Disastrous Portal Vein Embolization Turned into a Successful Intervention

Portal vein embolization (PVE) may be performed before hemihepatectomy to increase the volume of future liver remnant (FLR) and to reduce the risk of postoperative liver insufficiency. We report the case of a 71-year-old patient with hilar cholangiocarcinoma undergoing PVE with access from the right portal vein using a mixture of n-butyl-2-cyanoacrylate and ethiodized oil. During the procedure, nontarget embolization of the left portal vein occurred. An aspiration maneuver of the polymerized plug failed; however, the embolus obstructing portal venous flow in the FLR was successfully relocated into the right portal vein while carefully bypassing the plug with a balloon catheter, inflating the balloon, and pulling the plug into the main right portal vein

Molecular Mechanisms in Cell Differentiation and Cell Division

p63 ist eines von drei Mitgliedern der p53 Familie von Transkriptionsfaktoren. Die Transkription des p63 Gens führt zu zwei verschiedenen Isoformen, der Isoform TA-p63 mit einer N-terminalen Transaktivierungsdomäne und der Isoform DeltaN-p63 ohne diese Domäne. Die hier beschriebene Untersuchung der Expression von p63 in Geweben und die Studie von p63-defizienten Mäusen zeigte, dass p63 in der Entwicklung von epithelialen Geweben, des Schädels und der Extremitäten eine wichtige Rolle spielt. Die Bedeutung von p63 in diesen Vorgängen wurde weiterhin verdeutlicht durch das Auftreten von p63 Mutationen in der menschlichen Keimbahn, die zu schweren Defekten in der Entwicklung von Extremitäten und zu epidermalen Fehlbildungen führen. Die genaue Funktion von p63 in der epidermalen Entwicklung ist noch immer stark umstritten. Während einerseits p63 als entscheidender Faktor in der Differenzierung des embryonalen Ektoderms zu epidermalen Geweben beschrieben wird, wird es andererseits als Stammzellfaktor für die Aufrechterhaltung des Teilungsvermögens und der Regeneration von epidermalen Stammzellen beschrieben. Darüber hinaus existieren unterschiedliche Meinungen zu der jeweiligen Bedeutung der TA- und der DeltaN-p63-Isoform in diesen Prozessen. Jüngste Studien haben gefunden, dass TA-p63 eine entscheidende Rolle zum Schutz der weiblichen Keimbahn vor DNS Schädigung spielt. Die vorliegende Arbeit beschreibt die Anfertigung einer TA-p63 defizienten Maus zur Aufklärung der spezifischen Funktion von TA-p63 in der epidermalen Entwicklung und anderen Prozessen in vivo. In der Zellteilung ist es von großer Bedeutung, dass die Aufteilung von Schwesterchromatiden mit hoher Genauigkeit erfolgt. Das Auftreten von Fehlern in diesem Prozess kann zu Zellen mit unterschiedlicher Anzahl von Chromosomen und damit zu Entwicklungsschäden und Tumorerkrankungen führen. Der Spindle Assembly Checkpoint ist ein Schutzmechanismus der Zelle, der Fehler beim Binden der Mikrotubuli an die Kinetochore oder das Fehlen von Spannung zwischen den Kinetochoren bemerkt und die Zelle in der Metaphase aufhält, bis alle Fehler behoben sind. Seit der Entdeckung der ersten Komponenten des Spindle Assembly Checkpoint vor über 15 Jahren, ist ein hochkomplexes Proteinnetzwerk charakterisiert worden, das Schwesterchromatiden-Kohäsion, Kinetochoren und Mikrotubulizytoskelett mit dem Spindle Assembly Checkpoint verbindet. Eines der neuesten Mitglieder dieses Netzwerkes ist die Familie der Shugoshin (Sgo) Proteine. Die folgende Arbeit ist eine detaillierte Charakterisierung des Checkpoint Proteins BubR1, seiner post-translationalen Modifikationen und seiner Interaktionspartner in Interphase und Mitose. Weiterhin wurde die Funktion des mit BubR1 interagierenden Proteins Sgo2 in der Mitose untersucht.p63 is one of three members of the p53 family of transcription factors. Transcription of the p63 gene gives rise to two different N-terminal isoforms, one with (TA-p63) and one without (DeltaN-p63) a transactivation domain. Analysis of p63 protein expression in tissues and of mice deficient for all p63-isoforms revealed a function of p63 in epithelial, craniofacial, and limb development. The significance of p63 in epidermal development is further highlighted by the discovery of p63 germline mutations in severe human syndromes with limb defects and ectodermal dysplasia. Interestingly, the interpretation of p63 function in epidermal development is still controversial. On one hand, p63 is discussed as a commitment factor for the embryonic ectoderms to epidermal lineage, while on the other hand, it is suggested that p63 is a stem cell factor involved in maintenance of proliferative potential and regeneration of epidermal stem cells. Furthermore, there are different opinions about the relative significance of TA- and DeltaN-p63 in the commitment to epidermal lineages and in epidermal differentiation. Recently, studies in mice deficient for more than one p53 family member were conducted to reveal potential cross-regulation between them. Moreover, TA-p63 was found to be implicated in the protection of the female germline by inducing cell death in oocytes upon gamma-irradiation. The work presented here investigates the function of TA-p63 in the commitment of embryonic ectoderm to epidermal lineages and epithelial development to resolve the DeltaN-p63 in this process. Furthermore, mice deficient for TA-p63 mice are described. A high fidelity of chromosome segregation is crucial to ensure correct transmission of genetic material to daughter cells. Errors in this process result in aberrant chromosome numbers and can cause severe developmental defects, miscarriages, and cancer. The spindle assembly checkpoint is a surveillance mechanism that monitors chromosome segregation, detects attachment defects, and delays anaphase onset until errors are corrected. Moreover, passive mechanisms such as kinetochore geometry, architecture, and back-to-back orientation of sister kinetochores further reduce the risk of mis-attachment. Upon satisfaction of the spindle assembly checkpoint, inactivation of Cdk1/cyclin B and cleavage of cohesin leads to chromosome separation and cell cycle progression into anaphase. Since the identification of the first molecular components of the spindle assembly checkpoint over 15 years ago, many proteins were found to be involved in checkpoint signaling. A highly complex protein interaction network is emerging that connects sister chromatid cohesion, kinetochore biology, and microtubule cytoskeleton with the spindle assembly checkpoint. The conserved family of shugoshin proteins are one of the latest additions to this network and present a link between sister chromatid cohesion, checkpoint signaling, and microtubule dynamics. While initial investigations in yeast and drosophilia have been conducted, little is known about shugoshin functions in mammalian cells. The work presented here provides a detailed characterization of one of the key players in checkpoint signaling, BubR1, including its post-translation modifications and its interactions during the cell cycle. Furthermore, the work provides insight into the regulation and evolution of BubR1’s localization and function. Finally, the interaction of BubR1 and Sgo2 is shown to link checkpoint signaling and kinetochore geometry

