Novel Sites (novel + site)

Distribution by Scientific Domains

Selected Abstracts

Synovial Cell Sarcoma: Diagnosis, Treatment, and Outcomes

Swapna S. Kartha
Abstract Objectives/Hypothesis Synovial cell sarcoma is a mesenchymal tumor predominantly of the lower extremities. Three percent of cases arise in the head and neck region. It is thought that head and neck synovial sarcoma has a better prognosis than tumors of the extremities. Our experience has demonstrated aggressive behavior of this neoplasm in the head and neck. This compelled us to compare our experience with other studies. Study Design Retrospective chart review. Methods We obtained the records of patients diagnosed with head and neck synovial sarcoma from the Tumor Registry of the University of Louisville School of Medicine (Louisville, KY) and affiliated hospitals for data compiled between January 1990 and December 2000. Data on patient demographics, clinical findings and symptoms, histological findings, treatment, extent of disease, recurrence, and survival were recorded. The literature was reviewed identifying reports of synovial cell sarcoma. Results Five consecutive patients with synovial cell sarcoma were assessed at our facility. The median patient age was 28.2 years. All of the patients underwent an aggressive primary surgical excision followed by irradiation. All patients received chemotherapy after recurrence. Four of the five patients had local recurrence, and all five of the patients developed distant metastases. Three of the patients have died, and two are alive with evidence of disease. Novel sites are reported including the ethmoid sinus and the parotid gland. This group demonstrated a 40% 5-year overall survival, which was lower than the 60% 5-year survival reported in the literature for all sites. Conclusions Synovial cell sarcoma of the head and neck is a disease of young people and carries a poor prognosis. The aggressive nature of the disease may require modification of accepted treatment modalities and sequence. [source]

HOXA13 directly regulates EphA6 and EphA7 expression in the genital tubercle vascular endothelia

Carley A. Shaut
Abstract Hypospadias, a common defect affecting the growth and closure of the external genitalia, is often accompanied by gross enlargements of the genital tubercle (GT) vasculature. Because Hoxa13 homozygous mutant mice also exhibit hypospadias and GT vessel expansion, we examined whether genes playing a role in angiogenesis exhibit reduced expression in the GT. From this analysis, reductions in EphA6 and EphA7 were detected. Characterization of EphA6 and EphA7 expression in the GT confirmed colocalization with HOXA13 in the GT vascular endothelia. Analysis of the EphA6 and EphA7 promoter regions revealed a series of highly conserved cis -regulatory elements bound by HOXA13 with high affinity. GT chromatin immunoprecipitation confirmed that HOXA13 binds these gene-regulatory elements in vivo. In vitro, HOXA13 activates gene expression through the EphA6 and EphA7 gene-regulatory elements. Together these findings indicate that HOXA13 directly regulates EphA6 and EphA7 in the developing GT and identifies the GT vascular endothelia as a novel site for HOXA13-dependent expression of EphA6 and EphA7. Developmental Dynamics 236:951,960, 2007. 2007 Wiley-Liss, Inc. [source]

Maze Learning and Recall in a Weakly Electric Fish, Mormyrus rume proboscirostris Boulenger (Mormyridae, Teleostei),

ETHOLOGY, Issue 10 2010
Alice G. Walton
Mormyrus rume proboscirostris, African weakly electric fish, were trained to seek shelter in a meander maze, and following path acquisition released into the empty arena with all maze cues removed, either from the original start box or from a novel site (recall). We demonstrate that fish use their active electrosense, sight, and lateral line synergistically in maze acquisition and recall. In the presence of an electric roadmap consisting of an array of aluminum and Plexiglas objects, fish employed landmark orientation. But fish ignored visual markers and relied on internalized motor routines, which was inconsistent with evidence for cognitive mapping. [source]

Simultaneous inhibition of anti-coagulation and inflammation: crystal structure of phospholipase A2 complexed with indomethacin at 1.4, resolution reveals the presence of the new common ligand-binding site

