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71.
Stathis G Economopoulos N Mavraganis D Kelekis N Alexopoulou E 《Surgical and radiologic anatomy : SRA》2012,34(3):281-284
The paracondylar process is a rare osseous process arising at the cervicooccipital region that belongs to a large and heterogenic
group of developmental abnormalities of the craniovertebral junction. We present a rare case of a paracondylar process in
an 11-year-old girl, in which the diagnosis was made with the use of MRI, thereby skipping X-ray and CT scan, thus avoiding
exposure of the young patient to radiation. To our knowledge, the use of MRI has not previously been reported in the investigation
and diagnosis of such an abnormality. We describe the details of this variation emphasizing on awareness of this process,
its anatomic relationships and its problems to clinicians, radiologists, surgeons and chiropractors. 相似文献
72.
Houston CM McGee TP Mackenzie G Troyano-Cuturi K Rodriguez PM Kutsarova E Diamanti E Hosie AM Franks NP Brickley SG 《The Journal of neuroscience》2012,32(11):3887-3897
High-affinity extrasynaptic GABA(A) receptors are persistently activated by the low ambient GABA levels that are known to be present in extracellular space. The resulting tonic conductance generates a form of shunting inhibition that is capable of altering cellular and network behavior. It has been suggested that this tonic inhibition will be enhanced by neurosteroids, antiepileptics, and sedative/hypnotic drugs. However, we show that the ability of sedative/hypnotic drugs to enhance tonic inhibition in the mouse cerebellum will critically depend on ambient GABA levels. For example, we show that the intravenous anesthetic propofol enhances tonic inhibition only when ambient GABA levels are <100 nm. More surprisingly, the actions of the sleep-promoting drug 4,5,6,7-tetrahydroisothiazolo-[5,4-c]pyridin-3-ol (THIP) are attenuated at ambient GABA levels of just 20 nm. In contrast, our data suggest that neurosteroid enhancement of tonic inhibition will be greater at high ambient GABA concentrations. We present a model that takes into account realistic estimates of ambient GABA levels and predicted extrasynaptic GABA(A) receptor numbers when considering the ability of sedative/hypnotic drugs to enhance tonic inhibition. These issues will be important when considering drug strategies designed to target extrasynaptic GABA(A) receptors in the treatment of sleep disorders and other neurological conditions. 相似文献
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Juan M. Pericàs Jaume Llopis Maria Jesús Jiménez-Exposito Wissam M. Kourany Benito Almirante Giampiero Carosi Emanuele Durante-Mangoni Claudio Querido Fortes Efthymia Giannitsioti Stamatios Lerakis Rodrigo Montagna-Mella Juan Ambrosioni Ru-San Tan Carlos A. Mestres Dannah Wray Orathai Pachirat Asuncion Moreno Vivian H. Chu Christopher H. Cabell 《Journal of the American College of Cardiology》2021,77(13):1629-1640
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John G. Facciponte Stefano Ugel Francesco De Sanctis Chunsheng Li Liping Wang Gautham Nair Sandy Sehgal Arjun Raj Efthymia Matthaiou George Coukos Andrea Facciabene 《The Journal of clinical investigation》2014,124(4):1497-1511
Tumor endothelial marker 1 (TEM1; also known as endosialin or CD248) is a protein found on tumor vasculature and in tumor stroma. Here, we tested whether TEM1 has potential as a therapeutic target for cancer immunotherapy by immunizing immunocompetent mice with Tem1 cDNA fused to the minimal domain of the C fragment of tetanus toxoid (referred to herein as Tem1-TT vaccine). Tem1-TT vaccination elicited CD8+ and/or CD4+ T cell responses against immunodominant TEM1 protein sequences. Prophylactic immunization of animals with Tem1-TT prevented or delayed tumor formation in several murine tumor models. Therapeutic vaccination of tumor-bearing mice reduced tumor vascularity, increased infiltration of CD3+ T cells into the tumor, and controlled progression of established tumors. Tem1-TT vaccination also elicited CD8+ cytotoxic T cell responses against murine tumor-specific antigens. Effective Tem1-TT vaccination did not affect angiogenesis-dependent physiological processes, including wound healing and reproduction. Based on these data and the widespread expression of TEM1 on the vasculature of different tumor types, we conclude that targeting TEM1 has therapeutic potential in cancer immunotherapy. 相似文献
78.
