The IC3D classification of the corneal dystrophies.

BACKGROUND: The recent availability of genetic analyses has demonstrated the shortcomings of the current phenotypic method of corneal dystrophy classification. Abnormalities in different genes can cause a single phenotype, whereas different defects in a single gene can cause different phenotypes. Some disorders termed corneal dystrophies do not appear to have a genetic basis. PURPOSE: The purpose of this study was to develop a new classification system for corneal dystrophies, integrating up-to-date information on phenotypic description, pathologic examination, and genetic analysis. METHODS: The International Committee for Classification of Corneal Dystrophies (IC3D) was created to devise a current and accurate nomenclature. RESULTS: This anatomic classification continues to organize dystrophies according to the level chiefly affected. Each dystrophy has a template summarizing genetic, clinical, and pathologic information. A category number from 1 through 4 is assigned, reflecting the level of evidence supporting the existence of a given dystrophy. The most defined dystrophies belong to category 1 (a well-defined corneal dystrophy in which a gene has been mapped and identified and specific mutations are known) and the least defined belong to category 4 (a suspected dystrophy where the clinical and genetic evidence is not yet convincing). The nomenclature may be updated over time as new information regarding the dystrophies becomes available. CONCLUSIONS: The IC3D Classification of Corneal Dystrophies is a new classification system that incorporates many aspects of the traditional definitions of corneal dystrophies with new genetic, clinical, and pathologic information. Standardized templates provide key information that includes a level of evidence for there being a corneal dystrophy. The system is user-friendly and upgradeable and can be retrieved on the website www.corneasociety.org/ic3d.

Expression of prox1, lymphatic endothelial nuclear transcription factor, in Kaposiform hemangioendothelioma and tufted angioma.

Kaposiform hemangioendothelioma (KHE) and tufted angioma (TA) are rare tumors mainly occurring in early childhood. Our recent results showed that ectopic overexpression of human Prox1 gene, a lymphatic endothelial nuclear transcription factor, promoted an aggressive behavior in 2 murine models of KHE. This dramatic Prox1-induced phenotype prompted us to investigate immunohistochemical staining pattern of Prox1, podoplanin (D2-40), LYVE-1, and Prox1/CD34 as well as double immunofluorescent staining pattern of LYVE-1/CD31 in KHE and TA, compared with other pediatric vascular tumors. For this purpose, we examined 75 vascular lesions: KHE (n=18), TA (n=13), infantile hemangioma (n=13), pyogenic granuloma (n=18), and granulation tissue (n=13). Overall, KHE and TA shared an identical endothelial immunophenotype: the neoplastic spindle cells were Prox1, podoplanin, LYVE-1, CD31, and CD34, whereas endothelial cells within glomeruloid foci were Prox1, podoplanin, LYVE-1, CD31, and CD34. The lesional cells of all infantile hemangiomas and pyogenic granulomas were negative for Prox1 in the presence of positive internal control. These findings provide immunophenotypic evidence to support a preexisting notion that KHE and TA are closely related, if not identical. Overall, our results show, for the first time, that Prox1 is an immunohistochemical biomarker helpful in confirming the diagnosis of KHE/TA and in distinguishing it from infantile hemangioma and pyogenic granuloma.

Coronary magnetic resonance imaging.

Coronary magnetic resonance imaging is a powerful non-invasive technique for the combined assessment of coronary artery anatomy and function. In the present review article, challenges in coronary artery imaging are discussed and results obtained in both healthy volunteers and patients with cardiovascular disease are presented. This includes a short overview of coronary artery vessel lumen and wall imaging, contrast agents, permeability of the coronary vessel wall, high-field imaging and imaging of endothelial function.

Angiogenesis inhibition for the improvement of photodynamic therapy: The revival of a promising idea.

Photodynamic therapy (PDT) is a minimally invasive form of treatment, which is clinically approved for the treatment of angiogenic disorders, including certain forms of cancer and neovascular eye diseases. Although the concept of PDT has existed for a long time now, it has never made a solid entrance into the clinical management of cancer. This is likely due to secondary tissue reactions, such as inflammation and neoangiogenesis. The recent development of clinically effective angiogenesis inhibitors has lead to the initiation of research on the combination of PDT with such angiostatic targeted therapies. Preclinical studies in this research field have shown promising results, causing a revival in the field of PDT. This review reports on the current research efforts on PDT and vascular targeted combination therapies. Different combination strategies with angiogenesis inhibition and vascular targeting approaches are discussed. In addition, the concept of increasing PDT selectivity by targeted delivery of photosensitizers is presented. Furthermore, the current insights on sequencing the therapy arms of such combinations will be discussed in light of vascular normalization induced by angiogenesis inhibition.

