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[ { "id": "PMID-8423986__text", "type": "abstract", "text": [ "E mu-bcl-2 transgene facilitates spontaneous transformation of early pre-B and immunoglobulin-secreting cells but not T cells. \nTo assess the lymphoid tumorigenic potential of bcl-2, mice of five independent strains expressing a bcl-2 transgene in B and/or T cells were monitored for disease up to 12 months of age. Lymphoma prevalence was minimal in the T lineage but significant, although low (3-15%), in the B lineage. The principal types of tumors were plasmacytomas secreting immunoglobulin and novel lymphomas that expressed markers such as Sca-1, CD4, Thy-1, CD34 and CD45(B220), consistent with an origin very early in B-lymphoid development. Rearrangement of the c-myc gene was common in the plasmacytomas, implying a synergistic role for myc and bcl-2 in their etiology, but was not detected in the lymphomas.\n" ], "offsets": [ [ 0, 820 ] ] } ]

[ { "id": "PMID-8423986_T2", "type": "Cell", "text": [ "pre-B" ], "offsets": [ [ 69, 74 ] ], "normalized": [] }, { "id": "PMID-8423986_T4", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 104, 109 ] ], "normalized": [] }, { "id": "PMID-8423986_T5", "type": "Cell", "text": [ "T cells" ], "offsets": [ [ 118, 125 ] ], "normalized": [] }, { "id": "PMID-8423986_T6", "type": "Cell", "text": [ "lymphoid" ], "offsets": [ [ 142, 150 ] ], "normalized": [] }, { "id": "PMID-8423986_T10", "type": "Cell", "text": [ "B" ], "offsets": [ [ 248, 249 ] ], "normalized": [] }, { "id": "PMID-8423986_T11", "type": "Cell", "text": [ "T cells" ], "offsets": [ [ 257, 264 ] ], "normalized": [] }, { "id": "PMID-8423986_T12", "type": "Cancer", "text": [ "Lymphoma" ], "offsets": [ [ 316, 324 ] ], "normalized": [] }, { "id": "PMID-8423986_T13", "type": "Cell", "text": [ "T lineage" ], "offsets": [ [ 355, 364 ] ], "normalized": [] }, { "id": "PMID-8423986_T14", "type": "Cell", "text": [ "B lineage" ], "offsets": [ [ 411, 420 ] ], "normalized": [] }, { "id": "PMID-8423986_T15", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 445, 451 ] ], "normalized": [] }, { "id": "PMID-8423986_T16", "type": "Cancer", "text": [ "plasmacytomas" ], "offsets": [ [ 457, 470 ] ], "normalized": [] }, { "id": "PMID-8423986_T18", "type": "Cancer", "text": [ "lymphomas" ], "offsets": [ [ 506, 515 ] ], "normalized": [] }, { "id": "PMID-8423986_T25", "type": "Cell", "text": [ "B-lymphoid" ], "offsets": [ [ 627, 637 ] ], "normalized": [] }, { "id": "PMID-8423986_T27", "type": "Cancer", "text": [ "plasmacytomas" ], "offsets": [ [ 701, 714 ] ], "normalized": [] }, { "id": "PMID-8423986_T30", "type": "Cancer", "text": [ "lymphomas" ], "offsets": [ [ 809, 818 ] ], "normalized": [] } ]

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[ { "id": "PMID-16201626__text", "type": "abstract", "text": [ "Polybrominated diphenyl ethers in indoor dust in Ottawa, Canada: implications for sources and exposure.\nPolybrominated diphenyl ethers (PBDEs) are widely used as additive flame retardants in plastics, soft furnishings, electrical and electronic equipment, and insulation in the indoor environment, and may be released indoors via volatilization or as dusts. The penta-and octa-brominated mixes are now banned in most parts of Europe, and phasing out of their use has recently begun in North America. This study follows a previous investigation into indoor air levels of PBDEs. House dust was analyzed from the family vacuum cleaners of 68 of the same 74 randomly selected homes, in Ottawa, Canada during the winter of 2002-2003. PBDEs, comprising on average 42% BDE-209, were found in all samples. The levels were log-normally distributed with a geometric mean sigmaPBDE of 2000 ng g(-1), and a median of 1800 ng g(-1) dust. The levels in dust did not correlate with questionnaire information on house characteristics. Correlations were found between pentamix congener levels in dust and in air from the same homes, but not for congeners of the more highly brominated mixes. Exposure scenarios are presented for mean and high dust ingestion rates, and compared against exposures from other pathways, for both adults and toddlers (6 months-2 years). Assuming a mean dust ingestion rate and median dust and air concentrations, adults would be exposed to ca. 7.5 ng sigmaPBDE d(-1) via the dust ingestion pathway, which represents approximately 14% of total daily exposure when compared to diet (82%) and inhalation (4%). However, for toddlers the equivalent intakes would be 99 ng d(-1), representing 80% of their daily PBDE exposure. At high dust ingestion rates these values increase to 180 ng d(-1) (80% daily intake) for adults and 360 ng d(-1) (89% daily intake) for toddlers. The data give a clearer picture of sources of PBDE exposure in the home environment and suggest that dust could be a significant exposure pathway for some individuals, particularly children.\n" ], "offsets": [ [ 0, 2071 ] ] } ]

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[ { "id": "PMID-9421512__text", "type": "abstract", "text": [ "Effect of a mutation in the anticodon of human mitochondrial tRNAPro on its post-transcriptional modification pattern.\nAlthough the gene sequences of all 22 tRNAs encoded in the human mitochondrial genome are known, little information exists about their sequences at the RNA level. This becomes a crucial limitation when searching for a molecular understanding of the growing number of maternally inherited human diseases correlated with point mutations in tRNA genes. Here we describe the sequence of human mt-tRNAPropurified from placenta. It shows absence of editing events in this tRNA and highlights the presence of eight post-transcriptional modifications. These include T54, never found so far in an animal mt-tRNA, and m1G37, a modification known to have fundamental functional properties in a number of canonical tRNAs. Occurrence of m1G37 was further investigated in an analysis of the substrate properties of in vitro transcripts of human mt-tRNAProtowards pure Escherichia coli methylguanosine transferase. This enzyme properly methylates G37 in mt-tRNA and is sensitive to the presence of a second G at position 36, neighboring the target nucleotide for methylation. Since mutation of nt 36 was shown to be correlated with myopathy, the potential consequences of non-modification or under-modification of mt-tRNA nucleotides in expression of the particular myopathy and of mitochondrial diseases in general are discussed.\n" ], "offsets": [ [ 0, 1435 ] ] } ]

[ { "id": "PMID-9421512_T1", "type": "Cellular_component", "text": [ "mitochondrial" ], "offsets": [ [ 47, 60 ] ], "normalized": [] }, { "id": "PMID-9421512_T2", "type": "Cellular_component", "text": [ "mitochondrial genome" ], "offsets": [ [ 184, 204 ] ], "normalized": [] }, { "id": "PMID-9421512_T3", "type": "Organ", "text": [ "placenta" ], "offsets": [ [ 532, 540 ] ], "normalized": [] }, { "id": "PMID-9421512_T4", "type": "Cellular_component", "text": [ "mitochondrial" ], "offsets": [ [ 1386, 1399 ] ], "normalized": [] } ]

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[ { "id": "PMID-8643685__text", "type": "abstract", "text": [ "Human immunodeficiency virus type 1 viral background plays a major role in development of resistance to protease inhibitors.\nThe observed in vitro and in vivo benefit of combination treatment with anti-human immunodeficiency virus (HIV) agents prompted us to examine the potential of resistance development when two protease inhibitors are used concurrently. Recombinant HIV-1 (NL4-3) proteases containing combined resistance mutations associated with BMS-186318 and A-77003 (or saquinavir) were either inactive or had impaired enzyme activity. Subsequent construction of HIV-1 (NL4-3) proviral clones containing the same mutations yielded viruses that were severely impaired in growth or nonviable, confirming that combination therapy may be advantageous. However, passage of BMS-186318-resistant HIV-1 (RF) in the presence of either saquinavir or SC52151, which represented sequential drug treatment, produced viable viruses resistant to both BMS-186318 and the second compound. The predominant breakthrough virus contained the G48V/A71T/V82A protease mutations. The clone-purified RF (G48V/A71T/V82A) virus, unlike the corresponding defective NL4-3 triple mutant, grew well and displayed cross-resistance to four distinct protease inhibitors. Chimeric virus and in vitro mutagenesis studies indicated that the RF-specific protease sequence, specifically the Ile at residue 10, enabled the NL4-3 strain with the triple mutant to grow. Our results clearly indicate that viral genetic background will play a key role in determining whether cross-resistance variants will arise.\n" ], "offsets": [ [ 0, 1578 ] ] } ]

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[ { "id": "PMID-15595726__text", "type": "abstract", "text": [ "Proteome analysis of NIH3T3 cells transformed by activated Galpha12: regulation of leukemia-associated protein SET. \nGalpha(12), the alpha-subunit of the G12 family of heterotrimeric G proteins is involved in the regulation of cell proliferation and neoplastic transformation. GTPase-deficient, constitutively activated mutant of Galpha(12) (Galpha(12)Q229L or Galpha(12)QL) has been previously shown to induce oncogenic transformation of NIH3T3 cells promoting serum- and anchorage-independent growth. Reduced growth-factor dependent, autonomous cell growth forms a critical defining point at which a normal cell turns into an oncogenic one. To identify the underlying mechanism involved in such growth-factor/serum independent growth of Galpha(12)QL-transformed NIH3T3, we carried out a two-dimensional differential proteome analysis of Galpha(12)QL-transformed NIH3T3 cells and cells expressing vector control. This analysis revealed a total of 22 protein-spots whose expression was altered by more than 3-folds. Two of these spots were identified by MALDI-MS analysis as proliferating cell nuclear antigen (PCNA) and myeloid-leukemia-associated SET protein. The increased expressions of these proteins in Galpha(12)QL cells were validated by immunoblot analysis. Furthermore, transient transfection studies with NIH3T3 cells indicated that the expression of activated Galpha(12) readily increased the expression of SET protein by 24 h. As SET has been previously reported to be an inhibitor of phosphatase PP2A, the nuclear phosphatase activity was monitored in cells expressing activated Galpha(12). Our results indicate that the nuclear phosphatase activity is inhibited by greater than 50% in Galpha(12)QL cells compared to vector control cells. Thus, our results from differential proteome analysis presented here report for the first time a role for SET in Galpha(12)-mediated signaling pathways and a role for Galpha(12) in the regulation of the leukemia-associated SET-protein expression.\n" ], "offsets": [ [ 0, 2000 ] ] } ]

[ { "id": "PMID-15595726_T1", "type": "Cell", "text": [ "NIH3T3 cells" ], "offsets": [ [ 21, 33 ] ], "normalized": [] }, { "id": "PMID-15595726_T3", "type": "Cancer", "text": [ "leukemia" ], "offsets": [ [ 83, 91 ] ], "normalized": [] }, { "id": "PMID-15595726_T8", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 227, 231 ] ], "normalized": [] }, { "id": "PMID-15595726_T13", "type": "Cell", "text": [ "NIH3T3 cells" ], "offsets": [ [ 439, 451 ] ], "normalized": [] }, { "id": "PMID-15595726_T14", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 462, 467 ] ], "normalized": [] }, { "id": "PMID-15595726_T15", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 547, 551 ] ], "normalized": [] }, { "id": "PMID-15595726_T16", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 609, 613 ] ], "normalized": [] }, { "id": "PMID-15595726_T17", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 711, 716 ] ], "normalized": [] }, { "id": "PMID-15595726_T19", "type": "Cell", "text": [ "NIH3T3" ], "offsets": [ [ 764, 770 ] ], "normalized": [] }, { "id": "PMID-15595726_T21", "type": "Cell", "text": [ "NIH3T3 cells" ], "offsets": [ [ 864, 876 ] ], "normalized": [] }, { "id": "PMID-15595726_T22", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 881, 886 ] ], "normalized": [] }, { "id": "PMID-15595726_T25", "type": "Cancer", "text": [ "myeloid-leukemia" ], "offsets": [ [ 1121, 1137 ] ], "normalized": [] }, { "id": "PMID-15595726_T28", "type": "Cell", "text": [ "Galpha(12)QL cells" ], "offsets": [ [ 1209, 1227 ] ], "normalized": [] }, { "id": "PMID-15595726_T29", "type": "Cell", "text": [ "NIH3T3 cells" ], "offsets": [ [ 1316, 1328 ] ], "normalized": [] }, { "id": "PMID-15595726_T34", "type": "Cellular_component", "text": [ "nuclear" ], "offsets": [ [ 1520, 1527 ] ], "normalized": [] }, { "id": "PMID-15595726_T35", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1566, 1571 ] ], "normalized": [] }, { "id": "PMID-15595726_T37", "type": "Cellular_component", "text": [ "nuclear" ], "offsets": [ [ 1635, 1642 ] ], "normalized": [] }, { "id": "PMID-15595726_T39", "type": "Cell", "text": [ "Galpha(12)QL cells" ], "offsets": [ [ 1700, 1718 ] ], "normalized": [] }, { "id": "PMID-15595726_T40", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1746, 1751 ] ], "normalized": [] }, { "id": "PMID-15595726_T44", "type": "Cancer", "text": [ "leukemia" ], "offsets": [ [ 1956, 1964 ] ], "normalized": [] }, { "id": "PMID-15595726_T2", "type": "Cancer", "text": [ "neoplastic" ], "offsets": [ [ 250, 260 ] ], "normalized": [] } ]

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[ { "id": "PMC-3082541-caption-03__text", "type": "caption", "text": [ "Loss of body weight after challenge-infection with WNV.\nMice (n = 8) were vaccinated intranasally with Flu-NA-DIII (*) or Flu-NA-GFP (o) or by the subcutaneous route (^ and ^, respectively). The daily weights of each animal were calculated compared to their respective weight on the day of challenge, and data are shown as the average percentage of initial weight for each group. Error bars represent the standard error for all samples available at that time point. Subsequently, the mice were challenged subcutaneously with 106 TCID50 WNV-NY99 and weighed daily. The mean body weight is expressed as the percentage of the body weight before challenge infection (A). The survival rates of mice after challenge infection with WNV-NY99 are depicted as Kaplan-Meier survival curves (B). The difference in survival rate between Flu-NA-DIII and Flu-NA-GFP vaccinated mice was statistically significant as determined by the logrank test. The symbols for the respective groups are the same as in panel A.\n" ], "offsets": [ [ 0, 998 ] ] } ]

[ { "id": "PMC-3082541-caption-03_T1", "type": "Immaterial_anatomical_entity", "text": [ "intranasally" ], "offsets": [ [ 85, 97 ] ], "normalized": [] }, { "id": "PMC-3082541-caption-03_T2", "type": "Organism_subdivision", "text": [ "body" ], "offsets": [ [ 8, 12 ] ], "normalized": [] }, { "id": "PMC-3082541-caption-03_T3", "type": "Organism_subdivision", "text": [ "body" ], "offsets": [ [ 573, 577 ] ], "normalized": [] }, { "id": "PMC-3082541-caption-03_T4", "type": "Organism_subdivision", "text": [ "body" ], "offsets": [ [ 623, 627 ] ], "normalized": [] }, { "id": "PMC-3082541-caption-03_T5", "type": "Immaterial_anatomical_entity", "text": [ "subcutaneously" ], "offsets": [ [ 505, 519 ] ], "normalized": [] }, { "id": "PMC-3082541-caption-03_T6", "type": "Immaterial_anatomical_entity", "text": [ "subcutaneous" ], "offsets": [ [ 147, 159 ] ], "normalized": [] } ]

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[ { "id": "PMID-21975934__text", "type": "abstract", "text": [ "c-MYC functions as a molecular switch to alter the response of human mammary epithelial cells to oncostatin M. \nCytokines play an important role in creating an inflammatory microenvironment, which is now considered a hallmark of cancer. Although tumor cells can exploit cytokine signaling to promote growth, invasion, and metastasis, the response of normal and premalignant epithelial cells to cytokines present in a developing tumor microenvironment remains unclear. Oncostatin M (OSM), an IL-6 family cytokine responsible for STAT3 activation, has been implicated in cancer development, progression, invasion, and metastasis. Paradoxically, OSM can also suppress the growth of normal cells and certain tumor-derived cell lines. Using isogenic human mammary epithelial cells (HMEC) at different stages of neoplastic transformation, we found that OSM signaling suppressed c-MYC expression and engaged a p16- and p53-independent growth arrest that required STAT3 activity. Inhibition of STAT3 activation by expressing a dominant-negative STAT3 protein or a STAT3-shRNA prevented the OSM-mediated arrest. In addition, expression of c-MYC from a constitutive promoter also abrogated the STAT3-mediated arrest, and strikingly, cooperated with OSM to promote anchorage-independent growth (AIG), a property associated with malignant transformation. Cooperative transformation by c-MYC and OSM required PI3K and AKT signaling, showing the importance of multiple signaling pathways downstream of the OSM receptor in defining the cellular response to cytokines. These findings identify c-MYC as an important molecular switch that alters the cellular response to OSM-mediated signaling from tumor suppressive to tumor promoting.\n" ], "offsets": [ [ 0, 1719 ] ] } ]

[ { "id": "PMID-21975934_T3", "type": "Cell", "text": [ "mammary epithelial cells" ], "offsets": [ [ 69, 93 ] ], "normalized": [] }, { "id": "PMID-21975934_T5", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 229, 235 ] ], "normalized": [] }, { "id": "PMID-21975934_T6", "type": "Cell", "text": [ "tumor cells" ], "offsets": [ [ 246, 257 ] ], "normalized": [] }, { "id": "PMID-21975934_T7", "type": "Cell", "text": [ "premalignant epithelial cells" ], "offsets": [ [ 361, 390 ] ], "normalized": [] }, { "id": "PMID-21975934_T8", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 428, 433 ] ], "normalized": [] }, { "id": "PMID-21975934_T13", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 569, 575 ] ], "normalized": [] }, { "id": "PMID-21975934_T15", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 686, 691 ] ], "normalized": [] }, { "id": "PMID-21975934_T16", "type": "Cell", "text": [ "certain tumor-derived cell lines" ], "offsets": [ [ 696, 728 ] ], "normalized": [] }, { "id": "PMID-21975934_T18", "type": "Cell", "text": [ "mammary epithelial cells" ], "offsets": [ [ 751, 775 ] ], "normalized": [] }, { "id": "PMID-21975934_T19", "type": "Cell", "text": [ "HMEC" ], "offsets": [ [ 777, 781 ] ], "normalized": [] }, { "id": "PMID-21975934_T37", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 1521, 1529 ] ], "normalized": [] }, { "id": "PMID-21975934_T39", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 1632, 1640 ] ], "normalized": [] }, { "id": "PMID-21975934_T41", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1681, 1686 ] ], "normalized": [] }, { "id": "PMID-21975934_T42", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1702, 1707 ] ], "normalized": [] }, { "id": "PMID-21975934_T1", "type": "Cancer", "text": [ "neoplastic" ], "offsets": [ [ 806, 816 ] ], "normalized": [] } ]

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[ { "id": "PMID-12432255__text", "type": "abstract", "text": [ "Downregulation of c-FLIP sensitizes DU145 prostate cancer cells to Fas-mediated apoptosis. \nAlthough DU145 prostate cancer cells are resistant to exogenously applied Fas agonist CH-11 (anti-Fas monoclonal antibody), Fas-resistance can be overcome using a FasL expressing adenovirus (AdGFPFasL(TET)) [Hyer et al., Molecular Therapy, 2000; 2:348-58 (ref.12)]. The purpose of this study was to try to understand why DU145 cells are resistant to CH-11 and determine the signaling pathway utilized by AdGFPFasL(TET) to induce apoptosis in these Fas-resistant cells. Using immunoblot analysis, we show that AdGFPFasL(TET) is capable of initiating the classic Fas-mediated apoptotic pathway in DU145 cells, which includes activation of caspases-8, -3, -7, and -9, BID cleavage, cytochrome c release from mitochondria, and PARP cleavage. In contrast, CH-11 binds to Fas, but is unable to transmit the death signal beyond the plasma membrane suggesting a block at the DISC (death inducing signaling complex). The anti-apoptotic protein c-FLIP (cellular Flice-like inhibitory protein), which has been shown to inhibit Fas-mediated apoptosis at the DISC, was down-regulated following AdGFPFasL(TET) treatment prompting us to investigate its role in inhibiting CH-11-induced cell death. Using c-FLIP anti-sense oligonucleotides to down-regulate c-FLIP we sensitized DU145 cells to CH-11-induced apoptosis. These data suggest that c-FLIP may play a critical role in regulating Fas-mediated apoptosis in prostate cancer cells and that modulation of c-FLIP may enhance Fas signaling based therapies.\n" ], "offsets": [ [ 0, 1585 ] ] } ]

[ { "id": "PMID-12432255_T2", "type": "Cell", "text": [ "DU145 prostate cancer cells" ], "offsets": [ [ 36, 63 ] ], "normalized": [] }, { "id": "PMID-12432255_T4", "type": "Cell", "text": [ "DU145 prostate cancer cells" ], "offsets": [ [ 101, 128 ] ], "normalized": [] }, { "id": "PMID-12432255_T11", "type": "Cell", "text": [ "DU145 cells" ], "offsets": [ [ 413, 424 ] ], "normalized": [] }, { "id": "PMID-12432255_T14", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 554, 559 ] ], "normalized": [] }, { "id": "PMID-12432255_T17", "type": "Cell", "text": [ "DU145 cells" ], "offsets": [ [ 687, 698 ] ], "normalized": [] }, { "id": "PMID-12432255_T24", "type": "Cellular_component", "text": [ "mitochondria" ], "offsets": [ [ 797, 809 ] ], "normalized": [] }, { "id": "PMID-12432255_T27", "type": "Cellular_component", "text": [ "plasma membrane" ], "offsets": [ [ 917, 932 ] ], "normalized": [] }, { "id": "PMID-12432255_T35", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1263, 1267 ] ], "normalized": [] }, { "id": "PMID-12432255_T38", "type": "Cell", "text": [ "DU145 cells" ], "offsets": [ [ 1354, 1365 ] ], "normalized": [] }, { "id": "PMID-12432255_T41", "type": "Cell", "text": [ "prostate cancer cells" ], "offsets": [ [ 1490, 1511 ] ], "normalized": [] } ]

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[ { "id": "PMID-2129802__text", "type": "abstract", "text": [ "Ras p21 onco-protein in the sera of mice carrying an experimentally induced tumor and in human cancer patients. \nWe have established a model system to detect the presence of ras p21 in the sera of Balb/c mice carrying tumors induced by a mouse cell line transformed with the Harvey murine sarcoma virus in the presence of a helper Friend murine leukemia virus. As determined by ELISA and immunoblot assays, ras p21 in the serum increased with increased tumor growth. Since ras genes have been found to be frequently activated in human tumours, we examined the levels of ras p21 in the sera of a variety of human cancer patients. In only 3 out of 13 cases, representing patients with adenocarcinomas of the stomach receiving chemotherapy, was ras p21 detected at elevated levels, whereas in patients with the following types of cancer no substantial change in serum ras p21 was observed; nine with breast, 5 colon, 5 lung, 5 ovarian and 5 hepatocellular carcinomas.\n" ], "offsets": [ [ 0, 965 ] ] } ]

[ { "id": "PMID-2129802_T2", "type": "Organism_substance", "text": [ "sera" ], "offsets": [ [ 28, 32 ] ], "normalized": [] }, { "id": "PMID-2129802_T4", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 76, 81 ] ], "normalized": [] }, { "id": "PMID-2129802_T6", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 95, 101 ] ], "normalized": [] }, { "id": "PMID-2129802_T9", "type": "Organism_substance", "text": [ "sera" ], "offsets": [ [ 189, 193 ] ], "normalized": [] }, { "id": "PMID-2129802_T11", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 218, 224 ] ], "normalized": [] }, { "id": "PMID-2129802_T13", "type": "Cell", "text": [ "cell line" ], "offsets": [ [ 244, 253 ] ], "normalized": [] }, { "id": "PMID-2129802_T17", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 422, 427 ] ], "normalized": [] }, { "id": "PMID-2129802_T18", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 453, 458 ] ], "normalized": [] }, { "id": "PMID-2129802_T21", "type": "Cancer", "text": [ "tumours" ], "offsets": [ [ 535, 542 ] ], "normalized": [] }, { "id": "PMID-2129802_T23", "type": "Organism_substance", "text": [ "sera" ], "offsets": [ [ 585, 589 ] ], "normalized": [] }, { "id": "PMID-2129802_T25", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 612, 618 ] ], "normalized": [] }, { "id": "PMID-2129802_T28", "type": "Cancer", "text": [ "adenocarcinomas" ], "offsets": [ [ 683, 698 ] ], "normalized": [] }, { "id": "PMID-2129802_T29", "type": "Organ", "text": [ "stomach" ], "offsets": [ [ 706, 713 ] ], "normalized": [] }, { "id": "PMID-2129802_T32", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 827, 833 ] ], "normalized": [] }, { "id": "PMID-2129802_T33", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 859, 864 ] ], "normalized": [] }, { "id": "PMID-2129802_T35", "type": "Cancer", "text": [ "breast" ], "offsets": [ [ 897, 903 ] ], "normalized": [] }, { "id": "PMID-2129802_T36", "type": "Cancer", "text": [ "colon" ], "offsets": [ [ 907, 912 ] ], "normalized": [] }, { "id": "PMID-2129802_T37", "type": "Cancer", "text": [ "lung" ], "offsets": [ [ 916, 920 ] ], "normalized": [] }, { "id": "PMID-2129802_T38", "type": "Cancer", "text": [ "ovarian" ], "offsets": [ [ 924, 931 ] ], "normalized": [] }, { "id": "PMID-2129802_T39", "type": "Cancer", "text": [ "hepatocellular carcinomas" ], "offsets": [ [ 938, 963 ] ], "normalized": [] } ]

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[ { "id": "PMID-12923331__text", "type": "abstract", "text": [ "Expression of osteoprotegerin and RANK ligand in breast cancer bone metastasis. \nBone destruction is primarily mediated by osteoclastic bone resorption, and cancer cells stimulate the formation and activation of osteoclasts next to metastatic foci. Accumulating evidences indicate that receptor activator of NF-kB ligand (RANKL) is the ultimate extracellular mediator that stimulates osteoclast differentiation into mature osteoclasts. In contrast, osteoprotegerin (OPG) inhibits osteoclast development. In order to elucidate a mechanism for cancer-induced osteoclastogenesis, cells from a human breast cancer line, MDA-MB-231, were directly co-cultured with ST2, MC3T3-E1, or with primary mouse calvarial cells. Osteoclast-like cells and tartarate resistant acid phosphatase (TRAP) activities were then quantitated. We examined these cell lines and samples from breast cancer by RT-PCR for the expressions of OPG and RANKL mRNA. Compared to controls, co-culture of MDA-MB-231 cells with stromal or osteoblastic cells induced an increase in number of osteoclasts and TRAP activities. MDA-MB-231 cells alone or breast cancer samples did not express RANKL mRNA. However, co-culture of these cancer cells with stromal or osteoblastic cells induced RANKL mRNA expression and decreased OPG mRNA expression. These experiments demonstrate that direct interactions between breast cancer and stromal or osteoblastic cells induce osteoclastogenesis in vitro through modulating RANKL expression.\n" ], "offsets": [ [ 0, 1485 ] ] } ]

[ { "id": "PMID-12923331_T3", "type": "Cancer", "text": [ "breast cancer" ], "offsets": [ [ 49, 62 ] ], "normalized": [] }, { "id": "PMID-12923331_T4", "type": "Tissue", "text": [ "bone" ], "offsets": [ [ 63, 67 ] ], "normalized": [] }, { "id": "PMID-12923331_T5", "type": "Tissue", "text": [ "Bone" ], "offsets": [ [ 81, 85 ] ], "normalized": [] }, { "id": "PMID-12923331_T6", "type": "Cell", "text": [ "osteoclastic" ], "offsets": [ [ 123, 135 ] ], "normalized": [] }, { "id": "PMID-12923331_T7", "type": "Tissue", "text": [ "bone" ], "offsets": [ [ 136, 140 ] ], "normalized": [] }, { "id": "PMID-12923331_T8", "type": "Cell", "text": [ "cancer cells" ], "offsets": [ [ 157, 169 ] ], "normalized": [] }, { "id": "PMID-12923331_T9", "type": "Cell", "text": [ "osteoclasts" ], "offsets": [ [ 212, 223 ] ], "normalized": [] }, { "id": "PMID-12923331_T10", "type": "Cancer", "text": [ "metastatic foci" ], "offsets": [ [ 232, 247 ] ], "normalized": [] }, { "id": "PMID-12923331_T13", "type": "Immaterial_anatomical_entity", "text": [ "extracellular" ], "offsets": [ [ 345, 358 ] ], "normalized": [] }, { "id": "PMID-12923331_T14", "type": "Cell", "text": [ "osteoclast" ], "offsets": [ [ 384, 394 ] ], "normalized": [] }, { "id": "PMID-12923331_T15", "type": "Cell", "text": [ "osteoclasts" ], "offsets": [ [ 423, 434 ] ], "normalized": [] }, { "id": "PMID-12923331_T18", "type": "Cell", "text": [ "osteoclast" ], "offsets": [ [ 480, 490 ] ], "normalized": [] }, { "id": "PMID-12923331_T19", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 542, 548 ] ], "normalized": [] }, { "id": "PMID-12923331_T20", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 577, 582 ] ], "normalized": [] }, { "id": "PMID-12923331_T22", "type": "Cell", "text": [ "breast cancer line" ], "offsets": [ [ 596, 614 ] ], "normalized": [] }, { "id": "PMID-12923331_T23", "type": "Cell", "text": [ "MDA-MB-231" ], "offsets": [ [ 616, 626 ] ], "normalized": [] }, { "id": "PMID-12923331_T24", "type": "Cell", "text": [ "ST2" ], "offsets": [ [ 659, 662 ] ], "normalized": [] }, { "id": "PMID-12923331_T25", "type": "Cell", "text": [ "MC3T3-E1" ], "offsets": [ [ 664, 672 ] ], "normalized": [] }, { "id": "PMID-12923331_T27", "type": "Cell", "text": [ "calvarial cells" ], "offsets": [ [ 696, 711 ] ], "normalized": [] }, { "id": "PMID-12923331_T28", "type": "Cell", "text": [ "Osteoclast-like cells" ], "offsets": [ [ 713, 734 ] ], "normalized": [] }, { "id": "PMID-12923331_T31", "type": "Cell", "text": [ "cell lines" ], "offsets": [ [ 835, 845 ] ], "normalized": [] }, { "id": "PMID-12923331_T32", "type": "Cancer", "text": [ "samples" ], "offsets": [ [ 850, 857 ] ], "normalized": [] }, { "id": "PMID-12923331_T33", "type": "Cancer", "text": [ "breast cancer" ], "offsets": [ [ 863, 876 ] ], "normalized": [] }, { "id": "PMID-12923331_T36", "type": "Cell", "text": [ "MDA-MB-231 cells" ], "offsets": [ [ 966, 982 ] ], "normalized": [] }, { "id": "PMID-12923331_T37", "type": "Cell", "text": [ "stromal" ], "offsets": [ [ 988, 995 ] ], "normalized": [] }, { "id": "PMID-12923331_T38", "type": "Cell", "text": [ "osteoblastic cells" ], "offsets": [ [ 999, 1017 ] ], "normalized": [] }, { "id": "PMID-12923331_T39", "type": "Cell", "text": [ "osteoclasts" ], "offsets": [ [ 1051, 1062 ] ], "normalized": [] }, { "id": "PMID-12923331_T41", "type": "Cell", "text": [ "MDA-MB-231 cells" ], "offsets": [ [ 1084, 1100 ] ], "normalized": [] }, { "id": "PMID-12923331_T42", "type": "Cancer", "text": [ "breast cancer samples" ], "offsets": [ [ 1110, 1131 ] ], "normalized": [] }, { "id": "PMID-12923331_T44", "type": "Cell", "text": [ "cancer cells" ], "offsets": [ [ 1189, 1201 ] ], "normalized": [] }, { "id": "PMID-12923331_T45", "type": "Cell", "text": [ "stromal" ], "offsets": [ [ 1207, 1214 ] ], "normalized": [] }, { "id": "PMID-12923331_T46", "type": "Cell", "text": [ "osteoblastic cells" ], "offsets": [ [ 1218, 1236 ] ], "normalized": [] }, { "id": "PMID-12923331_T49", "type": "Cancer", "text": [ "breast cancer" ], "offsets": [ [ 1365, 1378 ] ], "normalized": [] }, { "id": "PMID-12923331_T50", "type": "Cell", "text": [ "stromal" ], "offsets": [ [ 1383, 1390 ] ], "normalized": [] }, { "id": "PMID-12923331_T51", "type": "Cell", "text": [ "osteoblastic cells" ], "offsets": [ [ 1394, 1412 ] ], "normalized": [] } ]

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[ { "id": "PMID-2255190__text", "type": "abstract", "text": [ "Expression of basic fibroblast growth factor in normal human tissues.\nThe distribution of basic fibroblast growth factor (bFGF) was studied immunohistochemically in fresh frozen sections of normal human tissues. Immunodetection was performed with a specific anti-bFGF mouse monoclonal antibody that was found to react with recombinant human bFGF in Western blot analysis, and to specifically neutralize the mitogenic activity of bFGF on bovine vascular endothelial cells. Expression of bFGF on normal human tissues was ubiquitously detected in the basement membranes of all size blood vessels, but was not found in epidermal or epithelial basement membranes of a variety of tissues tested. Intensity and patterns of localization in blood vessels was consistent in various tissues, but varied among different regions of the vascular bed. Whereas homogeneous and intense immunoreactivity were observed in large and intermediate size blood vessels, heterogeneity of expression was found in capillaries. The most intense immunoreactivity was observed in branching capillaries. Endothelial cell staining was heterogeneous and varied in different regions. Strong staining for bFGF was also found in cardiac muscle fibers, smooth muscle cells of mid-size blood vessels, the gut and the myometrium, in central nervous system neurons and cerebellar Purkinje cells, and on epithelial cells of the bronchi, colon, endometrium, and sweat gland ducts of the skin. The presence of bFGF in the extracellular compartment of a diverse variety of organs may play a role in angiogenesis. However, the function of bFGF in parenchymal cells remains to be determined.\n" ], "offsets": [ [ 0, 1646 ] ] } ]

[ { "id": "PMID-2255190_T3", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 61, 68 ] ], "normalized": [] }, { "id": "PMID-2255190_T7", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 203, 210 ] ], "normalized": [] }, { "id": "PMID-2255190_T14", "type": "Cell", "text": [ "vascular endothelial cells" ], "offsets": [ [ 444, 470 ] ], "normalized": [] }, { "id": "PMID-2255190_T17", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 507, 514 ] ], "normalized": [] }, { "id": "PMID-2255190_T18", "type": "Cellular_component", "text": [ "basement membranes" ], "offsets": [ [ 548, 566 ] ], "normalized": [] }, { "id": "PMID-2255190_T19", "type": "Multi-tissue_structure", "text": [ "blood vessels" ], "offsets": [ [ 579, 592 ] ], "normalized": [] }, { "id": "PMID-2255190_T20", "type": "Cellular_component", "text": [ "epidermal" ], "offsets": [ [ 615, 624 ] ], "normalized": [] }, { "id": "PMID-2255190_T21", "type": "Cellular_component", "text": [ "epithelial basement membranes" ], "offsets": [ [ 628, 657 ] ], "normalized": [] }, { "id": "PMID-2255190_T22", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 674, 681 ] ], "normalized": [] }, { "id": "PMID-2255190_T23", "type": "Multi-tissue_structure", "text": [ "blood vessels" ], "offsets": [ [ 732, 745 ] ], "normalized": [] }, { "id": "PMID-2255190_T24", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 772, 779 ] ], "normalized": [] }, { "id": "PMID-2255190_T25", "type": "Multi-tissue_structure", "text": [ "vascular bed" ], "offsets": [ [ 823, 835 ] ], "normalized": [] }, { "id": "PMID-2255190_T26", "type": "Multi-tissue_structure", "text": [ "blood vessels" ], "offsets": [ [ 931, 944 ] ], "normalized": [] }, { "id": "PMID-2255190_T27", "type": "Tissue", "text": [ "capillaries" ], "offsets": [ [ 987, 998 ] ], "normalized": [] }, { "id": "PMID-2255190_T28", "type": "Tissue", "text": [ "capillaries" ], "offsets": [ [ 1060, 1071 ] ], "normalized": [] }, { "id": "PMID-2255190_T29", "type": "Cell", "text": [ "Endothelial cell" ], "offsets": [ [ 1073, 1089 ] ], "normalized": [] }, { "id": "PMID-2255190_T31", "type": "Cell", "text": [ "cardiac muscle fibers" ], "offsets": [ [ 1193, 1214 ] ], "normalized": [] }, { "id": "PMID-2255190_T32", "type": "Cell", "text": [ "smooth muscle cells" ], "offsets": [ [ 1216, 1235 ] ], "normalized": [] }, { "id": "PMID-2255190_T33", "type": "Multi-tissue_structure", "text": [ "blood vessels" ], "offsets": [ [ 1248, 1261 ] ], "normalized": [] }, { "id": "PMID-2255190_T34", "type": "Organism_subdivision", "text": [ "gut" ], "offsets": [ [ 1267, 1270 ] ], "normalized": [] }, { "id": "PMID-2255190_T35", "type": "Multi-tissue_structure", "text": [ "myometrium" ], "offsets": [ [ 1279, 1289 ] ], "normalized": [] }, { "id": "PMID-2255190_T36", "type": "Cell", "text": [ "central nervous system neurons" ], "offsets": [ [ 1294, 1324 ] ], "normalized": [] }, { "id": "PMID-2255190_T37", "type": "Cell", "text": [ "cerebellar Purkinje cells" ], "offsets": [ [ 1329, 1354 ] ], "normalized": [] }, { "id": "PMID-2255190_T38", "type": "Cell", "text": [ "epithelial cells" ], "offsets": [ [ 1363, 1379 ] ], "normalized": [] }, { "id": "PMID-2255190_T39", "type": "Multi-tissue_structure", "text": [ "bronchi" ], "offsets": [ [ 1387, 1394 ] ], "normalized": [] }, { "id": "PMID-2255190_T40", "type": "Organ", "text": [ "colon" ], "offsets": [ [ 1396, 1401 ] ], "normalized": [] }, { "id": "PMID-2255190_T41", "type": "Multi-tissue_structure", "text": [ "endometrium" ], "offsets": [ [ 1403, 1414 ] ], "normalized": [] }, { "id": "PMID-2255190_T42", "type": "Multi-tissue_structure", "text": [ "sweat gland ducts" ], "offsets": [ [ 1420, 1437 ] ], "normalized": [] }, { "id": "PMID-2255190_T43", "type": "Organ", "text": [ "skin" ], "offsets": [ [ 1445, 1449 ] ], "normalized": [] }, { "id": "PMID-2255190_T45", "type": "Immaterial_anatomical_entity", "text": [ "extracellular compartment" ], "offsets": [ [ 1479, 1504 ] ], "normalized": [] }, { "id": "PMID-2255190_T46", "type": "Organ", "text": [ "organs" ], "offsets": [ [ 1529, 1535 ] ], "normalized": [] }, { "id": "PMID-2255190_T48", "type": "Cell", "text": [ "parenchymal cells" ], "offsets": [ [ 1602, 1619 ] ], "normalized": [] }, { "id": "PMID-2255190_T62", "type": "Tissue", "text": [ "sections" ], "offsets": [ [ 178, 186 ] ], "normalized": [] } ]

