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[ { "id": "PMC-194858-caption-04__text", "type": "caption", "text": [ "Extrapyramidal symptoms based on Extrapyramidal Symptoms Rating Scale\n" ], "offsets": [ [ 0, 70 ] ] } ]

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[ { "id": "PMID-20124444__text", "type": "abstract", "text": [ "Hormonal regulation and distinct functions of semaphorin-3B and semaphorin-3F in ovarian cancer. \nSemaphorins comprise a family of molecules that influence neuronal growth and guidance. Class-3 semaphorins, semaphorin-3B (SEMA3B) and semaphorin-3F (SEMA3F), illustrate their effects by forming a complex with neuropilins (NP-1 or NP-2) and plexins. We examined the status and regulation of semaphorins and their receptors in human ovarian cancer cells. A significantly reduced expression of SEMA3B (83 kDa), SEMA3F (90 kDa), and plexin-A3 was observed in ovarian cancer cell lines when compared with normal human ovarian surface epithelial cells. The expression of NP-1, NP-2, and plexin-A1 was not altered in human ovarian surface epithelial and ovarian cancer cells. The decreased expression of SEMA3B, SEMA3F, and plexin-A3 was confirmed in stage 3 ovarian tumors. The treatment of ovarian cancer cells with luteinizing hormone, follicle-stimulating hormone, and estrogen induced a significant upregulation of SEMA3B, whereas SEMA3F was upregulated only by estrogen. Cotreatment of cell lines with a hormone and its specific antagonist blocked the effect of the hormone. Ectopic expression of SEMA3B or SEMA3F reduced soft-agar colony formation, adhesion, and cell invasion of ovarian cancer cell cultures. Forced expression of SEMA3B, but not SEMA3F, inhibited viability of ovarian cancer cells. Overexpression of SEMA3B and SEMA3F reduced focal adhesion kinase phosphorylation and matrix metalloproteinase-2 and matrix metalloproteinase-9 expression in ovarian cancer cells. Forced expression of SEMA3F, but not SEMA3B in ovarian cancer cells, significantly inhibited endothelial cell tube formation. Collectively, our results suggest that the loss of SEMA3 expression could be a hallmark of cancer progression. Furthermore, gonadotropin- and/or estrogen-mediated maintenance of SEMA3 expression could control ovarian cancer angiogenesis and metastasis.\n" ], "offsets": [ [ 0, 1959 ] ] } ]

[ { "id": "PMID-20124444_T3", "type": "Cancer", "text": [ "ovarian cancer" ], "offsets": [ [ 81, 95 ] ], "normalized": [] }, { "id": "PMID-20124444_T5", "type": "Cell", "text": [ "neuronal" ], "offsets": [ [ 156, 164 ] ], "normalized": [] }, { "id": "PMID-20124444_T17", "type": "Cell", "text": [ "ovarian cancer cells" ], "offsets": [ [ 431, 451 ] ], "normalized": [] }, { "id": "PMID-20124444_T21", "type": "Cell", "text": [ "ovarian cancer cell lines" ], "offsets": [ [ 555, 580 ] ], "normalized": [] }, { "id": "PMID-20124444_T23", "type": "Cell", "text": [ "ovarian surface epithelial cells" ], "offsets": [ [ 613, 645 ] ], "normalized": [] }, { "id": "PMID-20124444_T28", "type": "Cell", "text": [ "ovarian surface epithelial" ], "offsets": [ [ 716, 742 ] ], "normalized": [] }, { "id": "PMID-20124444_T29", "type": "Cell", "text": [ "ovarian cancer cells" ], "offsets": [ [ 747, 767 ] ], "normalized": [] }, { "id": "PMID-20124444_T33", "type": "Cancer", "text": [ "ovarian tumors" ], "offsets": [ [ 852, 866 ] ], "normalized": [] }, { "id": "PMID-20124444_T34", "type": "Cell", "text": [ "ovarian cancer cells" ], "offsets": [ [ 885, 905 ] ], "normalized": [] }, { "id": "PMID-20124444_T41", "type": "Cell", "text": [ "cell lines" ], "offsets": [ [ 1085, 1095 ] ], "normalized": [] }, { "id": "PMID-20124444_T44", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1263, 1267 ] ], "normalized": [] }, { "id": "PMID-20124444_T45", "type": "Cell", "text": [ "ovarian cancer cell cultures" ], "offsets": [ [ 1280, 1308 ] ], "normalized": [] }, { "id": "PMID-20124444_T48", "type": "Cell", "text": [ "ovarian cancer cells" ], "offsets": [ [ 1378, 1398 ] ], "normalized": [] }, { "id": "PMID-20124444_T54", "type": "Cell", "text": [ "ovarian cancer cells" ], "offsets": [ [ 1558, 1578 ] ], "normalized": [] }, { "id": "PMID-20124444_T57", "type": "Cell", "text": [ "ovarian cancer cells" ], "offsets": [ [ 1627, 1647 ] ], "normalized": [] }, { "id": "PMID-20124444_T58", "type": "Tissue", "text": [ "endothelial cell tube" ], "offsets": [ [ 1673, 1694 ] ], "normalized": [] }, { "id": "PMID-20124444_T60", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 1797, 1803 ] ], "normalized": [] }, { "id": "PMID-20124444_T64", "type": "Cancer", "text": [ "ovarian cancer" ], "offsets": [ [ 1915, 1929 ] ], "normalized": [] }, { "id": "PMID-20124444_T105", "type": "Cell", "text": [ "colony" ], "offsets": [ [ 1231, 1237 ] ], "normalized": [] } ]

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[ { "id": "PMID-17607547__text", "type": "abstract", "text": [ "Selective activation of mast cells in rheumatoid synovial tissue results in production of TNF-alpha, IL-1beta and IL-1Ra.\nOBJECTIVES AND DESIGN:\nTo study the consequences of mast cell activation in human synovial tissue.\nMETHODS:\nSynovial tissue was obtained from 18 RA patients and mast cells was selectively activated in synovial tissue explant cultures. Expression of TNF-alpha, IL-1beta and IL-1Ra were determined and tissue distribution of IL-1beta was studied.\nRESULTS:\nCompared to untreated synovia, selective activation of synovial mast cells increased significantly the production of TNF-alpha (0.49 +/- 0.88 vs. 4.56 +/- 3.18 pg/mg wet tissue, p < 0.001) and IL-1beta (0.058 +/- 0.032 vs. 2.55 +/- 1.98 pg/mg wet tissue, p = 0.013). The expression of TNF-alpha and IL-1beta mRNA increased significantly (19-fold (p = 0.009) and 13-fold (p = 0.031), respectively). Mast cell activation induced IL-1beta expression in particular in nearby CD68 positive synovial macrophages. Secretion of IL-1Ra was also increased but to a lesser degree than that of IL-1beta.\nCONCLUSIONS:\nSynovial mast cells produce proinflammmatory cytokines and may thus contribute to the inflammation in RA.\n" ], "offsets": [ [ 0, 1187 ] ] } ]

[ { "id": "PMID-17607547_T1", "type": "Cell", "text": [ "mast cells" ], "offsets": [ [ 24, 34 ] ], "normalized": [] }, { "id": "PMID-17607547_T2", "type": "Tissue", "text": [ "rheumatoid synovial tissue" ], "offsets": [ [ 38, 64 ] ], "normalized": [] }, { "id": "PMID-17607547_T3", "type": "Cell", "text": [ "mast cell" ], "offsets": [ [ 174, 183 ] ], "normalized": [] }, { "id": "PMID-17607547_T4", "type": "Tissue", "text": [ "synovial tissue" ], "offsets": [ [ 204, 219 ] ], "normalized": [] }, { "id": "PMID-17607547_T5", "type": "Tissue", "text": [ "Synovial tissue" ], "offsets": [ [ 230, 245 ] ], "normalized": [] }, { "id": "PMID-17607547_T6", "type": "Cell", "text": [ "mast cells" ], "offsets": [ [ 283, 293 ] ], "normalized": [] }, { "id": "PMID-17607547_T7", "type": "Tissue", "text": [ "synovial tissue" ], "offsets": [ [ 323, 338 ] ], "normalized": [] }, { "id": "PMID-17607547_T8", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 422, 428 ] ], "normalized": [] }, { "id": "PMID-17607547_T9", "type": "Tissue", "text": [ "synovia" ], "offsets": [ [ 498, 505 ] ], "normalized": [] }, { "id": "PMID-17607547_T10", "type": "Cell", "text": [ "synovial mast cells" ], "offsets": [ [ 531, 550 ] ], "normalized": [] }, { "id": "PMID-17607547_T11", "type": "Cell", "text": [ "Mast cell" ], "offsets": [ [ 874, 883 ] ], "normalized": [] }, { "id": "PMID-17607547_T12", "type": "Cell", "text": [ "CD68 positive synovial macrophages" ], "offsets": [ [ 947, 981 ] ], "normalized": [] }, { "id": "PMID-17607547_T13", "type": "Cell", "text": [ "Synovial mast cells" ], "offsets": [ [ 1081, 1100 ] ], "normalized": [] }, { "id": "PMID-17607547_T17", "type": "Tissue", "text": [ "wet tissue" ], "offsets": [ [ 642, 652 ] ], "normalized": [] }, { "id": "PMID-17607547_T18", "type": "Tissue", "text": [ "wet tissue" ], "offsets": [ [ 719, 729 ] ], "normalized": [] } ]

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[ { "id": "PMID-19323937__text", "type": "abstract", "text": [ "Coagulation function in patients with pancreatic carcinoma. \nBACKGROUND: The coagulation function in patients with pancreatic carcinoma is abnormal and the reason is not very clear. In this study, we retrospectively analyzed the coagulation function in patients with pancreatic carcinoma. METHODS: From June 2004 to December 2007, 132 patients received diagnosis and treatment in our hospital. The coagulative parameters including the prothrombin time, activated partial thromboplastin time, and fibrinogen levels were collected and studied retrospectively. RESULTS: The average fibrinogen levels in patients with pancreatic carcinoma, (476.21 +/- 142.05) mg/dl, were significantly higher than in patients with cholangiolithiasis, (403.28 +/- 126.41) mg/dl (P < 0.05). In patients with pancreatic carcinoma, the levels of fibrinogen in the group with jaundice were significantly higher than in patients without jaundice (P < 0.05). In patients who received Pancreaticoduodenectomy, Whipple's operation, the level of fibrinogen in the group with local invasiveness was significantly higher than in the group without invasiveness. The group with lymphatic metastasis had higher levels than the group without lymphatic metastasis (P < 0.05). There was no significant difference of intraoperative blood loss between patients with vitamin K, (748.27 +/- 448.51) ml, and those without vitamin K, (767.31 +/- 547.89) ml (P > 0.05). CONCLUSIONS: The level of fibrinogen in patients with pancreatic carcinoma was elevated. The elevated fibrinogen level may be associated with invasiveness and lymphatic metastasis. Using vitamin K in perioperation management did not reduce intraoperative blood loss.\n" ], "offsets": [ [ 0, 1692 ] ] } ]

[ { "id": "PMID-19323937_T2", "type": "Cancer", "text": [ "pancreatic carcinoma" ], "offsets": [ [ 38, 58 ] ], "normalized": [] }, { "id": "PMID-19323937_T4", "type": "Cancer", "text": [ "pancreatic carcinoma" ], "offsets": [ [ 115, 135 ] ], "normalized": [] }, { "id": "PMID-19323937_T6", "type": "Cancer", "text": [ "pancreatic carcinoma" ], "offsets": [ [ 267, 287 ] ], "normalized": [] }, { "id": "PMID-19323937_T13", "type": "Cancer", "text": [ "pancreatic carcinoma" ], "offsets": [ [ 614, 634 ] ], "normalized": [] }, { "id": "PMID-19323937_T16", "type": "Cancer", "text": [ "pancreatic carcinoma" ], "offsets": [ [ 786, 806 ] ], "normalized": [] }, { "id": "PMID-19323937_T21", "type": "Organ", "text": [ "lymphatic" ], "offsets": [ [ 1144, 1153 ] ], "normalized": [] }, { "id": "PMID-19323937_T22", "type": "Organ", "text": [ "lymphatic" ], "offsets": [ [ 1206, 1215 ] ], "normalized": [] }, { "id": "PMID-19323937_T23", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 1293, 1298 ] ], "normalized": [] }, { "id": "PMID-19323937_T29", "type": "Cancer", "text": [ "pancreatic carcinoma" ], "offsets": [ [ 1479, 1499 ] ], "normalized": [] }, { "id": "PMID-19323937_T31", "type": "Organ", "text": [ "lymphatic" ], "offsets": [ [ 1584, 1593 ] ], "normalized": [] }, { "id": "PMID-19323937_T33", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 1680, 1685 ] ], "normalized": [] } ]

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[ { "id": "PMID-10543260__text", "type": "abstract", "text": [ "Increased serum levels of vascular endothelial growth factor in patients with renal cell carcinoma.\nNeovascularization, an essential event for the growth of solid tumors, is regulated by a number of angiogenic factors. One such factor, vascular endothelial growth factor (VEGF), is considered to exert a potent angiogenic activity, as indicated by immunohistochemical and molecular evidence. In this study we investigated the serum VEGF level (s-VEGF) in patients with renal cell carcinoma (RCC). s-VEGF in peripheral blood samples was analyzed in 40 RCC patients and 40 patients without cancer (controls) using a sandwich enzyme-linked immunoassay. In 20 RCC patients, serum samples were obtained separately from the bilateral renal veins. s-VEGF was also measured before, 4 and 8 weeks after nephrectomy in 11 patients. There were significant differences in s-VEGF between the RCC patients and the controls (207.3+/-32.9 vs. 71.5+/-9.1 pg/ml, mean+/-SE) (P less than 0.005), between the tumor-bearing renal veins and the contralateral ones (P less than 0.01), between the pre- and post-nephrectomy situations (P less than 0.01) and among the various parameters of tumor status such as tumor extent (P less than 0.001) and existence of metastasis (P less than 0.001). s-VEGF significantly correlated with the tumor volume obtained by a three-dimensional measurement (r=0.802, P less than 0.0001). The sensitivity and specificity of s-VEGF at the cut-off level of 100 pg/ml, as determined by the receiver-operating-characteristics curve, were 80.0% and 72.5%, respectively. The results indicate that tumor tissue of RCC liberates VEGF into the systemic blood flow and that s-VEGF is a possible marker for RCC.\n" ], "offsets": [ [ 0, 1710 ] ] } ]

[ { "id": "PMID-10543260_T1", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 10, 15 ] ], "normalized": [] }, { "id": "PMID-10543260_T4", "type": "Cancer", "text": [ "renal cell carcinoma" ], "offsets": [ [ 78, 98 ] ], "normalized": [] }, { "id": "PMID-10543260_T5", "type": "Cancer", "text": [ "solid tumors" ], "offsets": [ [ 157, 169 ] ], "normalized": [] }, { "id": "PMID-10543260_T8", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 426, 431 ] ], "normalized": [] }, { "id": "PMID-10543260_T12", "type": "Cancer", "text": [ "renal cell carcinoma" ], "offsets": [ [ 469, 489 ] ], "normalized": [] }, { "id": "PMID-10543260_T13", "type": "Cancer", "text": [ "RCC" ], "offsets": [ [ 491, 494 ] ], "normalized": [] }, { "id": "PMID-10543260_T15", "type": "Organism_substance", "text": [ "peripheral blood samples" ], "offsets": [ [ 507, 531 ] ], "normalized": [] }, { "id": "PMID-10543260_T16", "type": "Cancer", "text": [ "RCC" ], "offsets": [ [ 551, 554 ] ], "normalized": [] }, { "id": "PMID-10543260_T19", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 588, 594 ] ], "normalized": [] }, { "id": "PMID-10543260_T20", "type": "Cancer", "text": [ "RCC" ], "offsets": [ [ 656, 659 ] ], "normalized": [] }, { "id": "PMID-10543260_T22", "type": "Organism_substance", "text": [ "serum samples" ], "offsets": [ [ 670, 683 ] ], "normalized": [] }, { "id": "PMID-10543260_T23", "type": "Multi-tissue_structure", "text": [ "bilateral renal veins" ], "offsets": [ [ 718, 739 ] ], "normalized": [] }, { "id": "PMID-10543260_T27", "type": "Cancer", "text": [ "RCC" ], "offsets": [ [ 879, 882 ] ], "normalized": [] }, { "id": "PMID-10543260_T29", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 989, 994 ] ], "normalized": [] }, { "id": "PMID-10543260_T30", "type": "Multi-tissue_structure", "text": [ "renal veins" ], "offsets": [ [ 1003, 1014 ] ], "normalized": [] }, { "id": "PMID-10543260_T31", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1166, 1171 ] ], "normalized": [] }, { "id": "PMID-10543260_T32", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1187, 1192 ] ], "normalized": [] }, { "id": "PMID-10543260_T34", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1310, 1315 ] ], "normalized": [] }, { "id": "PMID-10543260_T36", "type": "Tissue", "text": [ "tumor tissue" ], "offsets": [ [ 1600, 1612 ] ], "normalized": [] }, { "id": "PMID-10543260_T37", "type": "Cancer", "text": [ "RCC" ], "offsets": [ [ 1616, 1619 ] ], "normalized": [] }, { "id": "PMID-10543260_T39", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 1653, 1658 ] ], "normalized": [] }, { "id": "PMID-10543260_T41", "type": "Cancer", "text": [ "RCC" ], "offsets": [ [ 1705, 1708 ] ], "normalized": [] }, { "id": "PMID-10543260_T2", "type": "Cancer", "text": [ "metastasis" ], "offsets": [ [ 1237, 1247 ] ], "normalized": [] } ]

