59 research outputs found

    Peripheral nervous system defects in erbB2 mutants following genetic rescue of heart development

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    The ErbB2 tyrosine kinase functions as coreceptor for the neuregulin receptors ErbB3 and ErbB4 and can participate in signaling of EGF receptor (ErbB1), interleukin receptor gp130, and G-protein coupled receptors. ErbB2−/− mice die at midgestation because of heart malformation. Here, we report a genetic rescue of their heart development by myocardial expression of erbB2 cDNA that allows survival of the mutants to birth. In rescued erbB2 mutants, Schwann cells are lacking. Motoneurons form and can project to muscle, but nerves are poorly fasciculated and disorganized. Neuromuscular junctions form, as reflected in clustering of AChR and postsynaptic expression of the genes encoding the a-AChR, AChE, e-AChR, and the RI subunit of the cAMP protein kinase. However, a severe loss of motoneurons on cervical and lumbar, but not on thoracic levels occurs. Our results define the roles of Schwann cells during motoneuron and synapse development, and reveal different survival requirements for distinct motoneuron population

    CD24 Expression is an Independent Prognostic Marker in Cholangiocarcinoma

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    CD24 has been described as an adverse prognostic marker in several malignancies. This study evaluates CD24 expression in cholangiocarcinoma and correlates the findings with clinicopathologic data and patient survival. Between 1996 and 2002, 22 consecutive patients with cholangiocarcinoma were treated at our institution. Demographic data, SEER stage, pathologic data, treatment, expression of CD24, mitogen-activated protein kinase (MAPK), phosphorylated MAPK, and survival were analyzed. The majority of the tumors demonstrated CD24 (81.8%) and p-MAPK (87%) expression. A negative association was noted between the expression of CD24 and p-MAPK. Median survival for patients with low expression of CD24 was 36 months and high expression was 8 months. Median survival for patients who received chemotherapy with low CD24 expression was 163 months, and for seven patients with high CD24 expression, it was 17 months (p = 0.04). With the addition of radiation therapy, median survival for patients with low expression of CD24 was 52 months and high expression was 17 months (p = 0.08). On multivariate analysis, the use of chemotherapy (p = 0.0014, hazard ratio 0.069) and the CD24 overexpression (p = 0.02, hazard ratio 7.528) were predictive of survival. CD24 is commonly expressed in cholangiocarcinoma, and overexpression is predictive of poor survival and possibly of lack of response to chemotherapy and radiation therapy. These findings may improve selection of patients for the appropriate treatment modality and the development of CD24-targeted therapy

    Endoskopische Diagnostik und Therapie bei perihilÀren Cholangiokarzinomen (Klatskintumore)

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    Die ERC ist der diagnostisch Goldstandard bei Patienten mit Klatskintumor und kann auch zur palliativen Stenttherapie eingesetzt werden. Wir konnten die MorbiditĂ€t und MortalitĂ€t der post-ERC-Cholangitis bei Patienten mit Klatskintumor deutlich reduzieren, in dem wir nach MRCP-gestĂŒtzter Bestimmung des Drainageziels nur eine unilaterale Kontrastierung und Stenteinlage durchfĂŒhrten. Die DNA-Zytometrie war der beste Prognosefaktore fĂŒr das postoperative Überleben von resezierten Patienten mit Klatskintumor. Im Gegensatz zu diploiden und polyploiden Klatskintumoren hatten Patienten mit aneuploiden Tumoren trotz kurativer Resektion eine sehr schlechte Prognose infolge frĂŒher Mikrometastasierung. Bei einigen Patienten mit Klatskintumor liegt eine Billroth II-Gastro-Jejunostomie vor. Trotz der erschwerten Endokoppassage gelang es uns meistens, sowohl die Majorpapille zu erreichen, als auch trotz der inversen Endoskopposition eine sichere Papillotomie durchzufĂŒhren. Die perkutane Drainagetherapie mittels PTCD ist eine wertvolle Alternative zur transpapillĂ€ren Stenttherapie. Als kurative Therapie bei nicht-resezierbaren Cholangiokarzinomen werden Lebertransplantationen durchgefĂŒhrt. Damit assoziierte biliĂ€re Komplikationen konnten bei uns in den meisten FĂ€llen erfolgreich durch endoskopische Therapie behandelt werden.ERC is considered as the diagnostic gold standard for patients with Klatskin tumor and can be also used for palliative stenting. We could reduce morbidity as well as mortality due to post-ERC-cholangitis performing MRCP-guided identification of the drainage target and subsequently unilateral contrasting and stenting. DNA-cytomtery was the best prognostic factor predicting the postoperative survival propability of patients with cholangiocarinoma. In contrast to patients resected due to diploid or polyploid Klatskin tumors patients with aneuploid tumors suffered from a bad prognosis due to early micrometastasis. Some patients afflicted from Klatskin tumors have a Billroth II gastro-jejunostomy. In spite of the more difficult endoscopic passage we were mostly able to advance the endoscope to the major papille and to perform a save papillotomy. The percutaneous drainage therapy by means of PTCD is an important alternative to transpapillary stenting. Liver transplantation is performed to cure patients with unresectable Klatskin tumor. Biliary complications which occur after transplantations can be successfully treated in most cases by means of endoscopic therapy

    Delayed life-threatening upper gastrointestinal bleeding as a complication of laparoscopic adjustable gastric banding: Case report and review of the literature

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    Morbid obesity is a common health problem worldwide. Laparoscopic adjustable gastric banding has been used extensively around the world for the treatment of morbid obesity. Life-threatening hemorrhage as a late complication of laparoscopic adjustable gastric banding is extremely rare. We report a case of massive upper gastrointestinal bleeding due to intragastric erosion of a gastric band 6 years postoperatively and review the English literature on this life-threatening rare condition. Initially, the patient was aggressively resuscitated and treated conservatively. After 1 year, the band was removed laparoscopically following an unsuccessful attempted removal by endoscopy. Clinicians who follow up patients with gastric banding should be aware of this condition. The early detection of erosion is important to avoid this serious complication
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