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[ { "id": "PMC-3199853-sec-07__text", "type": "sec", "text": [ "Patients and Study Design\nA prospective evaluation of the different CMR parameters for predicting LV segmental and global functional recovery was performed in 46 patients (63 +/- 10 years old, 3 with previous CABG, 35 with three-vessel disease, 3 with one-vessel disease) with LV systolic dysfunction (LVEF 35 +/- 8%) before they underwent surgical (n = 34) or percutaneous (n = 12) revascularisation. Sixty patients without contraindications for CMR were screened for the following inclusion criteria: (1) CAD (> 70% stenosis in one or more major epicardial vessels), scheduled for a revascularisation procedure; (2) LVEF <= 45%; (3) at least two adjacent segments with wall motion abnormalities at rest; and (4) no infarction or revascularisation within the last two months. Patients were included in the study only after a successful and complete coronary revascularisation. Of the 14 patients who did not complete the study, 3 decided not to undergo the repeated CMR scan or were lost during follow-up; 7 had significant periprocedural injury (new LGE zones on repeated CMR scans and clinically proven periprocedural myocardial infarction (MI) or MI between both scans); 3 had pacemakers or defibrillators implanted in the period between the MR scans; and 1 was excluded because of dilated cardiomyopathy with secondary CAD. None of the patients were excluded from the study for technical reasons or image quality.\nThe mean interval between CMR and revascularisation was 12 +/- 13 days, and none of the patients presented clinical evidence of infarction during this period. The mean interval between MI and the first CMR was 3.6 years. In 46 patients, the extent of regional contractility and LGE were determined repeatedly by CMR 28 +/- 4 weeks (6 months) after revascularisation.\nThe study was approved by the Lithuanian Bioethics Committee (Nr. 17), and informed written consent was obtained from each patient prior to inclusion in the study.\n" ], "offsets": [ [ 0, 1950 ] ] } ]

[ { "id": "PMC-3199853-sec-07_T1", "type": "Multi-tissue_structure", "text": [ "epicardial vessels" ], "offsets": [ [ 548, 566 ] ], "normalized": [] }, { "id": "PMC-3199853-sec-07_T2", "type": "Multi-tissue_structure", "text": [ "coronary" ], "offsets": [ [ 850, 858 ] ], "normalized": [] }, { "id": "PMC-3199853-sec-07_T3", "type": "Multi-tissue_structure", "text": [ "myocardial" ], "offsets": [ [ 1121, 1131 ] ], "normalized": [] }, { "id": "PMC-3199853-sec-07_T4", "type": "Pathological_formation", "text": [ "LGE" ], "offsets": [ [ 1052, 1055 ] ], "normalized": [] }, { "id": "PMC-3199853-sec-07_T5", "type": "Pathological_formation", "text": [ "LGE" ], "offsets": [ [ 1697, 1700 ] ], "normalized": [] }, { "id": "PMC-3199853-sec-07_T6", "type": "Multi-tissue_structure", "text": [ "wall" ], "offsets": [ [ 671, 675 ] ], "normalized": [] }, { "id": "PMC-3199853-sec-07_T7", "type": "Multi-tissue_structure", "text": [ "LV" ], "offsets": [ [ 98, 100 ] ], "normalized": [] }, { "id": "PMC-3199853-sec-07_T8", "type": "Multi-tissue_structure", "text": [ "LV" ], "offsets": [ [ 277, 279 ] ], "normalized": [] }, { "id": "PMC-3199853-sec-07_T9", "type": "Immaterial_anatomical_entity", "text": [ "percutaneous" ], "offsets": [ [ 361, 373 ] ], "normalized": [] } ]

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[ { "id": "PMID-19717942__text", "type": "abstract", "text": [ "[The value of intermittent ultrasound treatment in subacromial impingement syndrome].\nOBJECTIVES:\nThe role of intermittent ultrasound in the conservative treatment of subacromial impingement syndrome (SIS) has not been clarified. We aimed to evaluate the efficacy of ultrasound treatment in SIS.\nMETHODS:\nThirty-six patients (29 females, 7 males; mean age 51 years; range 40 to 69 years) with type II SIS were randomized to two groups to receive intermittent ultrasound (group 1, n=20) and placebo ultrasound (group 2, n=16) for three weeks (15 sessions). All the patients received the same standard physical therapy and rehabilitation modalities besides ultrasound treatment. Evaluations were made before and three and six weeks after treatment. Functional results were assessed by the Constant score, pain was assessed by a visual analog scale, and range of motion was measured.\nRESULTS:\nWithin-group comparisons showed significant improvements in both groups three and six weeks after treatment (p<0.05). Comparison between pretreatment and 6-week values were as follows: the mean flexion increased from 148.8+/-20.4 degrees to 175.6+/-6.0 degrees in group 1, and from 165.9+/-14.1 degrees to 177.4+/-4.4 degrees in group 2; internal and external rotation increased from 66.8+/-20.7 degrees and 61.9+/-22.9 degrees to 83.2+/-10.9 degrees and 84.4+/-9.6 degrees in group 1, and from 75.0+/-17.3 degrees and 70.0+/-19.8 degrees to 87.1+/-6.8 degrees and 84.6+/-8.4 degrees in group 2, respectively. There were no significant differences between the two groups with respect to the range of motion at the end of six weeks (p>0.05). The Constant score improved from 43.7+/-12.9 to 65.7+/-7.7 in group 1, and from 43.9+/-16.4 to 65.3+/-7.6 in group 2. Pain scores decreased from 5.5 to 2 and from 5 to 1 in group 1 and 2, respectively. Improvements in Constant scores and pain scores were similar in both groups (p>0.05).\nCONCLUSION:\nOur findings suggest that intermittent ultrasound added to conservative treatment of SIS do not provide an additional benefit to the patients.\n" ], "offsets": [ [ 0, 2074 ] ] } ]

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[ { "id": "PMID-9385933__text", "type": "abstract", "text": [ "CD56+ putative natural killer cell lymphomas: production of cytolytic effectors and related proteins mediating tumor cell apoptosis? \nApoptosis is a regulated form of cell death that may be triggered by natural killer (NK) or cytotoxic T cells, which effect target cell lysis by cytolytic effector and related proteins through complex intracellular signals. This study was aimed to investigate whether there is selective expression of these cytolytic markers in the putative NK-cell lymphomas and whether there is correlation with zonal tumor cell death in these tumors. Expression of the cytolytic effectors perforin, granzyme B9, and the granule membrane protein TIA1 were examined in 24 putative NK-cell lymphomas, 18 postthymic T-cell lymphomas (one case CD8+ CD56+ and three anaplastic large cell lymphomas (ALCL), three T-lymphoblastic lymphomas, and 20 B-cell lymphomas. Nineteen (79%) putative NK-cell lymphomas expressed perforin, and all 24 cases expressed granzyme B9 and TIA1. The only CD8+ CD56+ postthymic T-cell lymphoma also expressed all three cytolytic markers, two CD8- ALCL expressed TIA1; other postthymic T-cell, T-lymphoblastic, and B-cell lymphomas were consistently negative. There was strong correlation between percentage perforin-positive cells and zonal tumor cell death. Angioinvasion, in contrast, was present only in a proportion (37%) of these lymphomas despite the frequent presence of zonal tumor cell death (71%). We propose that cytolytic effector and related proteins produced by putative NK and some CD8+ CD56+ postthymic T-cell lymphomas, probably in conjunction with other mechanisms, may effect massive tumor cell apoptosis. The frequent expression of cytolytic effector markers in the CD2+ surface CD3- CD56+ putative NK-cell lymphomas lends further support to their probable NK cell origin.\n" ], "offsets": [ [ 0, 1835 ] ] } ]

[ { "id": "PMID-9385933_T2", "type": "Cancer", "text": [ "natural killer cell lymphomas" ], "offsets": [ [ 15, 44 ] ], "normalized": [] }, { "id": "PMID-9385933_T3", "type": "Cell", "text": [ "tumor cell" ], "offsets": [ [ 111, 121 ] ], "normalized": [] }, { "id": "PMID-9385933_T4", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 167, 171 ] ], "normalized": [] }, { "id": "PMID-9385933_T5", "type": "Cell", "text": [ "natural killer" ], "offsets": [ [ 203, 217 ] ], "normalized": [] }, { "id": "PMID-9385933_T6", "type": "Cell", "text": [ "NK" ], "offsets": [ [ 219, 221 ] ], "normalized": [] }, { "id": "PMID-9385933_T7", "type": "Cell", "text": [ "cytotoxic T cells" ], "offsets": [ [ 226, 243 ] ], "normalized": [] }, { "id": "PMID-9385933_T8", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 265, 269 ] ], "normalized": [] }, { "id": "PMID-9385933_T9", "type": "Immaterial_anatomical_entity", "text": [ "intracellular" ], "offsets": [ [ 335, 348 ] ], "normalized": [] }, { "id": "PMID-9385933_T10", "type": "Cancer", "text": [ "NK-cell lymphomas" ], "offsets": [ [ 475, 492 ] ], "normalized": [] }, { "id": "PMID-9385933_T11", "type": "Cell", "text": [ "tumor cell" ], "offsets": [ [ 537, 547 ] ], "normalized": [] }, { "id": "PMID-9385933_T12", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 563, 569 ] ], "normalized": [] }, { "id": "PMID-9385933_T15", "type": "Cellular_component", "text": [ "granule membrane" ], "offsets": [ [ 640, 656 ] ], "normalized": [] }, { "id": "PMID-9385933_T17", "type": "Cancer", "text": [ "NK-cell lymphomas" ], "offsets": [ [ 699, 716 ] ], "normalized": [] }, { "id": "PMID-9385933_T18", "type": "Cancer", "text": [ "postthymic T-cell lymphomas" ], "offsets": [ [ 721, 748 ] ], "normalized": [] }, { "id": "PMID-9385933_T20", "type": "Cancer", "text": [ "CD8+ CD56+" ], "offsets": [ [ 759, 769 ] ], "normalized": [] }, { "id": "PMID-9385933_T22", "type": "Cancer", "text": [ "anaplastic large cell lymphomas" ], "offsets": [ [ 780, 811 ] ], "normalized": [] }, { "id": "PMID-9385933_T23", "type": "Cancer", "text": [ "ALCL" ], "offsets": [ [ 813, 817 ] ], "normalized": [] }, { "id": "PMID-9385933_T24", "type": "Cancer", "text": [ "T-lymphoblastic lymphomas" ], "offsets": [ [ 826, 851 ] ], "normalized": [] }, { "id": "PMID-9385933_T25", "type": "Cancer", "text": [ "B-cell lymphomas" ], "offsets": [ [ 860, 876 ] ], "normalized": [] }, { "id": "PMID-9385933_T26", "type": "Cancer", "text": [ "NK-cell lymphomas" ], "offsets": [ [ 902, 919 ] ], "normalized": [] }, { "id": "PMID-9385933_T31", "type": "Cancer", "text": [ "CD8+ CD56+ postthymic T-cell lymphoma" ], "offsets": [ [ 998, 1035 ] ], "normalized": [] }, { "id": "PMID-9385933_T34", "type": "Cancer", "text": [ "CD8- ALCL" ], "offsets": [ [ 1084, 1093 ] ], "normalized": [] }, { "id": "PMID-9385933_T36", "type": "Cancer", "text": [ "postthymic T-cell" ], "offsets": [ [ 1116, 1133 ] ], "normalized": [] }, { "id": "PMID-9385933_T37", "type": "Cancer", "text": [ "T-lymphoblastic" ], "offsets": [ [ 1135, 1150 ] ], "normalized": [] }, { "id": "PMID-9385933_T38", "type": "Cancer", "text": [ "B-cell lymphomas" ], "offsets": [ [ 1156, 1172 ] ], "normalized": [] }, { "id": "PMID-9385933_T40", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1267, 1272 ] ], "normalized": [] }, { "id": "PMID-9385933_T41", "type": "Cell", "text": [ "tumor cell" ], "offsets": [ [ 1283, 1293 ] ], "normalized": [] }, { "id": "PMID-9385933_T42", "type": "Cancer", "text": [ "lymphomas" ], "offsets": [ [ 1377, 1386 ] ], "normalized": [] }, { "id": "PMID-9385933_T43", "type": "Cell", "text": [ "tumor cell" ], "offsets": [ [ 1426, 1436 ] ], "normalized": [] }, { "id": "PMID-9385933_T44", "type": "Cell", "text": [ "NK" ], "offsets": [ [ 1527, 1529 ] ], "normalized": [] }, { "id": "PMID-9385933_T46", "type": "Cancer", "text": [ "CD8+ CD56+ postthymic T-cell lymphomas" ], "offsets": [ [ 1539, 1577 ] ], "normalized": [] }, { "id": "PMID-9385933_T48", "type": "Cell", "text": [ "tumor cell" ], "offsets": [ [ 1645, 1655 ] ], "normalized": [] }, { "id": "PMID-9385933_T50", "type": "Cancer", "text": [ "CD2+ surface CD3- CD56+ putative NK-cell lymphomas" ], "offsets": [ [ 1728, 1778 ] ], "normalized": [] }, { "id": "PMID-9385933_T53", "type": "Cell", "text": [ "NK cell" ], "offsets": [ [ 1819, 1826 ] ], "normalized": [] } ]

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[ { "id": "PMID-15833857__text", "type": "abstract", "text": [ "Mouse p10, an alternative spliced form of p15INK4b, inhibits cell cycle progression and malignant transformation. \nThe INK4 family of proteins negatively regulates cell cycle progression at the G(1)-S transition by inhibiting cyclin-dependent kinases. Two of these cell cycle inhibitors, p16(INK4A) and p15(INK4B), have tumor suppressor activities and are inactivated in human cancer. Interestingly, both INK4 genes express alternative splicing variants. In addition to p16(INK4A), the INK4A locus encodes a splice variant, termed p12--specifically expressed in human pancreas--and ARF, a protein encoded by an alternative reading frame that acts as a tumor suppressor through the p53 pathway. Similarly, the human INK4B locus encodes the p15(INK4B) tumor suppressor and one alternatively spliced form, termed as p10. We show here that p10, which arises from the use of an alternative splice donor site within intron 1, is conserved in the mouse genome and is widely expressed in mouse tissues. Similarly to mouse p15(INK4B), p10 expression is also induced by oncogenic insults and transforming growth factor-beta treatment and acts as a cell cycle inhibitor. Importantly, we show that mouse p10 is able to induce cell cycle arrest in a p53-dependent manner. We also show that mouse p10 is able to inhibit foci formation and anchorage-independent growth in wild-type mouse embryonic fibroblasts, and that these antitransforming properties of mouse p10 are also p53-dependent. These results indicate that the INK4B locus, similarly to INK4A-ARF, harbors two different splicing variants that can be involved in the regulation of both the p53 and retinoblastoma pathways, the two major molecular pathways in tumor suppression.\n" ], "offsets": [ [ 0, 1724 ] ] } ]

[ { "id": "PMID-15833857_T4", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 61, 65 ] ], "normalized": [] }, { "id": "PMID-15833857_T6", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 164, 168 ] ], "normalized": [] }, { "id": "PMID-15833857_T8", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 265, 269 ] ], "normalized": [] }, { "id": "PMID-15833857_T13", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 320, 325 ] ], "normalized": [] }, { "id": "PMID-15833857_T15", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 377, 383 ] ], "normalized": [] }, { "id": "PMID-15833857_T22", "type": "Organ", "text": [ "pancreas" ], "offsets": [ [ 568, 576 ] ], "normalized": [] }, { "id": "PMID-15833857_T24", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 652, 657 ] ], "normalized": [] }, { "id": "PMID-15833857_T30", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 750, 755 ] ], "normalized": [] }, { "id": "PMID-15833857_T33", "type": "Cellular_component", "text": [ "intron 1" ], "offsets": [ [ 910, 918 ] ], "normalized": [] }, { "id": "PMID-15833857_T36", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 986, 993 ] ], "normalized": [] }, { "id": "PMID-15833857_T42", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1138, 1142 ] ], "normalized": [] }, { "id": "PMID-15833857_T45", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1214, 1218 ] ], "normalized": [] }, { "id": "PMID-15833857_T49", "type": "Cell", "text": [ "foci" ], "offsets": [ [ 1306, 1310 ] ], "normalized": [] }, { "id": "PMID-15833857_T51", "type": "Cell", "text": [ "embryonic fibroblasts" ], "offsets": [ [ 1373, 1394 ] ], "normalized": [] }, { "id": "PMID-15833857_T59", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1705, 1710 ] ], "normalized": [] } ]

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[ { "id": "PMC-3159351-sec-02__text", "type": "sec", "text": [ "Materials and Methods:\nA total of 75 brain abscess pus specimens were collected during neurosurgery, either by burr hole or by craniotomy. These specimens were further subjected to Gram stain, Ziehl-Neelsen (ZN) stain, and conventional microbiological culture. Only those cases which showed presence of AFB on ZN stain along with the growth of Mycobacterium tuberculosis were considered as TBAs. Such TBA cases were further presented along with their In vitro Proton Magnetic Resonance (MR) Spectroscopic findings.\n" ], "offsets": [ [ 0, 515 ] ] } ]

[ { "id": "PMC-3159351-sec-02_T1", "type": "Organism_substance", "text": [ "brain abscess pus specimens" ], "offsets": [ [ 37, 64 ] ], "normalized": [] }, { "id": "PMC-3159351-sec-02_T2", "type": "Organism_substance", "text": [ "specimens" ], "offsets": [ [ 145, 154 ] ], "normalized": [] } ]

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[ { "id": "PMID-18669910__text", "type": "abstract", "text": [ "Allogeneic injection of fetal membrane-derived mesenchymal stem cells induces therapeutic angiogenesis in a rat model of hind limb ischemia.\nBone marrow-derived mesenchymal stem cells (BM-MSC) have been demonstrated to be an attractive therapeutic cell source for tissue regeneration and repair. However, it remains unknown whether or not allogeneic transplantation of mesenchymal stem cells (MSC) derived from fetal membranes (FM), which are generally discarded as medical waste after delivery, has therapeutic potential. FM-MSC were obtained from Lewis rats and had surface antigen expression and multipotent potential partly similar to those of BM-MSC. Compared with BM-MSC, FM-MSC secreted a comparable amount of hepatocyte growth factor despite a small amount of vascular endothelial growth factor. FM-MSC and BM-MSC both expressed major histocompatibility complex (MHC) class I but not MHC class II antigens and did not elicit allogeneic lymphocyte proliferation in mixed lymphocyte culture. FM-MSC or BM-MSC obtained from Lewis rats were injected into a MHC-mismatched August-Copenhagen-Irish rat model of hind limb ischemia. Three weeks after injection, blood perfusion and capillary density were significantly higher in the FM-MSC and BM-MSC groups than in the phosphate-buffered saline group, and allogeneic FM-MSC and BM-MSC were still observed. In nonischemic hind limb tissues, allogeneic FM-MSC and BM-MSC injection were associated with a comparatively small amount of T lymphocyte infiltration, compared with the injection of allogeneic splenic lymphocytes. In conclusion, allogeneic FM-MSC injection did not elicit a lymphocyte proliferative response and provided significant improvement in a rat model of hind limb ischemia, comparable to the response to BM-MSC. Thus, allogeneic injection of FM-MSC may be a new therapeutic strategy for the treatment of severe peripheral vascular disease. Disclosure of potential conflicts of interest is found at the end of this article.\n" ], "offsets": [ [ 0, 1991 ] ] } ]

[ { "id": "PMID-18669910_T1", "type": "Cell", "text": [ "fetal membrane-derived mesenchymal stem cells" ], "offsets": [ [ 24, 69 ] ], "normalized": [] }, { "id": "PMID-18669910_T3", "type": "Organism_subdivision", "text": [ "hind limb" ], "offsets": [ [ 121, 130 ] ], "normalized": [] }, { "id": "PMID-18669910_T4", "type": "Cell", "text": [ "Bone marrow-derived mesenchymal stem cells" ], "offsets": [ [ 141, 183 ] ], "normalized": [] }, { "id": "PMID-18669910_T5", "type": "Cell", "text": [ "BM-MSC" ], "offsets": [ [ 185, 191 ] ], "normalized": [] }, { "id": "PMID-18669910_T6", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 248, 252 ] ], "normalized": [] }, { "id": "PMID-18669910_T7", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 264, 270 ] ], "normalized": [] }, { "id": "PMID-18669910_T8", "type": "Cell", "text": [ "mesenchymal stem cells" ], "offsets": [ [ 369, 391 ] ], "normalized": [] }, { "id": "PMID-18669910_T9", "type": "Cell", "text": [ "MSC" ], "offsets": [ [ 393, 396 ] ], "normalized": [] }, { "id": "PMID-18669910_T10", "type": "Multi-tissue_structure", "text": [ "fetal membranes" ], "offsets": [ [ 411, 426 ] ], "normalized": [] }, { "id": "PMID-18669910_T11", "type": "Multi-tissue_structure", "text": [ "FM" ], "offsets": [ [ 428, 430 ] ], "normalized": [] }, { "id": "PMID-18669910_T12", "type": "Cell", "text": [ "FM-MSC" ], "offsets": [ [ 523, 529 ] ], "normalized": [] }, { "id": "PMID-18669910_T14", "type": "Cell", "text": [ "BM-MSC" ], "offsets": [ [ 648, 654 ] ], "normalized": [] }, { "id": "PMID-18669910_T15", "type": "Cell", "text": [ "BM-MSC" ], "offsets": [ [ 670, 676 ] ], "normalized": [] }, { "id": "PMID-18669910_T16", "type": "Cell", "text": [ "FM-MSC" ], "offsets": [ [ 678, 684 ] ], "normalized": [] }, { "id": "PMID-18669910_T19", "type": "Cell", "text": [ "FM-MSC" ], "offsets": [ [ 804, 810 ] ], "normalized": [] }, { "id": "PMID-18669910_T20", "type": "Cell", "text": [ "BM-MSC" ], "offsets": [ [ 815, 821 ] ], "normalized": [] }, { "id": "PMID-18669910_T21", "type": "Cell", "text": [ "lymphocyte" ], "offsets": [ [ 944, 954 ] ], "normalized": [] }, { "id": "PMID-18669910_T22", "type": "Cell", "text": [ "lymphocyte culture" ], "offsets": [ [ 978, 996 ] ], "normalized": [] }, { "id": "PMID-18669910_T23", "type": "Cell", "text": [ "FM-MSC" ], "offsets": [ [ 998, 1004 ] ], "normalized": [] }, { "id": "PMID-18669910_T24", "type": "Cell", "text": [ "BM-MSC" ], "offsets": [ [ 1008, 1014 ] ], "normalized": [] }, { "id": "PMID-18669910_T27", "type": "Organism_subdivision", "text": [ "hind limb" ], "offsets": [ [ 1113, 1122 ] ], "normalized": [] }, { "id": "PMID-18669910_T28", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 1162, 1167 ] ], "normalized": [] }, { "id": "PMID-18669910_T29", "type": "Tissue", "text": [ "capillary" ], "offsets": [ [ 1182, 1191 ] ], "normalized": [] }, { "id": "PMID-18669910_T30", "type": "Cell", "text": [ "FM-MSC" ], "offsets": [ [ 1233, 1239 ] ], "normalized": [] }, { "id": "PMID-18669910_T31", "type": "Cell", "text": [ "BM-MSC" ], "offsets": [ [ 1244, 1250 ] ], "normalized": [] }, { "id": "PMID-18669910_T33", "type": "Cell", "text": [ "FM-MSC" ], "offsets": [ [ 1318, 1324 ] ], "normalized": [] }, { "id": "PMID-18669910_T34", "type": "Cell", "text": [ "BM-MSC" ], "offsets": [ [ 1329, 1335 ] ], "normalized": [] }, { "id": "PMID-18669910_T35", "type": "Tissue", "text": [ "hind limb tissues" ], "offsets": [ [ 1372, 1389 ] ], "normalized": [] }, { "id": "PMID-18669910_T36", "type": "Cell", "text": [ "FM-MSC" ], "offsets": [ [ 1402, 1408 ] ], "normalized": [] }, { "id": "PMID-18669910_T37", "type": "Cell", "text": [ "BM-MSC" ], "offsets": [ [ 1413, 1419 ] ], "normalized": [] }, { "id": "PMID-18669910_T38", "type": "Cell", "text": [ "T lymphocyte" ], "offsets": [ [ 1483, 1495 ] ], "normalized": [] }, { "id": "PMID-18669910_T39", "type": "Cell", "text": [ "splenic lymphocytes" ], "offsets": [ [ 1552, 1571 ] ], "normalized": [] }, { "id": "PMID-18669910_T40", "type": "Cell", "text": [ "FM-MSC" ], "offsets": [ [ 1599, 1605 ] ], "normalized": [] }, { "id": "PMID-18669910_T41", "type": "Cell", "text": [ "lymphocyte" ], "offsets": [ [ 1633, 1643 ] ], "normalized": [] }, { "id": "PMID-18669910_T43", "type": "Organism_subdivision", "text": [ "hind limb" ], "offsets": [ [ 1722, 1731 ] ], "normalized": [] }, { "id": "PMID-18669910_T44", "type": "Cell", "text": [ "BM-MSC" ], "offsets": [ [ 1772, 1778 ] ], "normalized": [] }, { "id": "PMID-18669910_T45", "type": "Cell", "text": [ "FM-MSC" ], "offsets": [ [ 1810, 1816 ] ], "normalized": [] }, { "id": "PMID-18669910_T46", "type": "Multi-tissue_structure", "text": [ "peripheral vascular" ], "offsets": [ [ 1879, 1898 ] ], "normalized": [] }, { "id": "PMID-18669910_T66", "type": "Cellular_component", "text": [ "surface" ], "offsets": [ [ 568, 575 ] ], "normalized": [] } ]

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[ { "id": "PMID-8144214__text", "type": "abstract", "text": [ "Kinins contribute to the improvement of insulin sensitivity during treatment with angiotensin converting enzyme inhibitor.\nAlthough angiotensin converting enzyme inhibitors and alpha 1-blockers have been reported to improve insulin sensitivity, their mechanisms of action have not been elucidated. To investigate the role of kinins in insulin sensitivity, we treated 4-week-old spontaneously hypertensive rats with either an angiotensin converting enzyme inhibitor (enalapril), an alpha 1-blocker (doxazosin), or an angiotensin II antagonist (losartan) for 3 weeks. A control group received no drugs. In addition, 18 rats treated with enalapril or doxazosin received a simultaneous administration of a kinin antagonist (Hoe 140). Glucose clamp testing was performed in each group. Enalapril (128 +/- 1 mmHg) and doxazosin (132 +/- 2 mmHg) decreased mean blood pressure compared with control levels (148 +/- 1 mmHg) (P < .01). The glucose requirement for the clamp test during the administration of enalapril (25.8 +/- 0.5 mg/kg per minute) or doxazosin (28.6 +/- 0.7 mg/kg per minute) was higher than that of the control group (19.8 +/- 0.5 mg/kg per minute) (P < .05). Although Hoe 140 did not alter the glucose requirement of doxazosin (27.8 +/- 0.5 mg/kg per minute), it decreased that of enalapril (22.6 +/- 0.9 mg/kg per minute) (P < .05) without affecting the changes in mean blood pressure induced by enalapril. In addition, losartan decreased mean blood pressure but did not affect the glucose requirement. Thus, the improvement in insulin sensitivity produced by an angiotensin converting enzyme inhibitor is mostly dependent on kinins but not on angiotensin II antagonism, and an alpha 1-blocker improves insulin sensitivity irrespective of kinins.\n" ], "offsets": [ [ 0, 1759 ] ] } ]

[ { "id": "PMID-8144214_T1", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 854, 859 ] ], "normalized": [] }, { "id": "PMID-8144214_T2", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 1382, 1387 ] ], "normalized": [] }, { "id": "PMID-8144214_T3", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 1456, 1461 ] ], "normalized": [] } ]

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[ { "id": "PMC-2822164-caption-01__text", "type": "caption", "text": [ "Demographic data of subjects\n" ], "offsets": [ [ 0, 29 ] ] } ]

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[ { "id": "PMID-21947854__text", "type": "abstract", "text": [ "Curcumin inhibits metastatic progression of breast cancer cell through suppression of urokinase-type plasminogen activator by NF-kappa B signaling pathways. \nCurcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), is extracted from the plant Curcuma longa. It was recently reported for its anticancer effect on several types of cancer cells in vitro however, the molecular mechanisms of this anticancer effect are not fully understood. In the present study, we evaluated the effects of curcumin on human mammary epithelial carcinoma MCF-7 cells. Cells were treated with curcumin and examined for cell viability by MTT assay. The cells invasion was demonstrated by transwell assay. The binding activity of NF-kappaB to DNA was examined in nuclear extracts using Trans-AM NF-kappaB ELISA kit. Western blot was performed to detect the effect of curcumin on the expression of uPA. Our results showed that curcumin dose-dependently inhibited (P < 0.05) the proliferation of MCF-7 cells. Meanwhile, the adhesion and invasion ability of MCF-7 cells were sharply inhibited when treated with different concentrations of curcumin. Curcumin also significantly decreased (P < 0.05) the expression of uPA and NF-kappaB DNA binding activity, respectively. It is concluded that curcumin inhibits the adhesion and invasion of MCF-7 cells through down-regulating the protein expression of uPA via of NF-kappaB activation. Accordingly, the therapeutic potential of curcumin for breast cancer deserves further study.\n" ], "offsets": [ [ 0, 1514 ] ] } ]

[ { "id": "PMID-21947854_T2", "type": "Cell", "text": [ "breast cancer cell" ], "offsets": [ [ 44, 62 ] ], "normalized": [] }, { "id": "PMID-21947854_T8", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 310, 316 ] ], "normalized": [] }, { "id": "PMID-21947854_T9", "type": "Cell", "text": [ "cancer cells" ], "offsets": [ [ 344, 356 ] ], "normalized": [] }, { "id": "PMID-21947854_T10", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 412, 418 ] ], "normalized": [] }, { "id": "PMID-21947854_T13", "type": "Cell", "text": [ "mammary epithelial carcinoma MCF-7 cells" ], "offsets": [ [ 520, 560 ] ], "normalized": [] }, { "id": "PMID-21947854_T14", "type": "Cell", "text": [ "Cells" ], "offsets": [ [ 562, 567 ] ], "normalized": [] }, { "id": "PMID-21947854_T16", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 612, 616 ] ], "normalized": [] }, { "id": "PMID-21947854_T17", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 645, 650 ] ], "normalized": [] }, { "id": "PMID-21947854_T20", "type": "Organism_substance", "text": [ "nuclear extracts" ], "offsets": [ [ 754, 770 ] ], "normalized": [] }, { "id": "PMID-21947854_T26", "type": "Cell", "text": [ "MCF-7 cells" ], "offsets": [ [ 985, 996 ] ], "normalized": [] }, { "id": "PMID-21947854_T27", "type": "Cell", "text": [ "MCF-7 cells" ], "offsets": [ [ 1046, 1057 ] ], "normalized": [] }, { "id": "PMID-21947854_T34", "type": "Cell", "text": [ "MCF-7 cells" ], "offsets": [ [ 1326, 1337 ] ], "normalized": [] }, { "id": "PMID-21947854_T38", "type": "Cancer", "text": [ "breast cancer" ], "offsets": [ [ 1476, 1489 ] ], "normalized": [] } ]

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[ { "id": "PMID-10741713__text", "type": "abstract", "text": [ "Ciprofloxacin mediated cell growth inhibition, S/G2-M cell cycle arrest, and apoptosis in a human transitional cell carcinoma of the bladder cell line. \nThe second most prevalent urological malignancy in middle aged and elderly men is bladder cancer, with 90% of the cases being transitional cell carcinomas. The success of current systemic and intravesical therapeutic agents, such as cisplatin, thiotepa, Adriamycin, mitomycin C, and bacillus Calmette-Guerin, is limited with recurrence rates reduced to 17-44%. In addition, most of these agents require instrumentation of the urinary tract and are delivered at a significant cost and potential morbidity to the patient. Fluroquinolone antibiotics such as ciprofloxacin, which can be administered p.o., may have a profound effect in bladder cancer management. This is primarily based on limited in vitro studies on tumor cells derived from transitional cell carcinoma of the bladder that revealed a dose- and time-dependent inhibition of cell growth by ciprofloxacin at concentrations that are easily attainable in the urine of patients. However, the mechanism(s) by which ciprofloxacin elicits its biological effects on bladder cancer cells is not well documented. Our experimental data confirm previous studies showing the in vitro cell growth inhibition of the transitional cell carcinoma of the bladder cell line HTB9 and further showed the induction of cell cycle arrest at the S/G2-M checkpoints. In addition, we found down-regulation of cyclin B, cyclin E, and dephosphorylation of cdk2 in ciprofloxacin-treated bladder tumor cells. There was also an up-regulation of Bax, which altered the Bax:Bcl-2 ratio, which may be responsible for mitochondrial depolarization reported to be involved prior to the induction of apoptosis. The cyclin-dependent kinase inhibitor p21WAF1 level was found to be decreased within 12 h of ciprofloxacin treatment and disappeared completely when HTB9 cells were treated with 200 microg/ml ciprofloxacin for 24 h. The down-regulation of p21WAF1 closely correlated with poly(ADP-ribose) polymerase cleavage and CPP32 activation. Recent studies revealed that p21WAF1 protects cells from apoptosis by arresting them in G1 and further binds to pro-caspase-3, preventing its activation and thus, inhibiting the apoptotic cascade. Hence, the down-regulation of p21WAF1, together with the alterations in Bax and cdk2 as observed in our studies, may define a novel mechanism by which ciprofloxacin inhibits tumor cell growth and induces apoptotic cell death. The results of our current studies provide strong experimental evidence for the use of ciprofloxacin as a potential preventive and/or therapeutic agent for the management of transitional cell carcinoma of the bladder.\n" ], "offsets": [ [ 0, 2757 ] ] } ]

[ { "id": "PMID-10741713_T2", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 23, 27 ] ], "normalized": [] }, { "id": "PMID-10741713_T3", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 54, 58 ] ], "normalized": [] }, { "id": "PMID-10741713_T5", "type": "Cancer", "text": [ "transitional cell carcinoma" ], "offsets": [ [ 98, 125 ] ], "normalized": [] }, { "id": "PMID-10741713_T6", "type": "Cell", "text": [ "bladder cell line" ], "offsets": [ [ 133, 150 ] ], "normalized": [] }, { "id": "PMID-10741713_T7", "type": "Cancer", "text": [ "urological malignancy" ], "offsets": [ [ 179, 200 ] ], "normalized": [] }, { "id": "PMID-10741713_T9", "type": "Cancer", "text": [ "bladder cancer" ], "offsets": [ [ 235, 249 ] ], "normalized": [] }, { "id": "PMID-10741713_T10", "type": "Cancer", "text": [ "transitional cell carcinomas" ], "offsets": [ [ 279, 307 ] ], "normalized": [] }, { "id": "PMID-10741713_T16", "type": "Organism_subdivision", "text": [ "urinary tract" ], "offsets": [ [ 579, 592 ] ], "normalized": [] }, { "id": "PMID-10741713_T20", "type": "Cancer", "text": [ "bladder cancer" ], "offsets": [ [ 785, 799 ] ], "normalized": [] }, { "id": "PMID-10741713_T21", "type": "Cell", "text": [ "tumor cells" ], "offsets": [ [ 867, 878 ] ], "normalized": [] }, { "id": "PMID-10741713_T22", "type": "Cancer", "text": [ "transitional cell carcinoma" ], "offsets": [ [ 892, 919 ] ], "normalized": [] }, { "id": "PMID-10741713_T23", "type": "Organ", "text": [ "bladder" ], "offsets": [ [ 927, 934 ] ], "normalized": [] }, { "id": "PMID-10741713_T24", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 990, 994 ] ], "normalized": [] }, { "id": "PMID-10741713_T26", "type": "Organism_substance", "text": [ "urine" ], "offsets": [ [ 1071, 1076 ] ], "normalized": [] }, { "id": "PMID-10741713_T29", "type": "Cell", "text": [ "bladder cancer cells" ], "offsets": [ [ 1173, 1193 ] ], "normalized": [] }, { "id": "PMID-10741713_T30", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1286, 1290 ] ], "normalized": [] }, { "id": "PMID-10741713_T31", "type": "Cancer", "text": [ "transitional cell carcinoma" ], "offsets": [ [ 1316, 1343 ] ], "normalized": [] }, { "id": "PMID-10741713_T32", "type": "Cell", "text": [ "bladder cell line HTB9" ], "offsets": [ [ 1351, 1373 ] ], "normalized": [] }, { "id": "PMID-10741713_T33", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1410, 1414 ] ], "normalized": [] }, { "id": "PMID-10741713_T38", "type": "Cell", "text": [ "bladder tumor cells" ], "offsets": [ [ 1571, 1590 ] ], "normalized": [] }, { "id": "PMID-10741713_T42", "type": "Cellular_component", "text": [ "mitochondrial" ], "offsets": [ [ 1696, 1709 ] ], "normalized": [] }, { "id": "PMID-10741713_T46", "type": "Cell", "text": [ "HTB9 cells" ], "offsets": [ [ 1935, 1945 ] ], "normalized": [] }, { "id": "PMID-10741713_T52", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 2162, 2167 ] ], "normalized": [] }, { "id": "PMID-10741713_T58", "type": "Cell", "text": [ "tumor cell" ], "offsets": [ [ 2487, 2497 ] ], "normalized": [] }, { "id": "PMID-10741713_T59", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 2527, 2531 ] ], "normalized": [] }, { "id": "PMID-10741713_T61", "type": "Cancer", "text": [ "transitional cell carcinoma" ], "offsets": [ [ 2713, 2740 ] ], "normalized": [] }, { "id": "PMID-10741713_T62", "type": "Organ", "text": [ "bladder" ], "offsets": [ [ 2748, 2755 ] ], "normalized": [] } ]