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[ { "id": "PMID-20129250__text", "type": "abstract", "text": [ "Tobacco smoke promotes lung tumorigenesis by triggering IKKbeta- and JNK1-dependent inflammation. \nChronic exposure to tobacco smoke, which contains over 60 tumor-initiating carcinogens, is the major risk factor for development of lung cancer, accounting for a large portion of cancer-related deaths worldwide. It is well established that tobacco smoke is a tumor initiator, but we asked whether it also acts as a tumor promoter once malignant initiation, such as caused by K-ras activation, has taken place. Here we demonstrate that repetitive exposure to tobacco smoke promotes tumor development both in carcinogen-treated mice and in transgenic mice undergoing sporadic K-ras activation in lung epithelial cells. Tumor promotion is due to induction of inflammation that results in enhanced pneumocyte proliferation and is abrogated by IKKbeta ablation in myeloid cells or inactivation of JNK1.\n" ], "offsets": [ [ 0, 897 ] ] } ]

[ { "id": "PMID-20129250_T2", "type": "Organ", "text": [ "lung" ], "offsets": [ [ 23, 27 ] ], "normalized": [] }, { "id": "PMID-20129250_T7", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 157, 162 ] ], "normalized": [] }, { "id": "PMID-20129250_T8", "type": "Cancer", "text": [ "lung cancer" ], "offsets": [ [ 231, 242 ] ], "normalized": [] }, { "id": "PMID-20129250_T9", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 278, 284 ] ], "normalized": [] }, { "id": "PMID-20129250_T11", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 358, 363 ] ], "normalized": [] }, { "id": "PMID-20129250_T12", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 414, 419 ] ], "normalized": [] }, { "id": "PMID-20129250_T15", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 580, 585 ] ], "normalized": [] }, { "id": "PMID-20129250_T19", "type": "Cell", "text": [ "lung epithelial cells" ], "offsets": [ [ 693, 714 ] ], "normalized": [] }, { "id": "PMID-20129250_T20", "type": "Cancer", "text": [ "Tumor" ], "offsets": [ [ 716, 721 ] ], "normalized": [] }, { "id": "PMID-20129250_T22", "type": "Cell", "text": [ "pneumocyte" ], "offsets": [ [ 793, 803 ] ], "normalized": [] }, { "id": "PMID-20129250_T24", "type": "Cell", "text": [ "myeloid cells" ], "offsets": [ [ 858, 871 ] ], "normalized": [] } ]

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[ { "id": "PMID-3338202__text", "type": "abstract", "text": [ "The posterior tether in scoliosis.\nThe hypothesis that a localized lordosis, or tethering of the posterior elements of the spine, is the primary cause of the vertebral rotation in idiopathic scoliosis was investigated in anatomic specimens of human and calf spinal columns. The specimens were axially loaded with and without a posterior tether created using Zielke instrumentation. Lateral deflection and axial rotation were monitored roentgenographically. The vertebrae of tethered spines showed increased rotation in the direction associated with idiopathic scoliosis. The spinous processes moved toward the concavity at the apex of the induced lateral curve. Conversely, untethered spines either exhibited little rotation or rotated in the opposite direction; the spinous processes moved toward the convexity of the curve. Rotations toward the convexity occur in rotational kyphosis. Thus the hypothesis that idiopathic scoliosis is a rotational lordosis is substantiated; the characteristic rotation can be explained with the aid of a geometric model.\n" ], "offsets": [ [ 0, 1056 ] ] } ]

[ { "id": "PMID-3338202_T1", "type": "Organism_subdivision", "text": [ "spine" ], "offsets": [ [ 123, 128 ] ], "normalized": [] }, { "id": "PMID-3338202_T2", "type": "Organ", "text": [ "vertebral" ], "offsets": [ [ 158, 167 ] ], "normalized": [] }, { "id": "PMID-3338202_T3", "type": "Organism_subdivision", "text": [ "spinal columns" ], "offsets": [ [ 258, 272 ] ], "normalized": [] }, { "id": "PMID-3338202_T4", "type": "Organ", "text": [ "vertebrae" ], "offsets": [ [ 461, 470 ] ], "normalized": [] }, { "id": "PMID-3338202_T5", "type": "Organism_subdivision", "text": [ "spines" ], "offsets": [ [ 483, 489 ] ], "normalized": [] }, { "id": "PMID-3338202_T6", "type": "Multi-tissue_structure", "text": [ "specimens" ], "offsets": [ [ 278, 287 ] ], "normalized": [] }, { "id": "PMID-3338202_T7", "type": "Multi-tissue_structure", "text": [ "anatomic specimens" ], "offsets": [ [ 221, 239 ] ], "normalized": [] }, { "id": "PMID-3338202_T8", "type": "Organism_subdivision", "text": [ "spines" ], "offsets": [ [ 685, 691 ] ], "normalized": [] } ]

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[ { "id": "PMC-2948674-sec-02__text", "type": "sec", "text": [ "Historical Background of PTSD\nPTSD gained acceptance in the medical and psychiatric community after a number of studies appeared in prominent medical and psychiatric journals describing the psychiatric symptoms of soldiers who had served and fought in the Vietnam War (Fox 1972; Goldsmith and Cretekos 1969). Subsequent publications described the profound psychological and emotional sequelae secondary to being exposed to extremely traumatic events such as fires, explosions, floods, torture, serious motor vehicle accidents (MVAs), violent crimes, and sexual assault (e.g., Horowitz 1976). These publications posited that individuals with PTSD no longer felt in control of their lives, viewed the world as an unpredictable and dangerous place, lived in fear, and reported a loss of trust in a \"just world.\" These studies also reported that individuals with PTSD avoided thoughts or situations that might trigger traumatic memories, complained of feelings of emotional numbness, and exhibited symptoms of blunted affect.\nThe conceptual refinements coupled with the empirical information generated by these studies significantly advanced our understanding of individuals who have been exposed to a traumatic stressor. This led in 1980 to the inclusion of the diagnostic criteria for PTSD in the Diagnostic and Statistical Manual of Mental Disorders III (DSM-III; American Psychiatric Association 1980). At that time, PTSD was defined as a syndrome that developed in response to a \"stressor that would evoke significant symptoms of distress in almost everyone\" (p. 238). The DSM-III criteria also required that the individual who developed PTSD had to have been directly exposed to a traumatic event. The DSM-IV criteria (APA 1994) significantly broadened the definition of PTSD to include (a) a \"personal experience of an event that involves actual or threatened death or serious injury, or other threat to one's physical integrity\" (p. 463) or (b) witnessing a comparable traumatic event or even \"learning about unexpected or violent death, serious harm, or threat of death or injury experienced by a family member or a close associate\" (p. 462). As a consequence of these modifications, the DSM-IV diagnostic criteria for PTSD have been criticized for failing to discriminate between symptoms of PTSD and normal stress reactions (e.g., learning about the 9/11 disaster; Wakefield and Spitzer 2002).\n\n" ], "offsets": [ [ 0, 2402 ] ] } ]

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[ { "id": "PMID-19843246__text", "type": "abstract", "text": [ "AKT2 is a downstream target of metabotropic glutamate receptor 1 (Grm1). \nWe reported earlier on the oncogenic properties of Grm1 by demonstrating that stable Grm1-mouse-melanocytic clones proliferate in the absence of growth supplement and anchorage in vitro. In addition, these clones also exhibit aggressive tumorigenic phenotypes in vivo with short latency in tumor formation in both immunodeficient and syngeneic mice. We also detected strong activation of AKT in allograft tumors specifically AKT2 as the predominant isoform involved. In parallel, we assessed several human melanoma biopsy samples and found again that AKT2 was the predominantly activated AKT in these human melanoma biopsies. In cultured stable Grm1-mouse-melanocytic clones, as well as an metabotropic glutamate receptor 1 (Grm1) expressing human melanoma cell line, C8161, stimulation of Grm1 by its agonist led to the activation of AKT, while preincubation with Grm1-antagonist abolished Grm1-agonist-induced AKT activation. In addition, a reduction in tumor volume of Grm1-mouse-melanocytic-allografts was detected in the presence of small interfering AKT2 RNA (siAKT2). Taken together, these results showed that, in addition to the MAPK pathway previously reported being a downstream target of stimulated Grm1, AKT2 is another downstream target in Grm1 mediated melanocyte transformation.\n" ], "offsets": [ [ 0, 1368 ] ] } ]

[ { "id": "PMID-19843246_T7", "type": "Cell", "text": [ "melanocytic clones" ], "offsets": [ [ 170, 188 ] ], "normalized": [] }, { "id": "PMID-19843246_T8", "type": "Cell", "text": [ "clones" ], "offsets": [ [ 280, 286 ] ], "normalized": [] }, { "id": "PMID-19843246_T9", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 364, 369 ] ], "normalized": [] }, { "id": "PMID-19843246_T13", "type": "Cancer", "text": [ "allograft tumors" ], "offsets": [ [ 469, 485 ] ], "normalized": [] }, { "id": "PMID-19843246_T16", "type": "Tissue", "text": [ "melanoma biopsy samples" ], "offsets": [ [ 580, 603 ] ], "normalized": [] }, { "id": "PMID-19843246_T20", "type": "Tissue", "text": [ "melanoma biopsies" ], "offsets": [ [ 681, 698 ] ], "normalized": [] }, { "id": "PMID-19843246_T23", "type": "Cell", "text": [ "melanocytic clones" ], "offsets": [ [ 730, 748 ] ], "normalized": [] }, { "id": "PMID-19843246_T27", "type": "Cell", "text": [ "melanoma cell line, C8161" ], "offsets": [ [ 822, 847 ] ], "normalized": [] }, { "id": "PMID-19843246_T33", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1030, 1035 ] ], "normalized": [] }, { "id": "PMID-19843246_T36", "type": "Tissue", "text": [ "melanocytic-allografts" ], "offsets": [ [ 1057, 1079 ] ], "normalized": [] }, { "id": "PMID-19843246_T43", "type": "Cell", "text": [ "melanocyte" ], "offsets": [ [ 1341, 1351 ] ], "normalized": [] } ]

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[ { "id": "PMID-16927570__text", "type": "abstract", "text": [ "[The prevalence of ADHD and attention problems in preschool-aged children. A comparison of two diagnostic instruments].\nOBJECTIVES:\nIn order to analyse the prevalence of ADHD and attention problems in preschool-aged children, mothers were asked to rate their children using two measuring instruments.\nMETHODS:\nThe analysis is part of a prospective, randomised control study of N = 280 children aged three to six years, whose mothers rated them using the Child Behaviour Checklist/CBCL 1 1/2-5 and the Parent Rating Scale for Attention-Deficit Hyperactivity Disorder (ADHD).\nRESULTS:\nThe prevalence rates ranged from 2.7% to 9.9%. There was no significant gender effect in this age group.\nCONCLUSIONS:\nThe study delivers initial findings and provides support for decisions to implement in Germany new assessment methods for preschool-aged children with ADHD or hyperkinetic syndrome. Finally, the different rates of prevalence and the implications of the findings for epidemiology and the prevention of ADHD and attention problems among preschool-aged children are discussed.\n" ], "offsets": [ [ 0, 1075 ] ] } ]

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[ { "id": "PMID-15795514__text", "type": "abstract", "text": [ "Hereditary paraganglioma/pheochromocytoma and inherited succinate dehydrogenase deficiency. \nMitochondrial complex II, or succinate dehydrogenase, is a key enzymatic complex involved in both the tricarboxylic acid (TCA) cycle and oxidative phosphorylation as part of the mitochondrial respiratory chain. Germline succinate dehydrogenase subunit A (SDHA) mutations have been reported in a few patients with a classical mitochondrial neurodegenerative disease. Mutations in the genes encoding the three other succinate dehydrogenase subunits (SDHB, SDHC and SDHD) have been identified in patients affected by familial or 'apparently sporadic' paraganglioma and/or pheochromocytoma, an autosomal inherited cancer-susceptibility syndrome. These discoveries have dramatically changed the work-up and genetic counseling of patients and families with paragangliomas and/or pheochromocytomas. The subsequent identification of germline mutations in the gene encoding fumarase--another TCA cycle enzyme--in a new hereditary form of susceptibility to renal, uterine and cutaneous tumors has highlighted the potential role of the TCA cycle and, more generally, of the mitochondria in cancer.\n" ], "offsets": [ [ 0, 1180 ] ] } ]

[ { "id": "PMID-15795514_T1", "type": "Cancer", "text": [ "paraganglioma" ], "offsets": [ [ 11, 24 ] ], "normalized": [] }, { "id": "PMID-15795514_T2", "type": "Cancer", "text": [ "pheochromocytoma" ], "offsets": [ [ 25, 41 ] ], "normalized": [] }, { "id": "PMID-15795514_T4", "type": "Cellular_component", "text": [ "Mitochondrial" ], "offsets": [ [ 93, 106 ] ], "normalized": [] }, { "id": "PMID-15795514_T9", "type": "Cellular_component", "text": [ "mitochondrial" ], "offsets": [ [ 271, 284 ] ], "normalized": [] }, { "id": "PMID-15795514_T13", "type": "Cellular_component", "text": [ "mitochondrial" ], "offsets": [ [ 418, 431 ] ], "normalized": [] }, { "id": "PMID-15795514_T19", "type": "Cancer", "text": [ "paraganglioma" ], "offsets": [ [ 641, 654 ] ], "normalized": [] }, { "id": "PMID-15795514_T20", "type": "Cancer", "text": [ "pheochromocytoma" ], "offsets": [ [ 662, 678 ] ], "normalized": [] }, { "id": "PMID-15795514_T21", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 703, 709 ] ], "normalized": [] }, { "id": "PMID-15795514_T23", "type": "Cancer", "text": [ "paragangliomas" ], "offsets": [ [ 844, 858 ] ], "normalized": [] }, { "id": "PMID-15795514_T24", "type": "Cancer", "text": [ "pheochromocytomas" ], "offsets": [ [ 866, 883 ] ], "normalized": [] }, { "id": "PMID-15795514_T27", "type": "Cancer", "text": [ "renal" ], "offsets": [ [ 1040, 1045 ] ], "normalized": [] }, { "id": "PMID-15795514_T28", "type": "Cancer", "text": [ "uterine" ], "offsets": [ [ 1047, 1054 ] ], "normalized": [] }, { "id": "PMID-15795514_T29", "type": "Cancer", "text": [ "cutaneous tumors" ], "offsets": [ [ 1059, 1075 ] ], "normalized": [] }, { "id": "PMID-15795514_T31", "type": "Cellular_component", "text": [ "mitochondria" ], "offsets": [ [ 1156, 1168 ] ], "normalized": [] }, { "id": "PMID-15795514_T32", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 1172, 1178 ] ], "normalized": [] } ]

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[ { "id": "PMC-2949661-caption-02__text", "type": "caption", "text": [ "Summary of instrument characteristics\n" ], "offsets": [ [ 0, 38 ] ] } ]

