking behaviour for a product representing a complex decision making. The literature proves the importance of culture for the decision process while there are hardly any studies available for the real-estate sector. Using a cultural specific approach, the influence of culture (represented by the dimensions of horizontal and vertical individualism and collectivism, risk aversion, and future time perspective) on information seeking behaviour (importance of information sources, information search effort, cognitive effort and perceived risk) is analyzed. The study, with a sample of people from three European countries - Spain, Germany and United Kingdom - who bought a house for residential tourism within the last four years in the Costa Blanca area found significant influences of culture on the different groups and variables considered. Se realiza un análisis de la influencia de la cultura sobre el proceso de decisión de compra, centrándose en la etapa de búsqueda de información en un bien de decisión de compra compleja. La literatura ha incidido en la importancia de la cultura como factor importante, aunque apenas hay literatura en el ámbito del marketing del sector inmobiliario. Tras adoptar un enfoque específico-cultural, se analiza la influencia diferencial de la cultura (medida mediante las dimensiones 'verticalidad-horizontalidad' y 'colectiva-individual', la aversión al riesgo y la orientación al tiempo) sobre la búsqueda de información medida mediante la importancia dada a las fuentes de información, los esfuerzos de búsqueda y cognitivo y el riesgo percibido. El estudio, realizado en una muestra de compradores de vivienda para turismo residencial en los últimos 4 años en la CostaBlanca, procedentes de 3 países europeos -España, Alemania y Reino Unido- muestra la influencia real y significativa de la cultura en los diversos colectivos y variables consideradas.: Marketing Inmobiliario, Comportamiento del consumidor cross-cultural, Estudio Intercultural, Vivienda, Turismo Residencial, Cultura, Búsqueda de Información, Proceso de Toma de Decisiones. Real-estate marketing, Cross-cultural consumer behaviour, Intercultural study, Residential tourism, Culture, Information seeking, Decision making process.

Patterns and Scales in Gastrointestinal Microbial Ecology

The body surfaces of humans and other animals are colonized at birth by microorganisms. The majority of microbial residents on the human body exist within gastrointestinal (GI) tract communities, where they contribute to many aspects of host biology and pathobiology. Recent technological advances have expanded our ability to perceive the membership and physiologic traits of microbial communities along the GI tract. To translate this information into a mechanistic and practical understanding of host-microbe and microbe-microbe relationships, it is necessary to recast our conceptualization of the GI tract and its resident microbial communities in ecological terms. This review depicts GI microbial ecology in the context of 2 fundamental ecological concepts: (1) the patterns of biodiversity within the GI tract and (2) the scales of time, space, and environment within which we perceive those patterns. We show how this conceptual framework can be used to integrate our existing knowledge and identify important open questions in GI microbial ecology

Methods for generating and colonizing gnotobiotic zebrafish

Vertebrates are colonized at birth by complex and dynamic communities of microorganisms that can contribute significantly to host health and disease. The ability to raise animals in the absence of microorganisms has been a powerful tool for elucidating the relationships between animal hosts and their microbial residents. The optical transparency of the developing zebrafish and relative ease of generating germ-free zebrafish makes it an attractive model organism for gnotobiotic research. Here we provide a protocol for: generating zebrafish embryos; deriving and rearing germ-free zebrafish; and colonizing zebrafish with microorganisms. Using these methods, we typically obtain 80–90% sterility rates in our germ-free derivations with 90% survival in germ-free animals and 50–90% survival in colonized animals through larval stages. Obtaining embryos for derivation requires approximately 1–2 hours with a 3–8 hour incubation period prior to derivation. Derivation of germ-free animals takes 1–1.5 hours, and daily maintenance requires 1–2 hours

Commensal microbiota stimulate systemic neutrophil migration through induction of Serum amyloid A: Microbiota regulate systemic neutrophil function