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[ { "id": "PMID-19758109__text", "type": "abstract", "text": [ "AVE8062: a new combretastatin derivative vascular disrupting agent.\nAngiogenesis has an essential role in promoting and supporting tumor growth and it is an important therapeutic target. The tumor vascular network is the result of pro-angiogenic and inhibitory factors as well as of the interaction between endothelial cells and extracellular matrix. Different antiangiogenic therapeutics have been developed to improve tumor control through vascular-targeting agents (VTA). VTAs can be divided into two groups: antiangiogenic agents and vascular-disrupting agents (VDAs). VTAs inhibit specific factors required to induce and direct the angiogenic process, with major activity against small tumor masses and at the tumor periphery, encompassing monoclonal antibodies and small molecules inhibitors of the tyrosine kinase domain of the VEGF receptor. VDAs specifically target and destroy well-established tumor vessels with ischemia and destruction of large masses with central hemorrhagic necrosis and survival of a thin peripheral tumor layer. VDAs can be divided into biologics, such as ligand-based, and small-molecule agents; this second group includes small-molecule VDAs like flavonoids, such as 5,6-dimethylxanthenone-4-acetic acid (DMXAA), and microtubule-destabilizing agents. In this review we will discuss the mechanism of action, as well as the preclinical and clinical results, of one of the most promising antitubulin agents: the combretastatin A4-phosphate derivative, AVE8062A.\n" ], "offsets": [ [ 0, 1494 ] ] } ]

[ { "id": "PMID-19758109_T3", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 41, 49 ] ], "normalized": [] }, { "id": "PMID-19758109_T4", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 131, 136 ] ], "normalized": [] }, { "id": "PMID-19758109_T5", "type": "Multi-tissue_structure", "text": [ "tumor vascular network" ], "offsets": [ [ 191, 213 ] ], "normalized": [] }, { "id": "PMID-19758109_T6", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 307, 324 ] ], "normalized": [] }, { "id": "PMID-19758109_T7", "type": "Cellular_component", "text": [ "extracellular matrix" ], "offsets": [ [ 329, 349 ] ], "normalized": [] }, { "id": "PMID-19758109_T8", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 420, 425 ] ], "normalized": [] }, { "id": "PMID-19758109_T16", "type": "Cancer", "text": [ "tumor masses" ], "offsets": [ [ 691, 703 ] ], "normalized": [] }, { "id": "PMID-19758109_T17", "type": "Tissue", "text": [ "tumor periphery" ], "offsets": [ [ 715, 730 ] ], "normalized": [] }, { "id": "PMID-19758109_T20", "type": "Multi-tissue_structure", "text": [ "tumor vessels" ], "offsets": [ [ 904, 917 ] ], "normalized": [] }, { "id": "PMID-19758109_T21", "type": "Cancer", "text": [ "masses" ], "offsets": [ [ 957, 963 ] ], "normalized": [] }, { "id": "PMID-19758109_T22", "type": "Cancer", "text": [ "peripheral tumor layer" ], "offsets": [ [ 1021, 1043 ] ], "normalized": [] }, { "id": "PMID-19758109_T1", "type": "Cellular_component", "text": [ "microtubule" ], "offsets": [ [ 1252, 1263 ] ], "normalized": [] }, { "id": "PMID-19758109_T2", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 442, 450 ] ], "normalized": [] }, { "id": "PMID-19758109_T9", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 538, 546 ] ], "normalized": [] } ]

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[ { "id": "PMC-3039624-sec-11__text", "type": "sec", "text": [ "The importance in identifying genes involved in spinal curvature\nSpinal curvature is a prevalent and costly deformity among humans and teleosts. The estimated annual cost of treating children hospitalized with idiopathic scoliosis (IS) in the United States alone is over $3 billion. This cost estimate does not consider Scheuermann kyphosis, or adults with idiopathic-type spinal curvature who suffer from chronic back pain, contributing to the estimated $849 billion cost of treatment and lost wages associated with musculoskeletal disease [24]. Among teleosts, spinal column deformities reduce total production in the aquaculture industry substantially [12]. In contrast to humans, teleost curve phenotypes are less well characterized; although heritable curves are acknowledged to account for many cases among cultured stocks, whether these cases are from congenital defects or are idiopathic-type is often not known.\nDespite the prevalence and impact of this type of deformity, the genetic architecture and specific genes involved are unknown. The current view is that human idiopathic-type scoliosis is a complex genetic disorder with multiple genes segregating in the population exhibiting complex genotype by environment interactions [25-30]. In aquaculture stocks, inheritance for spinal curvature has been described as Mendelian recessive or dominant, as well as polygenic, depending on how well the phenotype is characterized and what stock is considered (reviewed in [13], [16]). The guppy curveback phenotype has been extensively characterized so that the lineage can be applied as a model for understanding the biological context of heritable spinal curvature [1,7-9]. Future studies can use approaches to map QTL affecting shape based on digital photos [31,32], rather than the qualitative scale used in the present study. The identification of QTL in this study is a first step in understanding the genetics of this type of deformity and will lead to the identification of biological pathways associated with spinal integrity.\n" ], "offsets": [ [ 0, 2042 ] ] } ]

[ { "id": "PMC-3039624-sec-11_T1", "type": "Organism_subdivision", "text": [ "spinal" ], "offsets": [ [ 48, 54 ] ], "normalized": [] }, { "id": "PMC-3039624-sec-11_T2", "type": "Organism_subdivision", "text": [ "Spinal" ], "offsets": [ [ 65, 71 ] ], "normalized": [] }, { "id": "PMC-3039624-sec-11_T3", "type": "Organism_subdivision", "text": [ "back" ], "offsets": [ [ 414, 418 ] ], "normalized": [] }, { "id": "PMC-3039624-sec-11_T4", "type": "Organism_subdivision", "text": [ "spinal" ], "offsets": [ [ 373, 379 ] ], "normalized": [] }, { "id": "PMC-3039624-sec-11_T5", "type": "Anatomical_system", "text": [ "musculoskeletal" ], "offsets": [ [ 517, 532 ] ], "normalized": [] }, { "id": "PMC-3039624-sec-11_T6", "type": "Organism_subdivision", "text": [ "spinal column" ], "offsets": [ [ 563, 576 ] ], "normalized": [] }, { "id": "PMC-3039624-sec-11_T7", "type": "Organism_subdivision", "text": [ "spinal" ], "offsets": [ [ 1289, 1295 ] ], "normalized": [] }, { "id": "PMC-3039624-sec-11_T8", "type": "Organism_subdivision", "text": [ "spinal" ], "offsets": [ [ 1656, 1662 ] ], "normalized": [] }, { "id": "PMC-3039624-sec-11_T9", "type": "Organism_subdivision", "text": [ "spinal" ], "offsets": [ [ 2024, 2030 ] ], "normalized": [] } ]

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[ { "id": "PMID-1869637__text", "type": "abstract", "text": [ "Intracerebral grafting of cultured autologous skin fibroblasts into the rat striatum: an assessment of graft size and ultrastructure.\nTo identify a suitable donor cell population for gene therapy applications to the central nervous system, primary fibroblasts isolated from skin biopsies and maintained in culture are employed as autologous cells for intracerebral grafting within the adult rat striatum. Results from the present investigation reveal that cultured primary skin fibroblasts cease to proliferate once they reach confluence; these cells are thus contact inhibited in vitro. Following implantation within the striatum, the volume of the primary fibroblast grafts, stained immunohistochemically for fibronectin, does not differ significantly at 3 and 8 weeks. The graft size is dependent on the density of the cell suspension, but not dependent on either the number of passages the cells are taken through in culture prior to grafting or on the postoperative survival period. Ultrastructural evidence reveals that at 8 weeks the grafts are composed primarily of collagen and fibroblasts with rough endoplasmic reticulum and vesicles. Reactive astrocytic processes and phagocytic cells are also present in the grafts. The grafts are extensively vascularized with capillaries composed of nonfenestrated endothelium; intercellular junctions are evident at sites of apposition between endothelial cells. It is concluded that primary skin fibroblasts are able to survive for at least 8 weeks following intracerebral implantation and continue to synthesize collagen and fibronectin in vivo. Also, the grafts maintain a constant volume between 3 and 8 weeks, thereby indicating that primary skin fibroblasts do not produce tumors. Finally, dynamic host-to-graft interactions--including phagocytic migration, astrocytic hypertrophy and infiltration within the grafts, and angiogenesis--are features that constitute the structural integration of primary skin fibroblasts grafted within the adult rat central nervous system.\n" ], "offsets": [ [ 0, 2027 ] ] } ]

[ { "id": "PMID-1869637_T1", "type": "Cell", "text": [ "skin fibroblasts" ], "offsets": [ [ 46, 62 ] ], "normalized": [] }, { "id": "PMID-1869637_T3", "type": "Multi-tissue_structure", "text": [ "striatum" ], "offsets": [ [ 76, 84 ] ], "normalized": [] }, { "id": "PMID-1869637_T4", "type": "Tissue", "text": [ "graft" ], "offsets": [ [ 103, 108 ] ], "normalized": [] }, { "id": "PMID-1869637_T5", "type": "Cell", "text": [ "donor cell population" ], "offsets": [ [ 157, 178 ] ], "normalized": [] }, { "id": "PMID-1869637_T6", "type": "Anatomical_system", "text": [ "central nervous system" ], "offsets": [ [ 216, 238 ] ], "normalized": [] }, { "id": "PMID-1869637_T7", "type": "Cell", "text": [ "fibroblasts" ], "offsets": [ [ 248, 259 ] ], "normalized": [] }, { "id": "PMID-1869637_T8", "type": "Multi-tissue_structure", "text": [ "skin biopsies" ], "offsets": [ [ 274, 287 ] ], "normalized": [] }, { "id": "PMID-1869637_T10", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 341, 346 ] ], "normalized": [] }, { "id": "PMID-1869637_T11", "type": "Immaterial_anatomical_entity", "text": [ "intracerebral" ], "offsets": [ [ 351, 364 ] ], "normalized": [] }, { "id": "PMID-1869637_T13", "type": "Multi-tissue_structure", "text": [ "striatum" ], "offsets": [ [ 395, 403 ] ], "normalized": [] }, { "id": "PMID-1869637_T14", "type": "Cell", "text": [ "skin fibroblasts" ], "offsets": [ [ 473, 489 ] ], "normalized": [] }, { "id": "PMID-1869637_T15", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 545, 550 ] ], "normalized": [] }, { "id": "PMID-1869637_T16", "type": "Multi-tissue_structure", "text": [ "striatum" ], "offsets": [ [ 622, 630 ] ], "normalized": [] }, { "id": "PMID-1869637_T17", "type": "Tissue", "text": [ "fibroblast grafts" ], "offsets": [ [ 658, 675 ] ], "normalized": [] }, { "id": "PMID-1869637_T19", "type": "Tissue", "text": [ "graft" ], "offsets": [ [ 776, 781 ] ], "normalized": [] }, { "id": "PMID-1869637_T20", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 822, 826 ] ], "normalized": [] }, { "id": "PMID-1869637_T21", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 894, 899 ] ], "normalized": [] }, { "id": "PMID-1869637_T22", "type": "Tissue", "text": [ "grafts" ], "offsets": [ [ 1041, 1047 ] ], "normalized": [] }, { "id": "PMID-1869637_T24", "type": "Cell", "text": [ "fibroblasts" ], "offsets": [ [ 1087, 1098 ] ], "normalized": [] }, { "id": "PMID-1869637_T25", "type": "Cellular_component", "text": [ "endoplasmic reticulum" ], "offsets": [ [ 1110, 1131 ] ], "normalized": [] }, { "id": "PMID-1869637_T26", "type": "Cellular_component", "text": [ "vesicles" ], "offsets": [ [ 1136, 1144 ] ], "normalized": [] }, { "id": "PMID-1869637_T27", "type": "Cellular_component", "text": [ "astrocytic processes" ], "offsets": [ [ 1155, 1175 ] ], "normalized": [] }, { "id": "PMID-1869637_T28", "type": "Cell", "text": [ "phagocytic cells" ], "offsets": [ [ 1180, 1196 ] ], "normalized": [] }, { "id": "PMID-1869637_T29", "type": "Tissue", "text": [ "grafts" ], "offsets": [ [ 1221, 1227 ] ], "normalized": [] }, { "id": "PMID-1869637_T30", "type": "Tissue", "text": [ "grafts" ], "offsets": [ [ 1233, 1239 ] ], "normalized": [] }, { "id": "PMID-1869637_T31", "type": "Tissue", "text": [ "capillaries" ], "offsets": [ [ 1274, 1285 ] ], "normalized": [] }, { "id": "PMID-1869637_T32", "type": "Tissue", "text": [ "endothelium" ], "offsets": [ [ 1313, 1324 ] ], "normalized": [] }, { "id": "PMID-1869637_T33", "type": "Cellular_component", "text": [ "intercellular junctions" ], "offsets": [ [ 1326, 1349 ] ], "normalized": [] }, { "id": "PMID-1869637_T34", "type": "Cellular_component", "text": [ "sites" ], "offsets": [ [ 1365, 1370 ] ], "normalized": [] }, { "id": "PMID-1869637_T35", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 1393, 1410 ] ], "normalized": [] }, { "id": "PMID-1869637_T36", "type": "Cell", "text": [ "skin fibroblasts" ], "offsets": [ [ 1441, 1457 ] ], "normalized": [] }, { "id": "PMID-1869637_T37", "type": "Immaterial_anatomical_entity", "text": [ "intracerebral" ], "offsets": [ [ 1509, 1522 ] ], "normalized": [] }, { "id": "PMID-1869637_T40", "type": "Tissue", "text": [ "grafts" ], "offsets": [ [ 1607, 1613 ] ], "normalized": [] }, { "id": "PMID-1869637_T41", "type": "Cell", "text": [ "skin fibroblasts" ], "offsets": [ [ 1696, 1712 ] ], "normalized": [] }, { "id": "PMID-1869637_T42", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 1728, 1734 ] ], "normalized": [] }, { "id": "PMID-1869637_T43", "type": "Tissue", "text": [ "graft" ], "offsets": [ [ 1761, 1766 ] ], "normalized": [] }, { "id": "PMID-1869637_T44", "type": "Tissue", "text": [ "grafts" ], "offsets": [ [ 1864, 1870 ] ], "normalized": [] }, { "id": "PMID-1869637_T45", "type": "Cell", "text": [ "skin fibroblasts" ], "offsets": [ [ 1957, 1973 ] ], "normalized": [] }, { "id": "PMID-1869637_T47", "type": "Anatomical_system", "text": [ "central nervous system" ], "offsets": [ [ 2003, 2025 ] ], "normalized": [] } ]

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[ { "id": "PMID-17981770__text", "type": "abstract", "text": [ "Role of telomeres in vascular senescence.\nTelomeres are DNA regions composed of TTAGGG repeats that are located at the ends of chromosomes. Specific proteins associate with the telomeres and form non-nucleosomal DNA-protein complexes that serve as protective caps for the chromosome ends. There is accumulating evidence that progressive telomere shortening is closely related to cardiovascular disease. For example, vascular cell senescence has been reported to occur in human atherosclerotic lesions and this change is associated with telomere shortening. Impairment of telomere integrity causes vascular dysfunction, which is prevented by the activation of telomerase. Mice with short telomeres develop hypertension and exhibit impaired neovascularization. Short telomeres have also been reported in the leukocytes of patients with cardiovascular disease or various cardiovascular risk factors. Although it remains unclear whether short telomeres directly cause cardiovascular disease, manipulation of telomere function is potentially an attractive strategy for the treatment of vascular senescence.\n" ], "offsets": [ [ 0, 1102 ] ] } ]

[ { "id": "PMID-17981770_T3", "type": "Cellular_component", "text": [ "chromosomes" ], "offsets": [ [ 127, 138 ] ], "normalized": [] }, { "id": "PMID-17981770_T5", "type": "Cellular_component", "text": [ "chromosome" ], "offsets": [ [ 272, 282 ] ], "normalized": [] }, { "id": "PMID-17981770_T8", "type": "Cell", "text": [ "vascular cell" ], "offsets": [ [ 416, 429 ] ], "normalized": [] }, { "id": "PMID-17981770_T17", "type": "Cell", "text": [ "leukocytes" ], "offsets": [ [ 806, 816 ] ], "normalized": [] }, { "id": "PMID-17981770_T9", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 597, 605 ] ], "normalized": [] }, { "id": "PMID-17981770_T22", "type": "Pathological_formation", "text": [ "atherosclerotic lesions" ], "offsets": [ [ 477, 500 ] ], "normalized": [] }, { "id": "PMID-17981770_T1", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 21, 29 ] ], "normalized": [] }, { "id": "PMID-17981770_T2", "type": "Anatomical_system", "text": [ "cardiovascular" ], "offsets": [ [ 379, 393 ] ], "normalized": [] }, { "id": "PMID-17981770_T4", "type": "Anatomical_system", "text": [ "cardiovascular" ], "offsets": [ [ 834, 848 ] ], "normalized": [] }, { "id": "PMID-17981770_T6", "type": "Anatomical_system", "text": [ "cardiovascular" ], "offsets": [ [ 868, 882 ] ], "normalized": [] }, { "id": "PMID-17981770_T7", "type": "Anatomical_system", "text": [ "cardiovascular" ], "offsets": [ [ 964, 978 ] ], "normalized": [] }, { "id": "PMID-17981770_T10", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 1081, 1089 ] ], "normalized": [] }, { "id": "PMID-17981770_T11", "type": "Cellular_component", "text": [ "telomeres" ], "offsets": [ [ 8, 17 ] ], "normalized": [] }, { "id": "PMID-17981770_T12", "type": "Cellular_component", "text": [ "Telomeres" ], "offsets": [ [ 42, 51 ] ], "normalized": [] }, { "id": "PMID-17981770_T13", "type": "Cellular_component", "text": [ "telomeres" ], "offsets": [ [ 177, 186 ] ], "normalized": [] }, { "id": "PMID-17981770_T14", "type": "Cellular_component", "text": [ "telomere" ], "offsets": [ [ 337, 345 ] ], "normalized": [] }, { "id": "PMID-17981770_T15", "type": "Cellular_component", "text": [ "telomere" ], "offsets": [ [ 536, 544 ] ], "normalized": [] }, { "id": "PMID-17981770_T16", "type": "Cellular_component", "text": [ "telomere" ], "offsets": [ [ 571, 579 ] ], "normalized": [] }, { "id": "PMID-17981770_T18", "type": "Cellular_component", "text": [ "telomeres" ], "offsets": [ [ 687, 696 ] ], "normalized": [] }, { "id": "PMID-17981770_T19", "type": "Cellular_component", "text": [ "telomeres" ], "offsets": [ [ 765, 774 ] ], "normalized": [] }, { "id": "PMID-17981770_T20", "type": "Cellular_component", "text": [ "telomeres" ], "offsets": [ [ 939, 948 ] ], "normalized": [] }, { "id": "PMID-17981770_T21", "type": "Cellular_component", "text": [ "telomere" ], "offsets": [ [ 1004, 1012 ] ], "normalized": [] } ]

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[ { "id": "PMID-14663884__text", "type": "abstract", "text": [ "[Laboratory diagnostics of Crimean hemorrhagic fever by polymerase chain reaction].\nOur group developed, within the present case study, two techniques' variations, i.e. a single-step RT-PCR and nested RT-PCR assays, for the purpose of detecting the Crimean-Congo hemorrhagic fever RNA virus in human samples. The above assays as well as those previously recommended by the Ministry of Health of the Russian Federation were simultaneously used in 14 clinical samples obtained from patients with Crimean hemorrhagic fever. After assessing the detection accuracy, it was found that the developed-by-us test system displayed the same or even better diagnostic values versus the previously recommended nested RT-PCR and a 1000-fold advantage over the previously recommended single-step RT-PCA. The single-step RT-PCR assay variation is always more preferable in sense of technical and economic motivations. Finally, the test system developed by us has every reason to become the method of choice in routine PCR diagnosis of Crimean hemorrhagic fever after all official trials and approvals are duly complied with.\n" ], "offsets": [ [ 0, 1109 ] ] } ]

[ { "id": "PMID-14663884_T1", "type": "Tissue", "text": [ "samples" ], "offsets": [ [ 300, 307 ] ], "normalized": [] }, { "id": "PMID-14663884_T2", "type": "Tissue", "text": [ "samples" ], "offsets": [ [ 458, 465 ] ], "normalized": [] } ]

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[ { "id": "PMID-9641893__text", "type": "abstract", "text": [ "Prophylactic thyroidectomy in MEN IIA: does the calcitonin level correlate with tumor spread? \nBACKGROUND: The fate of patients with multiple endocrine neoplasia of type II A (MEN II A) is determined by medullary thyroid carcinoma, which occurs in all cases. This has led to the therapeutic concept of prophylactic thyroidectomy in affected family members with the goal of removing the thyroid before the manifestation of carcinoma. We investigated a prophylactically thyroidectomized MEN II A population to determine whether the highly specific and sensitive tumor marker calcitonin correlates with tumor spread. PATIENTS AND METHODS: Fifteen patients with MEN II A (aged 4-24 years) who had undergone prophylactic thyroidectomy since 1990 were included in the study. Baseline and pentagastrin-stimulated calcitonin levels were preoperatively determined in all cases. The indication for surgery was established on the basis of pathologic calcitonin levels in the first seven patients and on the basis of detected RET proto-oncogene mutation in the other eight patients. Bilateral central lymphadenectomy was performed in all patients in addition to thyroidectomy. RESULTS: Histology demonstrated C-cell hyperplasia in five patients (aged 4-13 years), unilateral medullary microcarcinoma in six (aged 9-17 years) and a bilateral medullary microcarcinoma in three cases (aged 17-24 years). One 9-year-old boy with bilateral microcarcinoma already had a lymph node metastasis. The mean baseline calcitonin level correlated with the histologic findings (r=0.71, P=0.003) but there was no correlation between pentagastrin-stimulated calcitonin levels and histology (r=0.21, P=0.47). CONCLUSION: In MEN II A patients undergoing prophylactic thyroidectomy, baseline but not stimulated calcitonin levels already correlate with the histologic tumor stage at the stage of clinically occult C-cell hyperplasia or medullary microcarcinoma. However, biochemical screening cannot reliably discriminate the transition from C-cell hyperplasia to invasive microcarcinoma. Individuals with MEN IIA should therefore undergo early prophylactic thyroidectomy once the diagnosis is confirmed by molecular genetic testing.\n" ], "offsets": [ [ 0, 2201 ] ] } ]

[ { "id": "PMID-9641893_T1", "type": "Cancer", "text": [ "MEN IIA" ], "offsets": [ [ 30, 37 ] ], "normalized": [] }, { "id": "PMID-9641893_T3", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 80, 85 ] ], "normalized": [] }, { "id": "PMID-9641893_T5", "type": "Cancer", "text": [ "multiple endocrine neoplasia of type II A" ], "offsets": [ [ 133, 174 ] ], "normalized": [] }, { "id": "PMID-9641893_T6", "type": "Cancer", "text": [ "MEN II A" ], "offsets": [ [ 176, 184 ] ], "normalized": [] }, { "id": "PMID-9641893_T7", "type": "Cancer", "text": [ "medullary thyroid carcinoma" ], "offsets": [ [ 203, 230 ] ], "normalized": [] }, { "id": "PMID-9641893_T8", "type": "Organ", "text": [ "thyroid" ], "offsets": [ [ 386, 393 ] ], "normalized": [] }, { "id": "PMID-9641893_T9", "type": "Cancer", "text": [ "carcinoma" ], "offsets": [ [ 422, 431 ] ], "normalized": [] }, { "id": "PMID-9641893_T10", "type": "Cancer", "text": [ "MEN II A" ], "offsets": [ [ 485, 493 ] ], "normalized": [] }, { "id": "PMID-9641893_T11", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 560, 565 ] ], "normalized": [] }, { "id": "PMID-9641893_T13", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 600, 605 ] ], "normalized": [] }, { "id": "PMID-9641893_T15", "type": "Cancer", "text": [ "MEN II A" ], "offsets": [ [ 658, 666 ] ], "normalized": [] }, { "id": "PMID-9641893_T23", "type": "Cell", "text": [ "C-cell" ], "offsets": [ [ 1197, 1203 ] ], "normalized": [] }, { "id": "PMID-9641893_T25", "type": "Cancer", "text": [ "medullary microcarcinoma" ], "offsets": [ [ 1263, 1287 ] ], "normalized": [] }, { "id": "PMID-9641893_T26", "type": "Cancer", "text": [ "medullary microcarcinoma" ], "offsets": [ [ 1329, 1353 ] ], "normalized": [] }, { "id": "PMID-9641893_T28", "type": "Cancer", "text": [ "microcarcinoma" ], "offsets": [ [ 1423, 1437 ] ], "normalized": [] }, { "id": "PMID-9641893_T29", "type": "Multi-tissue_structure", "text": [ "lymph node" ], "offsets": [ [ 1452, 1462 ] ], "normalized": [] }, { "id": "PMID-9641893_T33", "type": "Cancer", "text": [ "MEN II A" ], "offsets": [ [ 1694, 1702 ] ], "normalized": [] }, { "id": "PMID-9641893_T36", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1835, 1840 ] ], "normalized": [] }, { "id": "PMID-9641893_T37", "type": "Cell", "text": [ "C-cell" ], "offsets": [ [ 1881, 1887 ] ], "normalized": [] }, { "id": "PMID-9641893_T38", "type": "Cancer", "text": [ "medullary microcarcinoma" ], "offsets": [ [ 1903, 1927 ] ], "normalized": [] }, { "id": "PMID-9641893_T39", "type": "Cell", "text": [ "C-cell" ], "offsets": [ [ 2009, 2015 ] ], "normalized": [] }, { "id": "PMID-9641893_T40", "type": "Cancer", "text": [ "invasive microcarcinoma" ], "offsets": [ [ 2031, 2054 ] ], "normalized": [] }, { "id": "PMID-9641893_T41", "type": "Cancer", "text": [ "MEN IIA" ], "offsets": [ [ 2073, 2080 ] ], "normalized": [] } ]

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[ { "id": "PMID-21822531__text", "type": "abstract", "text": [ "Massive osteolysis in a dog resembling Gorham's disease in humans.\nAn eight-month-old mixed-breed dog was presented with a history of sudden onset pelvic limb lameness. Radiographic and computed tomographic examinations demonstrated an osteolytic process involving the lumbar spine and pelvis. A comprehensive work-up including serial radiographic skeletal survey, biopsy, routine laboratory investigation and evaluation of parathyroid hormone (PTH) and 25-hydroxy-vitamin D levels failed to reveal any underlying cause for the osteolysis. Conservative treatment using the bisphosphonate drug alendronate and oral analgesic medications resulted in a return to nearly normal long-term function, despite massive lumbar and pelvic osteolysis. The clinical, radiological and histopathological features in this dog are reported, and similarities with the human condition known as Gorham's disease are discussed.\n" ], "offsets": [ [ 0, 907 ] ] } ]

[ { "id": "PMID-21822531_T1", "type": "Organism_subdivision", "text": [ "pelvic limb" ], "offsets": [ [ 147, 158 ] ], "normalized": [] }, { "id": "PMID-21822531_T2", "type": "Organ", "text": [ "lumbar spine" ], "offsets": [ [ 269, 281 ] ], "normalized": [] }, { "id": "PMID-21822531_T3", "type": "Organ", "text": [ "pelvis" ], "offsets": [ [ 286, 292 ] ], "normalized": [] }, { "id": "PMID-21822531_T4", "type": "Anatomical_system", "text": [ "skeletal" ], "offsets": [ [ 348, 356 ] ], "normalized": [] }, { "id": "PMID-21822531_T6", "type": "Organism_subdivision", "text": [ "oral" ], "offsets": [ [ 609, 613 ] ], "normalized": [] } ]

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[ { "id": "PMC-2677866-sec-12__text", "type": "sec", "text": [ "Nucleotide features of free-standing homing-endonucleases\nGene control elements were identified for several members of each type of intervening homing endonuclease genes described in this study. In 15 out of 16, 5' untranslated regions of the endonucleases we identified RNA hairpin structures upstream of initiation codons (Figures 1 and 4A). This may be a translational regulatory hairpin structure known from various phage genes, including homing endonucleases (22,47-49). The hairpins we found are in fractured gene loci with different protein host types, including gp41, IMPDH, DnaE, NrdJ and NrdA. Ten of these hairpins also include a conserved sequence of Aeh1 phage late promoter element (TATAAATA), which was recently shown to inhibit the translation of a gene-fracturing endonuclease gene, by sequestering its ribosome binding site (22,23). Analysis of the endonuclease 5' untranslated regions revealed two conserved motifs (Figures 4A and Supplementary Figure S4), which usually complement each other on the stem of the conserved hairpin structures. \nFigure 4.\nNucleotide features of endonuclease genes. (A) RNA hairpin structures at the 5' untranslated region of endonuclease ORFs in the gp41-1 (representing the very similar sequences of gp41-1-7), nrdA-5 and DnaE-1 gene loci. Initiator codons are marked by arrows, conserved putative T4 late promoter elements are boxed, and conserved sequence motifs (Supplementary Figure S4) are highlighted in grey. The expected values for motifs 1 and 2 are 1.7-10 and 9.9-3, respectively. RNA structures were calculated using the Vienna package (http://rna.tbi.univie.ac.at/cgi-bin/RNAfold.cgi), and sequence motifs were identified using the MEME program. (B) Overlapping#protein coding regions of endonuclease 3' termini and the 5' termini of their downstream genes.\nAdditionally, 15 loci included an overlapping region of 6-69 bp between the coding regions of the probable endonuclease C-termini and the downstream N-termini of the split-intein part (Figures 1 and 4B). This overlap is present in both types of endonucleases, and is independent on the presence of a split-intein part in the fractured gene, also occurring in the putative sbcD DNA-repair gene that we found, as well as in the Aeh1 fractured nrdA found by Gibb and Edgell (22).\n" ], "offsets": [ [ 0, 2298 ] ] } ]

[ { "id": "PMC-2677866-sec-12_T1", "type": "Cellular_component", "text": [ "ribosome" ], "offsets": [ [ 820, 828 ] ], "normalized": [] } ]

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[ { "id": "PMC-2721088-sec-10__text", "type": "sec", "text": [ "Chicken CCN3 expression in embryonic and extraembryonic tissues\nExpression of CCN3 in axial structure becomes visible in the presegmentation stage and reaches to the highest level at the beginning of somitogenesis (HH stage 7, Fig. 1a). Strong similarity between CCN3 and Sonic Hedgehog was observed for the expression pattern in axial structure (notochord and floor plate), in which the left-right asymmetrical pattern in the node area is also conserved (Fig. 1b). However, Sonic Hedgehog expression is slightly broader than that of CCN3. Since CCN3 stimulates Notch signaling (Sakamoto et al. 2002), we investigated the expression of Notch signal genes. Among them, Serrate1, a ligand of Notch is unique because its expression is apparently a right deviated pattern in the node area (Fig. 1c). Another Notch ligand, Delta1 shows a right deviated pattern, but is more caudal area of the node extending to the primitive streak (data not shown). The expression of CCN3 in axial structure was followed by the presomitic mesoderm although it is diminished (Sakamoto et al. 2002). \nFig. 1\nExpression of mRNA in early stage chicken embryo; CCN3 (a), Sonic Hedgehog (b) and Serrate1 (c) at the beginning stage of somitogenesis (Hamburger and Hamilton (HH) Stage 7). Arrowheads indicate Hensen's node. Demonstrates the schematic view of tissue organization at this stage (d). Expression of CCN3 mRNA in blood islands of chicken extraembryonic tissue (HH stage 10) (e). Ventral part of the endothelial precursor cells in blood islands is positive for CCN3 expression. Coloration was stopped before the background staining started in sense probes (negative control)\nThere is accumulating evidence of CCN3 commitment to hematopoiesis and therefore we investigated the CCN3 expression in extraembryonic tissues. Blood islands are formed in the yolk sac mesodermal area just between the visceral endodermal and ectodermal layers, which supply the red blood cells at the primary stage. The cells in blood islands are called hemangioblasts since they also differentiate into the endothelial cells of extraembryonic blood vessel structure. In chicken embryo, differentiating endothelial cells in the ventral part of blood islands express CCN3 from the initial stage (Fig. 1e). Erythroblasts in the center of blood islands (spherical cells in Fig. 1e) weakly express CCN3 and their expression is mildly enhanced in later stage (data not shown).\n" ], "offsets": [ [ 0, 2429 ] ] } ]

[ { "id": "PMC-2721088-sec-10_T1", "type": "Tissue", "text": [ "embryonic" ], "offsets": [ [ 27, 36 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T2", "type": "Tissue", "text": [ "extraembryonic tissues" ], "offsets": [ [ 41, 63 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T3", "type": "Developing_anatomical_structure", "text": [ "embryo" ], "offsets": [ [ 1127, 1133 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T4", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 1330, 1336 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T6", "type": "Tissue", "text": [ "extraembryonic tissue" ], "offsets": [ [ 1421, 1442 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T7", "type": "Cell", "text": [ "endothelial precursor cells" ], "offsets": [ [ 1482, 1509 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T8", "type": "Tissue", "text": [ "blood islands" ], "offsets": [ [ 1396, 1409 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T5", "type": "Tissue", "text": [ "blood islands" ], "offsets": [ [ 1513, 1526 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T9", "type": "Tissue", "text": [ "extraembryonic tissues" ], "offsets": [ [ 1777, 1799 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T10", "type": "Tissue", "text": [ "Blood islands" ], "offsets": [ [ 1801, 1814 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T11", "type": "Tissue", "text": [ "yolk sac mesodermal area" ], "offsets": [ [ 1833, 1857 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T12", "type": "Tissue", "text": [ "visceral endodermal" ], "offsets": [ [ 1875, 1894 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T13", "type": "Tissue", "text": [ "ectodermal layers" ], "offsets": [ [ 1899, 1916 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T14", "type": "Cell", "text": [ "red blood cells" ], "offsets": [ [ 1935, 1950 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T15", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1977, 1982 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T16", "type": "Tissue", "text": [ "blood islands" ], "offsets": [ [ 1986, 1999 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T17", "type": "Cell", "text": [ "hemangioblasts" ], "offsets": [ [ 2011, 2025 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T18", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 2065, 2082 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T19", "type": "Multi-tissue_structure", "text": [ "extraembryonic blood vessel structure" ], "offsets": [ [ 2086, 2123 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T20", "type": "Developing_anatomical_structure", "text": [ "embryo" ], "offsets": [ [ 2136, 2142 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T21", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 2160, 2177 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T22", "type": "Tissue", "text": [ "blood islands" ], "offsets": [ [ 2201, 2214 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T23", "type": "Cell", "text": [ "Erythroblasts" ], "offsets": [ [ 2262, 2275 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T24", "type": "Tissue", "text": [ "blood islands" ], "offsets": [ [ 2293, 2306 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T25", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 2318, 2323 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T26", "type": "Tissue", "text": [ "ventral part" ], "offsets": [ [ 2185, 2197 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T27", "type": "Tissue", "text": [ "Ventral part" ], "offsets": [ [ 1462, 1474 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T28", "type": "Developing_anatomical_structure", "text": [ "notochord" ], "offsets": [ [ 347, 356 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T29", "type": "Developing_anatomical_structure", "text": [ "floor plate" ], "offsets": [ [ 361, 372 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T30", "type": "Tissue", "text": [ "axial structure" ], "offsets": [ [ 86, 101 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T31", "type": "Tissue", "text": [ "axial structure" ], "offsets": [ [ 330, 345 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T32", "type": "Tissue", "text": [ "axial structure" ], "offsets": [ [ 971, 986 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T33", "type": "Tissue", "text": [ "node area" ], "offsets": [ [ 427, 436 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T34", "type": "Tissue", "text": [ "node area" ], "offsets": [ [ 775, 784 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T35", "type": "Tissue", "text": [ "caudal area" ], "offsets": [ [ 869, 880 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T36", "type": "Developing_anatomical_structure", "text": [ "primitive streak" ], "offsets": [ [ 910, 926 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T37", "type": "Developing_anatomical_structure", "text": [ "node" ], "offsets": [ [ 888, 892 ] ], "normalized": [] }, { "id": "PMC-2721088-sec-10_T38", "type": "Developing_anatomical_structure", "text": [ "Hensen's node" ], "offsets": [ [ 1280, 1293 ] ], "normalized": [] } ]