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[ { "id": "PMC-2946364-caption-05__text", "type": "caption", "text": [ "Effect of the deletion of IRE1alpha on the liver.\n(A) HE-stained sections of the liver tissue (scale bar: 50 mum). (B) Comparison of the serum AST and ALT levels between the IRE1alpha CKO mice and the control mice. Data are expressed as mean +/- S.E.M (n = 5). (C) Quantitative PCR analysis of lipid synthesis genes in the liver of mice fed normal or high-fructose feed. Columns indicate mean and error bars denote S.E.M (n = 3). All the data were obtained from 20 weeks old male mice.\n" ], "offsets": [ [ 0, 486 ] ] } ]

[ { "id": "PMC-2946364-caption-05_T1", "type": "Organ", "text": [ "liver" ], "offsets": [ [ 43, 48 ] ], "normalized": [] }, { "id": "PMC-2946364-caption-05_T2", "type": "Tissue", "text": [ "liver tissue" ], "offsets": [ [ 81, 93 ] ], "normalized": [] }, { "id": "PMC-2946364-caption-05_T3", "type": "Tissue", "text": [ "sections" ], "offsets": [ [ 65, 73 ] ], "normalized": [] }, { "id": "PMC-2946364-caption-05_T4", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 137, 142 ] ], "normalized": [] }, { "id": "PMC-2946364-caption-05_T5", "type": "Organ", "text": [ "liver" ], "offsets": [ [ 323, 328 ] ], "normalized": [] } ]

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[ { "id": "PMC-2709655-sec-17__text", "type": "sec", "text": [ "Discussion\nBecause Netherton syndrome exhibits allergic phenotype, it is reasonable to speculate that SPINK5, which is mutated in Netherton syndrome, may act as a candidate gene for asthma and other allergic diseases [9]. An extensive search for single nucleotide polymorphisms in the SPINK5 led to the identification of a number of SNPs, including six nonsynonymous SNPs in coding region that might perturb its immune function. Subsequent genotyping of three nonsynonymous SNPs, A1103G, G1156A and G1258A in two independent panels of British families showed a significant association between SNP G1258A (Glu420Lys) and atopy, atopic dermatitis, elevated serum IgE levels and asthma [10]. This association was confirmed in a large German population and two Japanese populations [16-18]. Kato et al analyzed eight SNPs in exon 13 and 14 of the SPINK5 including G1258A (Glu420Lys), and found a positive association of seven SNPs with atopic dermatitis in a Japanese study sample using a case-control study design [16]. Nishio et al surveyed five of six previously reported nonsynonymous SPINK5 SNPs in Japanese atopic families identified through asthmatic children or subjects with atopic dermatitis and found that SPINK5 was associated with development of atopic dermatitis but not asthma [17]. Kabesch M et al. analyzed G1258A (Glu420Lys) in a German population of school children, and found its association with asthma as well as a concomitant occurrence of asthma and atopic dermatitis [18]. However, two subsequent studies failed to replicate the original SPINK5 findings for allergic diseases [19,20]. Folster-Holst et al genotyped four nonsynonymous SNPs (Asp106Asn, Asn368Ser, Asp386Asn, and Glu420Lys), and detected no association between SPINK5 and atopic dermatitis in populations of Northern German origin [20]. Jongepier H et al. failed to detect any association between SPINK5 and asthma, atopic phenotypes and atopic dermatitis in a Dutch population [19]. These discordant findings probably reflect different genetic and environmental backgrounds in various populations. To determine whether nonsynonymous SNPs of the SPINK5 are involved in the pathogenesis of asthma in the Chinese Han population, we performed a case-control study by genotyping four nonsynonymous SNPs in the SPINK5. We did not detect any significant association between these nonsynonymous SNPs and asthma in our Chinese samples. With our sample size, we expected a power of at least 80% in detecting an effect of OR >=1.3 for each of these SNPs. Therefore, our failure to detect an association for these 4 SNPs was not due to the sample size. These results suggest that the polymorphisms in the coding region of the SPINK5 are unlikely to contribute to asthma risk in the Chinese Han population. However, because our patients were ascertained for asthma, we could not exclude a role of the coding SNPs of the SPINK5 in atopic dermatitis in our population.\nThe variations in the regulatory sequences of genes may determine risks to common diseases by causing different levels of expression. Therefore, the identification and functional evaluation of polymorphisms in promoter region are of great value in understanding the genetic susceptibility to asthma. In order to determine the role of the SPINK5 promoter polymorphism in the pathogenesis of asthma, we genotyped a promoter polymorphism, -206G>A, in 422 asthma patients and 410 controls, and found a marginal association. The frequency of allele G was significantly higher in asthmatic patients than that in controls (p = 0.022). To confirm the association, additional 267 asthma patients and 301 controls newly recruited from the same hospital were genotyped, and the -206G>A polymorphism remained significantly associated with asthma (P = 0.001), even after Bonferroni correction(adjusted P = 0.01). To our knowledge, this is the first report of an association of -206G>A polymorphism with asthma. We further examined the potential functional role of this promoter polymorphism, and found that the G to A substitution at -206 generated a GATA-3 transcription factor binding site.\nMajor transcription factors controlling Th1 and Th2 development, such as T-box transcription factor and GATA3, are possibly involved in asthma and atopic diseases. GATA-3, a transcription factor specifically expressed in T helper 2 (Th2) cells, plays a critical role in the differentiation of Th2 cells from uncommitted CD4+ lymphocytes. In addition, GATA-3 is essential for the expression of the cytokines IL-4, IL-5 and IL-13 that mediate allergic inflammation [23]. Our luciferase reporter assay confirmed that SNP -206G>A is associated with the transcriptional activity of SPINK5. The G allele was associated with decreased transcriptional activity of the SPINK5. The mechanism by which the -206G>A SNP affects SPINK5 expression may be explained by the potential differential transcription factor binding of GATA binding factor, since -206G>A is located at the core sequence of GATA binding factor binding site. Electrophoretic mobility shift assay confirmed that the A to G substitution at -206 significantly reduced the binding efficiency of nuclear proteins to this element. Our data suggest that loss of GATA transcription factor regulation with the -206G may decrease the SPINK5 expression and thereby potentially perturb the immunosuppressive function of LEKTI.\n" ], "offsets": [ [ 0, 5392 ] ] } ]

[ { "id": "PMC-2709655-sec-17_T1", "type": "Cell", "text": [ "T helper 2 (Th2) cells" ], "offsets": [ [ 4341, 4363 ] ], "normalized": [] }, { "id": "PMC-2709655-sec-17_T2", "type": "Cell", "text": [ "Th2 cells" ], "offsets": [ [ 4413, 4422 ] ], "normalized": [] }, { "id": "PMC-2709655-sec-17_T3", "type": "Cell", "text": [ "CD4+ lymphocytes" ], "offsets": [ [ 4440, 4456 ] ], "normalized": [] }, { "id": "PMC-2709655-sec-17_T4", "type": "Cellular_component", "text": [ "nuclear" ], "offsets": [ [ 5168, 5175 ] ], "normalized": [] }, { "id": "PMC-2709655-sec-17_T5", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 655, 660 ] ], "normalized": [] } ]

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[ { "id": "PMID-16809940__text", "type": "abstract", "text": [ "Defective expression of HRK is associated with promoter methylation in primary central nervous system lymphomas. \nOBJECTIVES: Recently, it has been reported that expression of the HRK gene was significantly reduced by hypermethylation in astrocytic tumors. Our aim is to verify the alterations in the HRK gene in primary central nervous system lymphomas (PCNSLs). METHODS: We analyzed the hypermethylation status and expression of the gene and 12q13.1 loss of heterozygosity in 31 PCNSLs. RESULTS: A total of 13 PCNSLs (31%) demonstrated hypermethylation in either the promoter or exon 1; loss of HRK expression was immunohistochemically observed in 9 tumors and was significantly associated with promoter methylation. In addition, higher apoptotic counts were associated with HRK positivity. PCNSLs with HRK methylation also showed methylation of multiple genes, such as p14ARF, p16INK4a, RB1, p27Kip1 and O6-MGMT. Patients with tumors demonstrating concurrent methylation of more than half of their genes demonstrated significantly poorer survival and earlier recurrence. Hypermethylation of the HRK promoter alone was not associated with overall outcome, but relapse-free survival was significantly shorter. CONCLUSIONS: Our findings suggest that transcriptional repression of HRK is caused by promoter hypermethylation in PCNSL, and that the loss of HRK associated with the methylation profile of other genes is a potential step in the modulation of cellular death by apoptosis during PCNSL tumorigenesis.\n" ], "offsets": [ [ 0, 1510 ] ] } ]

[ { "id": "PMID-16809940_T2", "type": "Cancer", "text": [ "primary central nervous system lymphomas" ], "offsets": [ [ 71, 111 ] ], "normalized": [] }, { "id": "PMID-16809940_T4", "type": "Cancer", "text": [ "astrocytic tumors" ], "offsets": [ [ 238, 255 ] ], "normalized": [] }, { "id": "PMID-16809940_T6", "type": "Cancer", "text": [ "primary central nervous system lymphomas" ], "offsets": [ [ 313, 353 ] ], "normalized": [] }, { "id": "PMID-16809940_T7", "type": "Cancer", "text": [ "PCNSLs" ], "offsets": [ [ 355, 361 ] ], "normalized": [] }, { "id": "PMID-16809940_T8", "type": "Cancer", "text": [ "PCNSLs" ], "offsets": [ [ 481, 487 ] ], "normalized": [] }, { "id": "PMID-16809940_T9", "type": "Cancer", "text": [ "PCNSLs" ], "offsets": [ [ 512, 518 ] ], "normalized": [] }, { "id": "PMID-16809940_T11", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 652, 658 ] ], "normalized": [] }, { "id": "PMID-16809940_T13", "type": "Cancer", "text": [ "PCNSLs" ], "offsets": [ [ 793, 799 ] ], "normalized": [] }, { "id": "PMID-16809940_T21", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 930, 936 ] ], "normalized": [] }, { "id": "PMID-16809940_T24", "type": "Cancer", "text": [ "PCNSL" ], "offsets": [ [ 1326, 1331 ] ], "normalized": [] }, { "id": "PMID-16809940_T26", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 1454, 1462 ] ], "normalized": [] }, { "id": "PMID-16809940_T27", "type": "Cancer", "text": [ "PCNSL" ], "offsets": [ [ 1489, 1494 ] ], "normalized": [] } ]

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[ { "id": "PMC-2982831-sec-18__text", "type": "sec", "text": [ "Different ROC analysis\nWhen the true positive peptides are not known a priori, there exist various strategies in classifying hits into true or false positives when making a ROC plot. These strategies, unfortunately, will make a notable difference in retrieval assessment. For example, in a cell lysate experiment of a certain organism, it is customary to estimate the number of false positive hits by introducing a decoy database during the data analysis. The main idea there is to first sort the peptide hits according to their scores. Then for each decoy hit, one assumes that there is just one corresponding false hit in the target database. This strategy has been used extensively [24]. ROC analyses done this way generally count false positives, which are highly homologous to the target peptides, towards true positives. This has two effects: an overcount of true positives and a undercount of false positives. As a consequence, the ROC curves will appear more impressive. To mimick this situation, we used BLAST to find in the NCBI's nr database highly homologous proteins to the target proteins used in the experiment and include those proteins in our true positive set. This strategy produces ROC curves shown as the solid curves of Figure S8. When compared to Figure 6 and Figure S6, the ROC curves produced by this strategy seem much more impressive.\nNot counting highly homologous proteins as false positives would probably be agreeable. However, counting those peptides/proteins as true positives could be exaggerating. Therefore one may use a slightly different strategy: removing from consideration proteins homologous to the target proteins, which is called the cluster removal strategy [11]. The dashed curves of Figure S9 are ROC curves obtained this way. This strategy also produces slightly more impressive ROC curves than in Figure 6 and Figure S6. Apparently, this indicates the highly homologous false positive hits are the ones that degrade the retrieval performance. Thus, it can be useful to remove those false positives from consideration. Keeping only the best hit per spectrum turns out to be one way to achieve this goal.\n" ], "offsets": [ [ 0, 2152 ] ] } ]

[ { "id": "PMC-2982831-sec-18_T1", "type": "Organism_substance", "text": [ "cell lysate" ], "offsets": [ [ 290, 301 ] ], "normalized": [] } ]

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[ { "id": "PMID-15034798__text", "type": "abstract", "text": [ "Role of thrombin in angiogenesis and tumor progression.\nClinical, laboratory, histopathological, and pharmacological evidence support the notion that the coagulation system, which is activated in most cancer patients, plays an important role in tumor biology. Our laboratory has provided evidence that thrombin activates angiogenesis, a process which is essential in tumor growth and metastasis. This event is independent of fibrin formation. At the cellular level many actions of thrombin can contribute to activation of angiogenesis: (1). Thrombin decreases the ability of endothelial cells to attach to basement membrane proteins. (2). Thrombin greatly potentiates vascular endothelial growth factor- (VEGF-) induced endothelial cell proliferation. This potentiation is accompanied by up-regulation of the expression of VEGF receptors (kinase insert domain-containing receptor [KDR] and fms-like tyrosine kinase [Flt-1]). (3). Thrombin increases the mRNA and protein levels of alpha (v)beta (3) integrin and serves as a ligand to this receptor. Furthermore, thrombin increases the secretion of VEGF and enhances the expression and protein synthesis of matrix metalloprotease-9 and alpha (v)beta (3) integrin in human prostate cancer PC-3 cells. These results could explain the angiogenic and tumor-promoting effect of thrombin and provide the basis for development of thrombin receptor mimetics or antagonists for therapeutic application.\n" ], "offsets": [ [ 0, 1442 ] ] } ]

[ { "id": "PMID-15034798_T2", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 37, 42 ] ], "normalized": [] }, { "id": "PMID-15034798_T3", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 201, 207 ] ], "normalized": [] }, { "id": "PMID-15034798_T5", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 245, 250 ] ], "normalized": [] }, { "id": "PMID-15034798_T7", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 367, 372 ] ], "normalized": [] }, { "id": "PMID-15034798_T9", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 450, 458 ] ], "normalized": [] }, { "id": "PMID-15034798_T12", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 575, 592 ] ], "normalized": [] }, { "id": "PMID-15034798_T13", "type": "Cellular_component", "text": [ "basement membrane" ], "offsets": [ [ 606, 623 ] ], "normalized": [] }, { "id": "PMID-15034798_T17", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 720, 736 ] ], "normalized": [] }, { "id": "PMID-15034798_T30", "type": "Cell", "text": [ "prostate cancer PC-3 cells" ], "offsets": [ [ 1220, 1246 ] ], "normalized": [] }, { "id": "PMID-15034798_T31", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1295, 1300 ] ], "normalized": [] } ]

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[ { "id": "PMID-12796408__text", "type": "abstract", "text": [ "Truncated galectin-3 inhibits tumor growth and metastasis in orthotopic nude mouse model of human breast cancer. \nPURPOSE: The goal of this research was to evaluate a potential therapeutic agent for breast cancer based on galectin-3 that has been implicated in tumorigenicity and metastasis of breast cancer. The hypothesis was that therapy with NH(2)-terminally truncated form of galectin-3 (galectin-3C) will be efficacious for reduction in tumor growth and for inhibition of metastases. EXPERIMENTAL DESIGN: Recombinant human galectin-3 was produced in Escherichia coli from which galectin-3C was derived by collagenase enzyme digestion. Toxicity, pharmacokinetic, and organ biodistribution studies were performed in nude mice. For efficacy studies, nude mice bearing orthotopically implanted tumors derived from breast cancer cell line MDA-MB-435 were treated with galectin-3C or a vehicle control i.m. twice daily for 90 days. RESULTS: The maximum tolerated dose of galectin-3C in nude mice was determined to be >125 mg/kg without overt adverse effects. The elimination half-life when administered i.m. was found to be 3.0 h in the serum and 4.3 h in the cellular fraction of the blood. Organ biodistribution studies revealed that galectin-3C localized in the liver, kidneys, and spleen but not in the heart or lungs. We found that the mean tumor volumes and weights were statistically significantly less in mice treated with galectin-3C compared with control mice, and that fewer numbers of mice exhibited lymph node metastases in the treated group compared with the control group. CONCLUSIONS: Galectin-3C is not overtly toxic, and is efficacious in reducing metastases and tumor volumes and weights in primary tumors in an orthotopic nude mouse model of human breast cancer.\n" ], "offsets": [ [ 0, 1783 ] ] } ]