Le concept de test relationnel en psychothérapie: origine, développements et applications aux troubles de la personnalité = The test concept in psychotherapy: origins, developments and application to personality disorders

Le concept de test relationnel (test, en anglais ; Weiss et Sampson, 1986 [16]) est présenté. Ses origines dans les écrits de Freud sont brièvement retracées et son inscription dans la théorie des croyances pathogènes de Weiss présentée. Par ailleurs, les autres éléments de la théorie psychanalytique de Weiss sont présentés (buts thérapeutiques, obstacles, traumas, insight, test relationnel). Toutes ces étapes sont illustrées par des exemples tirés de la littérature. Un développement récent du concept de test relationnel est présenté et appliqué à la psychothérapie des troubles de la personnalité (Sachse, 2003 [14]). Finalement, les auteurs donnent deux brefs exemples de tests relationnels tirés de leur propre pratique de psychothérapeute et discutent des modèles en les comparant entre eux. Des conclusions concernant l'utilité du concept de test relationnel pour la pratique psychothérapeutique et la recherche en psychothérapie sont proposées. The test concept (Weiss and Sampson, 1986 [16]) is presented. Its origins in Freud's works are briefly evoked and its place within the theory of pathogenic beliefs by Weiss presented. We present also the remaining elements of Weiss' psychoanalytic theory which are objectives, obstacles, traumas and insight. Every step of the reflection is illustrated with case examples, drawn from the literature. A recent development of the test concept is presented and applied to the psychotherapy of personality disorders (Sachse, 2003 [14]). Finally, the authors give brief examples of tests having occurred in their own practice as psychotherapists and discuss the models by comparing them among each other. Conclusions are drawn concerning the usefulness of the test concept for psychotherapy practice and research.

Enhanced heat shock protein 70 expression alters proteasomal degradation of IkappaB kinase in experimental acute respiratory distress syndrome.

OBJECTIVES: Acute respiratory distress syndrome is a common and highly lethal inflammatory lung syndrome. We previously have shown that an adenoviral vector expressing the heat shock protein (Hsp)70 (AdHSP) protects against experimental sepsis-induced acute respiratory distress syndrome in part by limiting neutrophil accumulation in the lung. Neutrophil accumulation and activation is modulated, in part, by the nuclear factor-kappaB (NF-kappaB) signal transduction pathway. NF-kappaB activation requires dissociation/degradation of a bound inhibitor, IkappaBalpha. IkappaBalpha degradation requires phosphorylation by IkappaB kinase, ubiquitination by the SCFbeta-TrCP (Skp1/Cullin1/Fbox beta-transducing repeat-containing protein) ubiquitin ligase, and degradation by the 26S proteasome. We tested the hypothesis that Hsp70 attenuates NF-kappaB activation at multiple points in the IkappaBalpha degradative pathway. DESIGN: Laboratory investigation. SETTING: University medical center research laboratory. SUBJECTS: Adolescent (200 g) Sprague-Dawley rats and murine lung epithelial-12 cells in culture. INTERVENTIONS: Lung injury was induced in rats via cecal ligation and double puncture. Thereafter, animals were treated with intratracheal injection of 1) phosphate buffer saline, 2) AdHSP, or 3) an adenovirus expressing green fluorescent protein. Murine lung epithelial-12 cells were stimulated with tumor necrosis factor-alpha and transfected. NF-kappaB was examined using molecular biological tools. MEASUREMENTS AND MAIN RESULTS: Intratracheal administration of AdHSP to rats with cecal ligation and double puncture limited nuclear translocation of NF-kappaB and attenuated phosphorylation of IkappaBalpha. AdHSP treatment reduced, but did not eliminate, phosphorylation of the beta-subunit of IkappaB kinase. In vitro kinase activity assays and gel filtration chromatography revealed that treatment of sepsis-induced lung injury with AdHSP induced fragmentation of the IkappaB kinase signalosome. This stabilized intermediary complexes containing IkappaB kinase components, IkappaBalpha, and NF-kappaB. Cellular studies indicate that although ubiquitination of IkappaBalpha was maintained, proteasomal degradation was impaired by an indirect mechanism. CONCLUSIONS: Treatment of sepsis-induced lung injury with AdHSP limits NF-kappaB activation. This results from stabilization of intermediary NF-kappaB/IkappaBalpha/IkappaB kinase complexes in a way that impairs proteasomal degradation of IkappaBalpha. This novel mechanism by which Hsp70 attenuates an intracellular process may be of therapeutic value.

Phase-sensitive black-blood coronary vessel wall imaging.