Ein Practica practicirt, auss der heylgen Bibel, vff vil zukünfftig jar, Selig syn die, die jr war nemen, vnd darnach richten, Die zeyt ist hie, das man solich practica[m] mer acht hab, dan[n] der astronomy, got wil selber regirn über seyn volck ...

http://www.ester.ee/record=b3525414*es

Genome-wide mapping indicates that p73 and p63 Co-occupy target sites and have similar DNA-binding profiles in vivo

Background: The p53 homologs, p63 and p73, share, ~85% amino acid identity in their DNA-binding domains, but they have distinct biological functions. Principal Findings: Using chromatin immunoprecipitation and high-resolution tiling arrays covering the human genome, we identify p73 DNA binding sites on a genome-wide level in ME180 human cervical carcinoma cells. Strikingly, the p73 binding profile is indistinguishable from the previously described binding profile for p63 in the same cells. Moreover, the p73:p63 binding ratio is similar at all genomic loci tested, suggesting that there are few, if any, targets that are specific for one of these factors. As assayed by sequential chromatin immunoprecipitation, p63 and p73 co-occupy DNA target sites in vivo, suggesting that p63 and p73 bind primarily as heterotetrameric complexes in ME180 cells. Conclusions: The observation that p63 and p73 associate with the same genomic targets suggest that their distinct biological functions are due to cell-type specific expression and/or protein domains that involve functions other than DNA binding. © 2010 Yang et al

“The Power of Many Minds Working Together”: Qualitative Study of an Interprofessional, Service-Learning Capstone Course

Background: An interprofessional faculty group analyzed a critical reflection assignment of students in a service-learning practicum interprofessional education (IPE) course. Students were from ten programs: physical therapy, occupational therapy, nuclear medicine technology, radiation therapy, athletic training, nursing, investigative medical science, cytotechnology, nutrition and dietetics, and clinical laboratory science. Research questions investigated what the assignments revealed about students’ application of beliefs, emotions, and behaviours, and if course objectives were met.Methods and Findings: This qualitative study retrospectively analyzed one critical reflection from the course conducted in 2011. Researchers selected a stratified sample of 40 assignments from a population of 278. Nine major themes emerged: achieving IPE outcomes, engaging in team process, learning culture/community engagement, being client/patient centred, becoming aware of behaviours, experiencing barriers, articulating beliefs, connecting with course objectives, and expressing emotions.Conclusions: In an IPE practicum course, transformative learning was evident. Students articulated beliefs, emotions, and behaviours related to interprofessional teamwork. Students expressed detailed understanding of team processes. For future research, critical reflection assignments were useful to assess student beliefs, emotions, and behaviours in a practicum course. We suggest studying practice among health professionals who have experienced IPE compared with those who have not had IPE in their professional curricula

Protective Embolization of the Gastroduodenal Artery with a One-HydroCoil Technique in Radioembolization Procedures

Purpose: Protective occlusion of the gastroduodenal artery (GDA) is required to avoid severe adverse effects and complications in radioembolization procedures. Because of the expandable features of HydroCoils, our goal was to occlude the GDA with only one HydroCoil to provide particle reflux protection. Methods: Twenty-three subjects with unresectable liver tumors, who were scheduled for protective occlusion of the GDA before radioembolization therapy, were included. The primary end point was to achieve a proximal occlusion of the GDA with only one detachable HydroCoil. Evaluated parameters were duration of deployment, and early (during the intervention) and late (7-21days) occlusion rates of GDA. Secondary end points included complete duration of the intervention, amount of contrast medium used, fluoroscopy rates, and adverse effects. Results: In all cases, the GDA was successfully occluded with only one HydroCoil. The selected diameter/length range was 4/10mm in 2 patients, 4/15mm in 6 patients, and 4/20mm in 15 patients. HydroCoils were implanted, on average, 3.75mm from the origin of the GDA (range 1.5-6.8mm), with an average deployment time of 2:47 (median 2:42, range 2:30-3:07) min. In 21 (91%) of 23 patients, a complete occlusion of the GDA was achieved during the first 30min after the coil implantation; however, in all patients, a late occlusion of the GDA was present after 6 to 29days. No clinical or technical complications were reported. Conclusion: We demonstrated that occlusion of the GDA with a single HydroCoil is a safe procedure and successfully prevents extrahepatic embolization before radioembolizatio