[ { "id": "PMID-12796408_T2", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 30, 35 ] ], "normalized": [] }, { "id": "PMID-12796408_T5", "type": "Cancer", "text": [ "breast cancer" ], "offsets": [ [ 98, 111 ] ], "normalized": [] }, { "id": "PMID-12796408_T6", "type": "Cancer", "text": [ "breast cancer" ], "offsets": [ [ 199, 212 ] ], "normalized": [] }, { "id": "PMID-12796408_T8", "type": "Cancer", "text": [ "breast cancer" ], "offsets": [ [ 294, 307 ] ], "normalized": [] }, { "id": "PMID-12796408_T11", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 443, 448 ] ], "normalized": [] }, { "id": "PMID-12796408_T17", "type": "Organ", "text": [ "organ" ], "offsets": [ [ 672, 677 ] ], "normalized": [] }, { "id": "PMID-12796408_T20", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 796, 802 ] ], "normalized": [] }, { "id": "PMID-12796408_T21", "type": "Cell", "text": [ "breast cancer cell line MDA-MB-435" ], "offsets": [ [ 816, 850 ] ], "normalized": [] }, { "id": "PMID-12796408_T25", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 1137, 1142 ] ], "normalized": [] }, { "id": "PMID-12796408_T26", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 1160, 1168 ] ], "normalized": [] }, { "id": "PMID-12796408_T27", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 1185, 1190 ] ], "normalized": [] }, { "id": "PMID-12796408_T29", "type": "Organ", "text": [ "liver" ], "offsets": [ [ 1265, 1270 ] ], "normalized": [] }, { "id": "PMID-12796408_T30", "type": "Organ", "text": [ "kidneys" ], "offsets": [ [ 1272, 1279 ] ], "normalized": [] }, { "id": "PMID-12796408_T31", "type": "Organ", "text": [ "spleen" ], "offsets": [ [ 1285, 1291 ] ], "normalized": [] }, { "id": "PMID-12796408_T32", "type": "Organ", "text": [ "heart" ], "offsets": [ [ 1307, 1312 ] ], "normalized": [] }, { "id": "PMID-12796408_T33", "type": "Organ", "text": [ "lungs" ], "offsets": [ [ 1316, 1321 ] ], "normalized": [] }, { "id": "PMID-12796408_T34", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1346, 1351 ] ], "normalized": [] }, { "id": "PMID-12796408_T39", "type": "Cancer", "text": [ "lymph node metastases" ], "offsets": [ [ 1512, 1533 ] ], "normalized": [] }, { "id": "PMID-12796408_T41", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1681, 1686 ] ], "normalized": [] }, { "id": "PMID-12796408_T42", "type": "Cancer", "text": [ "primary tumors" ], "offsets": [ [ 1710, 1724 ] ], "normalized": [] }, { "id": "PMID-12796408_T45", "type": "Cancer", "text": [ "breast cancer" ], "offsets": [ [ 1768, 1781 ] ], "normalized": [] }, { "id": "PMID-12796408_T1", "type": "Cancer", "text": [ "metastases" ], "offsets": [ [ 1666, 1676 ] ], "normalized": [] } ]

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[ { "id": "PMID-6653557__text", "type": "abstract", "text": [ "Purification and characterization of various esterases from rat liver.\nThe major rat liver microsomal esterases acting on o-nitrophenylacetate with isoelectric points 5.0, 5.5, 6.1 and 6.4 were resolved by isoelectric focusing. Molecular weights were determined by sedimentation analysis in isokinetic gradients of sucrose and, after purification, in sodium dodecyl sulphate/polyacrylamide gel electrophoresis. Their subunit molecular weights were between 57 000 and 60 000. They behaved as monomers except the pI-6.1 enzyme which behaved as a trimer. Esterases of pI 5.0, pI 6.1 and pI 6.4 behaved like glycoproteins of the polymannose type in the presence of 125I-labelled concanavalin A. Preparations of the pI-5.0 enzyme contained two esterases of highly homologous structure. Antibodies directed against this preparation did not inhibit but precipitated pI-5.0 esterase activity quantitatively. They did not react with the pI-6.1 and pI-6.4 esterases but precipitated several nonimmunologically related esterases. Two of these enzymes were inducible by phenobarbital. Total activity was very low in 3-day-old animals. Individual esterase activities rose at different rates during development; the enzyme focusing near pI 5.0 was about three times more active in adult females than in males. All microsomal esterases are located on the luminal side of the endoplasmic reticulum.\n" ], "offsets": [ [ 0, 1383 ] ] } ]

[ { "id": "PMID-6653557_T1", "type": "Organ", "text": [ "liver" ], "offsets": [ [ 64, 69 ] ], "normalized": [] }, { "id": "PMID-6653557_T2", "type": "Cellular_component", "text": [ "liver microsomal" ], "offsets": [ [ 85, 101 ] ], "normalized": [] }, { "id": "PMID-6653557_T3", "type": "Cellular_component", "text": [ "endoplasmic reticulum" ], "offsets": [ [ 1360, 1381 ] ], "normalized": [] }, { "id": "PMID-6653557_T4", "type": "Immaterial_anatomical_entity", "text": [ "luminal" ], "offsets": [ [ 1340, 1347 ] ], "normalized": [] } ]

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[ { "id": "PMID-18670636__text", "type": "abstract", "text": [ "Regulation of the Warburg effect in early-passage breast cancer cells. \nMalignancy in cancer is associated with aerobic glycolysis (Warburg effect) evidenced by increased trapping of [(18)F]deoxyglucose (FdG) in patients imaged by positron emission tomography (PET). [(18)F]deoxyglucose uptake correlates with glucose transporter (GLUT-1) expression, which can be regulated by hypoxia-inducible factor 1 alpha (HIF-1alpha). We have previously reported in established breast lines that HIF-1alpha levels in the presence of oxygen leads to the Warburg effect. However, glycolysis and GLUT-1 can also be induced independent of HIF-1alpha by other factors, such as c-Myc and phosphorylated Akt (pAkt). This study investigates HIF-1alpha, c-Myc, pAkt, and aerobic glycolysis in low-passage breast cancer cells under the assumption that these represent the in vivo condition better than established lines. Similar to in vivo FdG-PET or primary breast cancers, rates of glycolysis were diverse, being higher in cells expressing both c-Myc and HIF-1alpha and lower in cell lines low or negative in both transcription factors. No correlations were observed between glycolytic rates and pAkt levels. Two of 12 cell lines formed xenografts in mice. Both were positive for HIF-1alpha and phosphorylated c-Myc, and only one was positive for pAkt. Glycolysis was affected by pharmacological regulation of c-Myc and HIF-1alpha. These findings suggest that c-Myc and/or HIF-1alpha activities are both involved in the regulation of glycolysis in breast cancers.\n" ], "offsets": [ [ 0, 1545 ] ] } ]

[ { "id": "PMID-18670636_T1", "type": "Cell", "text": [ "early-passage breast cancer cells" ], "offsets": [ [ 36, 69 ] ], "normalized": [] }, { "id": "PMID-18670636_T2", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 86, 92 ] ], "normalized": [] }, { "id": "PMID-18670636_T11", "type": "Cell", "text": [ "breast lines" ], "offsets": [ [ 467, 479 ] ], "normalized": [] }, { "id": "PMID-18670636_T22", "type": "Cell", "text": [ "breast cancer cells" ], "offsets": [ [ 785, 804 ] ], "normalized": [] }, { "id": "PMID-18670636_T23", "type": "Cell", "text": [ "lines" ], "offsets": [ [ 893, 898 ] ], "normalized": [] }, { "id": "PMID-18670636_T25", "type": "Cancer", "text": [ "primary breast cancers" ], "offsets": [ [ 930, 952 ] ], "normalized": [] }, { "id": "PMID-18670636_T26", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1004, 1009 ] ], "normalized": [] }, { "id": "PMID-18670636_T29", "type": "Cell", "text": [ "cell lines" ], "offsets": [ [ 1060, 1070 ] ], "normalized": [] }, { "id": "PMID-18670636_T31", "type": "Cell", "text": [ "cell lines" ], "offsets": [ [ 1200, 1210 ] ], "normalized": [] }, { "id": "PMID-18670636_T32", "type": "Cancer", "text": [ "xenografts" ], "offsets": [ [ 1218, 1228 ] ], "normalized": [] }, { "id": "PMID-18670636_T41", "type": "Cancer", "text": [ "breast cancers" ], "offsets": [ [ 1529, 1543 ] ], "normalized": [] } ]

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[ { "id": "PMID-19075960__text", "type": "abstract", "text": [ "VEGF, angiopoietin-1 and -2 in bronchial asthma: new molecular targets in airway angiogenesis and microvascular remodeling.\nAirway angiogenesis and microvascular remodeling are known features of bronchial asthma, but the mechanisms of these structural alterations are just beginning to be elucidated. Vascular endothelial growth factor (VEGF), one of the most potent angiogenic factors, stimulates endothelial cell proliferation and induces the angiogenesis. Recently, considerable attentions have been devoted to the physiological roles of angiopoietin (Ang)-1 and -2 as regulatory factors of VEGF. Ang-1 has been shown to induce the migration and sprouting of endothelial cells, and coexpression of Ang-1 and VEGF enhanced angiogenesis. In the presence of high levels of VEGF, Ang-2 also promotes rapid increase in capillary diameter, remodeling of the basal lamina, proliferation and migration of endothelial cells, and stimulates sprouting of new blood vessels. Thus, VEGF, Ang-1 and -2 may play complementary and coordinated roles in airway angiogenesis and microvascular remodeling, and these structural changes are potentially reversible by therapeutic intervention. The scope of the present review is to discuss from a clinical point of view the potential interactions between VEGF and angiopoietins in the asthmatic airways, and focus on the therapeutic implications targeting for these angiogenic factors. Recently, there is an increasing number of patents which have been focused on the inhibitors of VEGF action. These inhibitors are directed towards the receptors of VEGF or intracellular substrates for the receptors. We will also discuss several patents regarding inhibitors of VEGF action in the present review.\n" ], "offsets": [ [ 0, 1728 ] ] } ]

[ { "id": "PMID-19075960_T4", "type": "Multi-tissue_structure", "text": [ "airway" ], "offsets": [ [ 74, 80 ] ], "normalized": [] }, { "id": "PMID-19075960_T5", "type": "Tissue", "text": [ "microvascular" ], "offsets": [ [ 98, 111 ] ], "normalized": [] }, { "id": "PMID-19075960_T6", "type": "Multi-tissue_structure", "text": [ "Airway" ], "offsets": [ [ 124, 130 ] ], "normalized": [] }, { "id": "PMID-19075960_T7", "type": "Tissue", "text": [ "microvascular" ], "offsets": [ [ 148, 161 ] ], "normalized": [] }, { "id": "PMID-19075960_T10", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 398, 414 ] ], "normalized": [] }, { "id": "PMID-19075960_T15", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 662, 679 ] ], "normalized": [] }, { "id": "PMID-19075960_T20", "type": "Tissue", "text": [ "capillary" ], "offsets": [ [ 817, 826 ] ], "normalized": [] }, { "id": "PMID-19075960_T21", "type": "Cellular_component", "text": [ "basal lamina" ], "offsets": [ [ 855, 867 ] ], "normalized": [] }, { "id": "PMID-19075960_T22", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 900, 917 ] ], "normalized": [] }, { "id": "PMID-19075960_T23", "type": "Multi-tissue_structure", "text": [ "blood vessels" ], "offsets": [ [ 951, 964 ] ], "normalized": [] }, { "id": "PMID-19075960_T27", "type": "Multi-tissue_structure", "text": [ "airway" ], "offsets": [ [ 1039, 1045 ] ], "normalized": [] }, { "id": "PMID-19075960_T28", "type": "Tissue", "text": [ "microvascular" ], "offsets": [ [ 1063, 1076 ] ], "normalized": [] }, { "id": "PMID-19075960_T31", "type": "Multi-tissue_structure", "text": [ "airways" ], "offsets": [ [ 1325, 1332 ] ], "normalized": [] }, { "id": "PMID-19075960_T34", "type": "Immaterial_anatomical_entity", "text": [ "intracellular" ], "offsets": [ [ 1588, 1601 ] ], "normalized": [] } ]

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[ { "id": "PMID-16407289__text", "type": "abstract", "text": [ "Regulation of the composition of the extracellular matrix by low density lipoprotein receptor-related protein-1: activities based on regulation of mRNA expression.\nLow density lipoprotein receptor-related protein-1 (LRP-1) is a catabolic receptor for extracellular matrix (ECM) structural proteins and for proteins that bind to ECM. LRP-1 also is implicated in integrin maturation. In this study, we applied a proteomics strategy to identify novel proteins involved in ECM modeling that are regulated by LRP-1. We show that LRP-1 deficiency in murine embryonic fibroblasts (MEFs) is associated with increased levels of type III collagen and pigment epithelium-derived factor, which accumulate in the substratum surrounding cells. The collagen receptor, uPAR-AP/Endo-180, is also increased in LRP-1-deficient MEFs. Human LRP-1 reversed the changes in protein expression associated with LRP-1 deficiency; however, the endocytic activity of LRP-1 was not involved. Instead, regulation occurred at the mRNA level. Inhibition of c-Jun amino-terminal kinase (JNK) blocked type III collagen expression in LRP-1-deficient MEFs, suggesting regulation of JNK activity as a mechanism by which LRP-1 controls mRNA expression. The ability of LRP-1 to regulate expression of the factors identified here suggests a role for LRP-1 in determining blood vessel structure and in angiogenesis.\n" ], "offsets": [ [ 0, 1374 ] ] } ]

[ { "id": "PMID-16407289_T1", "type": "Cellular_component", "text": [ "extracellular matrix" ], "offsets": [ [ 37, 57 ] ], "normalized": [] }, { "id": "PMID-16407289_T5", "type": "Cellular_component", "text": [ "extracellular matrix" ], "offsets": [ [ 251, 271 ] ], "normalized": [] }, { "id": "PMID-16407289_T6", "type": "Cellular_component", "text": [ "ECM" ], "offsets": [ [ 273, 276 ] ], "normalized": [] }, { "id": "PMID-16407289_T7", "type": "Cellular_component", "text": [ "ECM" ], "offsets": [ [ 328, 331 ] ], "normalized": [] }, { "id": "PMID-16407289_T10", "type": "Cellular_component", "text": [ "ECM" ], "offsets": [ [ 469, 472 ] ], "normalized": [] }, { "id": "PMID-16407289_T14", "type": "Cell", "text": [ "embryonic fibroblasts" ], "offsets": [ [ 551, 572 ] ], "normalized": [] }, { "id": "PMID-16407289_T15", "type": "Cell", "text": [ "MEFs" ], "offsets": [ [ 574, 578 ] ], "normalized": [] }, { "id": "PMID-16407289_T18", "type": "Cellular_component", "text": [ "substratum" ], "offsets": [ [ 700, 710 ] ], "normalized": [] }, { "id": "PMID-16407289_T19", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 723, 728 ] ], "normalized": [] }, { "id": "PMID-16407289_T24", "type": "Cell", "text": [ "MEFs" ], "offsets": [ [ 808, 812 ] ], "normalized": [] }, { "id": "PMID-16407289_T33", "type": "Cell", "text": [ "MEFs" ], "offsets": [ [ 1114, 1118 ] ], "normalized": [] }, { "id": "PMID-16407289_T38", "type": "Multi-tissue_structure", "text": [ "blood vessel" ], "offsets": [ [ 1330, 1342 ] ], "normalized": [] } ]