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[ { "id": "PMC-2972690-sec-19__text", "type": "sec", "text": [ "Discussion\nOur results indicate beneficial effects of motivational incentives on cognitive performance and alleviating effects on cognitive decline. These beneficial effects were evident in healthy young and older adults and in patients with Parkinson's disease. Young adults showed improved antisaccade preparation when a reward was at stake; older adults and PD patients could utilize reward prospect to improve their impaired antisaccade preparation. Elderly participants and PD patients were not only better prepared by means of commonly used preparatory aids (i.e., more preparation time and advance information on the upcoming response) but also by means of motivational incentives. These beneficial effects of motivational incentives on cognitive action preparation in healthy and pathological aging further support views that question the notion of monotonic deterioration of cognitive function with age (Allen et al., 2001). They indicate that age-related declines can be modulated by emotion-cognition interactions.\nIn line with the predominant view that cognitive control deteriorates in aging and Parkinson's disease, and in line with previous findings on age-related changes in antisaccade control specifically (Eenshuistra et al., 2004; Chan et al., 2005; Amador et al., 2006; Abel and Douglas, 2007), the current results showed decline in antisaccade preparation in PD patients with severe motor symptoms as compared to healthy seniors. Mild-symptom patients and healthy elderly did not differ in antisaccade preparation. Healthy seniors showed declining antisaccade preparation as compared to young adults. Decline was evident on several oculomotor parameters and most pronounced on antisaccade onset latencies. In line with the notion that in general, elderly tend to prefer accuracy over speed, elderly showed no decreased antisaccade accuracy as compared to young adults. As compared to the young group, elderly and PD patients exhibited slightly, but not significantly more premature eye movements. Premature eye movements, however significantly increased in elderly and PD patients but only slightly in the young, when more specific information on the upcoming movement was available in advance. Presumably, this increase in premature eye movements reflects difficulties with the inhibition of externally guided movement and/or the suppression of strongly activated prepotent action plans. On the one hand, the choice for medicated PD patients represents a limitation of the current study as we cannot exclude differential effects of medication on behavior. On the other hand, PD patients generally take medication in their daily routine, such that the results can be generalized to clinical practice. Exploratory analysis within the PD patient group revealed that patients with more severe motoric symptoms (as indexed by their motoric subscore on the UPDRS) displayed more signs of antisaccade decline, such as longer antisaccade latencies and lower accuracy compared to mildly affected patients, who initiated saccades equally fast as healthy adults. This suggests that dopaminergic medication was not sufficient to raise the patient's antisaccadic preparation up to the level of the healthy older adults.\nOne intriguing observation was that despite the different extents of observed antisaccade performance decline in elderly and PD patients, reward prospect led to beneficial effects on antisaccade latency and accuracy in young, elderly, and PD patients alike. Young, elderly and PD patients benefited from reward prospect to the same extent, confirming that the expectancy of reward is a powerful mediator of cognitive control, even if cognitive control suffers from decline. The expectation of rewarding incentives thus seems to support older adults' and PD patients' ability to anticipate, prepare and initiate goal-directed behavior.\nThese findings imply that despite a general decline in the action preparation system as indexed by increased antisaccade latency, action preparation processes remain susceptible to the prospect of future reward. It could thus be argued that the neural representations of upcoming rewards influence neural systems concerned with action preparation and oculomotor control. Although the current behavioral results cannot exclude or confirm neural links between reward anticipation and action preparation systems in the brain, they suggest intact cross-talk among subcortical circuits that allow goal-directed action to be modified by motivational factors. The motivational neural reward anticipation signal presumably activates the reward network including the amygdala, orbitofrontal cortex, the more ventral and dorsal striatum (nucleus accumbens, putamen, and caudate), leading to an release of caudate/SNr inhibition on the executive oculomotor structure superior colliculus. This transiently decreased inhibitory force on superior colliculus may improve goal-directed oculomotor control. Thus reward anticipation might compensate for the age- and disease-related dopaminergic loss in the SNc projections to the caudate/SNr and may thus play a compensatory role in \"boosting\" the efficiency of interactions between motivational and impaired cognitive control processes.\nHowever the reward-related modulation of the oculomotor control system may not only apply to the basal ganglia part of the oculomotor network. Although speculative, it could extend to the cortical eyefields (frontal, supplementary, and parietal eyefields) and to parts of the visual cortex. Human research shows that more preparatory activation in the frontal eyefields leads to a faster antisaccade latency (Connolly et al., 2002, 2005). The compensatory effect on the antisaccade latency, therefore, could theoretically stem from a propagation of reward anticipation signal in the caudate to the frontal eyefields. Complex structural connections enable the striatum to exert a controlling influence over the cerebral cortex via a series of reentrant corticobasal ganglia circuits. Thus reward anticipation may increase the level of preparation in the intact cortical eyefields and thereby compensate for age- and disease-related subcortical decrements in the oculomotor network.\nTaken together, it seems plausible that motivational reward processes in the caudate enhance preparatory activation in subcortical as well as in cortical nodes of the oculomotor network. Several neurotransmission mechanisms may underlie the remedial effect of positive incentives on declining antisaccadic control. Given the convergence of dopamine and glutamate inputs at the spiny projection neurons in the striatum (Burns et al., 1994), an interaction between dopamine and glutamate might underlie striatal processes of reward anticipation and action preparation. However, it cannot be fully excluded that alterations in other neurotransmitter systems may also have an effect on declining oculomotor control and on remediating incentive effects. Non-dopaminergic changes such as noradrenergic, serotonergic, and cholinergic deafferentation of the cortex also occur in PD and can inflict cognitive deficits (Agid et al., 1987). Evidence from non-human primates suggests that basal ganglia dopamine acts to speed motor responding in response to rewarding cues (Niv, 2007; Niv et al., 2007). Among at least five types of DA receptors, mainly D1 and D2 receptors are expressed in caudate projection neurons (Nakamura and Hikosaka, 2006). Tendencies to speed responses to obtain large rewards have been found to be dependent on striatal D1 receptors (Dalley et al., 2005; Berridge, 2007). In contrast to this D1 modulated speeding in reward-motor tasks, evidence from saccade tasks in non-human primates suggests D2 receptor modulation of reward dependent improvements of performance (Nakamura and Hikosaka, 2006). Injections of a D1 antagonist and a D2 antagonist into the region of the caudate where saccade-related neurons are clustered while the monkey performed a reward-biased saccade task showed that D1 antagonists attenuate the reward modulation of saccade behavior whereas D2 antagonists into the same region enhanced the reward-dependent changes.\nFuture studies of Parkinson patients on versus off medication, could provide some information on the role of dopaminergic mechanisms in the remedial effects on antisaccadic performance. A recent study of reward learning in Parkinson patients on/off dopaminergic medication showed that patients adapted their behavior to maximize expected reward value dependent on their medication status (Moustafa et al., 2008). Whilst off dopaminergic medication, patients slowed their responses to avoid low expected values, but succeeded less well in speeding responses when a reward was at stake. The opposite pattern emerged when the same patients were on medication; patients showed better response speeding, and worse response slowing, to maximize expected value.\nThe current behavioral findings are in line with neuroimaging research showing intact neural representations of future reward in the aging striatum (Samanez-Larkin et al., 2007). The observation however that older adults and PD patients can use this intact neural representation of reward anticipation (a positive motivational incentive) to optimize their preparatory processes, cannot necessarily be generalized to cognitive contexts with negative motivational incentives. Samanez-Larkin et al.(2010) recently showed that older adults were not able to optimally use their intact neural reward anticipation system in risky financial decision making. Elderly made more suboptimal choices when they were to choose risky assets. The authors deemed it likely that these decrements in value-based decision making are explained by the fact that value-based decision making requires the weighting of behavioral alternatives, that may lead to either gain or loss. During anticipation of rewards older adults show similar neural responses as young adults but they show reduced neural activation during the anticipation of losses (Samanez-Larkin et al., 2007). The latter, together with the observation that older adults tend to shift their attention away from negative stimuli and attend to positive information instead (Mather and Carstensen, 2003, 2005), may have led to the underestimation of loss and therefore to more risky and suboptimal decisions.\nIn this respect, one limitation of the current task is that it built solely on reward prospect and not on the prospect of loss, such that the question of how the anticipation of loss influences action preparation was not tested. The impact of negative incentives might be an intriguing question for future research, as due to the decreased activation of the neural loss anticipation system (Samanez-Larkin et al., 2007) together with the observed differential attentional bias for negative and positive information (Mather and Carstensen, 2003), it seems likely that negative motivational incentives, i.e., the prospect of loss, might have a different impact on action preparation in older adults than in the young. Future approaches to the effect of loss anticipation on declining antisaccade control may ideally contain a sequence of experiments, starting with a separate (punishment only) approach before moving to combined reward-punishment designs. This might be necessary as previous evidence (from healthy young adults) suggests that the reward effect on oculomotor control disappears in the presence of punishment trials. The authors deemed it likely that the participants increased caution to all incentive (reward and punishment) trials (Blaukopf and DiGirolamo, 2006).\nAs of yet, age-related changes in neural reward anticipation have mainly been studied in isolation. Recently however, the interaction of neural reward processing with other cognitive functions and their underlying neural systems, such as the action control system, has gained increasing interest (Haber and Knutson, 2010). Initial evidence suggests coordinated activity between distant brain regions responsible for reward processing (Cohen et al., 2009). The current results encourage further neural network investigations on the role of coordinated brain network activity in motivated behavior. Behavioral benefits from motivation might be associated with changes in functional brain connectivity on a larger scale, e.g., between frontostriatal reward and action preparation structures.\nAnother important factor that emerges from the present and previous results, is the importance of the training of the motivational aspects of the instructions that need to be kept in working memory when performing a cognitive task. Samanez-Larkin et al. (2007) found intact neural reward anticipation processes specifically in the absence of learning (after the learning process of reward cue-reward associations was completed). Therefore it might be important for researchers doing experiments with motivation based instructions to keep in mind that, compared to young adults, elderly and PD patients are generally hampered on stimulus-response learning (Shohamy et al., 2004; Marschner et al., 2005). Reward instruction cues, as they were used in the current study require participants to form reward cue-reward associations. Impairments in the learning of associations between the cue signaling reward and the actual reward might conceal intact reward anticipation processes. When the formation of associations is weakened, it could appear as a failure to capitalize on the neural reward anticipation system, whereas it represents an indirect effect of non-available reward associations in working memory when preparing the response. Hence, one might circumvent the effect of potential learning impairments on reward anticipation processes by the training of abstract reward cues (as in the current and in Samanez-Larkin's study) or by using explicit and concrete rewards. Once the learning of reward cues is accomplished the intact reward anticipation processes might become evident.\nIn sum, the results confirmed that the preparation of goal-directed actions declined in PD patients compared to healthy seniors, and in healthy seniors compared to young adults. Due perhaps to deterioration in dopaminergic striatal circuitry, antisaccade performance is subject to decline in healthy seniors, and even more in individuals with Parkinson's disease. The prospect of future reward however provided a motivational incentive for optimizing oculomotor preparation in all groups alike. These results suggest that reward-processing networks and oculomotor-control networks in the brain are connected in such a way (presumably with the dorsal striatum as a common nexus) that reward anticipation can facilitate oculomotor control and alleviate the deficiencies experienced by healthy seniors and PD patients. Future investigations should examine whether the observed effects are specific for the current task or generalize to other tasks that show age- and PD-related cognitive decrements (e.g., in task switching) and have been related to dopaminergic denervation in the caudate (e.g., impaired verbal episodic memory, attention, and response inhibition; Rinne et al., 2000; Bruck et al., 2005). Future studies on network processes may help to localize the neural link between reward prospect and action preparation that enables alleviating effects of motivational incentives on cognitive decline.\n" ], "offsets": [ [ 0, 15437 ] ] } ]

[ { "id": "PMC-2972690-sec-19_T1", "type": "Multi-tissue_structure", "text": [ "oculomotor" ], "offsets": [ [ 1654, 1664 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T2", "type": "Organ", "text": [ "eye" ], "offsets": [ [ 2004, 2007 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T3", "type": "Organ", "text": [ "eye" ], "offsets": [ [ 2029, 2032 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T4", "type": "Organ", "text": [ "eye" ], "offsets": [ [ 2256, 2259 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T7", "type": "Multi-tissue_structure", "text": [ "neural" ], "offsets": [ [ 4110, 4116 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T8", "type": "Anatomical_system", "text": [ "neural systems" ], "offsets": [ [ 4163, 4177 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T9", "type": "Multi-tissue_structure", "text": [ "oculomotor" ], "offsets": [ [ 4216, 4226 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T10", "type": "Multi-tissue_structure", "text": [ "neural" ], "offsets": [ [ 4302, 4308 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T11", "type": "Organ", "text": [ "brain" ], "offsets": [ [ 4381, 4386 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T12", "type": "Multi-tissue_structure", "text": [ "subcortical" ], "offsets": [ [ 4425, 4436 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T13", "type": "Multi-tissue_structure", "text": [ "neural" ], "offsets": [ [ 4535, 4541 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T14", "type": "Multi-tissue_structure", "text": [ "orbitofrontal cortex" ], "offsets": [ [ 4633, 4653 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T15", "type": "Multi-tissue_structure", "text": [ "ventral" ], "offsets": [ [ 4664, 4671 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T16", "type": "Multi-tissue_structure", "text": [ "dorsal striatum" ], "offsets": [ [ 4676, 4691 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T17", "type": "Multi-tissue_structure", "text": [ "nucleus accumbens" ], "offsets": [ [ 4693, 4710 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T18", "type": "Multi-tissue_structure", "text": [ "putamen" ], "offsets": [ [ 4712, 4719 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T19", "type": "Multi-tissue_structure", "text": [ "caudate" ], "offsets": [ [ 4725, 4732 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T20", "type": "Multi-tissue_structure", "text": [ "oculomotor structure superior colliculus" ], "offsets": [ [ 4800, 4840 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T21", "type": "Multi-tissue_structure", "text": [ "superior colliculus" ], "offsets": [ [ 4889, 4908 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T22", "type": "Multi-tissue_structure", "text": [ "oculomotor" ], "offsets": [ [ 4935, 4945 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T23", "type": "Multi-tissue_structure", "text": [ "oculomotor control system" ], "offsets": [ [ 5281, 5306 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T24", "type": "Multi-tissue_structure", "text": [ "basal ganglia" ], "offsets": [ [ 5333, 5346 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T25", "type": "Multi-tissue_structure", "text": [ "oculomotor network" ], "offsets": [ [ 5359, 5377 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T26", "type": "Multi-tissue_structure", "text": [ "cortical eyefields" ], "offsets": [ [ 5424, 5442 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T27", "type": "Multi-tissue_structure", "text": [ "frontal" ], "offsets": [ [ 5444, 5451 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T28", "type": "Multi-tissue_structure", "text": [ "supplementary" ], "offsets": [ [ 5453, 5466 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T29", "type": "Multi-tissue_structure", "text": [ "parietal eyefields" ], "offsets": [ [ 5472, 5490 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T30", "type": "Multi-tissue_structure", "text": [ "visual cortex" ], "offsets": [ [ 5512, 5525 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T31", "type": "Multi-tissue_structure", "text": [ "frontal eyefields" ], "offsets": [ [ 5588, 5605 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T32", "type": "Multi-tissue_structure", "text": [ "frontal eyefields" ], "offsets": [ [ 5834, 5851 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T33", "type": "Multi-tissue_structure", "text": [ "striatum" ], "offsets": [ [ 5895, 5903 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T34", "type": "Multi-tissue_structure", "text": [ "cerebral cortex" ], "offsets": [ [ 5946, 5961 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T35", "type": "Multi-tissue_structure", "text": [ "reentrant corticobasal ganglia" ], "offsets": [ [ 5978, 6008 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T36", "type": "Multi-tissue_structure", "text": [ "cortical eyefields" ], "offsets": [ [ 6096, 6114 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T37", "type": "Multi-tissue_structure", "text": [ "subcortical" ], "offsets": [ [ 6167, 6178 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T38", "type": "Multi-tissue_structure", "text": [ "oculomotor network" ], "offsets": [ [ 6197, 6215 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T39", "type": "Multi-tissue_structure", "text": [ "caudate" ], "offsets": [ [ 6294, 6301 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T40", "type": "Multi-tissue_structure", "text": [ "subcortical" ], "offsets": [ [ 6336, 6347 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T41", "type": "Multi-tissue_structure", "text": [ "cortical nodes" ], "offsets": [ [ 6362, 6376 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T42", "type": "Multi-tissue_structure", "text": [ "oculomotor network" ], "offsets": [ [ 6384, 6402 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T43", "type": "Cell", "text": [ "spiny projection neurons" ], "offsets": [ [ 6594, 6618 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T44", "type": "Multi-tissue_structure", "text": [ "striatum" ], "offsets": [ [ 6626, 6634 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T45", "type": "Multi-tissue_structure", "text": [ "oculomotor" ], "offsets": [ [ 6909, 6919 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T46", "type": "Multi-tissue_structure", "text": [ "cortex" ], "offsets": [ [ 7067, 7073 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T47", "type": "Multi-tissue_structure", "text": [ "basal ganglia" ], "offsets": [ [ 7194, 7207 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T48", "type": "Multi-tissue_structure", "text": [ "speed motor" ], "offsets": [ [ 7225, 7236 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T49", "type": "Cell", "text": [ "caudate projection neurons" ], "offsets": [ [ 7396, 7422 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T50", "type": "Cell", "text": [ "neurons" ], "offsets": [ [ 7933, 7940 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T51", "type": "Multi-tissue_structure", "text": [ "neural" ], "offsets": [ [ 9014, 9020 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T52", "type": "Multi-tissue_structure", "text": [ "striatum" ], "offsets": [ [ 9067, 9075 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T53", "type": "Multi-tissue_structure", "text": [ "neural" ], "offsets": [ [ 9185, 9191 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T54", "type": "Multi-tissue_structure", "text": [ "neural" ], "offsets": [ [ 9508, 9514 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T55", "type": "Multi-tissue_structure", "text": [ "neural" ], "offsets": [ [ 9941, 9947 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T56", "type": "Multi-tissue_structure", "text": [ "neural" ], "offsets": [ [ 9996, 10002 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T57", "type": "Multi-tissue_structure", "text": [ "neural" ], "offsets": [ [ 10732, 10738 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T58", "type": "Multi-tissue_structure", "text": [ "oculomotor" ], "offsets": [ [ 11436, 11446 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T59", "type": "Multi-tissue_structure", "text": [ "neural" ], "offsets": [ [ 11688, 11694 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T60", "type": "Multi-tissue_structure", "text": [ "neural" ], "offsets": [ [ 11791, 11797 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T61", "type": "Anatomical_system", "text": [ "neural systems" ], "offsets": [ [ 11868, 11882 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T62", "type": "Anatomical_system", "text": [ "action control system" ], "offsets": [ [ 11896, 11917 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T63", "type": "Organ", "text": [ "brain" ], "offsets": [ [ 12040, 12045 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T64", "type": "Multi-tissue_structure", "text": [ "neural network" ], "offsets": [ [ 12148, 12162 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T65", "type": "Organ", "text": [ "brain" ], "offsets": [ [ 12205, 12210 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T66", "type": "Organ", "text": [ "brain" ], "offsets": [ [ 12334, 12339 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T67", "type": "Multi-tissue_structure", "text": [ "frontostriatal reward" ], "offsets": [ [ 12386, 12407 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T68", "type": "Multi-tissue_structure", "text": [ "neural" ], "offsets": [ [ 12717, 12723 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T69", "type": "Multi-tissue_structure", "text": [ "neural" ], "offsets": [ [ 13520, 13526 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T70", "type": "Multi-tissue_structure", "text": [ "oculomotor-control networks" ], "offsets": [ [ 14584, 14611 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T71", "type": "Organ", "text": [ "brain" ], "offsets": [ [ 14619, 14624 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T72", "type": "Multi-tissue_structure", "text": [ "dorsal striatum" ], "offsets": [ [ 14674, 14689 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T73", "type": "Multi-tissue_structure", "text": [ "oculomotor" ], "offsets": [ [ 14749, 14759 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T74", "type": "Multi-tissue_structure", "text": [ "caudate" ], "offsets": [ [ 15110, 15117 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T75", "type": "Multi-tissue_structure", "text": [ "neural" ], "offsets": [ [ 15296, 15302 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T76", "type": "Multi-tissue_structure", "text": [ "caudate" ], "offsets": [ [ 5819, 5826 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T77", "type": "Multi-tissue_structure", "text": [ "caudate" ], "offsets": [ [ 7903, 7910 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T78", "type": "Multi-tissue_structure", "text": [ "oculomotor" ], "offsets": [ [ 14482, 14492 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T79", "type": "Multi-tissue_structure", "text": [ "striatal" ], "offsets": [ [ 6718, 6726 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T80", "type": "Multi-tissue_structure", "text": [ "striatal" ], "offsets": [ [ 7543, 7551 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T81", "type": "Multi-tissue_structure", "text": [ "striatal" ], "offsets": [ [ 14254, 14262 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T5", "type": "Multi-tissue_structure", "text": [ "amygdala" ], "offsets": [ [ 4623, 4631 ] ], "normalized": [] }, { "id": "PMC-2972690-sec-19_T6", "type": "Multi-tissue_structure", "text": [ "action preparation structures" ], "offsets": [ [ 12412, 12441 ] ], "normalized": [] } ]

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[ { "id": "PMID-10752531__text", "type": "abstract", "text": [ "Vascular proliferation and enhanced expression of endothelial nitric oxide synthase in human peritoneum exposed to long-term peritoneal dialysis.\nLong-term peritoneal dialysis (PD) is associated with alterations in peritoneal permeability and loss of ultrafiltration. These changes originate from increased peritoneal surface area, but the morphologic and molecular mechanisms involved remain unknown. The hypothesis that modifications of activity and/or expression of nitric oxide synthase (NOS) isozymes might play a role in these modifications, via enhanced local production of nitric oxide, was tested in this study. NOS activities were measured by the L-citrulline assay in peritoneal biopsies from seven control subjects, eight uremic patients immediately before the onset of PD, and 13 uremic patients on short-term ( less than 18 mo, n = 6) or long-term( greater than 18 mo, n = 7) PD. Peritoneal NOS activity is increased fivefold in long-term PD patients compared with control subjects. In uremic patients, NOS activity is positively correlated with the duration of PD. Increased NOS activity is mediated solely by Ca(2+)-dependent NOS and, as shown by immunoblotting, an upregulation of endothelial NOS. The biologic relevance of increased NOS in long-term PD was demonstrated by enhanced nitrotyrosine immunoreactivity and a significant increase in vascular density and endothelial area in the peritoneum. Immunoblotting and immunostaining studies demonstrated an upregulation of vascular endothelial growth factor (VEGF) mostly along the endothelium lining peritoneal blood vessels in long-term PD patients. In the latter, VEGF colocalized with the advanced glycation end product pentosidine deposits. These data provide a morphologic (angiogenesis and increased endothelial area) and molecular (enhanced NOS activity and endothelial NOS upregulation) basis for explaining the permeability changes observed in long-term PD. They also support the implication of local advanced glycation end product deposits and liberation of VEGF in that process.\n" ], "offsets": [ [ 0, 2060 ] ] } ]

[ { "id": "PMID-10752531_T1", "type": "Multi-tissue_structure", "text": [ "Vascular" ], "offsets": [ [ 0, 8 ] ], "normalized": [] }, { "id": "PMID-10752531_T4", "type": "Multi-tissue_structure", "text": [ "peritoneum" ], "offsets": [ [ 93, 103 ] ], "normalized": [] }, { "id": "PMID-10752531_T5", "type": "Multi-tissue_structure", "text": [ "peritoneal" ], "offsets": [ [ 125, 135 ] ], "normalized": [] }, { "id": "PMID-10752531_T6", "type": "Multi-tissue_structure", "text": [ "peritoneal" ], "offsets": [ [ 156, 166 ] ], "normalized": [] }, { "id": "PMID-10752531_T7", "type": "Multi-tissue_structure", "text": [ "peritoneal" ], "offsets": [ [ 215, 225 ] ], "normalized": [] }, { "id": "PMID-10752531_T8", "type": "Tissue", "text": [ "peritoneal surface area" ], "offsets": [ [ 307, 330 ] ], "normalized": [] }, { "id": "PMID-10752531_T13", "type": "Multi-tissue_structure", "text": [ "peritoneal biopsies" ], "offsets": [ [ 679, 698 ] ], "normalized": [] }, { "id": "PMID-10752531_T16", "type": "Multi-tissue_structure", "text": [ "Peritoneal" ], "offsets": [ [ 894, 904 ] ], "normalized": [] }, { "id": "PMID-10752531_T26", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 1361, 1369 ] ], "normalized": [] }, { "id": "PMID-10752531_T27", "type": "Tissue", "text": [ "endothelial area" ], "offsets": [ [ 1382, 1398 ] ], "normalized": [] }, { "id": "PMID-10752531_T28", "type": "Multi-tissue_structure", "text": [ "peritoneum" ], "offsets": [ [ 1406, 1416 ] ], "normalized": [] }, { "id": "PMID-10752531_T31", "type": "Tissue", "text": [ "endothelium" ], "offsets": [ [ 1551, 1562 ] ], "normalized": [] }, { "id": "PMID-10752531_T32", "type": "Multi-tissue_structure", "text": [ "peritoneal blood vessels" ], "offsets": [ [ 1570, 1594 ] ], "normalized": [] }, { "id": "PMID-10752531_T36", "type": "Tissue", "text": [ "endothelial area" ], "offsets": [ [ 1776, 1792 ] ], "normalized": [] } ]

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[ { "id": "PMID-6370602__text", "type": "abstract", "text": [ "Rapid micromeasurement of lactate in whole blood.\nA new lactate sensor makes it possible to measure the lactate content of whole blood directly in less than 1 min, using only a 10-microL blood sample. The procedure works equally well with plasma, serum, spinal fluid, other body fluids, or tissue homogenates. The instrument is calibrated with lactate standards between 0 and 15 mMol/L. The sensor, a polarographic enzyme electrode, gives a current which is a linear function of the lactate concentration. There is no interference from glucose, pyruvate, alcohol, ascorbate, anticoagulants, lidocaine, acetaminophen, or other drugs and metabolites commonly encountered in critically ill patients. The lactate sensor is composed of a peroxide sensor and an enzyme transducer membrane. The lactate is stoichiometrically converted to pyruvate and hydrogen peroxide by lactate oxygen oxidoreductase derived from Pediococcus species. The oxygen required for the enzymatic oxidation is supplied via an air-permeable silicone elastomeric membrane used for stirring. Comparison of our new electroenzymatic method with the Boehringer-Mannheim photoenzymatic method gives correlations of 0.997 for both whole blood and plasma.\n" ], "offsets": [ [ 0, 1217 ] ] } ]

[ { "id": "PMID-6370602_T1", "type": "Organism_substance", "text": [ "whole blood" ], "offsets": [ [ 37, 48 ] ], "normalized": [] }, { "id": "PMID-6370602_T2", "type": "Organism_substance", "text": [ "whole blood" ], "offsets": [ [ 123, 134 ] ], "normalized": [] }, { "id": "PMID-6370602_T3", "type": "Organism_substance", "text": [ "blood sample" ], "offsets": [ [ 187, 199 ] ], "normalized": [] }, { "id": "PMID-6370602_T4", "type": "Organism_substance", "text": [ "plasma" ], "offsets": [ [ 239, 245 ] ], "normalized": [] }, { "id": "PMID-6370602_T5", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 247, 252 ] ], "normalized": [] }, { "id": "PMID-6370602_T6", "type": "Organism_substance", "text": [ "spinal fluid" ], "offsets": [ [ 254, 266 ] ], "normalized": [] }, { "id": "PMID-6370602_T7", "type": "Organism_substance", "text": [ "body fluids" ], "offsets": [ [ 274, 285 ] ], "normalized": [] }, { "id": "PMID-6370602_T8", "type": "Organism_substance", "text": [ "tissue homogenates" ], "offsets": [ [ 290, 308 ] ], "normalized": [] }, { "id": "PMID-6370602_T9", "type": "Organism_substance", "text": [ "whole blood" ], "offsets": [ [ 1193, 1204 ] ], "normalized": [] }, { "id": "PMID-6370602_T10", "type": "Organism_substance", "text": [ "plasma" ], "offsets": [ [ 1209, 1215 ] ], "normalized": [] } ]

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[ { "id": "PMID-1517352__text", "type": "abstract", "text": [ "Active respiratory syncytial virus purified by ion-exchange chromatography: characterization of binding and elution requirements.\nTwo viruses, respiratory syncytial virus (RSV) and vesicular stomatitis virus (VSV) were used to evaluate viral purification by an affinity resin column (Matrex Cellufine Sulfate (MCS); Amicon Division, WR Grace & Co.). Viable RSV was purified significantly from crude cell lysate by a single pass through a column containing the anionic MCS resin. Most cell protein and albumin eluted from the MCS resin with phosphate buffered saline (PBS) but RSV eluted at high ionic strength, i.e., greater than or equal to 0.6 M NaCl. Further purification was possible by sucrose step gradient centrifugation. The RSV prepared by column purification or by column plus sucrose gradient separation was both intact and infective. RSV and pure samples of VSV were used to optimize ionic strength and salts for elution from the MCS column: 0.8 M NaCl removed most of the viral protein. The capacity of the MCS gel for RSV or VSV was found to be about 0.6-0.8 mg viral protein per ml of hydrated resin. Detergent-solubilized viral membrane proteins bound to the MCS resin in 0.145 M NaCl and eluted with higher salt concentrations. Thus, this resin also may be a useful aid for relatively gentle purification of these proteins.\n" ], "offsets": [ [ 0, 1341 ] ] } ]

[ { "id": "PMID-1517352_T4", "type": "Organism_substance", "text": [ "cell lysate" ], "offsets": [ [ 399, 410 ] ], "normalized": [] }, { "id": "PMID-1517352_T5", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 484, 488 ] ], "normalized": [] }, { "id": "PMID-1517352_T6", "type": "Cellular_component", "text": [ "membrane" ], "offsets": [ [ 1144, 1152 ] ], "normalized": [] } ]

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[ { "id": "PMC-2648768-caption-01__text", "type": "caption", "text": [ "Power (Y-axis) as a function of main effects (x-axis). For a pure main-effects model (x-axis = a1 > 0; interaction effects a2 = a3 = 0 are all zero), Figure 1 shows that pattern (solid red line) and single-locus (broken blue line) approaches have virtually the same power.\n" ], "offsets": [ [ 0, 273 ] ] } ]

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[ { "id": "PMID-8078269__text", "type": "abstract", "text": [ "[Preliminary results of observing 18 cases of retinoblastoma carried within the international research program RICS].\nIn the years 1988-1989, the Ophthalmological Clinic in Cracow took part in the International Research Programme on Retinoblastoma as one of 28 clinical centres in 14 countries. The study included 18 children with retinoblastoma, in most cases in the advanced stadium of the disease. As a rule, the eyes filled with tumours were enucleated, and the less advanced cases were treated with combined methods applying radiation with 60Co plaques with xenon arc photocoagulation, cryopexy, and chemotherapy. In 18 treated children 23 eyes were enucleated (in 5 children both eyes, in 6 children with bilateral retinoblastoma 1 eye, and 7 eyes in all unilateral cases). Six eyes with less advanced lesions were treated with combined methods. One child died because of metastases to the brain. The obtained data reveal that retinoblastoma is diagnosed too late, which decreases the chance of cure and causes great danger for the life of the child.\n" ], "offsets": [ [ 0, 1057 ] ] } ]

[ { "id": "PMID-8078269_T1", "type": "Cancer", "text": [ "retinoblastoma" ], "offsets": [ [ 46, 60 ] ], "normalized": [] }, { "id": "PMID-8078269_T2", "type": "Cancer", "text": [ "Retinoblastoma" ], "offsets": [ [ 233, 247 ] ], "normalized": [] }, { "id": "PMID-8078269_T3", "type": "Cancer", "text": [ "retinoblastoma" ], "offsets": [ [ 331, 345 ] ], "normalized": [] }, { "id": "PMID-8078269_T4", "type": "Cancer", "text": [ "retinoblastoma" ], "offsets": [ [ 721, 735 ] ], "normalized": [] }, { "id": "PMID-8078269_T5", "type": "Organ", "text": [ "eye" ], "offsets": [ [ 738, 741 ] ], "normalized": [] }, { "id": "PMID-8078269_T6", "type": "Organ", "text": [ "eyes" ], "offsets": [ [ 749, 753 ] ], "normalized": [] }, { "id": "PMID-8078269_T7", "type": "Organ", "text": [ "eyes" ], "offsets": [ [ 784, 788 ] ], "normalized": [] }, { "id": "PMID-8078269_T8", "type": "Organ", "text": [ "brain" ], "offsets": [ [ 896, 901 ] ], "normalized": [] }, { "id": "PMID-8078269_T9", "type": "Cancer", "text": [ "retinoblastoma" ], "offsets": [ [ 933, 947 ] ], "normalized": [] }, { "id": "PMID-8078269_T10", "type": "Organ", "text": [ "eyes" ], "offsets": [ [ 645, 649 ] ], "normalized": [] }, { "id": "PMID-8078269_T11", "type": "Organ", "text": [ "eyes" ], "offsets": [ [ 686, 690 ] ], "normalized": [] }, { "id": "PMID-8078269_T12", "type": "Organ", "text": [ "eyes" ], "offsets": [ [ 416, 420 ] ], "normalized": [] }, { "id": "PMID-8078269_T13", "type": "Cancer", "text": [ "tumours" ], "offsets": [ [ 433, 440 ] ], "normalized": [] }, { "id": "PMID-8078269_T14", "type": "Cancer", "text": [ "lesions" ], "offsets": [ [ 808, 815 ] ], "normalized": [] }, { "id": "PMID-8078269_T15", "type": "Cancer", "text": [ "metastases" ], "offsets": [ [ 878, 888 ] ], "normalized": [] } ]

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[ { "id": "PMID-16969171__text", "type": "abstract", "text": [ "Medical adherence and childhood chronic illness: family daily management skills and emotional climate as emerging contributors.\nPURPOSE OF REVIEW:\nTo describe recent research that examines family factors that promote or derail adherence to medical regimens for children with chronic health conditions, primarily asthma, diabetes, and cystic fibrosis. From the past 2 years, eight correlational studies were identified which specifically examined the links between family management strategies, family climate and medical adherence.\nRECENT FINDINGS:\nFindings from the studies suggest that team-based management strategies and cohesive family climate promote adherence to medical treatments over time. Family interactions that are characterized by conflict and disengagement tend to disrupt adherence and inevitably cause a decline in child health. Moreover, these findings seem to be moderated by child age in that poorer adherence often occurs when a child reaches adolescence and is searching for greater autonomy.\nSUMMARY:\nFuture research should consider the challenges in measuring medical adherence in the family context as well as incorporating more naturalistic studies of family interactions. Randomized controlled trials using family-based interventions may consider focusing on medical adherence as an important mediator between family process and child health outcomes.\n" ], "offsets": [ [ 0, 1380 ] ] } ]

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[ { "id": "PMC-2892686-caption-01__text", "type": "caption", "text": [ "Large nodular hepatic flexure lesions as seen on Colonoscopy.\n" ], "offsets": [ [ 0, 62 ] ] } ]

[ { "id": "PMC-2892686-caption-01_T1", "type": "Pathological_formation", "text": [ "nodular hepatic flexure lesions" ], "offsets": [ [ 6, 37 ] ], "normalized": [] } ]

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[ { "id": "PMID-8479750__text", "type": "abstract", "text": [ "Tumorigenic activity of rho genes from Aplysia californica. \nrho genes have been found in both lower and higher eucaryotes. They code for proteins of 21 kDa, highly conserved in evolution, which belong to the superfamily of ras GTPases. Among the members of this superfamily there are proteins with a regulatory function, such as ras, and proteins involved in vesicular trafficking, such as the family of rab proteins. We have investigated the putative role of rho proteins from Aplysia californica as transforming GTPases utilizing the wild-type and a Val-14 mutant, equivalent to the oncogenic Val-12 mutation of ras genes found in animal and human tumors. Over-expression of either rho gene was sufficient to confer anchorage- and serum-independent growth. Moreover, when introduced into nude mice, selected clones generated from either gene were able to induce tumors, although those carrying the mutated version were more efficient. Pathological analysis indicated that generated tumors corresponded to well-differentiated fibrosarcomas with distinct and intersecting bundles and spindle cells. By contrast, ras-induced tumors were poorly differentiated fibrosarcomas. Thus, our results indicate that under appropriate conditions rho genes function as oncogenes and may have a role in the regulation of proliferation in fibroblast cells.\n" ], "offsets": [ [ 0, 1343 ] ] } ]

[ { "id": "PMID-8479750_T6", "type": "Multi-tissue_structure", "text": [ "vesicular" ], "offsets": [ [ 360, 369 ] ], "normalized": [] }, { "id": "PMID-8479750_T14", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 651, 657 ] ], "normalized": [] }, { "id": "PMID-8479750_T16", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 734, 739 ] ], "normalized": [] }, { "id": "PMID-8479750_T18", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 865, 871 ] ], "normalized": [] }, { "id": "PMID-8479750_T19", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 985, 991 ] ], "normalized": [] }, { "id": "PMID-8479750_T20", "type": "Cancer", "text": [ "fibrosarcomas" ], "offsets": [ [ 1028, 1041 ] ], "normalized": [] }, { "id": "PMID-8479750_T21", "type": "Cell", "text": [ "bundles" ], "offsets": [ [ 1073, 1080 ] ], "normalized": [] }, { "id": "PMID-8479750_T22", "type": "Cell", "text": [ "spindle cells" ], "offsets": [ [ 1085, 1098 ] ], "normalized": [] }, { "id": "PMID-8479750_T24", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 1125, 1131 ] ], "normalized": [] }, { "id": "PMID-8479750_T25", "type": "Cancer", "text": [ "fibrosarcomas" ], "offsets": [ [ 1159, 1172 ] ], "normalized": [] }, { "id": "PMID-8479750_T27", "type": "Cell", "text": [ "fibroblast cells" ], "offsets": [ [ 1325, 1341 ] ], "normalized": [] } ]

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[ { "id": "PMID-20564340__text", "type": "abstract", "text": [ "Betulin induces mitochondrial cytochrome c release associated apoptosis in human cancer cells. \nWe examined whether betulin, a naturally abundant compound, has anticancer functions in human cancer cells. The results showed that betulin significantly inhibited cell viability in cervix carcinoma HeLa cells, hepatoma HepG2 cells, lung adenocarcinoma A549 cells, and breast cancer MCF-7 cells with IC(50) values ranging from 10 to 15 microg/mL. While betulin exhibited only moderate anticancer activity in other human cancer cells such as hepatoma SK-HEP-1 cells, prostate carcinoma PC-3, and lung carcinoma NCI-H460, with IC(50) values ranging from 20 to 60 microg/mL, it showed minor growth inhibition in human erythroleukemia K562 cells (IC(50) > 100 microg/mL). We further investigated the mechanism of anticancer activity by betulin, using HeLa cells as an experimental model. Betulin (10 microg/mL) induces apoptotic cell death, as evidenced by morphological characteristics such as membrane phosphatidylserine translocation, nuclear condensation/fragmentation, and apoptotic body formation. A kinetics analysis showed that the depolarization of mitochondrial membrane potential and the release of mitochondrial cytochrome c occurred as early as 30 min after treatment with betulin. Betulin, unlike its chemical derivative betulinic acid, did not directly trigger mitochondrial cytochrome c release in isolated mitochondria. Importantly, Bax and Bak were rapidly translocated to the mitochondria 30 min after betulin treatment. The sequential activation of caspase-9 and caspase-3/-7 and the cleavage of poly(ADP-ribose) polymerase (PARP) were observed behind those mitochondrial events. Furthermore, specific downregulation of either caspase-9, Bax, or Bak by siRNA effectively reduced PARP cleavage and caspase-3 activation. Taken together, the lines of evidence demonstrate that betulin triggers apoptosis of human cancer cells through the intrinsic apoptotic pathway.\n" ], "offsets": [ [ 0, 1976 ] ] } ]