Black-blood MR coronary vessel wall imaging may become a powerful tool for the quantitative and noninvasive assessment of atherosclerosis and positive arterial remodeling. Although dual-inversion recovery is currently the gold standard, optimal lumen-to-vessel wall contrast is sometimes difficult to obtain, and the time window available for imaging is limited due to competing requirements between blood signal nulling time and period of minimal myocardial motion. Further, atherosclerosis is a spatially heterogeneous disease, and imaging at multiple anatomic levels of the coronary circulation is mandatory. However, this requirement of enhanced volumetric coverage comes at the expense of scanning time. Phase-sensitive inversion recovery has shown to be very valuable for enhancing tissue-tissue contrast and for making inversion recovery imaging less sensitive to tissue signal nulling time. This work enables multislice black-blood coronary vessel wall imaging in a single breath hold by extending phase-sensitive inversion recovery to phase-sensitive dual-inversion recovery, by combining it with spiral imaging and yet relaxing constraints related to blood signal nulling time and period of minimal myocardial motion.

Coronary magnetic resonance angiography.

Coronary magnetic resonance angiography (MRA) is a powerful noninvasive technique with high soft-tissue contrast for the visualization of the coronary anatomy without X-ray exposure. Due to the small dimensions and tortuous nature of the coronary arteries, a high spatial resolution and sufficient volumetric coverage have to be obtained. However, this necessitates scanning times that are typically much longer than one cardiac cycle. By collecting image data during multiple RR intervals, one can successfully acquire coronary MR angiograms. However, constant cardiac contraction and relaxation, as well as respiratory motion, adversely affect image quality. Therefore, sophisticated motion-compensation strategies are needed. Furthermore, a high contrast between the coronary arteries and the surrounding tissue is mandatory. In the present article, challenges and solutions of coronary imaging are discussed, and results obtained in both healthy and diseased states are reviewed. This includes preliminary data obtained with state-of-the-art techniques such as steady-state free precession (SSFP), whole-heart imaging, intravascular contrast agents, coronary vessel wall imaging, and high-field imaging. Simultaneously, the utility of electron beam computed tomography (EBCT) and multidetector computed tomography (MDCT) for the visualization of the coronary arteries is discussed.

Lektüren im intermedialen Dialog

Die Studie geht davon aus, dass das Zusammenspiel von Text und Bild auf dem Prinzip der Dialogizität und Komplementarität zwischen zwei einander fremden Systemen gründet. Texte generieren Bilder, Bilder evozieren Narrationen. Im Zusammentreffen zwischen den beiden Medien werden Energien freigesetzt und ein Mehr an Bedeutung entsteht. Sprache und Bild können rivalisieren oder sich gegenseitig inspirieren, einander ergänzen oder ersetzen, ineinandergreifen oder kontrastieren. Abhängig von der jeweiligen Inszenierung, von der visuellen Anordnung, von inhaltlichen llbereinstimmungen oder formalen Annäherungen setzen die Medien divergierende oder kongruierende Systeme in Szene. Aus dem weiten Feld der intermedialen Verknüpfungen von Text und Bild wählt die Studie eine Reihe von Text-Bild-Kombinationen, in denen skripturale und piktoriale Elemente nebeneinander inszeniert werden und in ihrem prozesshaften Zusammenwirken den Rezipienten zur Lekture von unterschiedlichen narrativen Möglichkeiten herausfordern: Max Ernsts Collageroman Rêve d'une petite fille qui voulut entrer au CarmeI ; Peter Weiss' Text- Bild-Ensemble Der Schatten des Kòrpers des Kutschers, Le rêve de Paul Delvaux, ein Text- Bild-Projekt, für das der Nouveau Romancier Michel Butor eine Erzählung zu einer Reihe von Bildern des Surrealisten Paul Delvaux verfasst ; die Ballade Minotaurus von Friedrich Dürrenmatt , sowie Der Schachspieler, eine Reaktion des Illustrators Hannes Binder auf einen posthum erschienenen Text Durrenmatts . In fünf Einzellektüren und fünf Kapiteln wird der Frage nachgegangen wie sich Narration im Text-Bild-Spiegel generiert und welche Rolle der Lektüreakt dabei spielt. Dabei interessieren die Werke als vergleichbare, aber heterogene Kombinationsformen von Text und Bild. Im Zentrum der Analysen stehen die Darstellung von Raum- und Zeitelementen, die sprachlichen Erzählinstanzen, die das Zusammenspiel von Stimme und Körper konstituieren, sowie der Informationstrager Buch als medialer wie auch materieller Gegenstand.

Guidelines for the use and interpretation of assays for monitoring autophagy.

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.