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[ { "id": "PMID-10744669__text", "type": "abstract", "text": [ "Genuine monovalent ligands of TrkA nerve growth factor receptors reveal a novel pharmacological mechanism of action.\nDeveloping small molecule agonistic ligands for tyrosine kinase receptors has been difficult, and it is generally thought that such ligands require bivalency. Moreover, multisubunit receptors are difficult to target, because each subunit contributes to ligand affinity, and each subunit may have distinct and sometimes opposing functions. Here, the nerve growth factor receptor subunits p75 and the tyrosine kinase TrkA were studied using artificial ligands that bind specifically to their extracellular domain. Bivalent TrkA ligands afford robust signals. However, genuine monomeric and monovalent TrkA ligands afford partial agonism, activate the tyrosine kinase activity, cause receptor internalization, and induce survival and differentiation in cell lines and primary neurons. Monomeric and monovalent TrkA ligands can synergize with ligands that bind the p75 subunit. However, the p75 ligands used in this study must be bivalent, and monovalent p75 ligands have no effect. These findings will be useful in designing and developing screens of small molecules selective for tyrosine kinase receptors and indicate that strategies for designing agonists of multisubunit receptors require consideration of the role of each subunit. Last, the strategy of using anti-receptor mAbs and small molecule hormone mimics as receptor ligands could be applied to the study of many other heteromeric cell surface receptors.\n" ], "offsets": [ [ 0, 1531 ] ] } ]

[ { "id": "PMID-10744669_T3", "type": "Cell", "text": [ "cell lines" ], "offsets": [ [ 867, 877 ] ], "normalized": [] }, { "id": "PMID-10744669_T4", "type": "Cell", "text": [ "primary neurons" ], "offsets": [ [ 882, 897 ] ], "normalized": [] }, { "id": "PMID-10744669_T5", "type": "Cellular_component", "text": [ "cell surface" ], "offsets": [ [ 1507, 1519 ] ], "normalized": [] }, { "id": "PMID-10744669_T6", "type": "Immaterial_anatomical_entity", "text": [ "extracellular" ], "offsets": [ [ 607, 620 ] ], "normalized": [] } ]

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[ { "id": "PMID-21423801__text", "type": "abstract", "text": [ "Saliva proteins of vector Culicoides modify structure and infectivity of bluetongue virus particles.\nBluetongue virus (BTV) and epizootic haemorrhagic disease virus (EHDV) are related orbiviruses, transmitted between their ruminant hosts primarily by certain haematophagous midge vectors (Culicoides spp.). The larger of the BTV outer-capsid proteins, 'VP2', can be cleaved by proteases (including trypsin or chymotrypsin), forming infectious subviral particles (ISVP) which have enhanced infectivity for adult Culicoides, or KC cells (a cell-line derived from C. sonorensis). We demonstrate that VP2 present on purified virus particles from 3 different BTV strains can also be cleaved by treatment with saliva from adult Culicoides. The saliva proteins from C. sonorensis (a competent BTV vector), cleaved BTV-VP2 more efficiently than those from C. nubeculosus (a less competent/non-vector species). Electrophoresis and mass spectrometry identified a trypsin-like protease in C. sonorensis saliva, which was significantly reduced or absent from C. nubeculosus saliva. Incubating purified BTV-1 with C. sonorensis saliva proteins also increased their infectivity for KC cells ~10 fold, while infectivity for BHK cells was reduced by 2-6 fold. Treatment of an 'eastern' strain of EHDV-2 with saliva proteins of either C. sonorensis or C. nubeculosus cleaved VP2, but a 'western' strain of EHDV-2 remained unmodified. These results indicate that temperature, strain of virus and protein composition of Culicoides saliva (particularly its protease content which is dependent upon vector species), can all play a significant role in the efficiency of VP2 cleavage, influencing virus infectivity. Saliva of several other arthropod species has previously been shown to increase transmission, infectivity and virulence of certain arboviruses, by modulating and/or suppressing the mammalian immune response. The findings presented here, however, demonstrate a novel mechanism by which proteases in Culicoides saliva can also directly modify the orbivirus particle structure, leading to increased infectivity specifically for Culicoides cells and, in turn, efficiency of transmission to the insect vector.\n" ], "offsets": [ [ 0, 2198 ] ] } ]

[ { "id": "PMID-21423801_T1", "type": "Cell", "text": [ "KC cells" ], "offsets": [ [ 526, 534 ] ], "normalized": [] }, { "id": "PMID-21423801_T2", "type": "Cell", "text": [ "cell-line" ], "offsets": [ [ 538, 547 ] ], "normalized": [] }, { "id": "PMID-21423801_T3", "type": "Cell", "text": [ "KC cells" ], "offsets": [ [ 1168, 1176 ] ], "normalized": [] }, { "id": "PMID-21423801_T4", "type": "Cell", "text": [ "BHK cells" ], "offsets": [ [ 1209, 1218 ] ], "normalized": [] }, { "id": "PMID-21423801_T5", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 2129, 2134 ] ], "normalized": [] } ]

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[ { "id": "PMID-12384438__text", "type": "abstract", "text": [ "Enforced expression of tissue inhibitor of matrix metalloproteinase-3 affects functional capillary morphogenesis and inhibits tumor growth in a murine tumor model.\nHomeostasis of the extracellular matrix is a delicate balance between degradation and remodeling, the balance being maintained by the interaction of activated matrix metalloproteinases (MMPs) and specific tissue inhibitors of matrix metalloproteinases (TIMPs). Up-regulation of MMP activity, favoring proteolytic degradation of the basement membrane and extracellular matrix, has been linked to tumor growth and metastasis, as well as tumor-associated angiogenesis, whereas inhibition of MMP activity appears to restrict these processes. We have used retroviral-mediated gene delivery to effect sustained autocrine expression of TIMP-3 in murine neuroblastoma and melanoma tumor cells in order to further examine the ability of TIMPs to inhibit angiogenesis in vivo. Growth of both histologic types of gene-modified tumor cells in severe combined immunodeficiency (SCID) mice was significantly restricted when compared with controls. Grossly, these tumors were small and had few feeding vessels. Histologic evaluation revealed that although tumors overexpressing TIMP-3 had an increased number of CD31(+) endothelial cells, these endothelial cells had not formed functional tubules, as evidenced by decreased vessel continuity and minimal pericyte recruitment. This effect appears to be mediated, in part, by decreased expression of vascular endothelial (VE)-cadherin by endothelial cells in the presence of TIMP-3 as seen both in an in vitro assay and in TIMP-3-overexpressing tumors. Taken together, these results demonstrate that overexpression of TIMP-3 can inhibit angiogenesis and associated tumor growth, and that the antiangiogenic effects of TIMP-3 appear to be mediated through the inhibition of functional capillary morphogenesis.\n" ], "offsets": [ [ 0, 1906 ] ] } ]

[ { "id": "PMID-12384438_T2", "type": "Tissue", "text": [ "capillary" ], "offsets": [ [ 89, 98 ] ], "normalized": [] }, { "id": "PMID-12384438_T3", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 126, 131 ] ], "normalized": [] }, { "id": "PMID-12384438_T5", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 151, 156 ] ], "normalized": [] }, { "id": "PMID-12384438_T6", "type": "Cellular_component", "text": [ "extracellular matrix" ], "offsets": [ [ 183, 203 ] ], "normalized": [] }, { "id": "PMID-12384438_T12", "type": "Cellular_component", "text": [ "basement membrane" ], "offsets": [ [ 496, 513 ] ], "normalized": [] }, { "id": "PMID-12384438_T13", "type": "Cellular_component", "text": [ "extracellular matrix" ], "offsets": [ [ 518, 538 ] ], "normalized": [] }, { "id": "PMID-12384438_T14", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 559, 564 ] ], "normalized": [] }, { "id": "PMID-12384438_T15", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 599, 604 ] ], "normalized": [] }, { "id": "PMID-12384438_T19", "type": "Cell", "text": [ "neuroblastoma" ], "offsets": [ [ 810, 823 ] ], "normalized": [] }, { "id": "PMID-12384438_T20", "type": "Cell", "text": [ "melanoma tumor cells" ], "offsets": [ [ 828, 848 ] ], "normalized": [] }, { "id": "PMID-12384438_T22", "type": "Cell", "text": [ "tumor cells" ], "offsets": [ [ 980, 991 ] ], "normalized": [] }, { "id": "PMID-12384438_T24", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 1113, 1119 ] ], "normalized": [] }, { "id": "PMID-12384438_T25", "type": "Multi-tissue_structure", "text": [ "feeding vessels" ], "offsets": [ [ 1143, 1158 ] ], "normalized": [] }, { "id": "PMID-12384438_T26", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 1205, 1211 ] ], "normalized": [] }, { "id": "PMID-12384438_T28", "type": "Cell", "text": [ "CD31(+) endothelial cells" ], "offsets": [ [ 1261, 1286 ] ], "normalized": [] }, { "id": "PMID-12384438_T30", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 1294, 1311 ] ], "normalized": [] }, { "id": "PMID-12384438_T31", "type": "Multi-tissue_structure", "text": [ "tubules" ], "offsets": [ [ 1338, 1345 ] ], "normalized": [] }, { "id": "PMID-12384438_T32", "type": "Multi-tissue_structure", "text": [ "vessel" ], "offsets": [ [ 1373, 1379 ] ], "normalized": [] }, { "id": "PMID-12384438_T33", "type": "Cell", "text": [ "pericyte" ], "offsets": [ [ 1403, 1411 ] ], "normalized": [] }, { "id": "PMID-12384438_T35", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 1535, 1552 ] ], "normalized": [] }, { "id": "PMID-12384438_T38", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 1642, 1648 ] ], "normalized": [] }, { "id": "PMID-12384438_T40", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1762, 1767 ] ], "normalized": [] }, { "id": "PMID-12384438_T42", "type": "Tissue", "text": [ "capillary" ], "offsets": [ [ 1881, 1890 ] ], "normalized": [] } ]

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[ { "id": "PMID-10357269__text", "type": "abstract", "text": [ "Enterococci at the crossroads of food safety?\nEnterococci are gram-positive bacteria and fit within the general definition of lactic acid bacteria. Modern classification techniques resulted in the transfer of some members of the genus Streptococcus, notably some of the Lancefield's group D streptococci, to the new genus Enterococcus. Enterococci can be used as indicators of faecal contamination. They have been implicated in outbreaks of foodborne illness, and they have been ascribed a beneficial or detrimental role in foods. In processed meats, enterococci may survive heat processing and cause spoilage, though in certain cheeses the growth of enterococci contributes to ripening and development of product flavour. Some enterococci of food origin produce bacteriocins that exert anti-Listeria activity. Enterococci are used as probiotics to improve the microbial balance of the intestine, or as a treatment for gastroenteritis in humans and animals. On the other hand, enterococci have become recognised as serious nosocomial pathogens causing bacteraemia, endocarditis, urinary tract and other infections. This is in part explained by the resistance of some of these bacteria to most antibiotics that are currently in use. Resistance is acquired by gene transfer systems, such as conjugative or nonconjugative plasmids or transposons. Virulence of enterococci is not well understood but adhesins, haemolysin, hyaluronidase, aggregation substance and gelatinase are putative virulence factors. It appears that foods could be a source of vancomycin-resistant enterococci. This review addresses the issue of the health risk of foods containing enterococci.\n" ], "offsets": [ [ 0, 1663 ] ] } ]

[ { "id": "PMID-10357269_T1", "type": "Organism_substance", "text": [ "faecal" ], "offsets": [ [ 377, 383 ] ], "normalized": [] }, { "id": "PMID-10357269_T2", "type": "Organism_subdivision", "text": [ "meats" ], "offsets": [ [ 544, 549 ] ], "normalized": [] }, { "id": "PMID-10357269_T3", "type": "Organ", "text": [ "intestine" ], "offsets": [ [ 886, 895 ] ], "normalized": [] }, { "id": "PMID-10357269_T4", "type": "Organism_subdivision", "text": [ "urinary tract" ], "offsets": [ [ 1079, 1092 ] ], "normalized": [] }, { "id": "PMID-10357269_T5", "type": "Cellular_component", "text": [ "conjugative" ], "offsets": [ [ 1289, 1300 ] ], "normalized": [] }, { "id": "PMID-10357269_T6", "type": "Cellular_component", "text": [ "nonconjugative plasmids" ], "offsets": [ [ 1304, 1327 ] ], "normalized": [] } ]

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[ { "id": "PMID-12748830__text", "type": "abstract", "text": [ "Impact of technology on the utilisation of positron emission tomography in lymphoma: current and future perspectives.\nPositron emission tomography (PET) has now gained a place in the management of patients with cancer, including those with Hodgkin's disease and non-Hodgkin's lymphoma. Restaging studies and those addressing the monitoring of response to treatment are especially in focus. Most of the knowledge gained has been achieved with dedicated BGO-based PET technology, but there are a number of developments that will impact on the use of this metabolic imaging technique in the investigation of patients with lymphoma. The challenges ahead are determined by the need for high-quality whole-body imaging associated with increased patient throughput and the need to investigate the role of new labelled ligands. The latter are likely to yield new insights into tumour cell characterisation, tumour behaviour and tumour outcome assessment. The study of new radiolabelled ligands will impose further demands for rapid dynamic data acquisition and accurate tracer quantification. Current and future developments in PET technology range from the use of new detector materials to different detector geometries and data acquisition modes. The search for alternatives to BGO scintillation materials for PET has led to the development of PET instruments utilising new crystals such as LSO and GSO. The use of these new detectors and the increased sensitivity achieved with 3D data acquisitions represent the most significant current developments in the field. With the increasing demands imposed on the clinical utilisation of PET, issues such as study cost and patient throughput will emerge as significant future factors. As a consequence, low-cost units are being offered by the manufacturers through the utilisation of gamma camera-based SPET systems for PET coincidence imaging. Unfortunately, clinical studies in lymphoma and other cancers have already demonstrated the limitations of this technology, with 20% of lesions <15 mm in size escaping detection. On the other hand, the recent development of combined PET/CT devices attempts to address the lack of anatomical information inherent with PET images, taking advantage of further improvement in patient throughput and hence cost-effectiveness. Preliminary studies using this multimodality imaging approach have already demonstrated the potential of the technique. Although the potential exists, certain technical issues with PET/CT require refinement of the methodology. Such issues include organ movement (such as respiratory motion), which strongly influences the image fusion of a rapidly acquired CT scan with the slower acquisition of a PET dataset, and the derivation of CT-based attenuation coefficients in the presence of contrast agents or metallic implants. The application of the technology for radiotherapy planning also poses a number of associated challenges. Finally, the development of dedicated PET systems based on planar detector arrangements with new detector components has the potential to improve clinical throughput by over 100%, but clinical trials using such systems have still to be carried out in order to establish the associated whole-body image quality.\n" ], "offsets": [ [ 0, 3246 ] ] } ]

[ { "id": "PMID-12748830_T1", "type": "Cancer", "text": [ "lymphoma" ], "offsets": [ [ 75, 83 ] ], "normalized": [] }, { "id": "PMID-12748830_T2", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 211, 217 ] ], "normalized": [] }, { "id": "PMID-12748830_T3", "type": "Cancer", "text": [ "non-Hodgkin's lymphoma" ], "offsets": [ [ 262, 284 ] ], "normalized": [] }, { "id": "PMID-12748830_T4", "type": "Cancer", "text": [ "lymphoma" ], "offsets": [ [ 619, 627 ] ], "normalized": [] }, { "id": "PMID-12748830_T5", "type": "Cell", "text": [ "tumour cell" ], "offsets": [ [ 869, 880 ] ], "normalized": [] }, { "id": "PMID-12748830_T6", "type": "Cancer", "text": [ "tumour" ], "offsets": [ [ 899, 905 ] ], "normalized": [] }, { "id": "PMID-12748830_T7", "type": "Cancer", "text": [ "tumour" ], "offsets": [ [ 920, 926 ] ], "normalized": [] }, { "id": "PMID-12748830_T8", "type": "Cancer", "text": [ "lymphoma" ], "offsets": [ [ 1919, 1927 ] ], "normalized": [] }, { "id": "PMID-12748830_T9", "type": "Cancer", "text": [ "cancers" ], "offsets": [ [ 1938, 1945 ] ], "normalized": [] }, { "id": "PMID-12748830_T10", "type": "Cancer", "text": [ "lesions" ], "offsets": [ [ 2020, 2027 ] ], "normalized": [] }, { "id": "PMID-12748830_T12", "type": "Organ", "text": [ "organ" ], "offsets": [ [ 2552, 2557 ] ], "normalized": [] }, { "id": "PMID-12748830_T13", "type": "Organism_subdivision", "text": [ "body" ], "offsets": [ [ 3226, 3230 ] ], "normalized": [] }, { "id": "PMID-12748830_T14", "type": "Anatomical_system", "text": [ "respiratory" ], "offsets": [ [ 2576, 2587 ] ], "normalized": [] } ]