Nagendra Singh
Abstract A novel ligand-binding site with functional implications has been identified in phospholipase A2 (PLA2). The binding of non-steroidal anti-inflammatory agent indomethacin at this site blocks both catalytic and anti-coagulant actions of PLA2. A group IIA PLA2 has been isolated from Daboia russelli pulchella (Russell's viper) which is enzymatically active as well as induces a strong anti-coagulant action. The binding studies have shown that indomethacin reduces the effects of both anti-coagulant and pro-inflammatory actions of PLA2. A group IIA PLA2 was co-crystallized with indomethacin and the structure of the complex has been determined at 1.4, resolution. The structure determination has revealed the presence of an indomethacin molecule in the structure of PLA2 at a site which is distinct from the conventional substrate-binding site. One of the carboxylic group oxygen atoms of indomethacin interacts with Asp 49 and His 48 through the catalytically important water molecule OW 18 while the second carboxylic oxygen atom forms an ionic interaction with the side chain of Lys 69. It is well known that the residues, His 48 and Asp 49 are essential for catalysis while Lys 69 is a part of the anti-coagulant loop (residues, 54,77). Indomethacin binds in such a manner that it blocks the access to both, it works as a dual inhibitor for catalytic and anti-coagulant actions of PLA2. This new binding site in PLA2 has been observed for the first time and indomethacin is the first compound that has been shown to bind at this novel site resulting in the prevention of anti-coagulation and inflammation. Copyright 2009 John Wiley & Sons, Ltd. [source]

Comprehensive expression atlas of fibroblast growth factors and their receptors generated by a novel robotic in situ hybridization platform

Murat Burak Yaylaoglu
Abstract A recently developed robotic platform termed "Genepaint" can carry out large-scale nonradioactive in situ hybridization (ISH) on tissue sections. We report a series of experiments that validate this novel platform. Signal-to-noise ratio and mRNA detection limits were comparable to traditional ISH procedures, and hybridization was transcript-specific, even in cases in which probes could have hybridized to several transcripts of a multigene family. We established an atlas of expression patterns of fibroblast growth factors (Fgfs) and their receptors (Fgfrs) for the embryonic day 14.5 mouse embryo. This atlas provides a comprehensive overview of previously known as well as novel sites of expression for this important family of signaling molecules. The Fgf/Fgfr atlas was integrated into the transcriptome database (, where individual Fgf and Fgfr expression patterns can be interactively viewed at cellular resolution and where sites of expressions can be retrieved using an anatomy-based search. Developmental Dynamics 234:371,386, 2005. 2005 Wiley-Liss, Inc. [source]

Multiple sites of L-histidine decarboxylase expression in mouse suggest novel developmental functions for histamine

Kaj Karlstedt
Abstract Histamine mediates many types of physiologic signals in multicellular organisms. To clarify the developmental role of histamine, we have examined the developmental expression of L-histidine decarboxylase (HDC) mRNA and the production of histamine during mouse development. The predominant expression of HDC in mouse development was seen in mast cells. The HDC expression was evident from embryonal day 13 (Ed13) until birth, and the mast cells were seen in most peripheral tissues. Several novel sites with a prominent HDC mRNA expression were revealed. In the brain, the choroid plexus showed HDC expression at Ed14 and the raphe neurons at Ed15. Close to the parturition, at Ed19, the neurons in the tuberomammillary (TM) area and the ventricular neuroepithelia also displayed a clear HDC mRNA expression and histamine immunoreactivity (HA-ir). From Ed14 until birth, the olfactory and nasopharyngeal epithelia showed an intense HDC mRNA expression and HA-ir. In the olfactory epithelia, the olfactory receptor neurons (ORN) were shown to have very prominent histamine immunoreactivity. The bipolar nerve cells in the epithelium extended both to the epithelial surface and into the subepithelial layers to be collected into thick nerve bundles extending caudally toward the olfactory bulbs. Also, in the nasopharynx, an extensive subepithelial network of histamine-immunoreactive nerve fibers were seen. Furthermore, in the peripheral tissues, the degenerating mesonephros (Ed14) and the convoluted tubules in the developing kidneys (Ed15) showed HDC expression, as did the prostate gland (Ed15). In adult mouse brain, the HDC expression resembled the neuronal pattern observed in rat brain. The expression was restricted to the TM area in the ventral hypothalamus, with the main expression in the five TM subgroups called E1,E5. A distinct mouse HDC mRNA expression was also seen in the ependymal wall of the third ventricle, which has not been reported in the rat. The tissue- and cell-specific expression patterns of HDC and histamine presented in this work indicate that histamine could have cell guidance or regulatory roles in development. 2001 Wiley-Liss, Inc. [source]

Regulation of mitotic function of Chk1 through phosphorylation at novel sites by cyclin-dependent kinase 1 (Cdk1)