Aaron D. Viny Christopher J. Ott Barbara Spitzer Martin Rivas Cem Meydan Efthymia Papalexi Dana Yelin Kaitlyn Shank Jaime Reyes April Chiu Yevgeniy Romin Vitaly Boyko Swapna Thota Jaroslaw P. Maciejewski Ari Melnick James E. Bradner Ross L. Levine 《The Journal of experimental medicine》2015,212(11):1819-1832
79.
Efthymia Papaevangelou Jessica K. R. Boult Guy S. Whitley Simon P. Robinson Franklyn A. Howe 《Angiogenesis》2018,21(4):737-749
Nitric oxide (NO) has been strongly implicated in glioma progression and angiogenesis. The endogenous inhibitors of NO synthesis, asymmetric dimethylarginine (ADMA) and N-monomethyl-l-arginine (l-NMMA), are metabolized by dimethylarginine dimethylaminohydrolase (DDAH), and hence, DDAH is an intracellular factor that regulates NO. However, DDAH may also have an NO-independent action. We aimed to investigate whether DDAH I has any direct role in tumour vascular development and growth independent of its NO-mediated effects, in order to establish the future potential of DDAH inhibition as an anti-angiogenic treatment strategy. A clone of rat C6 glioma cells deficient in NO production expressing a pTet Off regulatable element was identified and engineered to overexpress DDAH I in the absence of doxycycline. Xenografts derived from these cells were propagated in the presence or absence of doxycycline and susceptibility magnetic resonance imaging used to assess functional vasculature in vivo. Pathological correlates of tumour vascular density, maturation and function were also sought. In the absence of doxycycline, tumours exhibited high DDAH I expression and activity, which was suppressed in its presence. However, overexpression of DDAH I had no measurable effect on tumour growth, vessel density, function or maturation. These data suggest that in C6 gliomas DDAH has no NO-independent effects on tumour growth and angiogenesis, and that the therapeutic potential of targeting DDAH in gliomas should only be considered in the context of NO regulation. 相似文献
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Susan N. Thomas Efthymia Vokali Amanda W. Lund Jeffrey A. Hubbell Melody A. Swartz 《Biomaterials》2014
Accumulating evidence implicates the tumor-draining lymph node (TDLN) in tumor-induced immune escape, as it drains regulatory molecules and leukocytes from the tumor microenvironment. We asked whether targeted delivery of adjuvant to the TDLN, presumably already bathed in tumor antigens, could promote anti-tumor immunity and hinder tumor growth. To this end, we used 30 nm polymeric nanoparticles (NPs) that effectively target dendritic cells (DCs, CD11c+) within the lymph node (LN) after intradermal administration. These NPs accumulated within the TDLN when administered in the limb ipsilateral (i.l.) to the tumor or in the non-TDLN when administered in the contralateral (c.l.) limb. Incorporating the adjuvants CpG or paclitaxel into the NPs (CpG-NP and PXL-NP) induced DC maturation in vitro. When administered daily i.l. and thus targeting the TDLN of a B16–F10 melanoma, adjuvanted NPs induced DC maturation within the TDLN and reshaped the CD4+ T cell distribution within the tumor towards a Th1 (CXCR3+) phenotype. Importantly, this also led to an increase in the frequency of antigen-specific CD8+ T cells within the tumor. This correlated with slowed tumor growth, in contrast to unhindered tumor growth after c.l. delivery of adjuvanted NPs (targeting a non-TDLN) or i.l. delivery of free adjuvant. CpG-NP treatment in the i.l. limb also was associated with an increase in CD8+/CD4+ T cell ratios and frequencies of activated (CD25+) CD8+ T cells within the TDLN whereas PXL-NP treatment reduced the frequency of regulatory T (FoxP3+ CD4+) cells in the TDLN. Together, these data implicate the TDLN as a delivery target for adjuvant therapy of solid tumors. 相似文献