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[ { "id": "PMID-2539554__text", "type": "abstract", "text": [ "Type-A cholecystokinin receptors in CHP212 neuroblastoma cells: evidence for association with G protein and activation of phosphoinositide hydrolysis.\n125I-Bolton Hunter-cholecystokinin octapeptide (BH-CCK8) and (-)-[3H]L-364718 membrane binding assays were used to identify and characterize cholecystokinin (CCK) receptors in CHP212 human neuroblastoma cells. The ligand binding properties of CCK receptors in these cells are similar to those found in pancreas (CCK-A sites) and differ from the predominant type of CCK binding site found in brain (CCK-B sites). The specific binding of 125I-BH-CCK8 but not (-)-[3H]L-364718 was reduced by the metabolically stable GTP analog guanosine 5'-(beta-delta-imido)trisphosphate. A substantial difference in the Bmax for the radiolabeled agonist (125I-BH-CCK8) and antagonist [(-)-[3H]L-364718] was noted. These observations are consistent with CCK receptors existing in guanine nucleotide-binding protein-coupled and -uncoupled states. Similar to its action in pancreatic acinar cells, CCK8(S) stimulated the accumulation of [3H]inositol phosphates in cells prelabeled with [3H]myo-inositol (EC50 = 3.2 +/- 0.4 nM; maximum response = 4.5 +/- 0.4 x basal). The intrinsic activity of CCK analogues in stimulating phosphoinositide hydrolysis was substantially less than their reported intrinsic activity in stimulating phosphoinositide hydrolysis in pancreatic acinar cells. The CHP212 neuroblastoma cell may serve as a useful model for the recently reported CCK-A binding site found in the central nervous system.\n" ], "offsets": [ [ 0, 1555 ] ] } ]

[ { "id": "PMID-2539554_T1", "type": "Cell", "text": [ "CHP212 neuroblastoma cells" ], "offsets": [ [ 36, 62 ] ], "normalized": [] }, { "id": "PMID-2539554_T2", "type": "Cellular_component", "text": [ "membrane" ], "offsets": [ [ 229, 237 ] ], "normalized": [] }, { "id": "PMID-2539554_T3", "type": "Cell", "text": [ "CHP212" ], "offsets": [ [ 327, 333 ] ], "normalized": [] }, { "id": "PMID-2539554_T4", "type": "Cell", "text": [ "neuroblastoma cells" ], "offsets": [ [ 340, 359 ] ], "normalized": [] }, { "id": "PMID-2539554_T5", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 417, 422 ] ], "normalized": [] }, { "id": "PMID-2539554_T6", "type": "Organ", "text": [ "pancreas" ], "offsets": [ [ 453, 461 ] ], "normalized": [] }, { "id": "PMID-2539554_T7", "type": "Organ", "text": [ "brain" ], "offsets": [ [ 542, 547 ] ], "normalized": [] }, { "id": "PMID-2539554_T8", "type": "Cell", "text": [ "pancreatic acinar cells" ], "offsets": [ [ 1004, 1027 ] ], "normalized": [] }, { "id": "PMID-2539554_T9", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1095, 1100 ] ], "normalized": [] }, { "id": "PMID-2539554_T10", "type": "Cell", "text": [ "pancreatic acinar cells" ], "offsets": [ [ 1390, 1413 ] ], "normalized": [] }, { "id": "PMID-2539554_T11", "type": "Cell", "text": [ "CHP212 neuroblastoma cell" ], "offsets": [ [ 1419, 1444 ] ], "normalized": [] }, { "id": "PMID-2539554_T12", "type": "Anatomical_system", "text": [ "central nervous system" ], "offsets": [ [ 1531, 1553 ] ], "normalized": [] } ]

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[ { "id": "PMID-21390189__text", "type": "abstract", "text": [ "Use of DNA microarray and small animal positron emission tomography in preclinical drug evaluation of RAF265, a novel B-Raf/VEGFR-2 inhibitor. \nPositron emission tomography (PET) imaging has become a useful tool for assessing early biologic response to cancer therapy and may be particularly useful in the development of new cancer therapeutics. RAF265, a novel B-Raf/vascular endothelial growth factor receptor-2 inhibitor, was evaluated in the preclinical setting for its ability to inhibit the uptake of PET tracers in the A375M(B-Raf(V600E)) human melanoma cell line. RAF265 inhibited 2-deoxy-2-[(18)F]fluoro-d-glucose (FDG) accumulation in cell culture at 28 hours in a dose-dependent manner. RAF265 also inhibited FDG accumulation in tumor xenografts after 1 day of drug treatment. This decrease persisted for the remaining 2 weeks of treatment. DNA microarray analysis of treated tumor xenografts revealed significantly decreased expression of genes regulating glucose and thymidine metabolism and revealed changes in apoptotic genes, suggesting that the imaging tracers FDG, 3-deoxy-3-[(18)F]fluorothymidine, and annexin V could serve as potential imaging biomarkers for RAF265 therapy monitoring. We concluded that RAF265 is highly efficacious in this xenograft model of human melanoma and decreases glucose metabolism as measured by DNA microarray analysis, cell culture assays, and small animal FDG PET scans as early as 1 day after treatment. Our results support the use of FDG PET in clinical trials with RAF265 to assess early tumor response. DNA microarray analysis and small animal PET studies may be used as complementary technologies in drug development. DNA microarray analysis allows for analysis of drug effects on multiple pathways linked to cancer and can suggest corresponding imaging tracers for further analysis as biomarkers of tumor response.\n" ], "offsets": [ [ 0, 1871 ] ] } ]

[ { "id": "PMID-21390189_T5", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 253, 259 ] ], "normalized": [] }, { "id": "PMID-21390189_T6", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 325, 331 ] ], "normalized": [] }, { "id": "PMID-21390189_T10", "type": "Cell", "text": [ "A375M(B-Raf(V600E)) human melanoma cell line" ], "offsets": [ [ 526, 570 ] ], "normalized": [] }, { "id": "PMID-21390189_T15", "type": "Cell", "text": [ "cell culture" ], "offsets": [ [ 645, 657 ] ], "normalized": [] }, { "id": "PMID-21390189_T18", "type": "Cancer", "text": [ "tumor xenografts" ], "offsets": [ [ 740, 756 ] ], "normalized": [] }, { "id": "PMID-21390189_T20", "type": "Cancer", "text": [ "tumor xenografts" ], "offsets": [ [ 887, 903 ] ], "normalized": [] }, { "id": "PMID-21390189_T28", "type": "Cancer", "text": [ "xenograft" ], "offsets": [ [ 1261, 1270 ] ], "normalized": [] }, { "id": "PMID-21390189_T30", "type": "Cancer", "text": [ "melanoma" ], "offsets": [ [ 1286, 1294 ] ], "normalized": [] }, { "id": "PMID-21390189_T33", "type": "Cell", "text": [ "cell culture" ], "offsets": [ [ 1368, 1380 ] ], "normalized": [] }, { "id": "PMID-21390189_T37", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1541, 1546 ] ], "normalized": [] }, { "id": "PMID-21390189_T40", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 1764, 1770 ] ], "normalized": [] }, { "id": "PMID-21390189_T41", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1855, 1860 ] ], "normalized": [] } ]

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[ { "id": "PMID-9754701__text", "type": "abstract", "text": [ "Hemispheric control of motor function: a whole brain echo planar fMRI study.\nThe aim of this study was to explore whether recruitment of the ipsilateral motor cortex during non-dominant motor movement reflects left hemispheric control of motor function or simply the greater complexity or unfamiliarity of the motor task. BOLD fMRI was performed in normal right-handers during two motor tasks: (1) sequential finger movements (SM task) with the right or left hand; and (2) random finger movements (RM task) with the right hand. In all subjects, activation was predominantly in the contralateral motor areas (primary sensorimotor, lateral premotor, parietal and supplementary motor regions) and ipsilateral cerebellum. While the ipsilateral motor areas were also activated, single subject analysis revealed these areas to be more extensive and to be seen in more subjects during the non-dominant hand SM task and dominant hand RM task than during the more familiar dominant hand SM task. Similarly, group analysis also revealed ipsilateral activation in the primary sensorimotor and lateral premotor areas, but only during the non-dominant SM task and the dominant hand RM task. Non-dominant hand movements, perhaps because they are less 'automatic', appear to require more cortical activity similar to complex tasks with the dominant hand, and result in greater recruitment of ipsilateral cortical motor areas and striatum. The study also illustrates how potentially meaningful subtleties seen on individual maps may be obscured with group averaging approaches.\n" ], "offsets": [ [ 0, 1562 ] ] } ]

[ { "id": "PMID-9754701_T1", "type": "Organ", "text": [ "brain" ], "offsets": [ [ 47, 52 ] ], "normalized": [] }, { "id": "PMID-9754701_T2", "type": "Multi-tissue_structure", "text": [ "ipsilateral motor cortex" ], "offsets": [ [ 141, 165 ] ], "normalized": [] }, { "id": "PMID-9754701_T3", "type": "Organism_subdivision", "text": [ "finger" ], "offsets": [ [ 409, 415 ] ], "normalized": [] }, { "id": "PMID-9754701_T4", "type": "Organism_subdivision", "text": [ "left hand" ], "offsets": [ [ 454, 463 ] ], "normalized": [] }, { "id": "PMID-9754701_T5", "type": "Organism_subdivision", "text": [ "finger" ], "offsets": [ [ 480, 486 ] ], "normalized": [] }, { "id": "PMID-9754701_T6", "type": "Organism_subdivision", "text": [ "right hand" ], "offsets": [ [ 516, 526 ] ], "normalized": [] }, { "id": "PMID-9754701_T7", "type": "Multi-tissue_structure", "text": [ "ipsilateral cerebellum" ], "offsets": [ [ 694, 716 ] ], "normalized": [] }, { "id": "PMID-9754701_T8", "type": "Multi-tissue_structure", "text": [ "ipsilateral motor areas" ], "offsets": [ [ 728, 751 ] ], "normalized": [] }, { "id": "PMID-9754701_T9", "type": "Multi-tissue_structure", "text": [ "lateral premotor areas" ], "offsets": [ [ 1082, 1104 ] ], "normalized": [] }, { "id": "PMID-9754701_T10", "type": "Multi-tissue_structure", "text": [ "ipsilateral cortical motor areas" ], "offsets": [ [ 1377, 1409 ] ], "normalized": [] }, { "id": "PMID-9754701_T11", "type": "Multi-tissue_structure", "text": [ "striatum" ], "offsets": [ [ 1414, 1422 ] ], "normalized": [] }, { "id": "PMID-9754701_T12", "type": "Multi-tissue_structure", "text": [ "left hemispheric" ], "offsets": [ [ 210, 226 ] ], "normalized": [] }, { "id": "PMID-9754701_T13", "type": "Organism_subdivision", "text": [ "hand" ], "offsets": [ [ 973, 977 ] ], "normalized": [] }, { "id": "PMID-9754701_T14", "type": "Organism_subdivision", "text": [ "hand" ], "offsets": [ [ 1191, 1195 ] ], "normalized": [] }, { "id": "PMID-9754701_T15", "type": "Organism_subdivision", "text": [ "hand" ], "offsets": [ [ 1334, 1338 ] ], "normalized": [] }, { "id": "PMID-9754701_T16", "type": "Organism_subdivision", "text": [ "hand" ], "offsets": [ [ 1164, 1168 ] ], "normalized": [] }, { "id": "PMID-9754701_T17", "type": "Organism_subdivision", "text": [ "hand" ], "offsets": [ [ 895, 899 ] ], "normalized": [] }, { "id": "PMID-9754701_T18", "type": "Organism_subdivision", "text": [ "hand" ], "offsets": [ [ 921, 925 ] ], "normalized": [] }, { "id": "PMID-9754701_T19", "type": "Multi-tissue_structure", "text": [ "cortical" ], "offsets": [ [ 1273, 1281 ] ], "normalized": [] }, { "id": "PMID-9754701_T22", "type": "Multi-tissue_structure", "text": [ "contralateral motor areas" ], "offsets": [ [ 581, 606 ] ], "normalized": [] }, { "id": "PMID-9754701_T23", "type": "Multi-tissue_structure", "text": [ "primary sensorimotor" ], "offsets": [ [ 608, 628 ] ], "normalized": [] }, { "id": "PMID-9754701_T20", "type": "Multi-tissue_structure", "text": [ "lateral premotor" ], "offsets": [ [ 630, 646 ] ], "normalized": [] }, { "id": "PMID-9754701_T21", "type": "Multi-tissue_structure", "text": [ "parietal" ], "offsets": [ [ 648, 656 ] ], "normalized": [] }, { "id": "PMID-9754701_T24", "type": "Multi-tissue_structure", "text": [ "supplementary motor regions" ], "offsets": [ [ 661, 688 ] ], "normalized": [] }, { "id": "PMID-9754701_T26", "type": "Multi-tissue_structure", "text": [ "primary sensorimotor" ], "offsets": [ [ 1057, 1077 ] ], "normalized": [] }, { "id": "PMID-9754701_T25", "type": "Organism_subdivision", "text": [ "right" ], "offsets": [ [ 445, 450 ] ], "normalized": [] } ]

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[ { "id": "PMID-3533793__text", "type": "abstract", "text": [ "Suppression and re-expression of transformed phenotype in hybrids of HA-ras-1-transformed rat-1 cells and early-passage rat embryonic fibroblasts. \nRat-1 cells which had been transformed with the activated Ha-ras-1 gene from human EJ bladder carcinoma cells were fused with diploid embryonic rat fibroblasts. Four selected cell hybrids expressed the human transforming gene product p21 at levels of 10 to 30% compared to 100% in the transformed parental cells. The hybrid cells, however, exhibited normal morphology, anchorage requirement for proliferation, and largely extended latency periods of tumorigenicity in newborn rats. Tumorigenic hybrid derivatives contained lower numbers of chromosomes than the tetraploid parental hybrids. DNA of the non-tumorigenic cell hybrids transformed Rat-1 cells to anchorage-independent proliferation as expected for the transforming human Ha-ras gene present in the donor DNA. We conclude that the transforming properties of the activated Ha-ras gene in Rat-1 cells can be suppressed at the post-translational level by the presence of the genome from diploid embryonic rat fibroblasts but additional controls of expression of the transforming gene are likely to exist. Normal cells contain suppressor gene(s) which safeguard these cells against transformation by the product of the transforming Ha-ras-1 oncogene.\n" ], "offsets": [ [ 0, 1355 ] ] } ]

[ { "id": "PMID-3533793_T2", "type": "Cell", "text": [ "rat-1 cells" ], "offsets": [ [ 90, 101 ] ], "normalized": [] }, { "id": "PMID-3533793_T4", "type": "Cell", "text": [ "embryonic fibroblasts" ], "offsets": [ [ 124, 145 ] ], "normalized": [] }, { "id": "PMID-3533793_T5", "type": "Cell", "text": [ "Rat-1 cells" ], "offsets": [ [ 148, 159 ] ], "normalized": [] }, { "id": "PMID-3533793_T8", "type": "Cell", "text": [ "EJ bladder carcinoma cells" ], "offsets": [ [ 231, 257 ] ], "normalized": [] }, { "id": "PMID-3533793_T10", "type": "Cell", "text": [ "embryonic rat fibroblasts" ], "offsets": [ [ 282, 307 ] ], "normalized": [] }, { "id": "PMID-3533793_T11", "type": "Cell", "text": [ "cell hybrids" ], "offsets": [ [ 323, 335 ] ], "normalized": [] }, { "id": "PMID-3533793_T14", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 454, 459 ] ], "normalized": [] }, { "id": "PMID-3533793_T15", "type": "Cell", "text": [ "hybrid cells" ], "offsets": [ [ 465, 477 ] ], "normalized": [] }, { "id": "PMID-3533793_T17", "type": "Cell", "text": [ "hybrid derivatives" ], "offsets": [ [ 642, 660 ] ], "normalized": [] }, { "id": "PMID-3533793_T18", "type": "Cellular_component", "text": [ "chromosomes" ], "offsets": [ [ 688, 699 ] ], "normalized": [] }, { "id": "PMID-3533793_T19", "type": "Cell", "text": [ "parental hybrids" ], "offsets": [ [ 720, 736 ] ], "normalized": [] }, { "id": "PMID-3533793_T21", "type": "Cell", "text": [ "cell hybrids" ], "offsets": [ [ 765, 777 ] ], "normalized": [] }, { "id": "PMID-3533793_T22", "type": "Cell", "text": [ "Rat-1 cells" ], "offsets": [ [ 790, 801 ] ], "normalized": [] }, { "id": "PMID-3533793_T27", "type": "Cell", "text": [ "Rat-1 cells" ], "offsets": [ [ 995, 1006 ] ], "normalized": [] }, { "id": "PMID-3533793_T30", "type": "Cell", "text": [ "embryonic rat fibroblasts" ], "offsets": [ [ 1100, 1125 ] ], "normalized": [] }, { "id": "PMID-3533793_T31", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1217, 1222 ] ], "normalized": [] }, { "id": "PMID-3533793_T32", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1272, 1277 ] ], "normalized": [] }, { "id": "PMID-3533793_T63", "type": "Cell", "text": [ "hybrids" ], "offsets": [ [ 58, 65 ] ], "normalized": [] } ]

