70 research outputs found
Microsurgical third ventriculocisternostomy as an alternative to ETV: report of two cases
OBJECTIVE: To describe a microsurgical alternative to endoscopic third ventriculocisternostomy. METHODS: Two children with shunt-dependent hydrocephalus and multiple shunt revisions were considered candidates for third ventriculocisternostomy (TVS). Because of slit ventricles, an endoscopic approach was not possible and, therefore, both patients received a microsurgical TVS by a supraorbital approach. RESULTS: In both cases, microsurgical TVS was successful and the patients became shunt free. CONCLUSION: Microsurgical TVS by a supraorbital craniotomy is a viable alternative to endoscopic TVS in selected cases
Regional and developmental brain expression patterns of SNAP25 splice variants
SNAP25 is an essential SNARE protein for regulated exocytosis in neuronal cells. Differential splicing of the SNAP25 gene results in the expression of two transcripts, SNAP25a and SNAP25b. These splice variants differ by only 9 amino acids, and studies of their expression to date have been limited to analysis of the corresponding mRNAs. Although these studies have been highly informative, it is possible that factors such as differential turnover of the SNAP25 proteins could complicate interpretations based entirely on mRNA expression profiles
SRF modulates seizure occurrence, activity induced gene transcription and hippocampal circuit reorganization in the mouse pilocarpine epilepsy model
Comparison of Five Different Selective Agar for the Detection of Vancomycin-Resistant <i>Enterococcus faecium</i>
Five commercially available selective agar were evaluated regarding sensitivity and specificity to detect vancomycin-resistant Enterococcus (E.) faecium. Altogether 187 E. faecium strains were included, comprising 119 van-carrying strains (phenotypically vancomycin-resistant n = 105; phenotypically vancomycin-susceptible VVE-B n = 14) and 68 vancomycin-susceptible isolates. Limit of detection was calculated for each selective agar for pure cultures, stool suspensions and artificial rectal swabs. After 24-h incubation sensitivity ranged between 91.6% and 95.0%. It increased in 2 out of 5 agar after 48-h incubation. Specificity ranged between 94.1% and 100% and was highest after 24 h in 4 out of the 5 agar. Sensitivity of van-carrying phenotypically vancomycin-resistant strains was higher after 24 h (97.1â100%) and 48 h (99.1â100%) when compared to van-carrying strains that tested vancomycin-susceptible (50.0â57.1% after both incubation periods). Overall, chromID VRE, CHROMagar VRE and Brilliance VRE demonstrated the highest detection rates after 24 h. Detection rates of Chromatic VRE and VRESelect improved after 48 h. Adjustment of incubation time depending on the applied media may be advised. As detection of VVE-B was impeded with all selective agar, screening for vancomycin-resistant enterococci relying solely on selective media would not be recommended for critical clinical samples, but rather in combination with molecular methods to improve detection of these strains. Furthermore, stool samples were demonstrated to be superior to rectal swabs and should be favoured, if possible, in screening strategies
Single chain TNF derivatives with individually mutated receptor binding sites reveal differential stoichiometry of ligand receptor complex formation for TNFR1 and TNFR2
Selecting highly structure-specific antibodies using structured synthetic mimics of the cystine knot protein sclerostin
The sclerostin-neutralizing antibody AbD09097 recognizes an epitope adjacent to sclerostin's binding site for the Wnt co-receptor LRP6
The glycoprotein sclerostin has been identified as a negative regulator of bone growth. It exerts its function by interacting with the Wnt co-receptor LRP5/6, blocks the binding of Wnt factors and thereby inhibits Wnt signalling. Neutralizing anti-sclerostin antibodies are able to restore Wnt activity and enhance bone growth thereby presenting a new osteoanabolic therapy approach for diseases such as osteoporosis. We have generated various Fab antibodies against human and murine sclerostin using a phage display set-up. Biochemical analyses have identified one Fab developed against murine sclerostin, AbD09097 that efficiently neutralizes sclerostin's Wnt inhibitory activity. In vitro interaction analysis using sclerostin variants revealed that this neutralizing Fab binds to sclerostin's flexible second loop, which has been shown to harbour the LRP5/6 binding motif. Affinity maturation was then applied to AbD09097, providing a set of improved neutralizing Fab antibodies which particularly bind human sclerostin with enhanced affinity. Determining the crystal structure of AbD09097 provides first insights into how this antibody might recognize and neutralize sclerostin. Together with the structure-function relationship derived from affinity maturation these new data will foster the rational design of new and highly efficient anti-sclerostin antibodies for the therapy of bone loss diseases such as osteoporosis
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