GENES TO CELLS, Issue 5 2006
Takashi Shiromizu
Chk1 is phosphorylated at Ser317 and Ser345 by ATR in response to stalled replication and genotoxic stresses. This Chk1 activation is thought to play critical roles in the prevention of premature mitosis. However, the behavior of Chk1 in mitosis remains largely unknown. Here we reported that Chk1 was phosphorylated in mitosis. The reduction of this phosphorylation was observed at the metaphase-anaphase transition. Two-dimensional phosphopeptide mapping revealed that Chk1 phosphorylation sites in vivo were completely overlapped with the in vitro sites by cyclin-dependent protein kinase (Cdk) 1 or by p38 MAP kinase. Ser286 and Ser301 were identified as novel phosphorylation sites on Chk1. Treatment with Cdk inhibitor butyrolactone I induced the reduction of Chk1-S301 phosphorylation, although treatment with p38-specific inhibitor SB203580 or siRNA did not. In addition, ionizing radiation (IR) or ultraviolet (UV) light did not induce Chk1 phosphorylation at Ser317 and Ser345 in nocodazole-arrested mitotic cells. These observations imply the regulation of mitotic Chk1 function through Chk1 phosphorylation at novel sites by Cdk1. [source]

Molecular cytogenetic characterization of non-Hodgkin lymphoma cell lines

Sukvarsha Mehra
Spectral karyotyping (SKY) and comparative genomic hybridization (CGH) have greatly enhanced the resolution of cytogenetic analysis, enabling the identification of novel regions of rearrangement and amplification in tumor cells. Here we report the analysis of 10 malignant non-Hodgkin lymphoma (NHL) cell lines derived at the Ontario Cancer Institute (OCI), Toronto, designated as OCI-Ly1, OCI-Ly2, OCI-Ly3, OCI-LY4, OCI-Ly7, OCI-Ly8, OCI-Ly12, OCI-Ly13.2, OCI-Ly17, and OCI-Ly18, by G-banding, SKY, and CGH, and we present their comprehensive cytogenetic profiles. In contrast to the 52 breakpoints identified by G-banding, SKY identified 87 breakpoints, which clustered at 1q21, 7p15, 8p11, 13q21, 13q32, 14q32, 17q11, and 18q21. G-banding identified 10 translocations, including the previously described recurring translocations, t(8;14)(q24;q32) and t(14;18)(q32;q21). In contrast, SKY identified 60 translocations, including five that were recurring, t(8;14)(q24;q32), t(14;18)(q32;q21), t(4;7)(p12;q22), t(11;18)(q22;q21), and t(3;18)(q21;p11). SKY also identified the source of all the marker chromosomes. In addition, 10 chromosomes that were classified as normal by G-banding were found by SKY to be rearranged. CGH identified seven sites of high-level DNA amplification, 1q31-32, 2p12-16, 8q24, 11q23-25, 13q21-22, 13q32-34, and 18q21-23; of these, 1q31-32, 11q23-25, 13q21-22, and 13q32-34 have previously not been described as amplified in NHL. This comprehensive cytogenetic characterization of 10 NHL cell lines identified novel sites of rearrangement and amplification; it also enhances their value in experimental studies aimed at gene discovery and gene function. 2002 Wiley-Liss, Inc. [source]

Novel APC-cleavage sites in FVa provide insights into mechanisms of action of APC and its cofactor protein S

Summary.,Background: Activated protein C (APC) inhibits factor Va (FVa) by cleaving at Arg306, Arg506 and Arg679. Protein S serves as cofactor, in particular for the Arg306 site, and a protein S-mediated relocation of the active site of APC closer to the membrane has been proposed as a mechanism. Recently, it was demonstrated that FVa, which was mutated at all three APC-cleavage sites (FVa-306Q/506Q/679Q), could still be cleaved by APC. These sites were close to Arg306 and Arg506 but not further defined. Objective: To identify and characterize the additional APC-cleavage sites in FVa. Methods: The cDNA for FV-306Q/506Q/679Q was used as a template to create FV variants with one or more possible cleavage sites being mutated. The FV variants were expressed and their sensitivity for APC characterized functionally and with Western blotting. Results: The additional APC-cleavage sites were located at Lys309, Arg313, Arg316, Arg317 and Arg505. FVa-306Q/309Q/313Q/316Q/317Q/505Q/506Q/679Q (denoted 8M-FVa) was APC resistant. To investigate individual sites, they were mutated back using 8M-FV as a template. The kinetics of APC-degradation of these variants demonstrated that protein S was equally efficient in enhancing the APC effect for all the novel sites. Conclusions: Multiple APC-cleavage sites close to Arg306 and a single site close to Arg506 were identified. Protein S was equally efficient as APC cofactor for all novel sites. The stimulation by protein S of the Arg505 cleavage argues against a specific protein S-mediated stimulation of cleavage at Arg306 due to relocation of the APC active site closer to the membrane. [source]