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[ { "id": "PMID-19380174__text", "type": "abstract", "text": [ "FOXO3a elicits a pro-apoptotic transcription program and cellular response to human lung carcinogen nicotine-derived nitrosaminoketone (NNK). \nLong-term carcinogen exposure exerts continuous pressure on key mechanisms that repair or eliminate carcinogen-damaged cells giving rise to selective failures that contribute to lung cancer. FOXO3a is a transcription factor that elicits a protective response to diverse cellular stresses. Although implicated as a tumor suppressor, its role in sporadic cancer is uncertain. We recently observed that FOXO3a gene inactivation occurs frequently in carcinogen-induced lung adenocarcinoma (LAC). This suggests that FOXO3a may play a role in LAC suppression by eliciting a protective response to carcinogenic stress. Here we investigated this possibility by examining the role of FOXO3a in the cellular response to nicotine-derived nitrosaminoketone (NNK), a lung carcinogen implicated as a cause of human LAC. We show that restoration of FOXO3a in FOXO3a-deficient LAC cells increases sensitivity to apoptosis caused by a DNA-damaging intermediate of NNK. Prior to this cellular outcome, FOXO3a is functionally activated and mediates a large-scale transcription program in response to this damage involving a significant modulation of 440 genes. Genes most significantly represented in this program are those with roles in cell growth and proliferation>protein synthesis>gene expression>cell death>cell cycle. The results of this study show that FOXO3a directs an anti-carcinogenic transcription program that culminates in the elimination of carcinogen-damaged cells. This suggests that FOXO3a is a potential suppressor of carcinogenic damage in LAC.\n" ], "offsets": [ [ 0, 1690 ] ] } ]

[ { "id": "PMID-19380174_T2", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 57, 65 ] ], "normalized": [] }, { "id": "PMID-19380174_T4", "type": "Organ", "text": [ "lung" ], "offsets": [ [ 84, 88 ] ], "normalized": [] }, { "id": "PMID-19380174_T7", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 262, 267 ] ], "normalized": [] }, { "id": "PMID-19380174_T8", "type": "Cancer", "text": [ "lung cancer" ], "offsets": [ [ 321, 332 ] ], "normalized": [] }, { "id": "PMID-19380174_T10", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 413, 421 ] ], "normalized": [] }, { "id": "PMID-19380174_T11", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 457, 462 ] ], "normalized": [] }, { "id": "PMID-19380174_T12", "type": "Cancer", "text": [ "sporadic cancer" ], "offsets": [ [ 487, 502 ] ], "normalized": [] }, { "id": "PMID-19380174_T14", "type": "Cancer", "text": [ "lung adenocarcinoma" ], "offsets": [ [ 608, 627 ] ], "normalized": [] }, { "id": "PMID-19380174_T15", "type": "Cancer", "text": [ "LAC" ], "offsets": [ [ 629, 632 ] ], "normalized": [] }, { "id": "PMID-19380174_T17", "type": "Cancer", "text": [ "LAC" ], "offsets": [ [ 680, 683 ] ], "normalized": [] }, { "id": "PMID-19380174_T19", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 832, 840 ] ], "normalized": [] }, { "id": "PMID-19380174_T22", "type": "Organ", "text": [ "lung" ], "offsets": [ [ 897, 901 ] ], "normalized": [] }, { "id": "PMID-19380174_T24", "type": "Cancer", "text": [ "LAC" ], "offsets": [ [ 944, 947 ] ], "normalized": [] }, { "id": "PMID-19380174_T27", "type": "Cell", "text": [ "LAC cells" ], "offsets": [ [ 1004, 1013 ] ], "normalized": [] }, { "id": "PMID-19380174_T30", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 1109, 1117 ] ], "normalized": [] }, { "id": "PMID-19380174_T32", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1362, 1366 ] ], "normalized": [] }, { "id": "PMID-19380174_T33", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1426, 1430 ] ], "normalized": [] }, { "id": "PMID-19380174_T34", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1437, 1441 ] ], "normalized": [] }, { "id": "PMID-19380174_T36", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1600, 1605 ] ], "normalized": [] }, { "id": "PMID-19380174_T38", "type": "Cancer", "text": [ "LAC" ], "offsets": [ [ 1685, 1688 ] ], "normalized": [] } ]

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[ { "id": "PMID-20732829__text", "type": "abstract", "text": [ "Using a web-based orthopaedic clinic in the curricular teaching of a German university hospital: analysis of learning effect, student usage and reception.\nPURPOSE:\nModern teaching concepts for undergraduate medical students in Germany include problem based learning as a major component of the new licensing regulations for physicians. Here we describe the usage of a web-based virtual outpatient clinic in the teaching curriculum of undergraduate medical students, its effect on learning success, and student reception.\nMETHODS:\nFifth year medial students were requested to examine 7 virtual orthopaedic patients which had been created by the authors using the Inmedea-Simulator. They also had to take a multiple-choice examination on two different occasions and their utilisation of the simulator was analysed subjectively and objectively.\nRESULTS:\nOne hundred and sixty students took part in the study. The average age was 24.9 years, 60% were female. Most of the participants studied on their own using their private computer with a fast internet-connection at home. The average usage time was 263 min, most of the students worked with the system in the afternoon, although a considerable number used it late in the night. Regarding learning success, we found that the examination results were significantly better after using the system (7.66 versus 8.37, p<0.0001). Eighty percent of the students enjoyed dealing with the virtual patients emphasizing the completeness of patient cases, the artistic graphic design and the expert comments available, as well as the good applicability to real cases. Eighty-seven percent of the students graded the virtual orthopaedic clinic as appropriate to teach orthopaedic content.\nCONCLUSION:\nUsing the Inmedea-Simulator is an effective method to enhance students' learning efficacy. The way the system was used by the students emphasises the advantages of the internet-like free time management and the implementation of multimedia-based content.\n" ], "offsets": [ [ 0, 1991 ] ] } ]

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[ { "id": "PMID-1639185__text", "type": "abstract", "text": [ "Recent advances in minisatellite biology.\nHighly polymorphic tandemly repeated 'minisatellite' loci are very abundant in the human genome, and of considerable utility in human genetic analysis. This review describes the use of an ordered-array Charomid library in the systematic and efficient cloning of these regions, and in the analysis of the relative overlap between the different probes used to screen for hypervariable loci. Recent work on the process of mutation leading to the generation of new-length alleles is also discussed, including the observation that at least some mutations may be due to unequal exchanges.\n" ], "offsets": [ [ 0, 625 ] ] } ]

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[ { "id": "PMID-19444623__text", "type": "abstract", "text": [ "Activated platelets enhance ovarian cancer cell invasion in a cellular model of metastasis. \nIncreased platelet counts and systemic coagulation activation are associated with ovarian cancer progression. Platelet activation occurs in the tumor microenvironment and may influence local invasion and metastasis. We used a cellular model of tumor invasion to investigate the effect of activated platelets on the human ovarian cancer cell line, SKOV3. SKOV3 cells were exposed to washed, thrombin receptor activating peptide (TRAP)-activated or TRAP-naive platelets under various experimental conditions, and tumor cell invasion was assayed in Matrigel chambers. The effect of platelets on the content of urokinase plasminogen activator (uPA) and VEGF in SKOV3 cell conditioned medium was measured using an ELISA assay. TRAP-activated platelets stimulated a dose-dependent increase in SKOV3 cell invasion. Exposure to activated platelet membranes and to soluble proteins contained in activated platelet releasate both contributed to the observed increase in invasion. The inhibition of platelet activation with prostaglandin E1 (PGE(1)) attenuated the invasive capacity of SKOV3 cells. Exposure to platelets resulted in significantly increased uPA and VEGF content of SKOV3 cell conditioned medium. Activated platelets enhance SKOV3 human ovarian cancer cell invasion through Matrigel and increase the amount of uPA and VEGF secreted into SKOV3 cell conditioned medium. If generalizable to additional cell lines and human disease, this observation may partially explain the adverse prognosis associated with thrombocytosis in ovarian cancer. Platelets, therefore, may represent a potential target for therapeutic intervention in human ovarian cancer.\n" ], "offsets": [ [ 0, 1746 ] ] } ]

[ { "id": "PMID-19444623_T1", "type": "Cell", "text": [ "platelets" ], "offsets": [ [ 10, 19 ] ], "normalized": [] }, { "id": "PMID-19444623_T2", "type": "Cell", "text": [ "ovarian cancer cell" ], "offsets": [ [ 28, 47 ] ], "normalized": [] }, { "id": "PMID-19444623_T3", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 62, 70 ] ], "normalized": [] }, { "id": "PMID-19444623_T4", "type": "Cell", "text": [ "platelet" ], "offsets": [ [ 103, 111 ] ], "normalized": [] }, { "id": "PMID-19444623_T5", "type": "Cancer", "text": [ "ovarian cancer" ], "offsets": [ [ 175, 189 ] ], "normalized": [] }, { "id": "PMID-19444623_T6", "type": "Cell", "text": [ "Platelet" ], "offsets": [ [ 203, 211 ] ], "normalized": [] }, { "id": "PMID-19444623_T7", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 237, 242 ] ], "normalized": [] }, { "id": "PMID-19444623_T8", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 319, 327 ] ], "normalized": [] }, { "id": "PMID-19444623_T9", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 337, 342 ] ], "normalized": [] }, { "id": "PMID-19444623_T10", "type": "Cell", "text": [ "platelets" ], "offsets": [ [ 391, 400 ] ], "normalized": [] }, { "id": "PMID-19444623_T12", "type": "Cell", "text": [ "ovarian cancer cell line" ], "offsets": [ [ 414, 438 ] ], "normalized": [] }, { "id": "PMID-19444623_T13", "type": "Cell", "text": [ "SKOV3" ], "offsets": [ [ 440, 445 ] ], "normalized": [] }, { "id": "PMID-19444623_T14", "type": "Cell", "text": [ "SKOV3 cells" ], "offsets": [ [ 447, 458 ] ], "normalized": [] }, { "id": "PMID-19444623_T18", "type": "Cell", "text": [ "platelets" ], "offsets": [ [ 551, 560 ] ], "normalized": [] }, { "id": "PMID-19444623_T19", "type": "Cell", "text": [ "tumor cell" ], "offsets": [ [ 604, 614 ] ], "normalized": [] }, { "id": "PMID-19444623_T20", "type": "Cell", "text": [ "platelets" ], "offsets": [ [ 672, 681 ] ], "normalized": [] }, { "id": "PMID-19444623_T24", "type": "Cell", "text": [ "SKOV3 cell" ], "offsets": [ [ 750, 760 ] ], "normalized": [] }, { "id": "PMID-19444623_T26", "type": "Cell", "text": [ "platelets" ], "offsets": [ [ 830, 839 ] ], "normalized": [] }, { "id": "PMID-19444623_T27", "type": "Cell", "text": [ "SKOV3 cell" ], "offsets": [ [ 880, 890 ] ], "normalized": [] }, { "id": "PMID-19444623_T29", "type": "Cellular_component", "text": [ "platelet membranes" ], "offsets": [ [ 923, 941 ] ], "normalized": [] }, { "id": "PMID-19444623_T30", "type": "Cell", "text": [ "platelet" ], "offsets": [ [ 989, 997 ] ], "normalized": [] }, { "id": "PMID-19444623_T31", "type": "Cell", "text": [ "platelet" ], "offsets": [ [ 1081, 1089 ] ], "normalized": [] }, { "id": "PMID-19444623_T34", "type": "Cell", "text": [ "SKOV3 cells" ], "offsets": [ [ 1168, 1179 ] ], "normalized": [] }, { "id": "PMID-19444623_T35", "type": "Cell", "text": [ "platelets" ], "offsets": [ [ 1193, 1202 ] ], "normalized": [] }, { "id": "PMID-19444623_T38", "type": "Cell", "text": [ "SKOV3 cell" ], "offsets": [ [ 1263, 1273 ] ], "normalized": [] }, { "id": "PMID-19444623_T39", "type": "Cell", "text": [ "platelets" ], "offsets": [ [ 1304, 1313 ] ], "normalized": [] }, { "id": "PMID-19444623_T40", "type": "Cell", "text": [ "SKOV3" ], "offsets": [ [ 1322, 1327 ] ], "normalized": [] }, { "id": "PMID-19444623_T42", "type": "Cell", "text": [ "ovarian cancer cell" ], "offsets": [ [ 1334, 1353 ] ], "normalized": [] }, { "id": "PMID-19444623_T45", "type": "Cell", "text": [ "SKOV3 cell" ], "offsets": [ [ 1434, 1444 ] ], "normalized": [] }, { "id": "PMID-19444623_T46", "type": "Cell", "text": [ "cell lines" ], "offsets": [ [ 1496, 1506 ] ], "normalized": [] }, { "id": "PMID-19444623_T48", "type": "Cancer", "text": [ "ovarian cancer" ], "offsets": [ [ 1621, 1635 ] ], "normalized": [] }, { "id": "PMID-19444623_T49", "type": "Cell", "text": [ "Platelets" ], "offsets": [ [ 1637, 1646 ] ], "normalized": [] }, { "id": "PMID-19444623_T51", "type": "Cancer", "text": [ "ovarian cancer" ], "offsets": [ [ 1730, 1744 ] ], "normalized": [] } ]

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[ { "id": "PMC-2133064-sec-12__text", "type": "sec", "text": [ "Results\nThe observation that AP-3 is found in both cytosolic and membrane subcellular fractions, and that membrane-associated AP-3 can be extracted with salts (Dell'Angelica et al., 1997a) is consistent with its role as a membrane coat that can be recruited from a cytosolic pool. In addition, the punctate staining of AP-3 by immunofluorescence microscopy, its redistribution to the cytosol by BFA, and the reversibility of the BFA effect (Dell'Angelica et al., 1997a; Simpson et al., 1997) also indicate that AP-3 can cycle between the cytosol and membranes. The sensitivity of AP-3 to BFA in cells suggests that its membrane association may be regulated by ARF1, since BFA inhibits ARF1 guanine nucleotide exchange, and has been shown to prevent ARF1 membrane binding in vitro (Donaldson et al., 1992; Helms and Rothman, 1992; Randazzo et al., 1993).\n\n" ], "offsets": [ [ 0, 855 ] ] } ]

[ { "id": "PMC-2133064-sec-12_T1", "type": "Organism_substance", "text": [ "cytosolic" ], "offsets": [ [ 51, 60 ] ], "normalized": [] }, { "id": "PMC-2133064-sec-12_T2", "type": "Organism_substance", "text": [ "membrane subcellular fractions" ], "offsets": [ [ 65, 95 ] ], "normalized": [] }, { "id": "PMC-2133064-sec-12_T3", "type": "Cellular_component", "text": [ "membrane" ], "offsets": [ [ 106, 114 ] ], "normalized": [] }, { "id": "PMC-2133064-sec-12_T4", "type": "Cellular_component", "text": [ "membrane" ], "offsets": [ [ 222, 230 ] ], "normalized": [] }, { "id": "PMC-2133064-sec-12_T5", "type": "Organism_substance", "text": [ "cytosolic pool" ], "offsets": [ [ 265, 279 ] ], "normalized": [] }, { "id": "PMC-2133064-sec-12_T6", "type": "Organism_substance", "text": [ "cytosol" ], "offsets": [ [ 384, 391 ] ], "normalized": [] }, { "id": "PMC-2133064-sec-12_T7", "type": "Organism_substance", "text": [ "cytosol" ], "offsets": [ [ 538, 545 ] ], "normalized": [] }, { "id": "PMC-2133064-sec-12_T8", "type": "Cellular_component", "text": [ "membranes" ], "offsets": [ [ 550, 559 ] ], "normalized": [] }, { "id": "PMC-2133064-sec-12_T9", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 595, 600 ] ], "normalized": [] }, { "id": "PMC-2133064-sec-12_T10", "type": "Cellular_component", "text": [ "membrane" ], "offsets": [ [ 619, 627 ] ], "normalized": [] }, { "id": "PMC-2133064-sec-12_T11", "type": "Cellular_component", "text": [ "membrane" ], "offsets": [ [ 754, 762 ] ], "normalized": [] } ]