Neutrophils serve critical roles in inflammatory responses to infection and injury, and mechanisms governing their activity represent attractive targets for controlling inflammation. The commensal microbiota is known to regulate the activity of neutrophils and other leucocytes in the intestine, but the systemic impact of the microbiota on neutrophils remains unknown. Here we utilized in vivo imaging in gnotobiotic zebrafish to reveal diverse effects of microbiota colonization on systemic neutrophil development and function. The presence of a microbiota resulted in increased neutrophil number and myeloperoxidase expression, and altered neutrophil localization and migratory behaviours. These effects of the microbiota on neutrophil homeostasis were accompanied by an increased recruitment of neutrophils to injury. Genetic analysis identified the microbiota-induced acute phase protein serum amyloid A (Saa) as a host factor mediating microbial stimulation of tissue-specific neutrophil migratory behaviours. In vitro studies revealed that zebrafish cells respond to Saa exposure by activating NF-κB, and that Saa-dependent neutrophil migration requires NF-κB-dependent gene expression. These results implicate the commensal microbiota as an important environmental factor regulating diverse aspects of systemic neutrophil development and function, and reveal a critical role for a Saa-NF-κB signalling axis in mediating neutrophil migratory responses

Microbial Colonization Induces Dynamic Temporal and Spatial Patterns of NF-κB Activation in the Zebrafish Digestive Tract

The nuclear factor κ-light-chain enhancer of activated B cells (NF-κB) transcription factor pathway is activated in response to diverse microbial stimuli to regulate expression of genes involved in immune responses and tissue homeostasis. However, the temporal and spatial activation of NF-κB in response to microbial signals have not been determined in whole living organisms, and the molecular and cellular details of these responses are not well understood. We used in vivo imaging and molecular approaches to analyze NF-κB activation in response to the commensal microbiota in transparent gnotobiotic zebrafish

Age-related islet inflammation marks the proliferative decline of pancreatic beta-cells in zebrafish

The pancreatic islet, a cellular community harboring the insulin-producing beta-cells, is known to undergo age-related alterations. However, only a handful of signals associated with aging have been identified. By comparing beta-cells from younger and older zebrafish, here we show that the aging islets exhibit signs of chronic inflammation. These include recruitment of tnfα-expressing macrophages and the activation of NF-kB signaling in beta-cells. Using a transgenic reporter, we show that NF-kB activity is undetectable in juvenile beta-cells, whereas cells from older fish exhibit heterogeneous NF-kB activity. We link this heterogeneity to differences in gene expression and proliferation. Beta-cells with high NF-kB signaling proliferate significantly less compared to their neighbors with low activity. The NF-kB signalinghi cells also exhibit premature upregulation of socs2, an age-related gene that inhibits beta-cell proliferation. Together, our results show that NF-kB activity marks the asynchronous decline in beta-cell proliferation with advancing age

Zebrafish tissue injury causes upregulation of interleukin-1 and caspase-dependent amplification of the inflammatory response

Interleukin-1 (IL-1), the ‘gatekeeper’ of inflammation, is the apical cytokine in a signalling cascade that drives the early response to injury or infection. Expression, processing and secretion of IL-1 are tightly controlled, and dysregulated IL-1 signalling has been implicated in a number of pathologies ranging from atherosclerosis to complications of infection. Our understanding of these processes comes from in vitro monocytic cell culture models as lines or primary isolates, in which a range and spectra of IL-1 secretion mechanisms have been described. We therefore investigated whether zebrafish embryos provide a suitable in vivo model for studying IL-1-mediated inflammation. Structurally, zebrafish IL-1β shares a β-sheet-rich trefoil structure with its human counterpart. Functionally, leukocyte expression of IL-1β was detectable only following injury, which activated leukocytes throughout zebrafish embryos. Migration of macrophages and neutrophils was attenuated by inhibitors of either caspase-1 or P2X7, which similarly inhibited the activation of NF-κB at the site of injury. Zebrafish offer a new and versatile model to study the IL-1β pathway in inflammatory disease and should offer unique insights into IL-1 biology in vivo

Robotic injection of zebrafish embryos for high-throughput screening in disease models

The increasing use of zebrafish larvae for biomedical research applications is resulting in versatile models for a variety of human diseases. These models exploit the optical transparency of zebrafish larvae and the availability of a large genetic tool box. Here we present detailed protocols for the robotic injection of zebrafish embryos at very high accuracy with a speed of up to 2000 embryos per hour. These protocols are benchmarked for several applications: (1) the injection of DNA for obtaining transgenic animals, (2) the injection of antisense morpholinos that can be used for gene knock-down, (3) the injection of microbes for studying infectious disease, and (4) the injection of human cancer cells as a model for tumor progression. We show examples of how the injected embryos can be screened at high-throughput level using fluorescence analysis. Our methods open up new avenues for the use of zebrafish larvae for large compound screens in the search for new medicines