Über die stoffliche Grundlage der Darmbewegungen und des Darmvagusreizes

Ohne Zusammenfassung     

Statistische Methoden der kleinräumigen Versorgungsforschung

Accurate modeling of spatial dependencies between observations is a significant challenge in research on regional health-care services. This article provides insight into current methods of modeling relationships in regional health-care service research, with consideration of spatial dependencies. Spatial dependencies may be triggered by spillover effects between neighboring regions and spatially distributed differences in – e.g., morbidity – which are not observable. If not considered in the model, the results of the analyses may be biased. Spatial dependencies can be added to the regression model as a spatial lag or a spatial error term. Using an example study, we illustrate that failing to consider spatial autocorrelation may lead to biased coefficients and/or standard errors. Research on regional health-care services should, therefore, if possible, test for spatial autocorrelation in the data and adjust the model accordingly.     

Fas expression by tumor stroma is required for cancer eradication

The contribution of molecules such as perforin, IFN-γ (IFNγ), and particularly Fas ligand (FasL) by transferred CD8⁺ effector T (T_E) cells to rejection of large, established tumors is incompletely understood. Efficient attack against large tumors carrying a surrogate tumor antigen (mimicking a “passenger” mutation) by T_E cells requires action of IFNγ on tumor stroma cells to avoid selection of antigen-loss variants. Because “cancer-driving” antigens (CDAs) are rarely counterselected, IFNγ may be expected to be dispensable in elimination of cancers by targeting a CDA. Here, initial regression of large, established tumors required neither IFNγ, FasL, nor perforin by transferred CD8⁺ T_E cells targeting Simian Virus (SV) 40 large T as CDA. However, cytotoxic T_E cells lacking IFNγ or FasL could not prevent relapse despite retention of the rejection antigen by the cancer cells. Complete tumor rejection required IFNγ-regulated Fas by the tumor stroma. Therefore, T_E cells lacking IFNγ or FasL cannot prevent progression of antigenic cancer because the tumor stroma escapes destruction if its Fas expression is down-regulated.     

Generation of full‐thickness skin equivalents using hair follicle‐derived primary human keratinocytes and fibroblasts

Skin equivalents are increasingly used as human‐based test systems for basic and preclinical research. Most of the established skin equivalents are composed of primary keratinocytes and fibroblasts, isolated either from excised human skin or juvenile foreskin following circumcisions. Although the potential of hair follicle‐derived cells for the generation of skin equivalents has been shown, this approach normally requires microdissections from the scalp for which there is limited subject compliance or ethical approval. In the present study, we report a novel method to isolate and cultivate keratinocytes and fibroblasts from plucked hair follicles that were then used to generate skin equivalents. The procedure is non‐invasive, inflicts little‐pain, and may allow easy access to patient‐derived cells without taking punch biopsies. Overall, minor differences in morphology, ultrastructure, expression of important structural proteins, or barrier function were observed between skin equivalents generated from hair follicle‐derived or interfollicular keratinocytes and fibroblasts. Interestingly, improved basal lamina formation was seen in the hair follicle‐derived skin equivalents. The presented method here allows easy and non‐invasive access to keratinocytes and fibroblasts from plucked hair follicles that may be useful particularly for the generation of skin disease equivalents.