[ { "id": "PMID-20564340_T2", "type": "Cellular_component", "text": [ "mitochondrial" ], "offsets": [ [ 16, 29 ] ], "normalized": [] }, { "id": "PMID-20564340_T5", "type": "Cell", "text": [ "cancer cells" ], "offsets": [ [ 81, 93 ] ], "normalized": [] }, { "id": "PMID-20564340_T7", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 164, 170 ] ], "normalized": [] }, { "id": "PMID-20564340_T9", "type": "Cell", "text": [ "cancer cells" ], "offsets": [ [ 190, 202 ] ], "normalized": [] }, { "id": "PMID-20564340_T11", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 260, 264 ] ], "normalized": [] }, { "id": "PMID-20564340_T12", "type": "Cell", "text": [ "cervix carcinoma HeLa cells" ], "offsets": [ [ 278, 305 ] ], "normalized": [] }, { "id": "PMID-20564340_T13", "type": "Cell", "text": [ "hepatoma HepG2 cells" ], "offsets": [ [ 307, 327 ] ], "normalized": [] }, { "id": "PMID-20564340_T14", "type": "Cell", "text": [ "lung adenocarcinoma A549 cells" ], "offsets": [ [ 329, 359 ] ], "normalized": [] }, { "id": "PMID-20564340_T15", "type": "Cell", "text": [ "breast cancer MCF-7 cells" ], "offsets": [ [ 365, 390 ] ], "normalized": [] }, { "id": "PMID-20564340_T17", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 485, 491 ] ], "normalized": [] }, { "id": "PMID-20564340_T19", "type": "Cell", "text": [ "cancer cells" ], "offsets": [ [ 516, 528 ] ], "normalized": [] }, { "id": "PMID-20564340_T20", "type": "Cell", "text": [ "hepatoma SK-HEP-1 cells" ], "offsets": [ [ 537, 560 ] ], "normalized": [] }, { "id": "PMID-20564340_T21", "type": "Cell", "text": [ "prostate carcinoma PC-3" ], "offsets": [ [ 562, 585 ] ], "normalized": [] }, { "id": "PMID-20564340_T22", "type": "Cell", "text": [ "lung carcinoma NCI-H460" ], "offsets": [ [ 591, 614 ] ], "normalized": [] }, { "id": "PMID-20564340_T24", "type": "Cell", "text": [ "erythroleukemia K562 cells" ], "offsets": [ [ 711, 737 ] ], "normalized": [] }, { "id": "PMID-20564340_T25", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 809, 815 ] ], "normalized": [] }, { "id": "PMID-20564340_T27", "type": "Cell", "text": [ "HeLa cells" ], "offsets": [ [ 843, 853 ] ], "normalized": [] }, { "id": "PMID-20564340_T29", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 921, 925 ] ], "normalized": [] }, { "id": "PMID-20564340_T30", "type": "Cellular_component", "text": [ "membrane" ], "offsets": [ [ 987, 995 ] ], "normalized": [] }, { "id": "PMID-20564340_T32", "type": "Cellular_component", "text": [ "nuclear" ], "offsets": [ [ 1030, 1037 ] ], "normalized": [] }, { "id": "PMID-20564340_T33", "type": "Cellular_component", "text": [ "apoptotic body" ], "offsets": [ [ 1070, 1084 ] ], "normalized": [] }, { "id": "PMID-20564340_T34", "type": "Cellular_component", "text": [ "mitochondrial membrane" ], "offsets": [ [ 1150, 1172 ] ], "normalized": [] }, { "id": "PMID-20564340_T35", "type": "Cellular_component", "text": [ "mitochondrial" ], "offsets": [ [ 1202, 1215 ] ], "normalized": [] }, { "id": "PMID-20564340_T40", "type": "Cellular_component", "text": [ "mitochondrial" ], "offsets": [ [ 1368, 1381 ] ], "normalized": [] }, { "id": "PMID-20564340_T42", "type": "Cellular_component", "text": [ "mitochondria" ], "offsets": [ [ 1415, 1427 ] ], "normalized": [] }, { "id": "PMID-20564340_T45", "type": "Cellular_component", "text": [ "mitochondria" ], "offsets": [ [ 1487, 1499 ] ], "normalized": [] }, { "id": "PMID-20564340_T52", "type": "Cellular_component", "text": [ "mitochondrial" ], "offsets": [ [ 1670, 1683 ] ], "normalized": [] }, { "id": "PMID-20564340_T60", "type": "Cell", "text": [ "cancer cells" ], "offsets": [ [ 1922, 1934 ] ], "normalized": [] } ]

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[ { "id": "PMID-11222727__text", "type": "abstract", "text": [ "TRADD domain of Epstein-Barr virus transforming protein LMP1 is essential for inducing immortalization and suppressing senescence of primary rodent fibroblasts. \nMutation analysis of latent membrane protein 1 (LMP1) in Epstein-Barr virus (EBV)-induced B-cell immortalization revealed two transformation effector sites, TES1 and TES2. TES2 mediates the interaction with tumor necrosis factor receptor-associated death domain protein (TRADD) and plays a key role in transactivating NF-kappa B and AP-1. Recombinant EBV containing LMP1 with TES2 deleted induces a limited proliferation of B cells. The present study shows that a mutant with an LMP1 site-specific mutation at TES2, LMP1(TRADD), initially stimulates cell growth and significantly extends the life span of MEF. However, it is not sufficient for the immortalization of MEF, and MEF-LMP1(TRADD) cells eventually enter growth arrest. Further analysis reveals that although LMP1(TRADD) promotes cell growth, it does not prevent the eventual onset of senescence and the expression of tumor suppressor p16(Ink4a).\n" ], "offsets": [ [ 0, 1069 ] ] } ]

[ { "id": "PMID-11222727_T5", "type": "Cell", "text": [ "fibroblasts" ], "offsets": [ [ 148, 159 ] ], "normalized": [] }, { "id": "PMID-11222727_T10", "type": "Cell", "text": [ "B-cell" ], "offsets": [ [ 252, 258 ] ], "normalized": [] }, { "id": "PMID-11222727_T17", "type": "Cell", "text": [ "B cells" ], "offsets": [ [ 586, 593 ] ], "normalized": [] }, { "id": "PMID-11222727_T21", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 712, 716 ] ], "normalized": [] }, { "id": "PMID-11222727_T22", "type": "Cell", "text": [ "MEF" ], "offsets": [ [ 767, 770 ] ], "normalized": [] }, { "id": "PMID-11222727_T23", "type": "Cell", "text": [ "MEF" ], "offsets": [ [ 829, 832 ] ], "normalized": [] }, { "id": "PMID-11222727_T24", "type": "Cell", "text": [ "MEF-LMP1(TRADD) cells" ], "offsets": [ [ 838, 859 ] ], "normalized": [] }, { "id": "PMID-11222727_T29", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 952, 956 ] ], "normalized": [] }, { "id": "PMID-11222727_T30", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1040, 1045 ] ], "normalized": [] } ]

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[ { "id": "PMC-3113832-caption-05__text", "type": "caption", "text": [ "Concurrent disease in 33 cows with LDA.\n" ], "offsets": [ [ 0, 40 ] ] } ]

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[ { "id": "PMID-17215077__text", "type": "abstract", "text": [ "Relationship of cellular immunity, cytokines and CRP with clinical course in breast cancer patients with endocrine-dependent distant metastases treated with immunotherapy. \nWe have reported important benefits and survival with an immunotherapy schedule in patients with endocrine-dependent breast cancer and distant metastases. Here clinical outcome is updated and its correlation with new immunological data is shown. In 32 evaluated breast cancer patients with endocrine-dependent distant metastases treated with a new immunotherapy schedule (cyclic administration of beta-interferon and interleukin-2), cellular immunity, cytokines and CRP were related to the clinical course. Estimated and true 5-10 year overall survival rates from first line antiestrogen and distant metastases were higher than previously reported in a similar population. Interleukin-2 administration was followed by a significant increase in total lymphocytes, CD4+, CD8+, CD16+56+ (NK) cells, IL-6, IL-12, and CRP (from P<0.04 to P<0.000) but no change in IL-10 and TGFbeta1 during clinical benefit. During progressive disease no change was observed in the former parameters, concomitant with a significant increase in IL-10 (P=0.020) and a significant decrease in TGFbeta1 (P=0.023). These findings confirm that cellular immunity is significantly stimulated by IL-2 only during clinical benefit. Furthermore, these results demonstrate that different changes of proinflammatory cytokines, CRP and inhibiting factors are consistent with associated clinical benefit or with disease progression, respectively.\n" ], "offsets": [ [ 0, 1583 ] ] } ]

[ { "id": "PMID-17215077_T1", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 16, 24 ] ], "normalized": [] }, { "id": "PMID-17215077_T3", "type": "Cancer", "text": [ "breast cancer" ], "offsets": [ [ 77, 90 ] ], "normalized": [] }, { "id": "PMID-17215077_T5", "type": "Anatomical_system", "text": [ "endocrine" ], "offsets": [ [ 105, 114 ] ], "normalized": [] }, { "id": "PMID-17215077_T7", "type": "Anatomical_system", "text": [ "endocrine" ], "offsets": [ [ 270, 279 ] ], "normalized": [] }, { "id": "PMID-17215077_T8", "type": "Cancer", "text": [ "breast cancer" ], "offsets": [ [ 290, 303 ] ], "normalized": [] }, { "id": "PMID-17215077_T9", "type": "Cancer", "text": [ "breast cancer" ], "offsets": [ [ 435, 448 ] ], "normalized": [] }, { "id": "PMID-17215077_T11", "type": "Anatomical_system", "text": [ "endocrine" ], "offsets": [ [ 463, 472 ] ], "normalized": [] }, { "id": "PMID-17215077_T14", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 606, 614 ] ], "normalized": [] }, { "id": "PMID-17215077_T17", "type": "Cell", "text": [ "lymphocytes" ], "offsets": [ [ 923, 934 ] ], "normalized": [] }, { "id": "PMID-17215077_T19", "type": "Cell", "text": [ "CD4+, CD8+, CD16+56+ (NK) cells" ], "offsets": [ [ 936, 967 ] ], "normalized": [] }, { "id": "PMID-17215077_T30", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 1289, 1297 ] ], "normalized": [] }, { "id": "PMID-17215077_T2", "type": "Cancer", "text": [ "metastases" ], "offsets": [ [ 133, 143 ] ], "normalized": [] }, { "id": "PMID-17215077_T4", "type": "Cancer", "text": [ "metastases" ], "offsets": [ [ 316, 326 ] ], "normalized": [] }, { "id": "PMID-17215077_T6", "type": "Cancer", "text": [ "metastases" ], "offsets": [ [ 491, 501 ] ], "normalized": [] }, { "id": "PMID-17215077_T10", "type": "Cancer", "text": [ "metastases" ], "offsets": [ [ 773, 783 ] ], "normalized": [] } ]

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[ { "id": "PMID-17532651__text", "type": "abstract", "text": [ "Medical therapy for intermittent claudication.\nMedical therapy to improve symptoms, stabilise the underlying vascular disease and improve lower limb outcomes is an important and effective adjunct to lifestyle modification and surgical or endovascular interventions in patients with IC. Randomised placebo controlled trials have shown that the phosphodiesterase III inhibitor cilostazol 100mg bid improves pain-free and maximum walking distance, as well as quality of life, in a range of patients with intermittent claudication in whom there is no evidence of tissue necrosis or rest pain. This review summarises the evidence from 8 pivotal trials of cilostazol involving over 2000 patients with intermittent claudication treated for up to 6 months. There is comparatively less evidence to support the use of other treatment modalities for relief of symptoms in intermittent claudication, but there is considerable interest in therapeutic angiogenesis to promote new vessel formation and enhance collateralisation of the lower limb using recombinant growth factor proteins or gene transfer strategies. The rationale for therapeutic angiogenesis is discussed, together with the most recent results from randomised trials in patients with peripheral arterial disease.\n" ], "offsets": [ [ 0, 1265 ] ] } ]

[ { "id": "PMID-17532651_T1", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 109, 117 ] ], "normalized": [] }, { "id": "PMID-17532651_T2", "type": "Organism_subdivision", "text": [ "lower limb" ], "offsets": [ [ 138, 148 ] ], "normalized": [] }, { "id": "PMID-17532651_T3", "type": "Immaterial_anatomical_entity", "text": [ "endovascular" ], "offsets": [ [ 238, 250 ] ], "normalized": [] }, { "id": "PMID-17532651_T8", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 559, 565 ] ], "normalized": [] }, { "id": "PMID-17532651_T11", "type": "Multi-tissue_structure", "text": [ "vessel" ], "offsets": [ [ 966, 972 ] ], "normalized": [] }, { "id": "PMID-17532651_T12", "type": "Organism_subdivision", "text": [ "lower limb" ], "offsets": [ [ 1020, 1030 ] ], "normalized": [] }, { "id": "PMID-17532651_T14", "type": "Multi-tissue_structure", "text": [ "peripheral arterial" ], "offsets": [ [ 1236, 1255 ] ], "normalized": [] } ]

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[ { "id": "PMID-8925114__text", "type": "abstract", "text": [ "Functional model of benign paroxysmal positional vertigo using an isolated frog semicircular canal.\nBull frogs posterior semicircular canals (psc) wee used to simulate the condition of benign paroxysmal positional vertigo (BPPV). The psc was isolated in frog Ringer's solution, and the saccular otoconia were used as a responsible material to stimulate the cupula. When the otoconia were placed on the cupular surface to mimic the condition of cupulolithiasis, the psc ampullary nerve action potentials instantaneously changed according to the direction of the gravity produced by otoconia. When the otoconia were dropped into the canal to mimic the condition of moving otoconia in the canal, the action potentials changed together with the otoconial flow after a latent period. Both cupulolithiasis and moving otoconia are possibly valid mechanisms of BPPV, since they effectively stimulate the cupula. However, moving otoconia with a latent period would better explain clinical features of BPPV.\n" ], "offsets": [ [ 0, 998 ] ] } ]

[ { "id": "PMID-8925114_T1", "type": "Multi-tissue_structure", "text": [ "semicircular canal" ], "offsets": [ [ 80, 98 ] ], "normalized": [] }, { "id": "PMID-8925114_T2", "type": "Multi-tissue_structure", "text": [ "posterior semicircular canals" ], "offsets": [ [ 111, 140 ] ], "normalized": [] }, { "id": "PMID-8925114_T3", "type": "Multi-tissue_structure", "text": [ "psc" ], "offsets": [ [ 142, 145 ] ], "normalized": [] }, { "id": "PMID-8925114_T4", "type": "Multi-tissue_structure", "text": [ "psc" ], "offsets": [ [ 234, 237 ] ], "normalized": [] }, { "id": "PMID-8925114_T5", "type": "Organism_substance", "text": [ "saccular otoconia" ], "offsets": [ [ 286, 303 ] ], "normalized": [] }, { "id": "PMID-8925114_T6", "type": "Multi-tissue_structure", "text": [ "cupula" ], "offsets": [ [ 357, 363 ] ], "normalized": [] }, { "id": "PMID-8925114_T7", "type": "Organism_substance", "text": [ "otoconia" ], "offsets": [ [ 374, 382 ] ], "normalized": [] }, { "id": "PMID-8925114_T8", "type": "Multi-tissue_structure", "text": [ "cupular surface" ], "offsets": [ [ 402, 417 ] ], "normalized": [] }, { "id": "PMID-8925114_T9", "type": "Multi-tissue_structure", "text": [ "psc ampullary nerve" ], "offsets": [ [ 465, 484 ] ], "normalized": [] }, { "id": "PMID-8925114_T10", "type": "Organism_substance", "text": [ "otoconia" ], "offsets": [ [ 581, 589 ] ], "normalized": [] }, { "id": "PMID-8925114_T11", "type": "Organism_substance", "text": [ "otoconia" ], "offsets": [ [ 600, 608 ] ], "normalized": [] }, { "id": "PMID-8925114_T12", "type": "Multi-tissue_structure", "text": [ "canal" ], "offsets": [ [ 631, 636 ] ], "normalized": [] }, { "id": "PMID-8925114_T13", "type": "Organism_substance", "text": [ "otoconia" ], "offsets": [ [ 670, 678 ] ], "normalized": [] }, { "id": "PMID-8925114_T14", "type": "Multi-tissue_structure", "text": [ "canal" ], "offsets": [ [ 686, 691 ] ], "normalized": [] }, { "id": "PMID-8925114_T15", "type": "Organism_substance", "text": [ "otoconial" ], "offsets": [ [ 741, 750 ] ], "normalized": [] }, { "id": "PMID-8925114_T16", "type": "Organism_substance", "text": [ "otoconia" ], "offsets": [ [ 811, 819 ] ], "normalized": [] }, { "id": "PMID-8925114_T17", "type": "Multi-tissue_structure", "text": [ "cupula" ], "offsets": [ [ 896, 902 ] ], "normalized": [] }, { "id": "PMID-8925114_T18", "type": "Organism_substance", "text": [ "otoconia" ], "offsets": [ [ 920, 928 ] ], "normalized": [] } ]

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[ { "id": "PMC-3249382-caption-01__text", "type": "caption", "text": [ "Predicted methylation level of C. gigas genes categorized by biological processes compared to measured level of DNA methylation. Mean CpG O/E for 10,699 C. gigas genes categorized according to Biological Process Gene Ontology (GO) Slim terms are plotted on the x-axis (modified from Gavery and Roberts, 2010). DNA methylation was empirically measured by performing MBD-seq on the SOLiD 4 platform (Applied Biosystems). Genes identified in the MBD-library were associated with respective GO terms and enrichment analysis was performed based on the entire transcriptome (Fleury et al., 2009) using DAVID (Huang et al., 2009a,b). Results indicate the most underrepresented genes in the library are involved in cell adhesion and genes involved in DNA and protein metabolism were most prevalent in the MBD-library.\n" ], "offsets": [ [ 0, 810 ] ] } ]

[ { "id": "PMC-3249382-caption-01_T1", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 707, 711 ] ], "normalized": [] } ]

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[ { "id": "PMID-1377534__text", "type": "abstract", "text": [ "Angiogenesis--biomedical technology.\nAll of these studies show that angiogenesis research can benefit from new biomedical technology tools currently being developed, as well as contribute by providing new technologies that can be used in other areas of medicine. It is hoped that the chapters in this book in this area will provide the reader with an up-to-date appreciation of some of the exciting research that is currently being pursued.\n" ], "offsets": [ [ 0, 441 ] ] } ]

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[ { "id": "PMID-21617625__text", "type": "abstract", "text": [ "Non-heart-beating organ donation in Italy.\nIn 2007 the non-heart-beating organ donation (NHBD) \"Programma Alba\" (Sunrise Programme) started in Pavia, Italy. The initial plan was to cut down waiting list for kidney transplantation, while its final aim is to shorten organ transplantation waiting lists. When compared to European countries and the USA, the Italian NHBD program has taken longer to get established. Initially Italian physicians were not entirely aware of the NHBD organ viability for transplantation, furthermore ethical issues and the need to regulate medical requirements to Italian law slowed down the NHBD program. In particular, Italian legislation provides for death ascertainment after irreversible cardiac arrest, 20-minute flat electrocardiogram. This no-touch period is longer when compared to worldwide legislation, and organ viability has been a main concern for Italian transplant doctors over the years. However, recent data let up to 40-minute warm ischemia time to preserve organ viability; this has encouraged Pavia's group to establish the NHBD \"Programma Alba\". It was designed according to Italian legislation from death diagnosis to graft placement, from this perspective must the significant role of the Transplant coordinator be recognized. Since 2007 seven kidneys have been gathered from seven NHBD. Of these, six NHBD kidneys have been transplanted. Currently, four patients are out of dialysis. This report is a detailed description of NHBD \"Programma Alba\" and its preliminary results.\n" ], "offsets": [ [ 0, 1528 ] ] } ]

[ { "id": "PMID-21617625_T1", "type": "Organ", "text": [ "heart" ], "offsets": [ [ 4, 9 ] ], "normalized": [] }, { "id": "PMID-21617625_T2", "type": "Organ", "text": [ "organ" ], "offsets": [ [ 18, 23 ] ], "normalized": [] }, { "id": "PMID-21617625_T3", "type": "Organ", "text": [ "heart" ], "offsets": [ [ 59, 64 ] ], "normalized": [] }, { "id": "PMID-21617625_T4", "type": "Organ", "text": [ "organ" ], "offsets": [ [ 73, 78 ] ], "normalized": [] }, { "id": "PMID-21617625_T5", "type": "Organ", "text": [ "kidney" ], "offsets": [ [ 207, 213 ] ], "normalized": [] }, { "id": "PMID-21617625_T6", "type": "Organ", "text": [ "organ" ], "offsets": [ [ 265, 270 ] ], "normalized": [] }, { "id": "PMID-21617625_T7", "type": "Organ", "text": [ "organ" ], "offsets": [ [ 478, 483 ] ], "normalized": [] }, { "id": "PMID-21617625_T8", "type": "Organ", "text": [ "cardiac" ], "offsets": [ [ 720, 727 ] ], "normalized": [] }, { "id": "PMID-21617625_T9", "type": "Organ", "text": [ "graft" ], "offsets": [ [ 1168, 1173 ] ], "normalized": [] }, { "id": "PMID-21617625_T10", "type": "Organ", "text": [ "kidneys" ], "offsets": [ [ 1295, 1302 ] ], "normalized": [] }, { "id": "PMID-21617625_T11", "type": "Organ", "text": [ "kidneys" ], "offsets": [ [ 1358, 1365 ] ], "normalized": [] }, { "id": "PMID-21617625_T12", "type": "Organ", "text": [ "organ" ], "offsets": [ [ 1004, 1009 ] ], "normalized": [] }, { "id": "PMID-21617625_T13", "type": "Organ", "text": [ "organ" ], "offsets": [ [ 845, 850 ] ], "normalized": [] } ]

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[ { "id": "PMID-16463019__text", "type": "abstract", "text": [ "L-Carnitine ameliorates methotrexate-induced oxidative organ injury and inhibits leukocyte death. \nMethotrexate (MTX), a folic acid antagonist widely used for the treatment of a variety of tumors and inflammatory diseases, affects normal tissues that have a high rate of proliferation, including the hematopoietic cells of the bone marrow and the gastrointestinal mucosal cells. To elucidate the role of free radicals and leukocytes in MTX-induced oxidative organ damage and the putative protective effect of L-carnitine (L-Car), Wistar albino rats were administered a single dose of MTX (20 mg/kg) followed by either saline or L-Car (500 mg/kg) for 5 days. After decapitation of the rats, trunk blood was obtained, and the ileum, liver, and kidney were removed for histological examination and for the measurement of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, and collagen content. Our results showed that MTX administration increased the MDA and MPO activities and collagen content and decreased GSH levels in all tissues, while these alterations were reversed in L-Car-treated group. The elevated serum TNF-alpha level observed following MTX treatment was depressed with L-Car. The oxidative burst of neutrophils stimulated by Annexin V was reduced in the saline-treated MTX group, while L-Car abolished this inhibition. Similarly, flow cytometric measurements revealed that leukocyte apoptosis was increased in MTX-treated animals, while L-Car reversed these effects. Severe degeneration of the intestinal mucosa, liver parenchyma, and glomerular and tubular epithelium observed in the saline-treated MTX group was improved by L-Car treatment. These results suggest that L-Car, possibly via its free radical scavenging and antioxidant properties, ameliorates MTX-induced oxidative organ injury and inhibits leukocyte apoptosis. Thus, supplementation with L-Carnitine as an adjuvant therapy may be promising in alleviating the systemic side-effects of chemotherapeutics.\n" ], "offsets": [ [ 0, 2015 ] ] } ]

[ { "id": "PMID-16463019_T3", "type": "Organ", "text": [ "organ" ], "offsets": [ [ 55, 60 ] ], "normalized": [] }, { "id": "PMID-16463019_T4", "type": "Cell", "text": [ "leukocyte" ], "offsets": [ [ 81, 90 ] ], "normalized": [] }, { "id": "PMID-16463019_T8", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 189, 195 ] ], "normalized": [] }, { "id": "PMID-16463019_T9", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 238, 245 ] ], "normalized": [] }, { "id": "PMID-16463019_T10", "type": "Cell", "text": [ "hematopoietic cells" ], "offsets": [ [ 300, 319 ] ], "normalized": [] }, { "id": "PMID-16463019_T11", "type": "Multi-tissue_structure", "text": [ "bone marrow" ], "offsets": [ [ 327, 338 ] ], "normalized": [] }, { "id": "PMID-16463019_T12", "type": "Cell", "text": [ "gastrointestinal mucosal cells" ], "offsets": [ [ 347, 377 ] ], "normalized": [] }, { "id": "PMID-16463019_T13", "type": "Cell", "text": [ "leukocytes" ], "offsets": [ [ 422, 432 ] ], "normalized": [] }, { "id": "PMID-16463019_T15", "type": "Organ", "text": [ "organ" ], "offsets": [ [ 458, 463 ] ], "normalized": [] }, { "id": "PMID-16463019_T23", "type": "Organism_substance", "text": [ "trunk blood" ], "offsets": [ [ 690, 701 ] ], "normalized": [] }, { "id": "PMID-16463019_T24", "type": "Multi-tissue_structure", "text": [ "ileum" ], "offsets": [ [ 724, 729 ] ], "normalized": [] }, { "id": "PMID-16463019_T25", "type": "Organ", "text": [ "liver" ], "offsets": [ [ 731, 736 ] ], "normalized": [] }, { "id": "PMID-16463019_T26", "type": "Organ", "text": [ "kidney" ], "offsets": [ [ 742, 748 ] ], "normalized": [] }, { "id": "PMID-16463019_T39", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 1057, 1064 ] ], "normalized": [] }, { "id": "PMID-16463019_T41", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 1141, 1146 ] ], "normalized": [] }, { "id": "PMID-16463019_T45", "type": "Cell", "text": [ "neutrophils" ], "offsets": [ [ 1245, 1256 ] ], "normalized": [] }, { "id": "PMID-16463019_T50", "type": "Cell", "text": [ "leukocyte" ], "offsets": [ [ 1419, 1428 ] ], "normalized": [] }, { "id": "PMID-16463019_T53", "type": "Multi-tissue_structure", "text": [ "intestinal mucosa" ], "offsets": [ [ 1540, 1557 ] ], "normalized": [] }, { "id": "PMID-16463019_T54", "type": "Multi-tissue_structure", "text": [ "liver parenchyma" ], "offsets": [ [ 1559, 1575 ] ], "normalized": [] }, { "id": "PMID-16463019_T55", "type": "Tissue", "text": [ "glomerular" ], "offsets": [ [ 1581, 1591 ] ], "normalized": [] }, { "id": "PMID-16463019_T56", "type": "Tissue", "text": [ "tubular epithelium" ], "offsets": [ [ 1596, 1614 ] ], "normalized": [] }, { "id": "PMID-16463019_T62", "type": "Organ", "text": [ "organ" ], "offsets": [ [ 1826, 1831 ] ], "normalized": [] }, { "id": "PMID-16463019_T63", "type": "Cell", "text": [ "leukocyte" ], "offsets": [ [ 1852, 1861 ] ], "normalized": [] } ]

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[ { "id": "PMC-2804691-sec-05__text", "type": "sec", "text": [ "Background\nRefractive outcomes have become an increasingly important part of cataract surgery and the limbal relaxing incision (LRI) has been shown to be a safe and effective procedure to reduce astigmatism [1-4]. Currently, ophthalmic surgeons have only two material choices for knives to perform limbal relaxing incision, diamond and metal. BD (Becton, Dickinson and Company), Franklin Lakes, NJ has developed a safety engineered, single use, uni-directional cutting silicon knife for these incisions. Previous research has suggested that the silicon BD Atomic Edge(TM) knife has superior performance characteristics when compared to a metal knife and performance similar to diamond knife when making various incisions [5,6]. This study was designed to determine the performance characteristics of silicon accurate depth knives in comparison to diamond LRI knives and steel accurate depth knives in five performance characteristics.\n" ], "offsets": [ [ 0, 935 ] ] } ]

[ { "id": "PMC-2804691-sec-05_T1", "type": "Multi-tissue_structure", "text": [ "limbal" ], "offsets": [ [ 102, 108 ] ], "normalized": [] }, { "id": "PMC-2804691-sec-05_T2", "type": "Multi-tissue_structure", "text": [ "limbal" ], "offsets": [ [ 298, 304 ] ], "normalized": [] } ]

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[ { "id": "PMID-20808831__text", "type": "abstract", "text": [ "Constitutively nuclear FOXO3a localization predicts poor survival and promotes Akt phosphorylation in breast cancer. \nBACKGROUND: The PI3K-Akt signal pathway plays a key role in tumorigenesis and the development of drug-resistance. Cytotoxic chemotherapy resistance is linked to limited therapeutic options and poor prognosis. METHODOLOGY/PRINCIPAL FINDINGS: Examination of FOXO3a and phosphorylated-Akt (P-Akt) expression in breast cancer tissue microarrays showed nuclear FOXO3a was associated with lymph node positivity (p = 0.052), poor prognosis (p = 0.014), and P-Akt expression in invasive ductal carcinoma. Using tamoxifen and doxorubicin-sensitive and -resistant breast cancer cell lines as models, we found that doxorubicin- but not tamoxifen-resistance is associated with nuclear accumulation of FOXO3a, consistent with the finding that sustained nuclear FOXO3a is associated with poor prognosis. We also established that doxorubicin treatment induces proliferation arrest and FOXO3a nuclear relocation in sensitive breast cancer cells. Induction of FOXO3a activity in doxorubicin-sensitive MCF-7 cells was sufficient to promote Akt phosphorylation and arrest cell proliferation. Conversely, knockdown of endogenous FOXO3a expression reduced PI3K/Akt activity. Using MDA-MB-231 cells, in which FOXO3a activity can be induced by 4-hydroxytamoxifen, we showed that FOXO3a induction up-regulates PI3K-Akt activity and enhanced doxorubicin resistance. However FOXO3a induction has little effect on cell proliferation, indicating that FOXO3a or its downstream activity is deregulated in the cytotoxic drug resistant breast cancer cells. Thus, our results suggest that sustained FOXO3a activation can enhance hyperactivation of the PI3K/Akt pathway. CONCLUSIONS/SIGNIFICANCE: Together these data suggest that lymph node metastasis and poor survival in invasive ductal breast carcinoma are linked to an uncoupling of the Akt-FOXO3a signaling axis. In these breast cancers activated Akt fails to inactivate and re-localize FOXO3a to the cytoplasm, and nuclear-targeted FOXO3a does not induce cell death or cell cycle arrest. As such, sustained nuclear FOXO3a expression in breast cancer may culminate in cancer progression and the development of an aggressive phenotype similar to that observed in cytotoxic chemotherapy resistant breast cancer cell models.\n" ], "offsets": [ [ 0, 2361 ] ] } ]

[ { "id": "PMID-20808831_T1", "type": "Cellular_component", "text": [ "nuclear" ], "offsets": [ [ 15, 22 ] ], "normalized": [] }, { "id": "PMID-20808831_T4", "type": "Cancer", "text": [ "breast cancer" ], "offsets": [ [ 102, 115 ] ], "normalized": [] }, { "id": "PMID-20808831_T10", "type": "Cancer", "text": [ "breast cancer tissue" ], "offsets": [ [ 426, 446 ] ], "normalized": [] }, { "id": "PMID-20808831_T11", "type": "Cellular_component", "text": [ "nuclear" ], "offsets": [ [ 466, 473 ] ], "normalized": [] }, { "id": "PMID-20808831_T13", "type": "Multi-tissue_structure", "text": [ "lymph node" ], "offsets": [ [ 501, 511 ] ], "normalized": [] }, { "id": "PMID-20808831_T15", "type": "Cancer", "text": [ "invasive ductal carcinoma" ], "offsets": [ [ 588, 613 ] ], "normalized": [] }, { "id": "PMID-20808831_T18", "type": "Cell", "text": [ "breast cancer cell lines" ], "offsets": [ [ 672, 696 ] ], "normalized": [] }, { "id": "PMID-20808831_T21", "type": "Cellular_component", "text": [ "nuclear" ], "offsets": [ [ 783, 790 ] ], "normalized": [] }, { "id": "PMID-20808831_T23", "type": "Cellular_component", "text": [ "nuclear" ], "offsets": [ [ 858, 865 ] ], "normalized": [] }, { "id": "PMID-20808831_T27", "type": "Cellular_component", "text": [ "nuclear" ], "offsets": [ [ 995, 1002 ] ], "normalized": [] }, { "id": "PMID-20808831_T28", "type": "Cell", "text": [ "breast cancer cells" ], "offsets": [ [ 1027, 1046 ] ], "normalized": [] }, { "id": "PMID-20808831_T31", "type": "Cell", "text": [ "MCF-7 cells" ], "offsets": [ [ 1102, 1113 ] ], "normalized": [] }, { "id": "PMID-20808831_T33", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1171, 1175 ] ], "normalized": [] }, { "id": "PMID-20808831_T37", "type": "Cell", "text": [ "MDA-MB-231 cells" ], "offsets": [ [ 1278, 1294 ] ], "normalized": [] }, { "id": "PMID-20808831_T45", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1505, 1509 ] ], "normalized": [] }, { "id": "PMID-20808831_T47", "type": "Cell", "text": [ "breast cancer cells" ], "offsets": [ [ 1622, 1641 ] ], "normalized": [] }, { "id": "PMID-20808831_T51", "type": "Multi-tissue_structure", "text": [ "lymph node" ], "offsets": [ [ 1814, 1824 ] ], "normalized": [] }, { "id": "PMID-20808831_T52", "type": "Cancer", "text": [ "invasive ductal breast carcinoma" ], "offsets": [ [ 1857, 1889 ] ], "normalized": [] }, { "id": "PMID-20808831_T55", "type": "Cancer", "text": [ "breast cancers" ], "offsets": [ [ 1961, 1975 ] ], "normalized": [] }, { "id": "PMID-20808831_T58", "type": "Organism_substance", "text": [ "cytoplasm" ], "offsets": [ [ 2040, 2049 ] ], "normalized": [] }, { "id": "PMID-20808831_T59", "type": "Cellular_component", "text": [ "nuclear" ], "offsets": [ [ 2055, 2062 ] ], "normalized": [] }, { "id": "PMID-20808831_T61", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 2095, 2099 ] ], "normalized": [] }, { "id": "PMID-20808831_T62", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 2109, 2113 ] ], "normalized": [] }, { "id": "PMID-20808831_T63", "type": "Cellular_component", "text": [ "nuclear" ], "offsets": [ [ 2147, 2154 ] ], "normalized": [] }, { "id": "PMID-20808831_T65", "type": "Cancer", "text": [ "breast cancer" ], "offsets": [ [ 2176, 2189 ] ], "normalized": [] }, { "id": "PMID-20808831_T66", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 2207, 2213 ] ], "normalized": [] }, { "id": "PMID-20808831_T67", "type": "Cell", "text": [ "breast cancer cell" ], "offsets": [ [ 2334, 2352 ] ], "normalized": [] } ]

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[ { "id": "PMID-15542670__text", "type": "abstract", "text": [ "Human cytomegalovirus 5-kilobase immediate-early RNA is a stable intron.\nImmediate-early viral gene products of human cytomegalovirus (HCMV) are derived from several genomic loci and largely serve to establish a cellular environment conducive to viral replication. We have further examined an unusual immediate-early transcript known as the 5-kb RNA, concluding that it is a stable intron encoded by HCMV. The 5-kb RNA is highly AT rich in sequence and lacks open reading frames likely to be translated into protein. We confirmed the absence of polyadenylation of the transcript and showed that it is primarily nuclear localized during viral infection. We mapped the 5' end of the 5-kb RNA to a consensus splice donor site and localized the 3' end in the vicinity of a splice acceptor site. In transfection studies, we showed that the 5-kb RNA can be spliced from a heterologous primary transcript. Using bacterial artificial chromosome technology, we constructed a viral recombinant containing a mutation in the 5' splice donor site that defines the 5' end of the RNA and found that this mutation eliminates expression of the 5-kb RNA during viral infection. This mutant grows in human fibroblasts without complementation. Taken together, these data support the conclusion that the 5-kb RNA is a stable intron expressed by HCMV.\n" ], "offsets": [ [ 0, 1330 ] ] } ]

[ { "id": "PMID-15542670_T1", "type": "Cellular_component", "text": [ "nuclear" ], "offsets": [ [ 611, 618 ] ], "normalized": [] }, { "id": "PMID-15542670_T2", "type": "Cellular_component", "text": [ "chromosome" ], "offsets": [ [ 926, 936 ] ], "normalized": [] }, { "id": "PMID-15542670_T3", "type": "Cell", "text": [ "fibroblasts" ], "offsets": [ [ 1187, 1198 ] ], "normalized": [] }, { "id": "PMID-15542670_T4", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 212, 220 ] ], "normalized": [] } ]

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[ { "id": "PMID-8898364__text", "type": "abstract", "text": [ "Induction of p18INK4c and its predominant association with CDK4 and CDK6 during myogenic differentiation.\nTerminal cell differentiation involves permanent withdrawal from the cell division cycle. The inhibitors of cyclin-dependent kinases (CDKs) are potential molecules functioning to couple cell cycle arrest and cell differentiation. In murine C2C12 myoblast cells, G1 CDK enzymes (CDK2, CDK4, and CDK6) associate with four CDK inhibitors: p18INK4c, p19INK4d, p21, and p27Kip1. During induced myogenesis, p21 and its associated CDK proteins underwent an initial increase followed by a decrease as cells became terminally differentiated. The level of p27 protein gradually increased, but the amount of total associated CDK proteins remained unchanged. p19 protein decreased gradually during differentiation, as did its associated CDK4 protein. In contrast, p18 protein increased 50-fold, from negligible levels in proliferating myoblasts to clearly detectable levels within 8-12 h of myogenic induction. This initial rise was followed by a precipitous increase between 12 and 24 h postinduction, with p18 protein finally accumulating to its highest level in terminally differentiated cells. Induction of p18 correlated with increased and sequential complex formation--first increasing association with CDK6 and then with CDK4 over the course of myogenic differentiation. All of the CDK6 and half of the CDK4 were complexed with p18 in terminally differentiated C2C12 cells as well as in adult mouse muscle tissue. Finally, kinase activity of CDK2 and CDK4 decreases as C2C12 cells differentiate, whereas the CDK6 kinase activity is low in both proliferating myoblasts and differentiated myotubes. Our results indicate that p18 may play a critical role in causing and/or maintaining permanent cell cycle arrest associated with mature muscle formation.\n" ], "offsets": [ [ 0, 1852 ] ] } ]

[ { "id": "PMID-8898364_T1", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 115, 119 ] ], "normalized": [] }, { "id": "PMID-8898364_T2", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 175, 179 ] ], "normalized": [] }, { "id": "PMID-8898364_T3", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 292, 296 ] ], "normalized": [] }, { "id": "PMID-8898364_T4", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 314, 318 ] ], "normalized": [] }, { "id": "PMID-8898364_T5", "type": "Cell", "text": [ "C2C12 myoblast cells" ], "offsets": [ [ 346, 366 ] ], "normalized": [] }, { "id": "PMID-8898364_T6", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 599, 604 ] ], "normalized": [] }, { "id": "PMID-8898364_T7", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1185, 1190 ] ], "normalized": [] }, { "id": "PMID-8898364_T8", "type": "Cell", "text": [ "C2C12 cells" ], "offsets": [ [ 1462, 1473 ] ], "normalized": [] }, { "id": "PMID-8898364_T9", "type": "Tissue", "text": [ "muscle tissue" ], "offsets": [ [ 1500, 1513 ] ], "normalized": [] }, { "id": "PMID-8898364_T10", "type": "Cell", "text": [ "C2C12 cells" ], "offsets": [ [ 1570, 1581 ] ], "normalized": [] }, { "id": "PMID-8898364_T11", "type": "Cell", "text": [ "myoblasts" ], "offsets": [ [ 1659, 1668 ] ], "normalized": [] }, { "id": "PMID-8898364_T12", "type": "Tissue", "text": [ "myotubes" ], "offsets": [ [ 1688, 1696 ] ], "normalized": [] }, { "id": "PMID-8898364_T13", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1793, 1797 ] ], "normalized": [] }, { "id": "PMID-8898364_T14", "type": "Tissue", "text": [ "muscle" ], "offsets": [ [ 1834, 1840 ] ], "normalized": [] }, { "id": "PMID-8898364_T15", "type": "Cell", "text": [ "myoblasts" ], "offsets": [ [ 929, 938 ] ], "normalized": [] } ]

