Treatment with levetiracetam after status epilepticus: effect on epileptogenesis, neuronal damage and behavioral alterations in rats

AIB1, a candidate oncogene in human breast cancer, is frequently amplified and overexpressed in several types of human cancers, but the status of AIB1 amplification and expression in urothelial carcinoma of the bladder (UC) and its clinical/prognostic significance is unclear. In our study, the methods of immunohistochemistry and fluorescence in situ hybridization were utilized to examine protein expression and amplification of AIB1 in 163 primary UCs and in 30 samples of normal bladder mucosa. Overexpression of AIB1 and amplification of AIB1 was found in 32.5 and 7.0% of UCs, respectively. In univariate survival analysis of the UC cohorts, a highly significant association of overexpression of AIB1 with shortened patient survival (mean: 45.6 months vs. 59.0 months, p < 0.001, log rank test) was demonstrated. In different subsets of UC patients, overexpression of AIB1 was also a prognostic indicator in grade 1 (p = 0.007), grade 2 (p = 0.010) and grade 3 (p = 0.015) tumor patients, and in pTa (p = 0.025), pT2-4 (p = 0.004), pN0 (p < 0.001) and pT2-4/pN0 (p = 0.040) tumor patients. Importantly, AIB1 expression (p < 0.001) together with pT and pN status (p < 0.05) provided significant independent prognostic parameters in multivariate analysis. In addition, a significant correlation (p < 0.05) of overexpression of AIB1 with an increased UC labeling index of Ki-67 (a cell proliferation marker) was observed in these UCs. Thus, these findings provide evidence that an overexpression of AIB1, as detected by immunohistochemistry, is an independent molecular marker for poor prognosis (shortened survival time) of patients with UC. © 2008 Wiley-Liss, Inc.link_to_subscribed_fulltex

Evaluation of a Method for Standardized Antimicrobial Susceptibility Testing with Mycoplasma hyorhinis Field Isolates

Organizations like the Clinical and Laboratory Standards Institute (CLSI) or the European Committee of Antimicrobial Susceptibility Testing (EUCAST) provide standardized methodologies for antimicrobial susceptibility testing of a wide range of nonfastidious and fastidious bacteria, but so far not for Mycoplasma spp. of animal origin. Recently, a proposed method for the standardized broth microdilution testing of Mycoplasma hyorhinis using commercial Sensititre microtiter plates was presented. In this study, we evaluated this broth microdilution method with 37 field isolates and tested their susceptibility toward the following antimicrobial agents: doxycycline, enrofloxacin, erythromycin, florfenicol, gentamicin, marbofloxacin, tetracycline, tiamulin, tilmicosin, tulathromycin, and tylosin. The isolates originated from different countries, isolation sites, and years. The broth microdilution method was carried out using a modified Friis broth as the culture and test medium. For macrolides and lincosamides, a bimodal distribution with elevated MIC values could be observed for almost half of the tested field isolates, deducing reduced susceptibility toward these substances. With a recently published protocol, we were able to test a variety of field isolates, and consistent data could be obtained. Using this method, monitoring studies of Mycoplasma hyorhinis isolates can be carried out in a comparable manner, and the observed susceptibility profiles can be screened for possible changes in MIC values in the future

In vivo perivascular implantation of encapsulated packaging cells for prolonged retroviral gene transfer

Long-term benefits of coronary angioplasty remain limited by the treatment-induced renarrowing of arteries, termed restenosis. One of the mechanisms leading to restenosis is the proliferation of smooth muscle cells. Therefore, proliferating cells of the injured arterial wall, which can be selectively transduced by retroviruses, are potential targets for gene therapy strategies. A direct single-dose therapeutic application of retroviral vectors for inhibition of cell proliferation is normally limited by too low transduction efficiencies. Encapsulated retrovirus-producing cells release viral vectors from microcapsules for at least 6 weeks in vitro, and may enhance the transduction efficiency by prolonged infection. Capsules containing retrovirus-producing cells expressing the #beta#-galactosidase reporter gene were implanted into periarterial tissue of a pig model of restenosis. Three weeks following implantation #beta#-galactosidase activity was detected in the pericapsular tissue with a transduction efficiency of about 1 and 500 cells. Adventitial implantation of vector-producing encapsulated cells for gene therapy may therefore facilitate successful targeting of proliferating vascular smooth muscle cells and allow stable integration of therapeutic genes into surrounding cells. The encapsulation of vector-producing cells could represent a novel and feasible way to optimize local retroviral gene therapy. (orig.)Available from TIB Hannover: F00B247 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Bildung und Forschung (BMBF), Bonn (Germany)DEGerman

Data from: Postglacial climate changes and rise of three ecotypes of harbor porpoises, Phocoena phocoena, in western Palearctic waters

Despite no obvious barriers to gene flow in the marine realm, environmental variation and ecological specializations can lead to genetic differentiation in highly mobile predators. Here, we investigated the genetic structure of the harbor porpoise over the entire species distribution range in western Palearctic waters. Combined analyses of ten microsatellite loci and a 5,085 bases-pairs portion of the mitochondrial genome revealed the existence of three ecotypes, equally divergent at the mitochondrial genome, distributed in the Black Sea, the European continental shelf waters, and a previously overlooked ecotype in the upwelling zones of Iberia and Mauritania. Historical demographic inferences using Approximate Bayesian Computation (ABC) suggest that these ecotypes diverged during the Last Glacial Maximum (~23–19 kilo-years ago, kyrBP). ABC supports the hypothesis that the Black Sea and upwelling ecotypes share a more recent common ancestor (~14 kyrBP) than either does with the European continental shelf ecotype (~28 kyrBP), suggesting they likely descended from the extinct populations that once inhabited the Mediterranean during the glacial and post-glacial period. We showed that the two Atlantic ecotypes established a narrow admixture zone in the Bay of Biscay during the last millennium, with highly asymmetric gene flow. This study highlights the impacts that climate change may have on the distribution and speciation process in pelagic predators and shows that allopatric divergence can occur in these highly mobile species and be a source of genetic diversity. The data package contains two datasets