“Subtotal” hemispherectomy in children with intractable focal epilepsy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109835/1/epi12845.pd

Do elephants feel pain and if so, how do we know this?

The objective of this document is to identify the behavior of the academic international production in urban history, from the bibliographical records index-linked in Scopus between 1973 and 2010. We use bibliometric indicators from SCImago Group, applying them to the production in the field of arts and humanities. Afterward, we corroborate the results obtained with the indicators calculated exclusively for 1.098 records of urban history. A geographical concentration is observed in the mechanisms of diffusion, authors and institutional affiliation. Likewise, we identify that over 50% of the works published between 1973 and 2010 have not been used by other authors to create new knowledge.El propósito de este documento es identificar el comportamiento de la producción académica internacional en historia urbana, a partir de los registros bibliográficos indizados en Scopus entre 1973 y 2010. Para ello se emplean indicadores bibliométricos obtenidos de SCImago Group y aplicados a la producción en el área de artes y humanidades. Posteriormente, se contrastan los resultados obtenidos con los indicadores calculados exclusivamente para 1.098 registros de historia urbana. Se evidencia una concentración geográfica en los medios de difusión de los productos del área, los autores y su filiación. Se identifica también que más del 50% de los trabajos realizados entre 1973 y 2010 no ha sido empleado por otro autor para crear nuevo conocimientoO propósito deste documento é identificar o comportamento da produção acadêmica internacional em história urbana, a partir dos registros bibliográficos indexados em Scopus entre 1973 e 2010. Para isso, empregam-se indicadores bibliométricos obtidos de SCImago Group e aplicados à produção na área de artes e humanidades. Posteriormente, se contrastam os resultados obtidos com os indicadores calculados exclusivamente para 1,098 registros de historia urbana. Evidencia-se uma concentração geográfica nos meios de difusão dos produtos da área, os autores e sua filiação. Identifica-se também que mais do 50% dos trabalhos realizados entre 1973 e 2010 não tem sido empregados por outro autor para criar conhecimento novo

Targeted gene expression analysis in hemimegalencephaly: activation of beta-catenin signaling

Hemimegalencephaly (HMEG) is a developmental brain malformation characterized by unilateral hemispheric enlargement, cytoarchitectural abnormalities, and an association with epilepsy. To define the developmental pathogenesis of HMEG, the expression of 200 cell signaling, growth, angiogenic, and transcription factor genes was assayed in HMEG samples (n=8) with targeted cDNA arrays. Differential expression of 31 mRNAs across the 4 gene families was identified in HMEG compared with control cortex. Increases in growth and transcription factor genes included JNK-1, cyclic AMP response element binding protein (CREB), and tuberin mRNAs and decreases included insulin-like growth factor-1 (IGF-1), transforming growth factor beta-3 (TGF-beta3), and NFkB mRNAs. Increased expression of cyclin D1, c-myc, and WISP-1 mRNAs in HMEG suggested activation of the Wnt-1/beta-catenin cascade. Western analysis demonstrated increased levels of non-phosphorylated beta-catenin, which transcriptionally activates cyclin D7 and c-myc genes, but reduced levels of Ser33/Ser37/Thr41 phospho-beta-catenin, which is essential for beta-catenin-inactivation, in HMEG. Altered expression of 31 mRNAs from 4 gene families in human HMEG may lead to aberrant cell growth and hemispheric enlargement during brain development. Enhanced cyclin D1 and c-myc transcription likely reflects increased transcriptionally active beta-catenin due to decreased Ser33/Ser37/Thr41 phospho-beta-catenin and suggests activation of the Wnt-1/beta-catenin cascade in HME

Tryptophan PET Imaging of the Kynurenine Pathway in Patient-Derived Xenograft Models of Glioblastoma

Increasing evidence demonstrates the immunosuppressive kynurenine pathway’s (KP) role in the pathophysiology of human gliomas. To study the KP in vivo, we used the noninvasive molecular imaging tracer α-[ 11 C]-methyl- l -tryptophan (AMT). The AMT-positron emission tomography (PET) has shown high uptake in high-grade gliomas and predicted survival in patients with recurrent glioblastoma (GBM). We generated patient-derived xenograft (PDX) models from dissociated cells, or tumor fragments, from 5 patients with GBM. Mice bearing subcutaneous tumors were imaged with AMT-PET, and tumors were analyzed to detect the KP enzymes indoleamine 2,3-dioxygenase (IDO) 1, IDO2, tryptophan 2,3-dioxygenase, kynureninase, and kynurenine 3-monooxygenase. Overall, PET imaging showed robust tumoral AMT uptake in PDX mice with prolonged tracer accumulation over 60 minutes, consistent with AMT trapping seen in humans. Immunostained tumor tissues demonstrated positive detection of multiple KP enzymes. Furthermore, intracranial implantation of GBM cells was performed with imaging at both 9 and 14 days postimplant, with a marked increase in AMT uptake at 14 days and a corresponding high level of tissue immunostaining for KP enzymes. These results indicate that our PDX mouse models recapitulate human GBM, including aberrant tryptophan metabolism, and offer an in vivo system for development of targeted therapeutics for patients with GBM