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[ { "id": "PMID-8455978__text", "type": "abstract", "text": [ "[Prehospital service in Denmark].\nIn Denmark, emergency ambulances are dispatched by 41 centres manned either by trained firemen (in Copenhagen) or policemen (outside Copenhagen). In 1990, emergency ambulance calls totalled 284,000. Utilisation of emergency ambulance services increases with urbanisation. A doctor-manned ambulance is in operation in Copenhagen, and in some other large towns anaesthesiology and intensive care teams can be dispatched from hospital to give on-the-spot care. In less populated areas, some general practitioners give advanced life-support. Although many areas are serviced by ambulances equipped with defibrillators, the majority of patients receive only basic life-support from ambulance personnel. New initiatives resulting from a recent report by a commission appointed by central authorities, and focused on prehospital treatment, are expected to improve the service by raising the level of training given to ambulance personnel.\n" ], "offsets": [ [ 0, 966 ] ] } ]

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[ { "id": "PMID-19637749__text", "type": "abstract", "text": [ "[Ambiguity role of neutrophils in oncogenesis]\nThe review is focused on the participation of polymorphonuclear granulocytes (neutrophils) in development and spreading of a tumor. We consider both the well known functions of neutrophils (degranulation, production of reactive oxygen species (ROS)) and the recently shown one (presentation of an antigene). The special attention is focused on the ambiguity of the neutrophil role in oncogenesis. The dominant view is that neutrophils display exclusively antitumor properties. The update information testifies about protumoral activity of neutrophils: they migrate to a tumor and promote angiogenesis and metastasis at late stages of the tumor. It is interesting that certain components of neutrophil cytotoxic arsenal (ROS, cytokines, specific enzymes) participate both in antitumoral defenses of an organism and protumoral activity.\n" ], "offsets": [ [ 0, 882 ] ] } ]

[ { "id": "PMID-19637749_T1", "type": "Cell", "text": [ "neutrophils" ], "offsets": [ [ 19, 30 ] ], "normalized": [] }, { "id": "PMID-19637749_T2", "type": "Cell", "text": [ "polymorphonuclear granulocytes" ], "offsets": [ [ 93, 123 ] ], "normalized": [] }, { "id": "PMID-19637749_T3", "type": "Cell", "text": [ "neutrophils" ], "offsets": [ [ 125, 136 ] ], "normalized": [] }, { "id": "PMID-19637749_T4", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 172, 177 ] ], "normalized": [] }, { "id": "PMID-19637749_T5", "type": "Cell", "text": [ "neutrophils" ], "offsets": [ [ 224, 235 ] ], "normalized": [] }, { "id": "PMID-19637749_T8", "type": "Cell", "text": [ "neutrophil" ], "offsets": [ [ 412, 422 ] ], "normalized": [] }, { "id": "PMID-19637749_T9", "type": "Cell", "text": [ "neutrophils" ], "offsets": [ [ 470, 481 ] ], "normalized": [] }, { "id": "PMID-19637749_T10", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 506, 511 ] ], "normalized": [] }, { "id": "PMID-19637749_T11", "type": "Cancer", "text": [ "tumoral" ], "offsets": [ [ 566, 573 ] ], "normalized": [] }, { "id": "PMID-19637749_T12", "type": "Cell", "text": [ "neutrophils" ], "offsets": [ [ 586, 597 ] ], "normalized": [] }, { "id": "PMID-19637749_T13", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 617, 622 ] ], "normalized": [] }, { "id": "PMID-19637749_T14", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 685, 690 ] ], "normalized": [] }, { "id": "PMID-19637749_T15", "type": "Cell", "text": [ "neutrophil" ], "offsets": [ [ 737, 747 ] ], "normalized": [] }, { "id": "PMID-19637749_T17", "type": "Cancer", "text": [ "tumoral" ], "offsets": [ [ 825, 832 ] ], "normalized": [] }, { "id": "PMID-19637749_T18", "type": "Cancer", "text": [ "tumoral" ], "offsets": [ [ 864, 871 ] ], "normalized": [] } ]

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[ { "id": "PMC-2673029-caption-03__text", "type": "caption", "text": [ "Secchi depth in the Baltic Proper, June-August, 1957-1998.\nNumber of data: 3,452.\n" ], "offsets": [ [ 0, 82 ] ] } ]

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[ { "id": "PMC-2192393-sec-06__text", "type": "sec", "text": [ "Cytology and Histology\nFor semithin sections, embryoid bodies were washed twice in PBS, fixed in 4% paraformaldehyde at 4degreesC overnight, and after dehydration in ethanol were embedded in JB-4 resin (Polysciences, Inc.). 1-4-mum sections were cut with a glass knife. For cytology, the sections were stained with toluidine blue. In cell mixing experiments, the embryoid bodies were prefixed and stained for beta-galactosidase and the sections were counterstained with neutral red. Teratocarcinomas were fixed in Bouin fixative, embedded in Paraplast, and the sections were stained with hematoxylin and eosin. Microphotography was with a ZEISS Axiomat microscope. Films were scanned and figures were prepared with Photoshop 5.5 software.\n" ], "offsets": [ [ 0, 739 ] ] } ]

[ { "id": "PMC-2192393-sec-06_T1", "type": "Developing_anatomical_structure", "text": [ "embryoid bodies" ], "offsets": [ [ 46, 61 ] ], "normalized": [] }, { "id": "PMC-2192393-sec-06_T2", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 334, 338 ] ], "normalized": [] }, { "id": "PMC-2192393-sec-06_T3", "type": "Developing_anatomical_structure", "text": [ "embryoid bodies" ], "offsets": [ [ 363, 378 ] ], "normalized": [] }, { "id": "PMC-2192393-sec-06_T4", "type": "Multi-tissue_structure", "text": [ "sections" ], "offsets": [ [ 232, 240 ] ], "normalized": [] }, { "id": "PMC-2192393-sec-06_T5", "type": "Multi-tissue_structure", "text": [ "sections" ], "offsets": [ [ 36, 44 ] ], "normalized": [] }, { "id": "PMC-2192393-sec-06_T6", "type": "Multi-tissue_structure", "text": [ "sections" ], "offsets": [ [ 288, 296 ] ], "normalized": [] }, { "id": "PMC-2192393-sec-06_T7", "type": "Multi-tissue_structure", "text": [ "sections" ], "offsets": [ [ 436, 444 ] ], "normalized": [] }, { "id": "PMC-2192393-sec-06_T8", "type": "Multi-tissue_structure", "text": [ "sections" ], "offsets": [ [ 561, 569 ] ], "normalized": [] } ]

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[ { "id": "PMID-10805736__text", "type": "abstract", "text": [ "Neoplastic transformation by Notch requires nuclear localization. \nNotch proteins are plasma membrane-spanning receptors that mediate important cell fate decisions such as differentiation, proliferation, and apoptosis. The mechanism of Notch signaling remains poorly understood. However, it is clear that the Notch signaling pathway mediates its effects through intercellular contact between neighboring cells. The prevailing model for Notch signaling suggests that ligand, presented on a neighboring cell, triggers proteolytic processing of Notch. Following proteolysis, it is thought that the intracellular portion of Notch (N(ic)) translocates to the nucleus, where it is involved in regulating gene expression. There is considerable debate concerning where in the cell Notch functions and what proteins serve as effectors of the Notch signal. Several Notch genes have clearly been shown to be proto-oncogenes in mammalian cells. Activation of Notch proto-oncogenes has been associated with tumorigenesis in several human and other mammalian cancers. Transforming alleles of Notch direct the expression of truncated proteins that primarily consist of N(ic) and are not tethered to the plasma membrane. However, the mechanism by which Notch oncoproteins (generically termed here as N(ic)) induce neoplastic transformation is not known. Previously we demonstrated that N1(ic) and N2(ic) could transform E1A immortalized baby rat kidney cells (RKE) in vitro. We now report direct evidence that N1(ic) must accumulate in the nucleus to induce transformation of RKE cells. In addition, we define the minimal domain of N1(ic) required to induce transformation and present evidence that transformation of RKE cells by N1(ic) is likely to be through a CBF1-independent pathway.\n" ], "offsets": [ [ 0, 1773 ] ] } ]

[ { "id": "PMID-10805736_T2", "type": "Cellular_component", "text": [ "nuclear" ], "offsets": [ [ 44, 51 ] ], "normalized": [] }, { "id": "PMID-10805736_T4", "type": "Cellular_component", "text": [ "plasma membrane" ], "offsets": [ [ 86, 101 ] ], "normalized": [] }, { "id": "PMID-10805736_T5", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 144, 148 ] ], "normalized": [] }, { "id": "PMID-10805736_T8", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 404, 409 ] ], "normalized": [] }, { "id": "PMID-10805736_T10", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 501, 505 ] ], "normalized": [] }, { "id": "PMID-10805736_T12", "type": "Immaterial_anatomical_entity", "text": [ "intracellular" ], "offsets": [ [ 595, 608 ] ], "normalized": [] }, { "id": "PMID-10805736_T15", "type": "Cellular_component", "text": [ "nucleus" ], "offsets": [ [ 654, 661 ] ], "normalized": [] }, { "id": "PMID-10805736_T16", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 768, 772 ] ], "normalized": [] }, { "id": "PMID-10805736_T20", "type": "Cell", "text": [ "mammalian cells" ], "offsets": [ [ 916, 931 ] ], "normalized": [] }, { "id": "PMID-10805736_T23", "type": "Cancer", "text": [ "mammalian cancers" ], "offsets": [ [ 1035, 1052 ] ], "normalized": [] }, { "id": "PMID-10805736_T26", "type": "Cellular_component", "text": [ "plasma membrane" ], "offsets": [ [ 1188, 1203 ] ], "normalized": [] }, { "id": "PMID-10805736_T33", "type": "Cell", "text": [ "kidney cells" ], "offsets": [ [ 1430, 1442 ] ], "normalized": [] }, { "id": "PMID-10805736_T34", "type": "Cell", "text": [ "RKE" ], "offsets": [ [ 1444, 1447 ] ], "normalized": [] }, { "id": "PMID-10805736_T36", "type": "Cellular_component", "text": [ "nucleus" ], "offsets": [ [ 1524, 1531 ] ], "normalized": [] }, { "id": "PMID-10805736_T37", "type": "Cell", "text": [ "RKE cells" ], "offsets": [ [ 1560, 1569 ] ], "normalized": [] }, { "id": "PMID-10805736_T39", "type": "Cell", "text": [ "RKE cells" ], "offsets": [ [ 1701, 1710 ] ], "normalized": [] }, { "id": "PMID-10805736_T1", "type": "Cancer", "text": [ "Neoplastic" ], "offsets": [ [ 0, 10 ] ], "normalized": [] }, { "id": "PMID-10805736_T3", "type": "Cancer", "text": [ "neoplastic" ], "offsets": [ [ 1298, 1308 ] ], "normalized": [] }, { "id": "PMID-10805736_T6", "type": "Immaterial_anatomical_entity", "text": [ "intercellular" ], "offsets": [ [ 362, 375 ] ], "normalized": [] } ]

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[ { "id": "PMC-2903584-sec-40__text", "type": "sec", "text": [ "Treatment for patients with diabetes\nIt is notable that treatment of diabetes has not been directly monitored by OECD indicators, largely due to complexity in data collection. Treatment is tailored for individuals depending on the patient's disease status, and plays a crucial role in diabetes management. Clinical trials have found that a one percentage point reduction in HbA1c levels would reduce micro-vascular complications by 25% to 30% [49,50] and a 10 mmHg reduction in blood pressure would decrease macro- and micro-vascular complications and death rates by 32% [51]. Improved control of blood lipids can reduce risk of coronary heart disease by 39% and risk of death by 43% [52].\nRAND's Quality Assessment Tools System offers indicators relating to diabetes treatment [53], and application of these indicators in a national study in the US has provided insight into adherence to recommended treatment regimens. For people with newly diagnosed diabetes 56% received dietary and exercise counselling. In type 2 diabetes patients, use of oral hypoglycaemic agents for those inadequately controlled on dietary therapy was 38% and use of insulin for those inadequately controlled on oral hypoglycaemics was 39%. Fifty-five percent of diabetics were offered an ACE inhibitor within 3 months of the notation of proteinuria unless contraindicated.\nThe AusDiab study reported the treatment pattern among Australian adults with type 2 diabetes [37]. While 32% of diabetes patients were on diet regimen only, 58% used oral hypoglycaemic agents and diet only, and another 10% took insulin. Bailie and colleagues reported pharmaceutical interventions for diabetes patients in remote Aboriginal communities in the Northern Territory [54]. During the 3-years study period, 75-79% of Aboriginal patients took oral hypoglycaemic agents, and 4-7% used insulin.\n" ], "offsets": [ [ 0, 1853 ] ] } ]

[ { "id": "PMC-2903584-sec-40_T1", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 406, 414 ] ], "normalized": [] }, { "id": "PMC-2903584-sec-40_T2", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 478, 483 ] ], "normalized": [] }, { "id": "PMC-2903584-sec-40_T3", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 525, 533 ] ], "normalized": [] }, { "id": "PMC-2903584-sec-40_T4", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 597, 602 ] ], "normalized": [] }, { "id": "PMC-2903584-sec-40_T5", "type": "Multi-tissue_structure", "text": [ "coronary" ], "offsets": [ [ 629, 637 ] ], "normalized": [] }, { "id": "PMC-2903584-sec-40_T6", "type": "Organ", "text": [ "heart" ], "offsets": [ [ 638, 643 ] ], "normalized": [] }, { "id": "PMC-2903584-sec-40_T8", "type": "Organism_substance", "text": [ "proteinuria" ], "offsets": [ [ 1314, 1325 ] ], "normalized": [] }, { "id": "PMC-2903584-sec-40_T7", "type": "Organism_subdivision", "text": [ "oral" ], "offsets": [ [ 1045, 1049 ] ], "normalized": [] }, { "id": "PMC-2903584-sec-40_T9", "type": "Organism_subdivision", "text": [ "oral" ], "offsets": [ [ 1188, 1192 ] ], "normalized": [] }, { "id": "PMC-2903584-sec-40_T10", "type": "Organism_subdivision", "text": [ "oral" ], "offsets": [ [ 1517, 1521 ] ], "normalized": [] }, { "id": "PMC-2903584-sec-40_T11", "type": "Organism_subdivision", "text": [ "oral" ], "offsets": [ [ 1803, 1807 ] ], "normalized": [] } ]

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[ { "id": "PMC-2840784-sec-02__text", "type": "sec", "text": [ "CASE:\nHere for the first time a case of CDLS from Iran, a 15-week-old male infant who was refereed as a case of multiple congenital anomalies. Clinical investigation showed that the child was a case of CDLS.\n" ], "offsets": [ [ 0, 208 ] ] } ]

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[ { "id": "PMC-2579698-caption-02__text", "type": "caption", "text": [ "Characteristics of cases with childhood leukaemia (n=162) and matched controls (n=2125), all registered within 3 months of birth\n" ], "offsets": [ [ 0, 129 ] ] } ]

[ { "id": "PMC-2579698-caption-02_T1", "type": "Cancer", "text": [ "childhood leukaemia" ], "offsets": [ [ 30, 49 ] ], "normalized": [] } ]

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[ { "id": "PMID-18425334__text", "type": "abstract", "text": [ "MMTV-cre-mediated fur inactivation concomitant with PLAG1 proto-oncogene activation delays salivary gland tumorigenesis in mice. \nProprotein convertases are serine endoproteases implicated in the proteolytic processing of a large variety of regulatory proteins. An important role of proprotein convertases in tumorigenic processes has been suggested by various studies. In this study, the role of the proprotein convertase furin in PLAG1 proto-oncogene-induced salivary gland tumorigenesis was investigated. PLAG1 overexpression in salivary glands has previously been shown to result in salivary gland tumors in 100% of mice within 5 weeks after birth. MMTV-cre-mediated inactivation of fur without over-expression of PLAG1 caused smaller but histologically normal salivary glands. Moreover, the lymph nodes close to the salivary glands were enlarged, and histology showed that they had activated follicles. When genetic ablation of 1 or 2 alleles of fur and overexpression of the PLAG1 transgene were simultaneously achieved, a significant delay in tumorigenesis was observed. Collectively, these results suggest an important role for furin in PLAG1-induced salivary gland tumorigenesis in mice.\n" ], "offsets": [ [ 0, 1197 ] ] } ]

[ { "id": "PMID-18425334_T5", "type": "Multi-tissue_structure", "text": [ "salivary gland" ], "offsets": [ [ 91, 105 ] ], "normalized": [] }, { "id": "PMID-18425334_T10", "type": "Multi-tissue_structure", "text": [ "salivary gland" ], "offsets": [ [ 461, 475 ] ], "normalized": [] }, { "id": "PMID-18425334_T12", "type": "Organ", "text": [ "salivary glands" ], "offsets": [ [ 532, 547 ] ], "normalized": [] }, { "id": "PMID-18425334_T13", "type": "Cancer", "text": [ "salivary gland tumors" ], "offsets": [ [ 587, 608 ] ], "normalized": [] }, { "id": "PMID-18425334_T19", "type": "Organ", "text": [ "salivary glands" ], "offsets": [ [ 765, 780 ] ], "normalized": [] }, { "id": "PMID-18425334_T20", "type": "Multi-tissue_structure", "text": [ "lymph nodes" ], "offsets": [ [ 796, 807 ] ], "normalized": [] }, { "id": "PMID-18425334_T21", "type": "Organ", "text": [ "salivary glands" ], "offsets": [ [ 821, 836 ] ], "normalized": [] }, { "id": "PMID-18425334_T22", "type": "Multi-tissue_structure", "text": [ "follicles" ], "offsets": [ [ 897, 906 ] ], "normalized": [] }, { "id": "PMID-18425334_T27", "type": "Multi-tissue_structure", "text": [ "salivary gland" ], "offsets": [ [ 1159, 1173 ] ], "normalized": [] } ]

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[ { "id": "PMC-2739213-sec-17__text", "type": "sec", "text": [ "Authors' contributions\nPM carried out and analyzed molecular assay and sequencing data and drafted the manuscript. NS participated in study design and in the local coordination during the study. She helped to draft the manuscript. MD has made substantial contributions to the acquisition and analysis of data. He participated in design of the study and helped to draft the manuscript. MO has made substantial contributions to acquisition and analysis of data. GB has made substantial contributions to acquisition and analysis of data. GP carried out microscopy and microbiology analyses in Italy and contributed in drafting the manuscript. GBM has made substantial contributions in conceiving, analysing and writing the manuscript. AM participated in the design of the study and helped to draft the manuscript. DMC participated in the design of the study and conceived, and analysed the manuscript. All authors read and approved the final manuscript.\n" ], "offsets": [ [ 0, 951 ] ] } ]

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[ { "id": "PMID-17234724__text", "type": "abstract", "text": [ "Pro/antioxidant status and AP-1 transcription factor in murine skin following topical exposure to cumene hydroperoxide. \nOrganic peroxides, widely used in the chemical and pharmaceutical industries, can act as skin tumor promoters and cause epidermal hyperplasia. They are also known to trigger free radical generation. The present study evaluated the effect of cumene hydroperoxide (Cum-OOH) on the induction of activator protein-1 (AP-1), which is linked to the expression of genes regulating cell proliferation, growth and transformation. Previously, we reported that topical exposure to Cum-OOH caused formation of free radicals and oxidative stress in the skin of vitamin E-deficient mice. The present study used JB6 P+ mouse epidermal cells and AP-1-luciferase reporter transgenic mice to identify whether exposure to Cum-OOH caused activation of AP-1, oxidative stress, depletion of antioxidants and tumor formation during two-stage carcinogenesis. In vitro studies found that exposure to Cum-OOH reduced the level of glutathione (GSH) in mouse epidermal cells (JB6 P+) and caused the induction of AP-1. Mice primed with dimethyl-benz[a]anthracene (DMBA) were topically exposed to Cum-OOH (82.6 micromol) or the positive control, 12-O-tetradecanoylphorbol-13-acetate (TPA, 17 nmol), twice weekly for 29 weeks. Activation of AP-1 in skin was detected as early as 2 weeks following Cum-OOH or TPA exposure. No AP-1 expression was found 19 weeks after initiation. Papilloma formation was observed in both the DMBA-TPA- and DMBA-Cum-OOH-exposed animals, whereas skin carcinomas were found only in the DMBA-Cum-OOH-treated mice. A greater accumulation of peroxidative products (thiobarbituric acid-reactive substances), inflammation and decreased levels of GSH and total antioxidant reserves were also observed in the skin of DMBA-Cum-OOH-exposed mice. These results suggest that Cum-OOH-induced carcinogenesis is accompanied by increased AP-1 activation and changes in antioxidant status.\n" ], "offsets": [ [ 0, 1992 ] ] } ]

[ { "id": "PMID-17234724_T3", "type": "Organ", "text": [ "skin" ], "offsets": [ [ 63, 67 ] ], "normalized": [] }, { "id": "PMID-17234724_T6", "type": "Cancer", "text": [ "skin tumor" ], "offsets": [ [ 210, 220 ] ], "normalized": [] }, { "id": "PMID-17234724_T7", "type": "Pathological_formation", "text": [ "epidermal hyperplasia" ], "offsets": [ [ 241, 262 ] ], "normalized": [] }, { "id": "PMID-17234724_T13", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 495, 499 ] ], "normalized": [] }, { "id": "PMID-17234724_T16", "type": "Organ", "text": [ "skin" ], "offsets": [ [ 661, 665 ] ], "normalized": [] }, { "id": "PMID-17234724_T19", "type": "Cell", "text": [ "JB6 P+ mouse epidermal cells" ], "offsets": [ [ 718, 746 ] ], "normalized": [] }, { "id": "PMID-17234724_T26", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 907, 912 ] ], "normalized": [] }, { "id": "PMID-17234724_T31", "type": "Cell", "text": [ "epidermal cells" ], "offsets": [ [ 1052, 1067 ] ], "normalized": [] }, { "id": "PMID-17234724_T32", "type": "Cell", "text": [ "JB6 P+" ], "offsets": [ [ 1069, 1075 ] ], "normalized": [] }, { "id": "PMID-17234724_T41", "type": "Organ", "text": [ "skin" ], "offsets": [ [ 1339, 1343 ] ], "normalized": [] }, { "id": "PMID-17234724_T45", "type": "Pathological_formation", "text": [ "Papilloma" ], "offsets": [ [ 1468, 1477 ] ], "normalized": [] }, { "id": "PMID-17234724_T51", "type": "Cancer", "text": [ "skin carcinomas" ], "offsets": [ [ 1565, 1580 ] ], "normalized": [] }, { "id": "PMID-17234724_T57", "type": "Organ", "text": [ "skin" ], "offsets": [ [ 1820, 1824 ] ], "normalized": [] } ]

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[ { "id": "PMID-7257720__text", "type": "abstract", "text": [ "[Organization of pectoral muscle motor neurons in the rat. Contribution to the study of the axillary arch (Achselbogen)].\nIn spite of their role of the forelimb activity, the organization of the mammalian pectoral muscles remains unclear. In order to get more information, we have studied, qualitatively and quantitatively, the motor pools of the various pectoral muscles in the rat (musculus pectoralis major, musculus pectoralis minor and musculus panniculus carnosus). The method applied was the retrograde transport of horseradish peroxidase by the peripheral nerves supplying the various muscles. The results provided the precise localization within the ventral horn of the motor neurons from the pectoral muscles which were all in the most ventral part of the gray matter. Three distinct motor pools were observed, which confirms the functional identity of each muscle. The motor neurons of m. panniculus carnosus exhibited some particularities. They were 4 times more numerous than those from m. pectoralis major, they occupied the whole ventral edge of the ventral horn, from its medial part to its lateral tip. The cell size was different from that of the other muscles. These results were discussed, according to the role of this muscle, which links the forelimb to the whole trunk. In mammals, m. panniculus carnosus constitutes, with musculus latissimus dorsi, the axillary arch (Achselbogen). A small area of overlapping between the motor pools of these two muscles was observed. It was suggested that the muscular fibers from the axillary arch were innervated by the same, well-defined spinal area, independent of the muscle from which they originate.\n" ], "offsets": [ [ 0, 1666 ] ] } ]

[ { "id": "PMID-7257720_T1", "type": "Cell", "text": [ "pectoral muscle motor neurons" ], "offsets": [ [ 17, 46 ] ], "normalized": [] }, { "id": "PMID-7257720_T2", "type": "Organism_subdivision", "text": [ "forelimb" ], "offsets": [ [ 152, 160 ] ], "normalized": [] }, { "id": "PMID-7257720_T3", "type": "Organ", "text": [ "pectoral muscles" ], "offsets": [ [ 205, 221 ] ], "normalized": [] }, { "id": "PMID-7257720_T4", "type": "Organ", "text": [ "pectoral muscles" ], "offsets": [ [ 355, 371 ] ], "normalized": [] }, { "id": "PMID-7257720_T5", "type": "Organ", "text": [ "musculus pectoralis major" ], "offsets": [ [ 384, 409 ] ], "normalized": [] }, { "id": "PMID-7257720_T6", "type": "Organ", "text": [ "musculus pectoralis minor" ], "offsets": [ [ 411, 436 ] ], "normalized": [] }, { "id": "PMID-7257720_T7", "type": "Organ", "text": [ "musculus panniculus carnosus" ], "offsets": [ [ 441, 469 ] ], "normalized": [] }, { "id": "PMID-7257720_T8", "type": "Multi-tissue_structure", "text": [ "peripheral nerves" ], "offsets": [ [ 553, 570 ] ], "normalized": [] }, { "id": "PMID-7257720_T9", "type": "Organ", "text": [ "muscles" ], "offsets": [ [ 593, 600 ] ], "normalized": [] }, { "id": "PMID-7257720_T10", "type": "Multi-tissue_structure", "text": [ "ventral horn" ], "offsets": [ [ 659, 671 ] ], "normalized": [] }, { "id": "PMID-7257720_T11", "type": "Cell", "text": [ "motor neurons" ], "offsets": [ [ 679, 692 ] ], "normalized": [] }, { "id": "PMID-7257720_T12", "type": "Organ", "text": [ "pectoral muscles" ], "offsets": [ [ 702, 718 ] ], "normalized": [] }, { "id": "PMID-7257720_T13", "type": "Multi-tissue_structure", "text": [ "gray matter" ], "offsets": [ [ 766, 777 ] ], "normalized": [] }, { "id": "PMID-7257720_T14", "type": "Organ", "text": [ "muscle" ], "offsets": [ [ 868, 874 ] ], "normalized": [] }, { "id": "PMID-7257720_T15", "type": "Cell", "text": [ "motor neurons" ], "offsets": [ [ 880, 893 ] ], "normalized": [] }, { "id": "PMID-7257720_T17", "type": "Multi-tissue_structure", "text": [ "ventral edge" ], "offsets": [ [ 1045, 1057 ] ], "normalized": [] }, { "id": "PMID-7257720_T18", "type": "Multi-tissue_structure", "text": [ "ventral horn" ], "offsets": [ [ 1065, 1077 ] ], "normalized": [] }, { "id": "PMID-7257720_T19", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1124, 1128 ] ], "normalized": [] }, { "id": "PMID-7257720_T20", "type": "Organ", "text": [ "muscles" ], "offsets": [ [ 1171, 1178 ] ], "normalized": [] }, { "id": "PMID-7257720_T21", "type": "Organ", "text": [ "muscle" ], "offsets": [ [ 1240, 1246 ] ], "normalized": [] }, { "id": "PMID-7257720_T22", "type": "Organism_subdivision", "text": [ "forelimb" ], "offsets": [ [ 1264, 1272 ] ], "normalized": [] }, { "id": "PMID-7257720_T23", "type": "Organism_subdivision", "text": [ "trunk" ], "offsets": [ [ 1286, 1291 ] ], "normalized": [] }, { "id": "PMID-7257720_T24", "type": "Organ", "text": [ "muscles" ], "offsets": [ [ 1471, 1478 ] ], "normalized": [] }, { "id": "PMID-7257720_T25", "type": "Cell", "text": [ "muscular fibers" ], "offsets": [ [ 1519, 1534 ] ], "normalized": [] }, { "id": "PMID-7257720_T26", "type": "Organ", "text": [ "musculus latissimus dorsi" ], "offsets": [ [ 1346, 1371 ] ], "normalized": [] }, { "id": "PMID-7257720_T27", "type": "Multi-tissue_structure", "text": [ "axillary arch" ], "offsets": [ [ 1377, 1390 ] ], "normalized": [] }, { "id": "PMID-7257720_T28", "type": "Multi-tissue_structure", "text": [ "axillary arch" ], "offsets": [ [ 1544, 1557 ] ], "normalized": [] }, { "id": "PMID-7257720_T29", "type": "Organ", "text": [ "muscle" ], "offsets": [ [ 1632, 1638 ] ], "normalized": [] }, { "id": "PMID-7257720_T30", "type": "Multi-tissue_structure", "text": [ "ventral part" ], "offsets": [ [ 746, 758 ] ], "normalized": [] }, { "id": "PMID-7257720_T32", "type": "Organism_subdivision", "text": [ "spinal area" ], "offsets": [ [ 1600, 1611 ] ], "normalized": [] }, { "id": "PMID-7257720_T16", "type": "Multi-tissue_structure", "text": [ "axillary arch" ], "offsets": [ [ 92, 105 ] ], "normalized": [] }, { "id": "PMID-7257720_T33", "type": "Organ", "text": [ "m. pectoralis major" ], "offsets": [ [ 1000, 1019 ] ], "normalized": [] }, { "id": "PMID-7257720_T34", "type": "Organ", "text": [ "m. panniculus carnosus" ], "offsets": [ [ 1305, 1327 ] ], "normalized": [] }, { "id": "PMID-7257720_T35", "type": "Organ", "text": [ "m. panniculus carnosus" ], "offsets": [ [ 897, 919 ] ], "normalized": [] }, { "id": "PMID-7257720_T31", "type": "Multi-tissue_structure", "text": [ "lateral tip" ], "offsets": [ [ 1107, 1118 ] ], "normalized": [] }, { "id": "PMID-7257720_T36", "type": "Multi-tissue_structure", "text": [ "medial part" ], "offsets": [ [ 1088, 1099 ] ], "normalized": [] } ]

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[ { "id": "PMID-10698499__text", "type": "abstract", "text": [ "Oncogenic epidermal growth factor receptor mutants with tandem duplication: gene structure and effects on receptor function. \nA number of epidermal growth factor receptor (EGFR) deletion mutants have been identified in gliomas, in which the EGFR gene is frequently amplified and rearranged. We have previously characterized the structure of a gene in A-172 human glioma cells that encodes a 190-kDa EGFR mutant with tandem duplication of the tyrosine kinase (TK) and calcium-mediated internalization (CAIN) domains. Here we describe a 185-kDa tandem duplication mutant (TDM) that is expressed in KE and A-1235 glioma cells, along with certain functional characteristics of the mutants. The corresponding transcripts in KE and A-1235 cells contain 1053 additional nucleotides representing an in-frame duplication of exons 18 through 25 which encode the entire TK region and a portion of the CAIN domain. As with duplication of the entire TK/CAIN region (exons 18-26) in A-172 cells, duplication of exons 18-25 is associated with a specific genomic rearrangement between flanking introns. Involved introns contain homology to recombination signal sequence (RSS) heptamers present in the V(D)J region of the T lymphocyte receptor gene. In defined medium, both oncogenic TDM are constitutively autophosphorylated and inefficiently downregulated. High-affinity binding is reduced in EGFR.TDM/18-26, although the t1/2 of receptor internalization is not prolonged.\n" ], "offsets": [ [ 0, 1458 ] ] } ]

[ { "id": "PMID-10698499_T4", "type": "Cancer", "text": [ "gliomas" ], "offsets": [ [ 219, 226 ] ], "normalized": [] }, { "id": "PMID-10698499_T6", "type": "Cell", "text": [ "A-172 human glioma cells" ], "offsets": [ [ 351, 375 ] ], "normalized": [] }, { "id": "PMID-10698499_T9", "type": "Cell", "text": [ "KE" ], "offsets": [ [ 596, 598 ] ], "normalized": [] }, { "id": "PMID-10698499_T10", "type": "Cell", "text": [ "A-1235 glioma cells" ], "offsets": [ [ 603, 622 ] ], "normalized": [] }, { "id": "PMID-10698499_T11", "type": "Cell", "text": [ "KE" ], "offsets": [ [ 719, 721 ] ], "normalized": [] }, { "id": "PMID-10698499_T12", "type": "Cell", "text": [ "A-1235 cells" ], "offsets": [ [ 726, 738 ] ], "normalized": [] }, { "id": "PMID-10698499_T13", "type": "Cell", "text": [ "A-172 cells" ], "offsets": [ [ 969, 980 ] ], "normalized": [] }, { "id": "PMID-10698499_T1", "type": "Cell", "text": [ "T lymphocyte" ], "offsets": [ [ 1205, 1217 ] ], "normalized": [] } ]

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[ { "id": "PMC-2634619-caption-01__text", "type": "caption", "text": [ "Appendix Table\nDetection of Nipah virus antibody among bat serum samples collected from 10 provinces in China, 2004-2007*\n" ], "offsets": [ [ 0, 122 ] ] } ]

[ { "id": "PMC-2634619-caption-01_T1", "type": "Organism_substance", "text": [ "serum samples" ], "offsets": [ [ 59, 72 ] ], "normalized": [] } ]

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[ { "id": "PMID-9679735__text", "type": "abstract", "text": [ "Expression of two type II-like tumor hexokinase RNA transcripts in cancer cell lines.\nTo maintain an elevated glycolytic rate, cancerous or proliferating cells alter the expression pattern of rate limiting glycolytic enzymes. Since glucose phosphorylation is the first step in glycolysis, hexokinase (HK), the first rate limiting glycolytic enzyme, can play a key regulatory role in this process. A low-Km, mitochondrial type II-like tumor HK is described as the predominant form in hepatomas. However, recent identification of a high-Km glucose phosphorylating activity in a range of cancer cells prompted us to characterize glucose phosphorylating enzymes of cancer cells at the molecular level. Highly sensitive reverse-transcription polymerase chain reaction identifies an induction and overexpression of a type II-like tumor HK RNA in a range of cancer cell lines irrespective of tissue origin. In addition, we report here the identification of two RNA transcripts of type II-like tumor HK of approximately 5.5 and approximately 4.0 kb in these cancer cells lines, including muscle-derived L6 myoblast cells. Interestingly, under normal conditions muscle cells express only a approximately 5.5-kb type II HK RNA transcript. A significant amount of type I HK RNA was also found expressed in cancer cell lines. RNA encoding glucokinase (GK), the high-Km HK isozyme, was found only in cancer cells originating from liver and pancreas, which express GK under normal conditions.\n" ], "offsets": [ [ 0, 1479 ] ] } ]

[ { "id": "PMID-9679735_T2", "type": "Cell", "text": [ "cancer cell lines" ], "offsets": [ [ 67, 84 ] ], "normalized": [] }, { "id": "PMID-9679735_T3", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 154, 159 ] ], "normalized": [] }, { "id": "PMID-9679735_T9", "type": "Cellular_component", "text": [ "mitochondrial" ], "offsets": [ [ 407, 420 ] ], "normalized": [] }, { "id": "PMID-9679735_T11", "type": "Cancer", "text": [ "hepatomas" ], "offsets": [ [ 483, 492 ] ], "normalized": [] }, { "id": "PMID-9679735_T13", "type": "Cell", "text": [ "cancer cells" ], "offsets": [ [ 585, 597 ] ], "normalized": [] }, { "id": "PMID-9679735_T15", "type": "Cell", "text": [ "cancer cells" ], "offsets": [ [ 661, 673 ] ], "normalized": [] }, { "id": "PMID-9679735_T17", "type": "Cell", "text": [ "cancer cell lines" ], "offsets": [ [ 851, 868 ] ], "normalized": [] }, { "id": "PMID-9679735_T18", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 885, 891 ] ], "normalized": [] }, { "id": "PMID-9679735_T20", "type": "Cell", "text": [ "cancer cells lines" ], "offsets": [ [ 1050, 1068 ] ], "normalized": [] }, { "id": "PMID-9679735_T21", "type": "Organ", "text": [ "muscle" ], "offsets": [ [ 1080, 1086 ] ], "normalized": [] }, { "id": "PMID-9679735_T22", "type": "Cell", "text": [ "L6 myoblast cells" ], "offsets": [ [ 1095, 1112 ] ], "normalized": [] }, { "id": "PMID-9679735_T23", "type": "Cell", "text": [ "muscle cells" ], "offsets": [ [ 1153, 1165 ] ], "normalized": [] }, { "id": "PMID-9679735_T26", "type": "Cell", "text": [ "cancer cell lines" ], "offsets": [ [ 1295, 1312 ] ], "normalized": [] }, { "id": "PMID-9679735_T30", "type": "Cell", "text": [ "cancer cells" ], "offsets": [ [ 1387, 1399 ] ], "normalized": [] }, { "id": "PMID-9679735_T31", "type": "Organ", "text": [ "liver" ], "offsets": [ [ 1417, 1422 ] ], "normalized": [] }, { "id": "PMID-9679735_T32", "type": "Organ", "text": [ "pancreas" ], "offsets": [ [ 1427, 1435 ] ], "normalized": [] }, { "id": "PMID-9679735_T51", "type": "Cancer", "text": [ "cancerous" ], "offsets": [ [ 127, 136 ] ], "normalized": [] } ]

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[ { "id": "PMID-19118244__text", "type": "abstract", "text": [ "Involvement of PTEN promoter methylation in cerebral cavernous malformations.\nBACKGROUND AND PURPOSE: Cerebral cavernous malformations (CCMs) are prevalent cerebral vascular lesions involving aberrant angiogenesis. However, the underlying mechanism is poorly understood. Phosphatase and tension homolog deleted on chromosome 10 (PTEN), a tumor suppressor, is frequently deficient in various pathologies due to mutation or epigenetic alterations. PTEN promoter hypermethylation is a major epigenetic silencing mechanism leading to activation of angiogenesis in tumors. The present study aimed to investigate whether PTEN promoter methylation was involved in CCMs. METHODS: PTEN promoter methylation was detected in surgical specimens of CCMs (n=69) by methylation-specific polymerase chain reaction. The methylation status was correlated to the clinical manifestations and to PTEN expression, which was analyzed by both Western blot and immunohistochemistry. To investigate the endothelial proliferation and the potential signaling pathways affected by PTEN methylation, proliferating cell nuclear antigen as well as phosphor-Akt and phosphor-Erk1,2 were detected by immunofluorescence and Western blot, respectively, in CCM specimens. RESULTS: Methylation-specific polymerase chain reaction revealed PTEN promoter methylation in 15.9% CCMs. Strikingly, 5 of 6 familial CCMs showed PTEN promoter methylation (83.3%), which was significantly higher than in sporadic cases (9.4%; P<0.001). In addition, PTEN promoter methylation appeared more frequently in multiple CCMs, including familial cases (46.7%), than that in single-lesioned CCMs (11.8%; P<0.05). Immunostaining and Western blot revealed a more significant PTEN downregulation in PTEN-methylated CCMs in comparison to PTEN-unmethylated CCMs. Reduced PTEN expression was inversely correlated to the expression of proliferating cell nuclear antigen and to the activation of Erk1,2, but not of Akt. CONCLUSIONS: We reported here for the first time the involvement of PTEN promoter methylation in CCMs, particularly in familial CCMs, suggesting this epigenetic alteration as a potential pathomechanism of CCMs. The identification of Erk1,2 as triggered signaling in the lesions may be valuable for the development of effective therapy for this disease.\n" ], "offsets": [ [ 0, 2306 ] ] } ]

[ { "id": "PMID-19118244_T2", "type": "Pathological_formation", "text": [ "cerebral cavernous malformations" ], "offsets": [ [ 44, 76 ] ], "normalized": [] }, { "id": "PMID-19118244_T3", "type": "Pathological_formation", "text": [ "Cerebral cavernous malformations" ], "offsets": [ [ 102, 134 ] ], "normalized": [] }, { "id": "PMID-19118244_T4", "type": "Pathological_formation", "text": [ "CCMs" ], "offsets": [ [ 136, 140 ] ], "normalized": [] }, { "id": "PMID-19118244_T5", "type": "Pathological_formation", "text": [ "cerebral vascular lesions" ], "offsets": [ [ 156, 181 ] ], "normalized": [] }, { "id": "PMID-19118244_T8", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 338, 343 ] ], "normalized": [] }, { "id": "PMID-19118244_T10", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 560, 566 ] ], "normalized": [] }, { "id": "PMID-19118244_T12", "type": "Pathological_formation", "text": [ "CCMs" ], "offsets": [ [ 657, 661 ] ], "normalized": [] }, { "id": "PMID-19118244_T14", "type": "Pathological_formation", "text": [ "CCMs" ], "offsets": [ [ 736, 740 ] ], "normalized": [] }, { "id": "PMID-19118244_T16", "type": "Cell", "text": [ "endothelial" ], "offsets": [ [ 977, 988 ] ], "normalized": [] }, { "id": "PMID-19118244_T21", "type": "Pathological_formation", "text": [ "CCM specimens" ], "offsets": [ [ 1220, 1233 ] ], "normalized": [] }, { "id": "PMID-19118244_T23", "type": "Pathological_formation", "text": [ "CCMs" ], "offsets": [ [ 1335, 1339 ] ], "normalized": [] }, { "id": "PMID-19118244_T24", "type": "Pathological_formation", "text": [ "CCMs" ], "offsets": [ [ 1369, 1373 ] ], "normalized": [] }, { "id": "PMID-19118244_T27", "type": "Pathological_formation", "text": [ "CCMs" ], "offsets": [ [ 1563, 1567 ] ], "normalized": [] }, { "id": "PMID-19118244_T28", "type": "Pathological_formation", "text": [ "CCMs" ], "offsets": [ [ 1632, 1636 ] ], "normalized": [] }, { "id": "PMID-19118244_T31", "type": "Pathological_formation", "text": [ "CCMs" ], "offsets": [ [ 1753, 1757 ] ], "normalized": [] }, { "id": "PMID-19118244_T33", "type": "Pathological_formation", "text": [ "CCMs" ], "offsets": [ [ 1793, 1797 ] ], "normalized": [] }, { "id": "PMID-19118244_T40", "type": "Pathological_formation", "text": [ "CCMs" ], "offsets": [ [ 2050, 2054 ] ], "normalized": [] }, { "id": "PMID-19118244_T41", "type": "Pathological_formation", "text": [ "CCMs" ], "offsets": [ [ 2081, 2085 ] ], "normalized": [] }, { "id": "PMID-19118244_T42", "type": "Pathological_formation", "text": [ "CCMs" ], "offsets": [ [ 2158, 2162 ] ], "normalized": [] }, { "id": "PMID-19118244_T45", "type": "Pathological_formation", "text": [ "lesions" ], "offsets": [ [ 2223, 2230 ] ], "normalized": [] }, { "id": "PMID-19118244_T85", "type": "Pathological_formation", "text": [ "surgical specimens" ], "offsets": [ [ 714, 732 ] ], "normalized": [] } ]

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[ { "id": "PMID-18996355__text", "type": "abstract", "text": [ "A novel integrin alpha5beta1 antagonistic peptide, A5-1, screened by Protein Chip system as a potent angiogenesis inhibitor.\nIntegrin alpha5beta1 immobilized on a ProteoChip was used to screen new antagonistic peptides from multiple hexapeptide sub-libraries of the positional scanning synthetic peptide combinatorial library (PS-SPCL). The integrin alpha5beta1-Fibronectin interaction was demonstrated on the chip. A novel peptide ligand, A5-1 (VILVLF), with high affinity to integrin alpha5beta1 was identified from the hexapeptide libraries with this chip-based screening method on the basis of a competitive inhibition assay. A5-1 inhibits the integrin-fibronectin interaction in a dose-dependent manner (IC(50); 1.56+/-0.28 microM. In addition, it inhibits human umbilical vein endothelial cell proliferation, migration, adhesion, tubular network formation, and bFGF-induced neovascularization in a chick chorioallantoic membrane. These results suggest that A5-1 will be a potent inhibitor of neovascularization.\n" ], "offsets": [ [ 0, 1018 ] ] } ]

[ { "id": "PMID-18996355_T12", "type": "Cell", "text": [ "human umbilical vein endothelial cell" ], "offsets": [ [ 762, 799 ] ], "normalized": [] }, { "id": "PMID-18996355_T13", "type": "Multi-tissue_structure", "text": [ "tubular network" ], "offsets": [ [ 836, 851 ] ], "normalized": [] }, { "id": "PMID-18996355_T16", "type": "Multi-tissue_structure", "text": [ "chorioallantoic membrane" ], "offsets": [ [ 910, 934 ] ], "normalized": [] } ]

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[ { "id": "PMID-10214859__text", "type": "abstract", "text": [ "The TGF-beta type II receptor in chronic myeloid leukemia: analysis of microsatellite regions and gene expression. \nGenomic instability is one mechanism proposed to play a role in the disease progression of chronic myeloid leukemia (CML). Microsatellite regions in the type II transforming growth factor-beta receptor (TGF-beta RII) gene appear to be targets for mutation in some cancers displaying microsatellite instability (replication error phenotype, RER+). Furthermore, TGF-beta RII mutations in RER+ tumors have been associated with decreased TGF-beta RII mRNA levels. As TGF-beta is a potent negative growth regulator of hematopoietic cells, investigations were undertaken to determine whether inactivation of the receptor by microsatellite alteration might be involved in the progression of CML. Analysis of TGF-beta RII mRNA expression by RNase protection, with comparison of cells from the chronic, accelerated and blast phases of CML, showed no change in TGF-beta RII transcript levels during disease progression. However, during each phase of the disease, low levels of TGF-beta RII were detected when compared with the hematopoietic cells of normal donors. Furthermore, this decreased expression was also observed in the other myeloproliferative disorders, polycythemia rubra vera (PRV) and essential thrombocythemia (ET). The leukemia cell lines K562 and HL-60 had no detectable TGF-beta RII mRNA. Two microsatellite regions found altered in RER+ colon cancers were analyzed to establish if these sequences were aberrant in CML. No alteration was detected in either of these regions in any phase of the disease. These results suggest that alterations of the microsatellite regions in the TGF-beta RII gene are not involved in the progression of CML. Decreased expression of TGF-beta RII in CML cells and leukemia cell lines raises the possibility that altered expression of the receptor may play a role in the initiation and/or maintenance of the disease state.\n" ], "offsets": [ [ 0, 1977 ] ] } ]

[ { "id": "PMID-10214859_T2", "type": "Cancer", "text": [ "chronic myeloid leukemia" ], "offsets": [ [ 33, 57 ] ], "normalized": [] }, { "id": "PMID-10214859_T3", "type": "Cancer", "text": [ "chronic myeloid leukemia" ], "offsets": [ [ 207, 231 ] ], "normalized": [] }, { "id": "PMID-10214859_T4", "type": "Cancer", "text": [ "CML" ], "offsets": [ [ 233, 236 ] ], "normalized": [] }, { "id": "PMID-10214859_T7", "type": "Cancer", "text": [ "cancers" ], "offsets": [ [ 380, 387 ] ], "normalized": [] }, { "id": "PMID-10214859_T9", "type": "Cancer", "text": [ "RER+ tumors" ], "offsets": [ [ 502, 513 ] ], "normalized": [] }, { "id": "PMID-10214859_T12", "type": "Cell", "text": [ "hematopoietic cells" ], "offsets": [ [ 629, 648 ] ], "normalized": [] }, { "id": "PMID-10214859_T13", "type": "Cancer", "text": [ "CML" ], "offsets": [ [ 800, 803 ] ], "normalized": [] }, { "id": "PMID-10214859_T16", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 886, 891 ] ], "normalized": [] }, { "id": "PMID-10214859_T17", "type": "Cancer", "text": [ "CML" ], "offsets": [ [ 942, 945 ] ], "normalized": [] }, { "id": "PMID-10214859_T20", "type": "Cell", "text": [ "hematopoietic cells" ], "offsets": [ [ 1133, 1152 ] ], "normalized": [] }, { "id": "PMID-10214859_T22", "type": "Cell", "text": [ "leukemia cell lines K562" ], "offsets": [ [ 1341, 1365 ] ], "normalized": [] }, { "id": "PMID-10214859_T23", "type": "Cell", "text": [ "HL-60" ], "offsets": [ [ 1370, 1375 ] ], "normalized": [] }, { "id": "PMID-10214859_T25", "type": "Cancer", "text": [ "RER+ colon cancers" ], "offsets": [ [ 1457, 1475 ] ], "normalized": [] }, { "id": "PMID-10214859_T26", "type": "Cancer", "text": [ "CML" ], "offsets": [ [ 1539, 1542 ] ], "normalized": [] }, { "id": "PMID-10214859_T28", "type": "Cancer", "text": [ "CML" ], "offsets": [ [ 1760, 1763 ] ], "normalized": [] }, { "id": "PMID-10214859_T30", "type": "Cell", "text": [ "CML cells" ], "offsets": [ [ 1805, 1814 ] ], "normalized": [] }, { "id": "PMID-10214859_T31", "type": "Cell", "text": [ "leukemia cell lines" ], "offsets": [ [ 1819, 1838 ] ], "normalized": [] } ]

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[ { "id": "PMC-2993105-caption-03__text", "type": "caption", "text": [ "The thickness of the inner retina was established as the distance between retinal nerve fiber layer and inner nuclear layer and was measured using the 1,000 mum caliper available in the OCT-SLO Spectralis. Ten age-matched normal eyes were used as controls. Observe the decrease in the nasal and temporal inner retinal thickness in the right eye in comparison to the left and normal control eyes.\n" ], "offsets": [ [ 0, 396 ] ] } ]

[ { "id": "PMC-2993105-caption-03_T1", "type": "Multi-tissue_structure", "text": [ "inner retina" ], "offsets": [ [ 21, 33 ] ], "normalized": [] }, { "id": "PMC-2993105-caption-03_T2", "type": "Tissue", "text": [ "retinal nerve fiber layer" ], "offsets": [ [ 74, 99 ] ], "normalized": [] }, { "id": "PMC-2993105-caption-03_T3", "type": "Tissue", "text": [ "inner nuclear layer" ], "offsets": [ [ 104, 123 ] ], "normalized": [] }, { "id": "PMC-2993105-caption-03_T4", "type": "Organ", "text": [ "eyes" ], "offsets": [ [ 229, 233 ] ], "normalized": [] }, { "id": "PMC-2993105-caption-03_T5", "type": "Multi-tissue_structure", "text": [ "inner retinal" ], "offsets": [ [ 304, 317 ] ], "normalized": [] }, { "id": "PMC-2993105-caption-03_T6", "type": "Organ", "text": [ "right eye" ], "offsets": [ [ 335, 344 ] ], "normalized": [] }, { "id": "PMC-2993105-caption-03_T7", "type": "Organ", "text": [ "eyes" ], "offsets": [ [ 390, 394 ] ], "normalized": [] }, { "id": "PMC-2993105-caption-03_T8", "type": "Organism_subdivision", "text": [ "nasal" ], "offsets": [ [ 285, 290 ] ], "normalized": [] }, { "id": "PMC-2993105-caption-03_T9", "type": "Organ", "text": [ "left" ], "offsets": [ [ 366, 370 ] ], "normalized": [] } ]

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[ { "id": "PMC-2793023-sec-09__text", "type": "sec", "text": [ "Follow-up\nPatients were followed up at the outpatient clinic at 1, 4, and 7 months after the ablation procedure and every 6 months thereafter. Routine 24 or 48 h Holter monitoring was performed before each appointment, and a 12-lead electrocardiogram was obtained at each visit. Patients were asked to report to the emergency room or our arrhythmia unit for an ECG if any symptom suggestive of recurrence occurred between scheduled visits.\nAfter the ablation procedure, all patients received anti-arrhythmic treatment for at least 1 month to protect against early recurrences and continued oral anticoagulation for a minimum of 2 months to maintain an international normalized ratio between 2.0 and 3.0. Additionally, magnetic resonance angiography was repeated at 3-6 months after the procedure to evaluate the presence of PV stenosis.\nArrhythmia recurrence was defined as a documented AF or atrial flutter episode of >30 s. Arrhythmic episodes within the first 3 months after the CPVA (healing period) were not considered in the evaluation of final success rates because they are often described as transient recurrences related to atrial inflammatory processes following RF lesions.26\nThe endpoint of the study was freedom from arrhythmia recurrence after a single CPVA procedure, without anti-arrhythmic medication.\nA minimum follow-up of 3 months was required.\n" ], "offsets": [ [ 0, 1366 ] ] } ]

[ { "id": "PMC-2793023-sec-09_T1", "type": "Immaterial_anatomical_entity", "text": [ "atrial" ], "offsets": [ [ 893, 899 ] ], "normalized": [] }, { "id": "PMC-2793023-sec-09_T2", "type": "Immaterial_anatomical_entity", "text": [ "atrial" ], "offsets": [ [ 1134, 1140 ] ], "normalized": [] }, { "id": "PMC-2793023-sec-09_T3", "type": "Organism_subdivision", "text": [ "oral" ], "offsets": [ [ 590, 594 ] ], "normalized": [] } ]

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[ { "id": "PMID-6540195__text", "type": "abstract", "text": [ "Hemostasis and mechanism of action of selective antimetastatic drugs in mice bearing Lewis lung carcinoma. \nThe selective antimetastatic agents p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt (DM-COOK), 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) and (+/-)1,2-di(3,5-dioxopiperazin-1-yl)propane (ICRF-159) have been shown to markedly depress the formation of spontaneous hematogenous metastases in mice bearing s.c. Lewis lung carcinoma, with a mechanism unrelated to cytotoxicity for tumor cells. The effects on hemostasis of DM-COOK, DTIC and ICRF-159 have thus been examined in comparison with those of a purely cytotoxic agent, cyclophosphamide, in mice bearing i.m. Lewis lung carcinoma. The parameters considered are the number of platelets and their aggregability, prothrombin and partial thromboplastin times, plasma fibrinogen concentration and tumor cell procoagulant activity. Slight variations are caused by drug treatment in tumor-bearing mice as compared with untreated tumor-bearing controls; the pattern of effects of the selective antimetastatic agents does not differ from that of the reference cytotoxic compound used, cyclophosphamide. These data thus indicate that the effects on hemostasis of the drugs examined can contribute only marginally to their antimetastatic action, since more pronounced effects on hemostasis have been shown to be required to significantly affect metastasis formation.\n" ], "offsets": [ [ 0, 1439 ] ] } ]

[ { "id": "PMID-6540195_T2", "type": "Cancer", "text": [ "Lewis lung carcinoma" ], "offsets": [ [ 85, 105 ] ], "normalized": [] }, { "id": "PMID-6540195_T9", "type": "Cancer", "text": [ "metastases" ], "offsets": [ [ 405, 415 ] ], "normalized": [] }, { "id": "PMID-6540195_T11", "type": "Cancer", "text": [ "Lewis lung carcinoma" ], "offsets": [ [ 437, 457 ] ], "normalized": [] }, { "id": "PMID-6540195_T12", "type": "Cell", "text": [ "tumor cells" ], "offsets": [ [ 506, 517 ] ], "normalized": [] }, { "id": "PMID-6540195_T18", "type": "Cancer", "text": [ "Lewis lung carcinoma" ], "offsets": [ [ 692, 712 ] ], "normalized": [] }, { "id": "PMID-6540195_T19", "type": "Cell", "text": [ "platelets" ], "offsets": [ [ 758, 767 ] ], "normalized": [] }, { "id": "PMID-6540195_T22", "type": "Organism_substance", "text": [ "plasma" ], "offsets": [ [ 839, 845 ] ], "normalized": [] }, { "id": "PMID-6540195_T24", "type": "Cell", "text": [ "tumor cell" ], "offsets": [ [ 875, 885 ] ], "normalized": [] }, { "id": "PMID-6540195_T25", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 959, 964 ] ], "normalized": [] }, { "id": "PMID-6540195_T27", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1005, 1010 ] ], "normalized": [] } ]

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[ { "id": "PMID-9209451__text", "type": "abstract", "text": [ "Monitoring the efficiency of interferon-alpha therapy in chronic myelogenous leukemia (CML) patients by competitive polymerase chain reaction.\nInterferon alpha (IFN-alpha) induces cytogenetic responses of variable degree in patients with CML. We sought to establish the relationship between BCR-ABL transcript numbers measured by competitive two-step reverse transcription polymerase chain reaction (RT-PCR) and cytogenetic status in CML patients treated with IFN-alpha. All 398 samples from 163 patients investigated by RT-PCR were positive for BCR-ABL transcripts. In order to standardize results for variability in RNA and cDNA quality, we quantified total ABL transcripts in each sample as internal control. The BCR-ABL/ABL ratios correlated with the cytogenetic results. Quantitative nested PCR allowed the detection of residual BCR-ABL transcripts in all complete cytogenetic responders on IFN-alpha. We conclude that competitive PCR with internal controls is a reliable method for monitoring patients on IFN-alpha and reduces the need for repeated marrow investigations.\n" ], "offsets": [ [ 0, 1078 ] ] } ]

[ { "id": "PMID-9209451_T1", "type": "Multi-tissue_structure", "text": [ "marrow" ], "offsets": [ [ 1055, 1061 ] ], "normalized": [] }, { "id": "PMID-9209451_T3", "type": "Cancer", "text": [ "chronic myelogenous leukemia" ], "offsets": [ [ 57, 85 ] ], "normalized": [] }, { "id": "PMID-9209451_T4", "type": "Cancer", "text": [ "CML" ], "offsets": [ [ 87, 90 ] ], "normalized": [] }, { "id": "PMID-9209451_T5", "type": "Cancer", "text": [ "CML" ], "offsets": [ [ 238, 241 ] ], "normalized": [] }, { "id": "PMID-9209451_T6", "type": "Cancer", "text": [ "CML" ], "offsets": [ [ 434, 437 ] ], "normalized": [] }, { "id": "PMID-9209451_T2", "type": "Cancer", "text": [ "samples" ], "offsets": [ [ 479, 486 ] ], "normalized": [] }, { "id": "PMID-9209451_T7", "type": "Cancer", "text": [ "sample" ], "offsets": [ [ 684, 690 ] ], "normalized": [] } ]

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[ { "id": "PMC-3180158-sec-09__text", "type": "sec", "text": [ "ACKNOWLEDGEMENTS\nThe authors thank Mr. C. Roberto for providing animal care. This research was supported by the State of Rio de Janeiro Carlos Chagas Filho Research Foundation (FAPERJ) and the Coordination for the Enhancement of Higher Education Personnel (CAPES).\n" ], "offsets": [ [ 0, 265 ] ] } ]

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[ { "id": "PMID-17040495__text", "type": "abstract", "text": [ "Collagen-poly glycolic acid hybrid matrix with basic fibroblast growth factor accelerated angiogenesis and granulation tissue formation in diabetic mice.\nBecause poor skin wound healing associated with diabetes is thought to be partly a result from impaired angiogenesis, treatments that improve angiogenesis could have important clinical applications. We herein report the effects of novel developed material, collagen-poly glycolic acid fiber hybrid matrix, being used together with basic fibroblast growth factor to promote wound healing of full-thickness skin defects on the back of type 2 diabetic Lepr(db) mice. Our data indicates that this therapeutic approach markedly promotes angiogenesis and granulation tissue formation in comparison with other conditions 14 days after wounding.\n" ], "offsets": [ [ 0, 792 ] ] } ]

[ { "id": "PMID-17040495_T4", "type": "Tissue", "text": [ "granulation tissue" ], "offsets": [ [ 107, 125 ] ], "normalized": [] }, { "id": "PMID-17040495_T6", "type": "Pathological_formation", "text": [ "skin wound" ], "offsets": [ [ 167, 177 ] ], "normalized": [] }, { "id": "PMID-17040495_T10", "type": "Pathological_formation", "text": [ "wound" ], "offsets": [ [ 527, 532 ] ], "normalized": [] }, { "id": "PMID-17040495_T11", "type": "Organ", "text": [ "skin" ], "offsets": [ [ 559, 563 ] ], "normalized": [] }, { "id": "PMID-17040495_T14", "type": "Tissue", "text": [ "granulation tissue" ], "offsets": [ [ 703, 721 ] ], "normalized": [] } ]

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[ { "id": "PMID-8272146__text", "type": "abstract", "text": [ "Effect of 1-alkylpyrrolidine N-oxides on energy metabolism of cancer cells.\nThe main purpose of the present investigation was to study the effect of a homologous series of 1-alkylpyrrolidine N-oxides on ATP-producing processes in Ehrlich ascites and L1210 murine leukemia cells. The effect on aerobic glucose consumption, lactic acid formation, content of total (T-SH) and non-protein thiol groups (NP-SH), endogenous respiration and the level of ATP in tumor cells incubated in vitro was investigated. 1-Tetradecylpyrrolidine N-oxide (TPNO), one of the most active compounds, immediately after addition to the suspension of Ehrlich cells in an ice bath, decreased the level of ATP to the same extent over the whole concentration range. After 2 h incubation at 37 degrees C the drop in the ATP level was lower. The decrease in ATP level might be explained through the interaction of the amine oxide with the cell membrane integrity.\n" ], "offsets": [ [ 0, 933 ] ] } ]

[ { "id": "PMID-8272146_T2", "type": "Cell", "text": [ "cancer cells" ], "offsets": [ [ 62, 74 ] ], "normalized": [] }, { "id": "PMID-8272146_T5", "type": "Cell", "text": [ "Ehrlich ascites" ], "offsets": [ [ 230, 245 ] ], "normalized": [] }, { "id": "PMID-8272146_T6", "type": "Cell", "text": [ "L1210 murine leukemia cells" ], "offsets": [ [ 250, 277 ] ], "normalized": [] }, { "id": "PMID-8272146_T10", "type": "Cell", "text": [ "tumor cells" ], "offsets": [ [ 454, 465 ] ], "normalized": [] }, { "id": "PMID-8272146_T13", "type": "Cell", "text": [ "Ehrlich cells" ], "offsets": [ [ 625, 638 ] ], "normalized": [] }, { "id": "PMID-8272146_T18", "type": "Cellular_component", "text": [ "cell membrane" ], "offsets": [ [ 908, 921 ] ], "normalized": [] } ]

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[ { "id": "PMID-11781057__text", "type": "abstract", "text": [ "Phonology: a review and proposals from a connectionist perspective.\nA parallel distributed processing (PDP) model of phonological processing is developed, including components to support repetition, auditory processing, comprehension, and language production. From the performance of the PDP reading model of Plaut, McClelland, Seidenberg, and Patterson (1996), it is inferred that the acoustic-articulatory motor pattern associator that supports repetition provides the basis for phonological sequence knowledge. From the observation that many patients make phonemic paraphasic errors in language production, as in repetition, it is argued that there must be a direct link between distributed concept representations (lexical semantic knowledge) and this network representation of sequence knowledge. In this way, both lexical semantic and phonotactic constraints are brought to bear on language production. The literature on phonological function in normal subjects (slip-of-the-tongue corpora) and in patients with aphasia is critically reviewed from this perspective. The relationship between acoustic and articulatory motor representations in the process of phonetic perception is considered. Repetition and reproduction conduction aphasia are reviewed in detail and extended consideration is given to the representation of auditory verbal short-term memory in the model. Finally, the PDP model is reconciled with information processing models of phonological processing, including that of Lichtheim, and with current knowledge of the anatomic localization of phonological processing. Although no simulations of the model were run, a number of simulation studies are proposed.\n" ], "offsets": [ [ 0, 1682 ] ] } ]

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[ { "id": "PMID-7474125__text", "type": "abstract", "text": [ "A transcript from the long terminal repeats of a murine retrovirus associated with trans activation of cellular genes. \nInfection of human or murine cells with murine leukemia viruses rapidly increases the expression of a number of genes that belong to the immunoglobulin superfamily and are involved in T-lymphocyte activation, including the class I major histocompatibility complex antigens. We have reported recently that the long terminal repeat (LTR) of Moloney murine leukemia virus encodes a trans activator which induces transcription and expression of class I major histocompatibility complex genes and certain cytokine genes. The portion of the LTR responsible for trans activation was mapped by deletions to lie within the U3 region. We demonstrate here that a transcript is initiated within the U3 region and that its presence correlates with the trans-activating activity. Analysis of the LTR region reveals a potential internal promoter element for RNA polymerase III transcription within the U3 region. Studies with polymerase inhibitors suggest that this LTR transcript, designated let (LTR-encoded trans activator), is a product of RNA polymerase III. The mechanisms whereby RNA leukemia viruses cause lymphoid neoplasia after a long latent period have been extensively studied but are only partially understood. The region of the LTR identified here as being important in trans activation has recently been shown to be a critical determinant of the leukemogenicity and latency of Moloney murine leukemia virus. These findings suggest a novel mechanism of retrovirus-induced activation of cellular gene expression, potentially contributing to leukemogenesis.\n" ], "offsets": [ [ 0, 1676 ] ] } ]

[ { "id": "PMID-7474125_T1", "type": "Cellular_component", "text": [ "long terminal repeats" ], "offsets": [ [ 22, 43 ] ], "normalized": [] }, { "id": "PMID-7474125_T3", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 103, 111 ] ], "normalized": [] }, { "id": "PMID-7474125_T6", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 149, 154 ] ], "normalized": [] }, { "id": "PMID-7474125_T9", "type": "Cell", "text": [ "T-lymphocyte" ], "offsets": [ [ 304, 316 ] ], "normalized": [] }, { "id": "PMID-7474125_T11", "type": "Cellular_component", "text": [ "long terminal repeat" ], "offsets": [ [ 429, 449 ] ], "normalized": [] }, { "id": "PMID-7474125_T12", "type": "Cellular_component", "text": [ "LTR" ], "offsets": [ [ 451, 454 ] ], "normalized": [] }, { "id": "PMID-7474125_T16", "type": "Cellular_component", "text": [ "LTR" ], "offsets": [ [ 655, 658 ] ], "normalized": [] }, { "id": "PMID-7474125_T17", "type": "Cellular_component", "text": [ "LTR" ], "offsets": [ [ 902, 905 ] ], "normalized": [] }, { "id": "PMID-7474125_T19", "type": "Cellular_component", "text": [ "LTR" ], "offsets": [ [ 1071, 1074 ] ], "normalized": [] }, { "id": "PMID-7474125_T24", "type": "Cancer", "text": [ "lymphoid neoplasia" ], "offsets": [ [ 1219, 1237 ] ], "normalized": [] }, { "id": "PMID-7474125_T25", "type": "Cellular_component", "text": [ "LTR" ], "offsets": [ [ 1348, 1351 ] ], "normalized": [] }, { "id": "PMID-7474125_T28", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 1606, 1614 ] ], "normalized": [] } ]

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[ { "id": "PMID-16556061__text", "type": "abstract", "text": [ "Circulating endothelial cells in malignant disease.\nCancer is a disease largely dependent on neoangiogenesis. Cancer neoangiogenesis is often disordered and abnormal, with evidence of coexisting vascular endothelial dysfunction. A novel method of assessing vascular endothelial function in cancer is via the quantification of circulating endothelial cells (CEC). Unusual in healthy individuals, their presence in elevated numbers often indicates substantial vascular endothelial perturbation. Another interesting cell type is the endothelial progenitor cell (EPC), whose numbers increase in the presence of vascular damage. Recent research suggests that EPCs have an important role in tumor vasculogenesis. Another marker being investigated in the context of vascular dysfunction and coagulopathy is the endothelial microparticle (EMP). Thus, CECs, EPCs and EMPs may represent potentially novel methods for evaluating the vascular status of cancer patients. This review will summarize the current position of CECs, EPCs and EMPs in cell biology terms, with particular emphasis on their relationship to malignant disease.\n" ], "offsets": [ [ 0, 1121 ] ] } ]

[ { "id": "PMID-16556061_T1", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 12, 29 ] ], "normalized": [] }, { "id": "PMID-16556061_T2", "type": "Cancer", "text": [ "malignant disease" ], "offsets": [ [ 33, 50 ] ], "normalized": [] }, { "id": "PMID-16556061_T3", "type": "Cancer", "text": [ "Cancer" ], "offsets": [ [ 52, 58 ] ], "normalized": [] }, { "id": "PMID-16556061_T4", "type": "Cancer", "text": [ "Cancer" ], "offsets": [ [ 110, 116 ] ], "normalized": [] }, { "id": "PMID-16556061_T5", "type": "Tissue", "text": [ "vascular endothelial" ], "offsets": [ [ 195, 215 ] ], "normalized": [] }, { "id": "PMID-16556061_T6", "type": "Tissue", "text": [ "vascular endothelial" ], "offsets": [ [ 257, 277 ] ], "normalized": [] }, { "id": "PMID-16556061_T7", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 290, 296 ] ], "normalized": [] }, { "id": "PMID-16556061_T8", "type": "Cell", "text": [ "circulating endothelial cells" ], "offsets": [ [ 326, 355 ] ], "normalized": [] }, { "id": "PMID-16556061_T9", "type": "Cell", "text": [ "CEC" ], "offsets": [ [ 357, 360 ] ], "normalized": [] }, { "id": "PMID-16556061_T10", "type": "Tissue", "text": [ "vascular endothelial" ], "offsets": [ [ 458, 478 ] ], "normalized": [] }, { "id": "PMID-16556061_T11", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 513, 517 ] ], "normalized": [] }, { "id": "PMID-16556061_T12", "type": "Cell", "text": [ "endothelial progenitor cell" ], "offsets": [ [ 530, 557 ] ], "normalized": [] }, { "id": "PMID-16556061_T13", "type": "Cell", "text": [ "EPC" ], "offsets": [ [ 559, 562 ] ], "normalized": [] }, { "id": "PMID-16556061_T14", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 607, 615 ] ], "normalized": [] }, { "id": "PMID-16556061_T15", "type": "Cell", "text": [ "EPCs" ], "offsets": [ [ 654, 658 ] ], "normalized": [] }, { "id": "PMID-16556061_T16", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 685, 690 ] ], "normalized": [] }, { "id": "PMID-16556061_T17", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 759, 767 ] ], "normalized": [] }, { "id": "PMID-16556061_T18", "type": "Cellular_component", "text": [ "endothelial microparticle" ], "offsets": [ [ 804, 829 ] ], "normalized": [] }, { "id": "PMID-16556061_T19", "type": "Cellular_component", "text": [ "EMP" ], "offsets": [ [ 831, 834 ] ], "normalized": [] }, { "id": "PMID-16556061_T20", "type": "Cell", "text": [ "CECs" ], "offsets": [ [ 843, 847 ] ], "normalized": [] }, { "id": "PMID-16556061_T21", "type": "Cell", "text": [ "EPCs" ], "offsets": [ [ 849, 853 ] ], "normalized": [] }, { "id": "PMID-16556061_T22", "type": "Cellular_component", "text": [ "EMPs" ], "offsets": [ [ 858, 862 ] ], "normalized": [] }, { "id": "PMID-16556061_T23", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 922, 930 ] ], "normalized": [] }, { "id": "PMID-16556061_T24", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 941, 947 ] ], "normalized": [] }, { "id": "PMID-16556061_T26", "type": "Cell", "text": [ "CECs" ], "offsets": [ [ 1009, 1013 ] ], "normalized": [] }, { "id": "PMID-16556061_T27", "type": "Cell", "text": [ "EPCs" ], "offsets": [ [ 1015, 1019 ] ], "normalized": [] }, { "id": "PMID-16556061_T28", "type": "Cellular_component", "text": [ "EMPs" ], "offsets": [ [ 1024, 1028 ] ], "normalized": [] }, { "id": "PMID-16556061_T29", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1032, 1036 ] ], "normalized": [] }, { "id": "PMID-16556061_T30", "type": "Cancer", "text": [ "malignant disease" ], "offsets": [ [ 1102, 1119 ] ], "normalized": [] } ]

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[ { "id": "PMC-3009312-sec-10__text", "type": "sec", "text": [ "Refinement\nThe H-atoms were positioned geometrically (O-H = 0.82, C-H = 0.93 A) and were included in the refinement in the riding model approximation, with Uiso(H) = xUeq(C, O), where x = 1.2 for all H-atoms.\n" ], "offsets": [ [ 0, 209 ] ] } ]

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[ { "id": "PMID-19481797__text", "type": "abstract", "text": [ "Promoting angiogenesis via manipulation of VEGF responsiveness with notch signaling.\nPromoting angiogenesis via delivery of vascular endothelial growth factor (VEGF) and other angiogenic factors is both a potential therapy for cardiovascular diseases and a critical aspect for tissue regeneration. The recent demonstration that VEGF signaling is modulated by the Notch signaling pathway, however, suggests that inhibiting Notch signaling may enhance regional neovascularization, by altering the responsiveness of local endothelial cells to angiogenic stimuli. We tested this possibility with in vitro assays using human endothelial cells, as well as in a rodent hindlimb ischemia model. Treatment of cultured human endothelial cells with DAPT, a gamma secretase inhibitor, increased cell migration and sprout formation in response to VEGF stimulation with a biphasic dependence on DAPT concentration. Further, delivery of an appropriate combination of DAPT and VEGF from an injectable alginate hydrogel system into ischemic hindlimbs led to a faster recovery of blood flow than VEGF or DAPT alone; perfusion levels reached 80% of the normal level by week 4 with combined DAPT and VEGF delivery. Direct intramuscular or intraperitoneal injection of DAPT did not result in the same level of improvement, suggesting that appropriate presentation of DAPT (gel delivery) is important for its activity. DAPT delivery from the hydrogels also did not lead to any adverse side effects, in contrast to systemic introduction of DAPT. Altogether, these results suggest a new approach to promote angiogenesis by controlling Notch signaling, and may provide new options to treat patients with diseases that diminish angiogenic responsiveness.\n" ], "offsets": [ [ 0, 1729 ] ] } ]

[ { "id": "PMID-19481797_T5", "type": "Anatomical_system", "text": [ "cardiovascular" ], "offsets": [ [ 227, 241 ] ], "normalized": [] }, { "id": "PMID-19481797_T6", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 277, 283 ] ], "normalized": [] }, { "id": "PMID-19481797_T10", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 519, 536 ] ], "normalized": [] }, { "id": "PMID-19481797_T12", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 620, 637 ] ], "normalized": [] }, { "id": "PMID-19481797_T13", "type": "Organism_subdivision", "text": [ "hindlimb" ], "offsets": [ [ 662, 670 ] ], "normalized": [] }, { "id": "PMID-19481797_T15", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 715, 732 ] ], "normalized": [] }, { "id": "PMID-19481797_T18", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 783, 787 ] ], "normalized": [] }, { "id": "PMID-19481797_T19", "type": "Tissue", "text": [ "sprout" ], "offsets": [ [ 802, 808 ] ], "normalized": [] }, { "id": "PMID-19481797_T24", "type": "Organism_subdivision", "text": [ "hindlimbs" ], "offsets": [ [ 1024, 1033 ] ], "normalized": [] }, { "id": "PMID-19481797_T25", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 1062, 1067 ] ], "normalized": [] }, { "id": "PMID-19481797_T30", "type": "Immaterial_anatomical_entity", "text": [ "intramuscular" ], "offsets": [ [ 1202, 1215 ] ], "normalized": [] }, { "id": "PMID-19481797_T31", "type": "Immaterial_anatomical_entity", "text": [ "intraperitoneal" ], "offsets": [ [ 1219, 1234 ] ], "normalized": [] } ]

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[ { "id": "PMID-14604834__text", "type": "abstract", "text": [ "Expression, regulation, and function of IGF-1, IGF-1R, and IGF-1 binding proteins in blood vessels.\nThe vascular insulin-like growth factor (IGF)-1 system includes the IGFs, the IGF-1 receptor (IGF-1R), and multiple binding proteins. This growth factor system exerts multiple physiologic effects on the vasculature through both endocrine and autocrine/paracrine mechanisms. The effects of IGF-1 are mediated principally through the IGF-1R but are modulated by complex interactions with multiple IGF binding proteins that themselves are regulated by phosphorylation, proteolysis, polymerization, and cell or matrix association. During the last decade, a significant body of evidence has accumulated, indicating that expression of the components of the IGF system are regulated by multiple factors, including growth factors, cytokines, lipoproteins, reactive oxygen species, and hemodynamic forces. In addition, cross-talk between the IGF system and other growth factors and integrin receptors has been demonstrated. There is accumulating evidence of a role for IGF-1 in multiple vascular pathologies, including atherosclerosis, hypertension, restenosis, angiogenesis, and diabetic vascular disease. This review will discuss the regulation of expression of IGF-1, IGF-1R, and IGF binding proteins in the vasculature and summarize evidence implicating involvement of this system in vascular diseases.\n" ], "offsets": [ [ 0, 1398 ] ] } ]

[ { "id": "PMID-14604834_T4", "type": "Multi-tissue_structure", "text": [ "blood vessels" ], "offsets": [ [ 85, 98 ] ], "normalized": [] }, { "id": "PMID-14604834_T5", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 104, 112 ] ], "normalized": [] }, { "id": "PMID-14604834_T10", "type": "Anatomical_system", "text": [ "vasculature" ], "offsets": [ [ 303, 314 ] ], "normalized": [] }, { "id": "PMID-14604834_T14", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 599, 603 ] ], "normalized": [] }, { "id": "PMID-14604834_T15", "type": "Cellular_component", "text": [ "matrix" ], "offsets": [ [ 607, 613 ] ], "normalized": [] }, { "id": "PMID-14604834_T21", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 1078, 1086 ] ], "normalized": [] }, { "id": "PMID-14604834_T22", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 1180, 1188 ] ], "normalized": [] }, { "id": "PMID-14604834_T26", "type": "Anatomical_system", "text": [ "vasculature" ], "offsets": [ [ 1302, 1313 ] ], "normalized": [] }, { "id": "PMID-14604834_T27", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 1379, 1387 ] ], "normalized": [] }, { "id": "PMID-14604834_T44", "type": "Anatomical_system", "text": [ "endocrine" ], "offsets": [ [ 328, 337 ] ], "normalized": [] }, { "id": "PMID-14604834_T45", "type": "Anatomical_system", "text": [ "autocrine/paracrine" ], "offsets": [ [ 342, 361 ] ], "normalized": [] } ]

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[ { "id": "PMID-2769204__text", "type": "abstract", "text": [ "Invagination of the otic placode: normal development and experimental manipulation.\nThe inner ear forms from paired ectodermal primordia that lie to either side of the developing hindbrain. Initially each primordium forms a shallow depression in the ectodermal surface. Invagination to form an otic pit coincides with the formation of several deep folds in the epithelial surface. An initial fold appears parallel to the embryonic axis and at the junction of the rhombencephalon with somitomeric mesoderm. This is followed by formation of cranial and caudal folds perpendicular to the axis and minor folds that are within the pit formed by earlier folding. The central region of the otic primordium remains in close apposition to the lateral surface of the neural tube during the process of fold formation, until the otic pit becomes quite deep. At that time, mesenchymal cells penetrate between the two layers. Experimental analysis of invagination supports the conclusion that otic invagination is controlled differently from that of similar organ primordia, such as the eye and thyroid. Whereas these other primordia can be stimulated to undergo normal morphogenetic shape changes precociously by treatments that presumably activate motile processes in the cytoskeleton, the same conditions have little effect on the otic placode. Similarly, neither inhibitors of calcium transport nor inactivators of calmodulin activity prevent otic pit formation, while these drugs block invagination of other primordia. These results suggest that otic invagination may be caused by changes in the surrounding tissues rather than by an activation of motility within the primordium.\n" ], "offsets": [ [ 0, 1671 ] ] } ]

[ { "id": "PMID-2769204_T2", "type": "Multi-tissue_structure", "text": [ "inner ear" ], "offsets": [ [ 88, 97 ] ], "normalized": [] }, { "id": "PMID-2769204_T3", "type": "Developing_anatomical_structure", "text": [ "ectodermal primordia" ], "offsets": [ [ 116, 136 ] ], "normalized": [] }, { "id": "PMID-2769204_T4", "type": "Multi-tissue_structure", "text": [ "hindbrain" ], "offsets": [ [ 179, 188 ] ], "normalized": [] }, { "id": "PMID-2769204_T5", "type": "Developing_anatomical_structure", "text": [ "primordium" ], "offsets": [ [ 205, 215 ] ], "normalized": [] }, { "id": "PMID-2769204_T6", "type": "Tissue", "text": [ "ectodermal surface" ], "offsets": [ [ 250, 268 ] ], "normalized": [] }, { "id": "PMID-2769204_T1", "type": "Developing_anatomical_structure", "text": [ "otic placode" ], "offsets": [ [ 20, 32 ] ], "normalized": [] }, { "id": "PMID-2769204_T7", "type": "Immaterial_anatomical_entity", "text": [ "otic pit" ], "offsets": [ [ 294, 302 ] ], "normalized": [] }, { "id": "PMID-2769204_T8", "type": "Tissue", "text": [ "epithelial surface" ], "offsets": [ [ 361, 379 ] ], "normalized": [] }, { "id": "PMID-2769204_T9", "type": "Developing_anatomical_structure", "text": [ "embryonic axis" ], "offsets": [ [ 421, 435 ] ], "normalized": [] }, { "id": "PMID-2769204_T10", "type": "Developing_anatomical_structure", "text": [ "rhombencephalon" ], "offsets": [ [ 463, 478 ] ], "normalized": [] }, { "id": "PMID-2769204_T11", "type": "Developing_anatomical_structure", "text": [ "somitomeric mesoderm" ], "offsets": [ [ 484, 504 ] ], "normalized": [] }, { "id": "PMID-2769204_T12", "type": "Tissue", "text": [ "cranial" ], "offsets": [ [ 539, 546 ] ], "normalized": [] }, { "id": "PMID-2769204_T13", "type": "Tissue", "text": [ "caudal folds" ], "offsets": [ [ 551, 563 ] ], "normalized": [] }, { "id": "PMID-2769204_T14", "type": "Developing_anatomical_structure", "text": [ "axis" ], "offsets": [ [ 585, 589 ] ], "normalized": [] }, { "id": "PMID-2769204_T15", "type": "Immaterial_anatomical_entity", "text": [ "pit" ], "offsets": [ [ 626, 629 ] ], "normalized": [] }, { "id": "PMID-2769204_T16", "type": "Developing_anatomical_structure", "text": [ "otic primordium" ], "offsets": [ [ 683, 698 ] ], "normalized": [] }, { "id": "PMID-2769204_T17", "type": "Multi-tissue_structure", "text": [ "neural tube" ], "offsets": [ [ 757, 768 ] ], "normalized": [] }, { "id": "PMID-2769204_T18", "type": "Immaterial_anatomical_entity", "text": [ "otic pit" ], "offsets": [ [ 817, 825 ] ], "normalized": [] }, { "id": "PMID-2769204_T19", "type": "Cell", "text": [ "mesenchymal cells" ], "offsets": [ [ 860, 877 ] ], "normalized": [] }, { "id": "PMID-2769204_T20", "type": "Organism_subdivision", "text": [ "otic" ], "offsets": [ [ 979, 983 ] ], "normalized": [] }, { "id": "PMID-2769204_T21", "type": "Developing_anatomical_structure", "text": [ "organ primordia" ], "offsets": [ [ 1044, 1059 ] ], "normalized": [] }, { "id": "PMID-2769204_T22", "type": "Tissue", "text": [ "fold" ], "offsets": [ [ 791, 795 ] ], "normalized": [] }, { "id": "PMID-2769204_T23", "type": "Organ", "text": [ "eye" ], "offsets": [ [ 1073, 1076 ] ], "normalized": [] }, { "id": "PMID-2769204_T24", "type": "Organ", "text": [ "thyroid" ], "offsets": [ [ 1081, 1088 ] ], "normalized": [] }, { "id": "PMID-2769204_T25", "type": "Developing_anatomical_structure", "text": [ "primordia" ], "offsets": [ [ 1110, 1119 ] ], "normalized": [] }, { "id": "PMID-2769204_T26", "type": "Cellular_component", "text": [ "cytoskeleton" ], "offsets": [ [ 1260, 1272 ] ], "normalized": [] }, { "id": "PMID-2769204_T27", "type": "Developing_anatomical_structure", "text": [ "otic placode" ], "offsets": [ [ 1320, 1332 ] ], "normalized": [] }, { "id": "PMID-2769204_T28", "type": "Immaterial_anatomical_entity", "text": [ "otic pit" ], "offsets": [ [ 1433, 1441 ] ], "normalized": [] }, { "id": "PMID-2769204_T29", "type": "Developing_anatomical_structure", "text": [ "primordia" ], "offsets": [ [ 1499, 1508 ] ], "normalized": [] }, { "id": "PMID-2769204_T30", "type": "Organism_subdivision", "text": [ "otic" ], "offsets": [ [ 1537, 1541 ] ], "normalized": [] }, { "id": "PMID-2769204_T31", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 1599, 1606 ] ], "normalized": [] }, { "id": "PMID-2769204_T32", "type": "Developing_anatomical_structure", "text": [ "primordium" ], "offsets": [ [ 1659, 1669 ] ], "normalized": [] }, { "id": "PMID-2769204_T33", "type": "Tissue", "text": [ "fold" ], "offsets": [ [ 392, 396 ] ], "normalized": [] }, { "id": "PMID-2769204_T34", "type": "Multi-tissue_structure", "text": [ "lateral surface" ], "offsets": [ [ 734, 749 ] ], "normalized": [] }, { "id": "PMID-2769204_T35", "type": "Tissue", "text": [ "folds" ], "offsets": [ [ 348, 353 ] ], "normalized": [] }, { "id": "PMID-2769204_T36", "type": "Tissue", "text": [ "folds" ], "offsets": [ [ 600, 605 ] ], "normalized": [] }, { "id": "PMID-2769204_T37", "type": "Immaterial_anatomical_entity", "text": [ "depression" ], "offsets": [ [ 232, 242 ] ], "normalized": [] } ]

[]

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[]

[ { "id": "PMC-3181428-caption-05__text", "type": "caption", "text": [ "Absolute responder rates for medical management recommendations.\n" ], "offsets": [ [ 0, 65 ] ] } ]

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[ { "id": "PMC-3106602-sec-01__text", "type": "sec", "text": [ "Background\nInflammation plays a critical role in plaque initiation, progression, and disruption. As such, inflammation represents an emerging target for the treatment of atherosclerosis.\n" ], "offsets": [ [ 0, 187 ] ] } ]

[ { "id": "PMC-3106602-sec-01_T3", "type": "Pathological_formation", "text": [ "plaque" ], "offsets": [ [ 49, 55 ] ], "normalized": [] } ]

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[]

[ { "id": "PMID-8369040__text", "type": "abstract", "text": [ "Chelation treatment of neurological Wilson's disease.\nThe results of chelation treatment of 137 patients presenting with neurological Wilson's disease are described, together with the more commonly observed toxic reactions to the various drugs employed. Fifty-seven patients made an excellent response to treatment and became symptom free. Thirty-six patients made a good recovery, but were left with some minor neurological deficit. Twenty-four patients had a poor response: although the disease process was arrested they were left more or less disabled. Twenty patients died: nine had little or no treatment, but 11 died despite apparently adequate chelation therapy. There was no obvious reason for this failure. The liver copper level was estimated in six of these patients: it was still significantly elevated in only one, but in all four in whom it was possible to make the determination, the concentration of copper in the basal ganglia was in excess of 45 micrograms/g wet weight. It was not apparent why adequate therapy failed to remove copper from the brains of these patients. There was no obvious clinical, histological or biochemical indicator of failure to respond to treatment. Initial deterioration before improvement was seen in 30 patients: the prognosis for a useful recovery was not necessarily worse than that in patients who did not show this phenomenon.\n" ], "offsets": [ [ 0, 1378 ] ] } ]

[ { "id": "PMID-8369040_T1", "type": "Anatomical_system", "text": [ "neurological" ], "offsets": [ [ 23, 35 ] ], "normalized": [] }, { "id": "PMID-8369040_T2", "type": "Anatomical_system", "text": [ "neurological" ], "offsets": [ [ 121, 133 ] ], "normalized": [] }, { "id": "PMID-8369040_T3", "type": "Anatomical_system", "text": [ "neurological" ], "offsets": [ [ 412, 424 ] ], "normalized": [] }, { "id": "PMID-8369040_T4", "type": "Organ", "text": [ "liver" ], "offsets": [ [ 720, 725 ] ], "normalized": [] }, { "id": "PMID-8369040_T5", "type": "Multi-tissue_structure", "text": [ "basal ganglia" ], "offsets": [ [ 930, 943 ] ], "normalized": [] }, { "id": "PMID-8369040_T6", "type": "Organ", "text": [ "brains" ], "offsets": [ [ 1063, 1069 ] ], "normalized": [] } ]

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[]

[ { "id": "PMC-2858170-sec-04__text", "type": "sec", "text": [ "CONCLUSIONS\nThe lack of association between depression and glycemic control is not due to the use of a binary measure of depression. Findings further clarify the significant association between distress and A1C.\n" ], "offsets": [ [ 0, 212 ] ] } ]

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[ { "id": "PMID-18425820__text", "type": "abstract", "text": [ "Isotype-specific inhibitors of the glycolytic key regulator pyruvate kinase subtype M2 moderately decelerate tumor cell proliferation. \nTumor cells express the glycolytic regulator pyruvate kinase subtype M2 (M2-PK), which can occur in a tetrameric form with high affinity to its substrate phosphoenolpyruvate (PEP) and a dimeric form with a low PEP affinity. The transition between both conformations contributes to the control of glycolysis and is important for tumor cell proliferation and survival. Here we targeted M2-PK by synthetic peptide aptamers, which specifically bind to M2-PK and shift the isoenzyme into its low affinity dimeric conformation. The aptamer-induced dimerization and inactivation of M2-PK led to a significant decrease in the PK mass-action ratio as well as ATP:ADP ratio in the target cells. Furthermore, the expression of M2-PK-binding peptide aptamers moderately reduced the growth of immortalized NIH3T3 cell populations by decelerating cell proliferation, but without affecting apoptotic cell death. Moreover, the M2-PK-binding peptide aptamers also reduced the proliferation rate of human U-2 OS osteosarcoma cells. In the present study, we developed the first specific inhibitors of the pyruvate kinase isoenzyme type M2 and present evidence that these inhibitors moderately decelerate tumor cell proliferation.\n" ], "offsets": [ [ 0, 1347 ] ] } ]

[ { "id": "PMID-18425820_T2", "type": "Cell", "text": [ "tumor cell" ], "offsets": [ [ 109, 119 ] ], "normalized": [] }, { "id": "PMID-18425820_T3", "type": "Cell", "text": [ "Tumor cells" ], "offsets": [ [ 136, 147 ] ], "normalized": [] }, { "id": "PMID-18425820_T9", "type": "Cell", "text": [ "tumor cell" ], "offsets": [ [ 464, 474 ] ], "normalized": [] }, { "id": "PMID-18425820_T16", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 814, 819 ] ], "normalized": [] }, { "id": "PMID-18425820_T18", "type": "Cell", "text": [ "NIH3T3 cell populations" ], "offsets": [ [ 929, 952 ] ], "normalized": [] }, { "id": "PMID-18425820_T19", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 969, 973 ] ], "normalized": [] }, { "id": "PMID-18425820_T20", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1021, 1025 ] ], "normalized": [] }, { "id": "PMID-18425820_T23", "type": "Cell", "text": [ "U-2 OS osteosarcoma cells" ], "offsets": [ [ 1123, 1148 ] ], "normalized": [] }, { "id": "PMID-18425820_T25", "type": "Cell", "text": [ "tumor cell" ], "offsets": [ [ 1321, 1331 ] ], "normalized": [] } ]

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[]

[ { "id": "PMC-2646714-caption-02__text", "type": "caption", "text": [ "Sealant application criteria for molar fissures\n" ], "offsets": [ [ 0, 48 ] ] } ]

[ { "id": "PMC-2646714-caption-02_T1", "type": "Organ", "text": [ "molar" ], "offsets": [ [ 33, 38 ] ], "normalized": [] } ]

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[ { "id": "PMID-11592301__text", "type": "abstract", "text": [ "Antibodies to PAI-1 alter the invasive and migratory properties of human tumour cells in vitro. \nRecent reports suggest that elevated levels of plasminogen activator inhibitor-1 (PAI-1) may contribute to tumour progression. The studies reported here were designed to help elucidate PAI-1's contribution to the invasive and migratory phenotype. Antibodies to PA-1 dose-dependently, and significantly, inhibited the invasive and migratory potential of human HT1080 fibrosarcoma cells, as did an antibody to uPA and the plasmin inhibitor aprotinin. Invasion of the human melanoma cell line, BLM, was also attenuated by the anti-PAI-1 monoclonal antibody MAI-12. The non-invasive human melanoma cell line, IF6, which does not express uPA, provided further confirmation of PAI-1 and uPA's role as, upon transfection with uPA, this cell line attained an invasive phenotype, which was again attenuated by MAI-12. Although antibodies to PAI-1 did not affect the adhesion of HT1080 cells to vitronectin, the antibody to uPA reduced their attachment. Addition of exogenous PAI-1, however, prevented HT1080 cell adhesion (IC50 180 nM) and promoted cell detachment from vitronectin. Furthermore melanoma cells transfected with a uPA variant, which had an impaired interaction with PAI-1, were not invasive and had impaired binding to vitronectin. These data highlight the importance of a balanced proteolysis and suggest an additional role for PAI-1 distinct from its role in proteolysis. These data also suggest that uPA and PAI-1 may co-operate in the migratory process by respectively facilitating the attachment to, and subsequent detachment from, vitronectin in the extracellular matrix. These results support the clinical findings and indicate that modulation of PAI-1 activity may be of therapeutic benefit for the treatment of cancer.\n" ], "offsets": [ [ 0, 1831 ] ] } ]

[ { "id": "PMID-11592301_T3", "type": "Cell", "text": [ "tumour cells" ], "offsets": [ [ 73, 85 ] ], "normalized": [] }, { "id": "PMID-11592301_T6", "type": "Cancer", "text": [ "tumour" ], "offsets": [ [ 204, 210 ] ], "normalized": [] }, { "id": "PMID-11592301_T10", "type": "Cell", "text": [ "HT1080 fibrosarcoma cells" ], "offsets": [ [ 456, 481 ] ], "normalized": [] }, { "id": "PMID-11592301_T15", "type": "Cell", "text": [ "melanoma cell line" ], "offsets": [ [ 568, 586 ] ], "normalized": [] }, { "id": "PMID-11592301_T16", "type": "Cell", "text": [ "BLM" ], "offsets": [ [ 588, 591 ] ], "normalized": [] }, { "id": "PMID-11592301_T19", "type": "Cell", "text": [ "melanoma cell line" ], "offsets": [ [ 682, 700 ] ], "normalized": [] }, { "id": "PMID-11592301_T20", "type": "Cell", "text": [ "IF6" ], "offsets": [ [ 702, 705 ] ], "normalized": [] }, { "id": "PMID-11592301_T25", "type": "Cell", "text": [ "cell line" ], "offsets": [ [ 826, 835 ] ], "normalized": [] }, { "id": "PMID-11592301_T27", "type": "Cell", "text": [ "HT1080 cells" ], "offsets": [ [ 966, 978 ] ], "normalized": [] }, { "id": "PMID-11592301_T31", "type": "Cell", "text": [ "HT1080 cell" ], "offsets": [ [ 1089, 1100 ] ], "normalized": [] }, { "id": "PMID-11592301_T32", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1137, 1141 ] ], "normalized": [] }, { "id": "PMID-11592301_T34", "type": "Cell", "text": [ "melanoma cells" ], "offsets": [ [ 1183, 1197 ] ], "normalized": [] }, { "id": "PMID-11592301_T42", "type": "Cellular_component", "text": [ "extracellular matrix" ], "offsets": [ [ 1659, 1679 ] ], "normalized": [] }, { "id": "PMID-11592301_T44", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 1823, 1829 ] ], "normalized": [] } ]

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[ { "id": "PMID-9648911__text", "type": "abstract", "text": [ "Induction of Ets-1 in endothelial cells during reendothelialization after denuding injury.\nEts-1, a transcription factor, is induced in endothelial cells (ECs) during angiogenesis. Here, we investigated the expression of Ets-1 during reendothelialization. When a confluent monolayer of human umbilical vein endothelial cell line, ECV304, was denuded, ECV304 at the wound edge expressed Ets-1. An immunohistochemical analysis revealed that Ets-1 accumulated in migrating cells at the wound edge and returned to basal level when reendothelialization was accomplished. This induction of Ets-1 could be reproduced in in vivo denudation of rat aortic endothelium by a balloon catheter. The induction of Ets-1 in ECs after denudation was regulated transcriptionally, and humeral factors released from injured ECs might not be responsible. Mitogen-activated protein kinase (MAPK) activities were investigated to explore the mechanism of this induction. Although extracellular signal-regulated protein kinase 1/2 (ERK1/2), c-Jun N-terminal kinase 1 (JNK1), and p38 were activated after denudation, the activation of ERK1 and p38 was more rapid and prominent. PD98059, a specific MAPK/ERK kinase (MEK) 1 inhibitor, did not affect the induction of ets-1 mRNA, whereas SB203580, a specific p38 inhibitor, almost completely abrogated its induction. These results indicate that Ets-1 is induced in ECs after denudation through activation of p38. This induction of Ets-1 may be relevant for reendothelialization by regulating the expression of certain genes.\n" ], "offsets": [ [ 0, 1545 ] ] } ]

[ { "id": "PMID-9648911_T2", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 22, 39 ] ], "normalized": [] }, { "id": "PMID-9648911_T4", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 136, 153 ] ], "normalized": [] }, { "id": "PMID-9648911_T5", "type": "Cell", "text": [ "ECs" ], "offsets": [ [ 155, 158 ] ], "normalized": [] }, { "id": "PMID-9648911_T7", "type": "Cell", "text": [ "monolayer" ], "offsets": [ [ 273, 282 ] ], "normalized": [] }, { "id": "PMID-9648911_T8", "type": "Cell", "text": [ "human umbilical vein endothelial cell line" ], "offsets": [ [ 286, 328 ] ], "normalized": [] }, { "id": "PMID-9648911_T9", "type": "Cell", "text": [ "ECV304" ], "offsets": [ [ 330, 336 ] ], "normalized": [] }, { "id": "PMID-9648911_T10", "type": "Cell", "text": [ "ECV304" ], "offsets": [ [ 351, 357 ] ], "normalized": [] }, { "id": "PMID-9648911_T11", "type": "Pathological_formation", "text": [ "wound edge" ], "offsets": [ [ 365, 375 ] ], "normalized": [] }, { "id": "PMID-9648911_T14", "type": "Cell", "text": [ "migrating cells" ], "offsets": [ [ 460, 475 ] ], "normalized": [] }, { "id": "PMID-9648911_T15", "type": "Pathological_formation", "text": [ "wound edge" ], "offsets": [ [ 483, 493 ] ], "normalized": [] }, { "id": "PMID-9648911_T18", "type": "Tissue", "text": [ "aortic endothelium" ], "offsets": [ [ 639, 657 ] ], "normalized": [] }, { "id": "PMID-9648911_T20", "type": "Cell", "text": [ "ECs" ], "offsets": [ [ 707, 710 ] ], "normalized": [] }, { "id": "PMID-9648911_T22", "type": "Cell", "text": [ "ECs" ], "offsets": [ [ 803, 806 ] ], "normalized": [] }, { "id": "PMID-9648911_T40", "type": "Cell", "text": [ "ECs" ], "offsets": [ [ 1385, 1388 ] ], "normalized": [] } ]

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[ { "id": "PMC-1615867-sec-09__text", "type": "sec", "text": [ "Conclusion\nThe survey indicated that, the study area has plenty of medicinal plants to treat a wide spectrum of human ailments. Earlier studies on traditional medicinal plants also revealed that the economically backward local and tribal people of Tamil Nadu prefer folk medicine due to low cost and sometimes it is a part of their social life and culture [40-45]. It is evident from the interviews conducted in different villages, knowledge of medicinal plants is limited to traditional healers, herbalists and elderly persons who are living in rural areas. This study also points out that certain species of medicinal plants are being exploited by the local residents who are unaware of the importance of medicinal plants in the ecosystem.\nThis study concluded that even though the accessibility of Western medicine for simple and complicated diseases is available, many people in the studied parts of Kancheepuram district is still continue to depend on medicinal plants, at least for the treatment of some simple diseases such as, cold, cough, fever, headache, poison bites, skin diseases and tooth infections. Well-knowledged healers have good interactions with patients and this would improve the quality of healthcare delivery. The present-day traditional healers are very old. Due to lack of interest among the younger generation as well as their tendency to migrate to cities for lucrative jobs, there is a possibility of losing this wealth of knowledge in the near future. It thus becomes necessary to acquire and preserve this traditional system of medicine by proper documentation and identification of specimens.\n" ], "offsets": [ [ 0, 1626 ] ] } ]

[ { "id": "PMC-1615867-sec-09_T1", "type": "Organ", "text": [ "skin" ], "offsets": [ [ 1079, 1083 ] ], "normalized": [] }, { "id": "PMC-1615867-sec-09_T2", "type": "Organ", "text": [ "tooth" ], "offsets": [ [ 1097, 1102 ] ], "normalized": [] }, { "id": "PMC-1615867-sec-09_T3", "type": "Organism_substance", "text": [ "poison" ], "offsets": [ [ 1065, 1071 ] ], "normalized": [] } ]

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[ { "id": "PMID-6326669__text", "type": "abstract", "text": [ "Preliminary evidence for a pyridine nucleotide cycle in Bordetella pertussis.\nPreliminary evidence that Bordetella pertussis has a functional pyridine nucleotide cycle was the observation that [14C]-nicotinic acid was rapidly metabolized during its uptake by the bacteria to pyridine nucleotides and nicotinamide. Nicotinamide deamidase activity, necessary for the completion of the cycle by conversion of nicotinamide to nicotinic acid, was found in a soluble extract (20 000 X g supernatant) of B. pertussis cell lysates.\n" ], "offsets": [ [ 0, 524 ] ] } ]

[ { "id": "PMID-6326669_T1", "type": "Organism_substance", "text": [ "cell lysates" ], "offsets": [ [ 510, 522 ] ], "normalized": [] }, { "id": "PMID-6326669_T2", "type": "Organism_substance", "text": [ "extract" ], "offsets": [ [ 461, 468 ] ], "normalized": [] }, { "id": "PMID-6326669_T3", "type": "Organism_substance", "text": [ "supernatant" ], "offsets": [ [ 481, 492 ] ], "normalized": [] } ]

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[ { "id": "PMID-9891506__text", "type": "abstract", "text": [ "Effect of U-995, a potent shark cartilage-derived angiogenesis inhibitor, on anti-angiogenesis and anti-tumor activities.\nBACKGROUND: A potent angiogenesis inhibitor, U-995, has been purified from the cartilage of the blue shark (Prionace glauca). U-995 is composed of two single peptides with molecular mass of 10 and 14 kDa, respectively. MATERIALS AND METHODS: U-995 was designed to study human umbilical vein endothelial cell (HUVEC) migration and proliferation in vitro and angiogenesis induced by TNF alpha in chicken chorioallantoic membrane (CAM). Furthermore, we determined the ability of U-995 to inhibiting tumor cell growth and metastasis. RESULTS: U-995 (15 and 30 micrograms/ml) markedly inhibited HUVEC migration and, at 15-50 micrograms/ml produced a dose-dependent decline in [3H]-thymidine incorporation. 30 and 50 micrograms/ml of U-995, when added to TNF alpha-induced angiogenesis caused discontinuous and disrupted blood vessels. Moreover, U-995 (30 micrograms/ml) markedly prevented collagenase-induced collagenolysis. In addition, when 200 micrograms U-995 was injected i.p. into mice it suppressed sarcoma-180 cell growth and B16-F10 mouse melanoma cell metastasis in vivo. CONCLUSIONS: These results suggest that the anti-angiogenic effects of U-995 may be be due to interference with the proliferation and migration of HUVECs as well as inhibition of collagenolysis, thereby leading to inhibition of both angiogenesis and tumor cell growth.\n" ], "offsets": [ [ 0, 1468 ] ] } ]

[ { "id": "PMID-9891506_T3", "type": "Tissue", "text": [ "cartilage" ], "offsets": [ [ 32, 41 ] ], "normalized": [] }, { "id": "PMID-9891506_T4", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 104, 109 ] ], "normalized": [] }, { "id": "PMID-9891506_T6", "type": "Tissue", "text": [ "cartilage" ], "offsets": [ [ 201, 210 ] ], "normalized": [] }, { "id": "PMID-9891506_T11", "type": "Cell", "text": [ "human umbilical vein endothelial cell" ], "offsets": [ [ 392, 429 ] ], "normalized": [] }, { "id": "PMID-9891506_T12", "type": "Cell", "text": [ "HUVEC" ], "offsets": [ [ 431, 436 ] ], "normalized": [] }, { "id": "PMID-9891506_T15", "type": "Multi-tissue_structure", "text": [ "chorioallantoic membrane" ], "offsets": [ [ 524, 548 ] ], "normalized": [] }, { "id": "PMID-9891506_T16", "type": "Multi-tissue_structure", "text": [ "CAM" ], "offsets": [ [ 550, 553 ] ], "normalized": [] }, { "id": "PMID-9891506_T18", "type": "Cell", "text": [ "tumor cell" ], "offsets": [ [ 618, 628 ] ], "normalized": [] }, { "id": "PMID-9891506_T20", "type": "Cell", "text": [ "HUVEC" ], "offsets": [ [ 712, 717 ] ], "normalized": [] }, { "id": "PMID-9891506_T24", "type": "Multi-tissue_structure", "text": [ "blood vessels" ], "offsets": [ [ 937, 950 ] ], "normalized": [] }, { "id": "PMID-9891506_T29", "type": "Cell", "text": [ "sarcoma-180 cell" ], "offsets": [ [ 1123, 1139 ] ], "normalized": [] }, { "id": "PMID-9891506_T30", "type": "Cell", "text": [ "B16-F10 mouse melanoma cell" ], "offsets": [ [ 1151, 1178 ] ], "normalized": [] }, { "id": "PMID-9891506_T32", "type": "Cell", "text": [ "HUVECs" ], "offsets": [ [ 1346, 1352 ] ], "normalized": [] }, { "id": "PMID-9891506_T33", "type": "Cell", "text": [ "tumor cell" ], "offsets": [ [ 1449, 1459 ] ], "normalized": [] } ]

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[ { "id": "PMID-15528872__text", "type": "abstract", "text": [ "Thiazole orange positive platelets in a dog with Evans' syndrome.\nWe examined transition for the percentage of reticulated platelets (RP%) and platelet count in a canine case of Evans' syndrome. The result demonstrated that measurement of the RP% can be useful in evaluating platelet production in the bone marrow and response to treatment.\n" ], "offsets": [ [ 0, 341 ] ] } ]

[ { "id": "PMID-15528872_T1", "type": "Cell", "text": [ "platelets" ], "offsets": [ [ 25, 34 ] ], "normalized": [] }, { "id": "PMID-15528872_T2", "type": "Cell", "text": [ "reticulated platelets" ], "offsets": [ [ 111, 132 ] ], "normalized": [] }, { "id": "PMID-15528872_T3", "type": "Cell", "text": [ "RP" ], "offsets": [ [ 134, 136 ] ], "normalized": [] }, { "id": "PMID-15528872_T4", "type": "Cell", "text": [ "platelet" ], "offsets": [ [ 143, 151 ] ], "normalized": [] }, { "id": "PMID-15528872_T5", "type": "Cell", "text": [ "RP" ], "offsets": [ [ 243, 245 ] ], "normalized": [] }, { "id": "PMID-15528872_T6", "type": "Cell", "text": [ "platelet" ], "offsets": [ [ 275, 283 ] ], "normalized": [] }, { "id": "PMID-15528872_T7", "type": "Multi-tissue_structure", "text": [ "bone marrow" ], "offsets": [ [ 302, 313 ] ], "normalized": [] } ]

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[ { "id": "PMC-1592597-caption-02__text", "type": "caption", "text": [ "Correlation between sperm morphology and seminal plasma NO (a) and TBARS (b) levels in both groups.\n" ], "offsets": [ [ 0, 100 ] ] } ]

[ { "id": "PMC-1592597-caption-02_T1", "type": "Cell", "text": [ "sperm" ], "offsets": [ [ 20, 25 ] ], "normalized": [] }, { "id": "PMC-1592597-caption-02_T2", "type": "Organism_substance", "text": [ "seminal plasma" ], "offsets": [ [ 41, 55 ] ], "normalized": [] } ]

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[ { "id": "PMID-10586954__text", "type": "abstract", "text": [ "Insulin-induced vascular endothelial growth factor expression in retina.\nPURPOSE: Clinical studies have demonstrated that intensive insulin therapy causes a transient worsening of retinopathy. The mechanisms underlying the initial insulin-induced deterioration of retinal status in patients with diabetes remain unknown. Vascular endothelial growth factor (VEGF) is known to be operative in the pathogenesis of diabetic retinopathy. The current study was conducted to characterize the effect of insulin on retinal VEGF gene expression in vitro and in vivo. METHODS: The effect of insulin on VEGF expression in vivo was examined by in situ hybridization studies of rat retinal VEGF transcripts. To examine the mechanisms by which insulin regulates VEGF expression, human retinal pigment epithelial (RPE) cells were exposed to insulin, and VEGF mRNA levels were quantified with RNase protection assays (RPAs). Conditioned media from insulin-treated RPE cells were assayed for VEGF protein and capillary endothelial cell proliferation. The capacity of insulin to stimulate the VEGF promoter linked to a luciferase reporter gene was characterized in transient transfection assays. RESULTS: Insulin increased VEGF mRNA levels in the ganglion, inner nuclear, and RPE cell layers. In vitro, insulin increased VEGF mRNA levels in human RPE cells and enhanced VEGF promoter activity without affecting transcript stability. Insulin treatment also increased VEGF protein levels in conditioned RPE cell media in a dose-dependent manner with a median effective concentration of 5 nM. The insulin-conditioned RPE cell media stimulated capillary endothelial cell proliferation, an effect that was completely blocked by anti-VEGF neutralizing antibody. CONCLUSIONS: Insulin increases VEGF mRNA and secreted protein levels in RPE cells through enhanced transcription of the VEGF gene. Intensive insulin therapy may cause a transient worsening of retinopathy in patients with diabetes through increased retinal VEGF gene expression.\n" ], "offsets": [ [ 0, 2015 ] ] } ]

[ { "id": "PMID-10586954_T3", "type": "Multi-tissue_structure", "text": [ "retina" ], "offsets": [ [ 65, 71 ] ], "normalized": [] }, { "id": "PMID-10586954_T6", "type": "Multi-tissue_structure", "text": [ "retinal" ], "offsets": [ [ 264, 271 ] ], "normalized": [] }, { "id": "PMID-10586954_T11", "type": "Multi-tissue_structure", "text": [ "retinal" ], "offsets": [ [ 506, 513 ] ], "normalized": [] }, { "id": "PMID-10586954_T16", "type": "Multi-tissue_structure", "text": [ "retinal" ], "offsets": [ [ 668, 675 ] ], "normalized": [] }, { "id": "PMID-10586954_T21", "type": "Cell", "text": [ "retinal pigment epithelial (RPE) cells" ], "offsets": [ [ 770, 808 ] ], "normalized": [] }, { "id": "PMID-10586954_T26", "type": "Cell", "text": [ "RPE cells" ], "offsets": [ [ 947, 956 ] ], "normalized": [] }, { "id": "PMID-10586954_T28", "type": "Cell", "text": [ "capillary endothelial cell" ], "offsets": [ [ 991, 1017 ] ], "normalized": [] }, { "id": "PMID-10586954_T34", "type": "Tissue", "text": [ "ganglion" ], "offsets": [ [ 1228, 1236 ] ], "normalized": [] }, { "id": "PMID-10586954_T35", "type": "Tissue", "text": [ "inner nuclear" ], "offsets": [ [ 1238, 1251 ] ], "normalized": [] }, { "id": "PMID-10586954_T36", "type": "Tissue", "text": [ "RPE cell layers" ], "offsets": [ [ 1257, 1272 ] ], "normalized": [] }, { "id": "PMID-10586954_T40", "type": "Cell", "text": [ "RPE cells" ], "offsets": [ [ 1328, 1337 ] ], "normalized": [] }, { "id": "PMID-10586954_T44", "type": "Cell", "text": [ "RPE cell" ], "offsets": [ [ 1482, 1490 ] ], "normalized": [] }, { "id": "PMID-10586954_T46", "type": "Cell", "text": [ "RPE cell" ], "offsets": [ [ 1595, 1603 ] ], "normalized": [] }, { "id": "PMID-10586954_T47", "type": "Cell", "text": [ "capillary endothelial cell" ], "offsets": [ [ 1621, 1647 ] ], "normalized": [] }, { "id": "PMID-10586954_T51", "type": "Cell", "text": [ "RPE cells" ], "offsets": [ [ 1809, 1818 ] ], "normalized": [] }, { "id": "PMID-10586954_T55", "type": "Multi-tissue_structure", "text": [ "retinal" ], "offsets": [ [ 1985, 1992 ] ], "normalized": [] } ]

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[ { "id": "PMID-19636328__text", "type": "abstract", "text": [ "Targeting angiogenesis: progress with anti-VEGF treatment with large molecules.\nAngiogenesis--one of the hallmarks of cancer--has emerged as a valid therapeutic target in oncology. The VEGF system represents a key mediator of tumor-initiated angiogenesis and the first target of antiangiogenesis agents introduced in clinical practice. Although anti-VEGF therapies have clearly demonstrated antitumor efficacy in various malignancies, especially when combined with conventional cytotoxic chemotherapy, their mechanism of action is not fully understood. This Review will discuss the rationale for using antiangiogenic compounds and will focus on large molecules, such as antibodies, that target the VEGF system. Clinical data on bevacizumab is discussed in detail. Predictive markers for anti-VEGF agents have not yet been identified and questions regarding the usefulness of bevacizumab in the adjuvant setting as well as its continued use beyond progression remain unanswered, in spite of negative data on bevacizumab in treating patients with adjuvant colon cancer. Nonetheless, anti-VEGF therapy has enhanced the arsenal of anticancer therapies and has provided new insights into the biology of malignancy.\n" ], "offsets": [ [ 0, 1210 ] ] } ]

[ { "id": "PMID-19636328_T2", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 118, 124 ] ], "normalized": [] }, { "id": "PMID-19636328_T4", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 226, 231 ] ], "normalized": [] }, { "id": "PMID-19636328_T6", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 395, 400 ] ], "normalized": [] }, { "id": "PMID-19636328_T7", "type": "Cancer", "text": [ "malignancies" ], "offsets": [ [ 421, 433 ] ], "normalized": [] }, { "id": "PMID-19636328_T14", "type": "Cancer", "text": [ "colon cancer" ], "offsets": [ [ 1054, 1066 ] ], "normalized": [] }, { "id": "PMID-19636328_T16", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 1131, 1137 ] ], "normalized": [] }, { "id": "PMID-19636328_T17", "type": "Cancer", "text": [ "malignancy" ], "offsets": [ [ 1198, 1208 ] ], "normalized": [] } ]

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