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[ { "id": "PMID-20861187__text", "type": "abstract", "text": [ "Brick1 is an essential regulator of actin cytoskeleton required for embryonic development and cell transformation. \nBrick1 (Brk1) is the less-studied component of the Wave/Scar pathway involved in the branched nucleation of actin fibers. The clinical relevance of Brk1 is emphasized by correlative data showing that Von Hippel-Lindau (VHL) patients that also lose the BRK1 gene are protected against the development of tumors. This contrasts with recent evidence suggesting that the Wave complex may function as an invasion suppressor in epithelial cancers. Here, we show that the downregulation of Brk1 results in abnormal actin stress fiber formation and vinculin distribution and loss of Arp2/3 and Wave proteins at the cellular protrusions. Brk1 is required for cell proliferation and cell transformation by oncogenes. In addition, Brk1 downregulation results in defective directional migration and invasive growth in renal cell carcinoma cells as well as in other tumor cell types. Finally, genetic ablation of Brk1 results in dramatic defects in embryo compaction and development, suggesting an essential role for this protein in actin dynamics. Thus, genetic loss or inhibition of BRK1 is likely to be protective against tumor development due to proliferation and motility defects in affected cells.\n" ], "offsets": [ [ 0, 1307 ] ] } ]

[ { "id": "PMID-20861187_T3", "type": "Cellular_component", "text": [ "cytoskeleton" ], "offsets": [ [ 42, 54 ] ], "normalized": [] }, { "id": "PMID-20861187_T4", "type": "Developing_anatomical_structure", "text": [ "embryonic" ], "offsets": [ [ 68, 77 ] ], "normalized": [] }, { "id": "PMID-20861187_T5", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 94, 98 ] ], "normalized": [] }, { "id": "PMID-20861187_T11", "type": "Cellular_component", "text": [ "fibers" ], "offsets": [ [ 230, 236 ] ], "normalized": [] }, { "id": "PMID-20861187_T15", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 419, 425 ] ], "normalized": [] }, { "id": "PMID-20861187_T17", "type": "Cancer", "text": [ "epithelial cancers" ], "offsets": [ [ 538, 556 ] ], "normalized": [] }, { "id": "PMID-20861187_T20", "type": "Cellular_component", "text": [ "stress fiber" ], "offsets": [ [ 630, 642 ] ], "normalized": [] }, { "id": "PMID-20861187_T24", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 723, 731 ] ], "normalized": [] }, { "id": "PMID-20861187_T26", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 766, 770 ] ], "normalized": [] }, { "id": "PMID-20861187_T27", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 789, 793 ] ], "normalized": [] }, { "id": "PMID-20861187_T29", "type": "Cell", "text": [ "renal cell carcinoma cells" ], "offsets": [ [ 922, 948 ] ], "normalized": [] }, { "id": "PMID-20861187_T30", "type": "Cell", "text": [ "tumor cell" ], "offsets": [ [ 969, 979 ] ], "normalized": [] }, { "id": "PMID-20861187_T32", "type": "Developing_anatomical_structure", "text": [ "embryo" ], "offsets": [ [ 1052, 1058 ] ], "normalized": [] }, { "id": "PMID-20861187_T35", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1228, 1233 ] ], "normalized": [] }, { "id": "PMID-20861187_T36", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1300, 1305 ] ], "normalized": [] } ]

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[ { "id": "PMC-2892078-sec-02__text", "type": "sec", "text": [ "2.\nCLINICAL PROTEOMICS AT THE BEDSIDE\nClinically-based proteomics has a large potential for the development of strategies which aim to alleviate risk associated with cardiac disease. Biomarkers that are used in clinical practice are highly useful in that they support medical decision making, by complementing other diagnostic tests, such as the medical history, physical examination, and various other special tests. Theoretically, there are three criteria that, if satisfied, would provide an optimal biomarker of the disease state. First, the potential biomarkers must be easily measurable in a short time period at a cost that is practical. Second, elevation of this protein would offer diagnostic information that was not previously present in the absence of the protein. Third, the information obtained would aid in the medical decision making process performed by the clinician [11]. Fulfillment of such criteria encourages follow-up of such a biomarker in other model systems or patient cohort samples. For instance, cardiac troponin I has been previously shown to fulfill such criteria, and further follow-up in patient cohorts is underway. Recently, this approach was utilized to ascertain whether Cardiac Troponin I (CTN I) or Creatine Kinase-Myoglobin (CK-MB) could be used as short-term or long-term markers of risk associated with cardiac surgery [12]. In this study, a patient cohort of 252 individuals who had undergone cardiac surgery was used to analyze levels of these two proteins in blood. Not only was CTN-I shown to be a strong predictor of mortality, but increases in the levels of this protein also correlated well with increases in mortality. Findings from this study support the utilization of patient cohorts as a means to ease the transition from bench to bedside.\n" ], "offsets": [ [ 0, 1794 ] ] } ]

[ { "id": "PMC-2892078-sec-02_T1", "type": "Organ", "text": [ "cardiac" ], "offsets": [ [ 166, 173 ] ], "normalized": [] }, { "id": "PMC-2892078-sec-02_T2", "type": "Organ", "text": [ "cardiac" ], "offsets": [ [ 1436, 1443 ] ], "normalized": [] }, { "id": "PMC-2892078-sec-02_T3", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 1504, 1509 ] ], "normalized": [] }, { "id": "PMC-2892078-sec-02_T5", "type": "Organ", "text": [ "cardiac" ], "offsets": [ [ 1345, 1352 ] ], "normalized": [] } ]

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[ { "id": "PMID-10792950__text", "type": "abstract", "text": [ "Neuroblastoma and hepatocyte coculture conditioned media alter apoptosis. \nBACKGROUND: Neuroblastoma is a childhood tumor that often displays unusual biological behavior. The tumor may present with widespread metastases that are unresponsive to aggressive treatment. At other times, both the metastases and the primary tumor may spontaneously regress without treatment. Apoptosis, or programmed cell death, is thought to play a role in the dichotomous behavior of neuroblastoma. We hypothesize that neuroblastoma cells will interact with host tissues to release mediators that affect apoptosis. MATERIALS AND METHODS: Human neuroblastoma cells and human Chang hepatocytes are grown in a noncontact, coculture system. After incubation for 4 days, the medium from the coculture system is collected. Neuroblastoma cells and Chang hepatocytes are then plated separately with the conditioned medium and their own standard growth medium as controls. After 4 days, these cells are harvested and cytospins made for immunostaining. Tumor necrosis factor alpha (TNF-alpha), Fas ligand, and Bcl-2, are measured with immunohistochemistry. Apoptosis is detected with the TUNEL method. Immunostaining data are interpreted with computer image analysis and reported as stain index. TUNEL data are reported as percentage apoptotic cells. All data are reported as means +/- SEM. Statistical analysis is performed and P < 0.05 considered significant. RESULTS: Chang hepatocytes grown in the coculture conditioned media have an increase in TNF-alpha and Fas ligand. The neuroblastoma cells have a significant decrease in Fas ligand. There is a significant increase in the number of apoptotic hepatocytes when they are cultured in the conditioned media. In contrast, the neuroblastoma cells grown in the coculture conditioned media show no increase in apoptosis. Finally, Bcl-2 is significantly increased in the neuroblastoma cells cultured in the conditioned media. CONCLUSIONS: Neuroblastoma cells grown in coculture conditioned media show increased expression of Bcl-2 and decreased Fas ligand levels. These changes should diminish apoptosis activity in the tumor cells. In contrast, the conditioned media induce elevated levels of proapoptotic mediators in the Chang hepatocytes. A tumor's ability to successfully metastasize may be dependent on mediators generated in the tumor-host interaction, and may not be just an independent characteristic of the tumor itself.\n" ], "offsets": [ [ 0, 2451 ] ] } ]

[ { "id": "PMID-10792950_T1", "type": "Cancer", "text": [ "Neuroblastoma" ], "offsets": [ [ 0, 13 ] ], "normalized": [] }, { "id": "PMID-10792950_T2", "type": "Cell", "text": [ "hepatocyte" ], "offsets": [ [ 18, 28 ] ], "normalized": [] }, { "id": "PMID-10792950_T3", "type": "Cancer", "text": [ "Neuroblastoma" ], "offsets": [ [ 87, 100 ] ], "normalized": [] }, { "id": "PMID-10792950_T4", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 116, 121 ] ], "normalized": [] }, { "id": "PMID-10792950_T5", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 175, 180 ] ], "normalized": [] }, { "id": "PMID-10792950_T6", "type": "Cancer", "text": [ "primary tumor" ], "offsets": [ [ 311, 324 ] ], "normalized": [] }, { "id": "PMID-10792950_T7", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 395, 399 ] ], "normalized": [] }, { "id": "PMID-10792950_T8", "type": "Cancer", "text": [ "neuroblastoma" ], "offsets": [ [ 464, 477 ] ], "normalized": [] }, { "id": "PMID-10792950_T9", "type": "Cell", "text": [ "neuroblastoma cells" ], "offsets": [ [ 499, 518 ] ], "normalized": [] }, { "id": "PMID-10792950_T10", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 543, 550 ] ], "normalized": [] }, { "id": "PMID-10792950_T12", "type": "Cell", "text": [ "neuroblastoma cells" ], "offsets": [ [ 624, 643 ] ], "normalized": [] }, { "id": "PMID-10792950_T14", "type": "Cell", "text": [ "Chang hepatocytes" ], "offsets": [ [ 654, 671 ] ], "normalized": [] }, { "id": "PMID-10792950_T15", "type": "Cell", "text": [ "Neuroblastoma cells" ], "offsets": [ [ 797, 816 ] ], "normalized": [] }, { "id": "PMID-10792950_T16", "type": "Cell", "text": [ "Chang hepatocytes" ], "offsets": [ [ 821, 838 ] ], "normalized": [] }, { "id": "PMID-10792950_T17", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 964, 969 ] ], "normalized": [] }, { "id": "PMID-10792950_T22", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1314, 1319 ] ], "normalized": [] }, { "id": "PMID-10792950_T23", "type": "Cell", "text": [ "Chang hepatocytes" ], "offsets": [ [ 1441, 1458 ] ], "normalized": [] }, { "id": "PMID-10792950_T26", "type": "Cell", "text": [ "neuroblastoma cells" ], "offsets": [ [ 1550, 1569 ] ], "normalized": [] }, { "id": "PMID-10792950_T28", "type": "Cell", "text": [ "hepatocytes" ], "offsets": [ [ 1672, 1683 ] ], "normalized": [] }, { "id": "PMID-10792950_T29", "type": "Cell", "text": [ "neuroblastoma cells" ], "offsets": [ [ 1750, 1769 ] ], "normalized": [] }, { "id": "PMID-10792950_T31", "type": "Cell", "text": [ "neuroblastoma cells" ], "offsets": [ [ 1891, 1910 ] ], "normalized": [] }, { "id": "PMID-10792950_T32", "type": "Cell", "text": [ "Neuroblastoma cells" ], "offsets": [ [ 1959, 1978 ] ], "normalized": [] }, { "id": "PMID-10792950_T35", "type": "Cell", "text": [ "tumor cells" ], "offsets": [ [ 2140, 2151 ] ], "normalized": [] }, { "id": "PMID-10792950_T36", "type": "Cell", "text": [ "Chang hepatocytes" ], "offsets": [ [ 2244, 2261 ] ], "normalized": [] }, { "id": "PMID-10792950_T37", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 2265, 2270 ] ], "normalized": [] }, { "id": "PMID-10792950_T38", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 2356, 2361 ] ], "normalized": [] }, { "id": "PMID-10792950_T39", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 2437, 2442 ] ], "normalized": [] }, { "id": "PMID-10792950_T11", "type": "Cancer", "text": [ "metastases" ], "offsets": [ [ 209, 219 ] ], "normalized": [] }, { "id": "PMID-10792950_T13", "type": "Cancer", "text": [ "metastases" ], "offsets": [ [ 292, 302 ] ], "normalized": [] } ]

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[ { "id": "PMID-8874330__text", "type": "abstract", "text": [ "c-erb B2 overexpression decreases the benefit of adjuvant tamoxifen in early-stage breast cancer without axillary lymph node metastases. \nPURPOSE: We studied retrospectively the interaction between c-erbB2 overexpression and adjuvant tomoxifen in node-negative breast cancer patients enrolled in the Gruppo Universitario Napoletano 1 (GUN-1) trial. PATIENTS AND METHODS: c-erbB2, evaluated by immunohistochemistry in 145 of 173 patients randomly assigned to 2-year adjuvant tamoxifen or no further therapy, was considered overexpressed if greater than 10% of the cells showed specific membrane staining. The role of each prognostic variable and their independent effect were studied using the Cox model. Disease-free (DFS) and overall (OAS) survival curves were estimated by the Kaplan-Meier method. RESULTS: As of November 30, 1994, the median follow-up period was 12 years. c-erbB2 was overexpressed in 43 of 145 patients (29.7%), which directly correlated with tumor size and inversely with estrogen receptor (ER) level. At univariate analysis, overexpression of c-erbB2 did not affect either DFS or OAS; tamoxifen had a greater effect on reducing the risk of recurrence than of death. Addition of c-erbB2 to a multivariate Cox model that contained menopausal status, tumor size, nuclear grade, and treatment as covariates did not affect the significance of the model for DSF or OAS, whereas addition of the first-order interaction between c-erbB2 and tamoxifen was statistically significant both for DFS and OAS. The same result was obtained when the model contained ER status and ER-tamoxifen interaction. Indeed, adjuvant tamoxifen significantly prolonged DFS and OAS in c-erbB2-negative cases, whereas it had no effect on DFS and OAS in c-erbB2-positive patients. CONCLUSION: In early-stage breast cancer patients, overexpression of c-erbB2 is a marker of lack of efficacy of adjuvant tamoxifen.\n" ], "offsets": [ [ 0, 1903 ] ] } ]

[ { "id": "PMID-8874330_T3", "type": "Cancer", "text": [ "early-stage breast cancer" ], "offsets": [ [ 71, 96 ] ], "normalized": [] }, { "id": "PMID-8874330_T4", "type": "Cancer", "text": [ "axillary lymph node metastases" ], "offsets": [ [ 105, 135 ] ], "normalized": [] }, { "id": "PMID-8874330_T7", "type": "Multi-tissue_structure", "text": [ "node" ], "offsets": [ [ 247, 251 ] ], "normalized": [] }, { "id": "PMID-8874330_T8", "type": "Cancer", "text": [ "breast cancer" ], "offsets": [ [ 261, 274 ] ], "normalized": [] }, { "id": "PMID-8874330_T13", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 563, 568 ] ], "normalized": [] }, { "id": "PMID-8874330_T14", "type": "Cellular_component", "text": [ "membrane" ], "offsets": [ [ 585, 593 ] ], "normalized": [] }, { "id": "PMID-8874330_T17", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 964, 969 ] ], "normalized": [] }, { "id": "PMID-8874330_T23", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1271, 1276 ] ], "normalized": [] }, { "id": "PMID-8874330_T24", "type": "Cellular_component", "text": [ "nuclear" ], "offsets": [ [ 1283, 1290 ] ], "normalized": [] }, { "id": "PMID-8874330_T34", "type": "Cancer", "text": [ "early-stage breast cancer" ], "offsets": [ [ 1786, 1811 ] ], "normalized": [] } ]

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[ { "id": "PMID-21915357__text", "type": "abstract", "text": [ "Burns from hot wheat bags: a public safety issue.\nIntroduction: Wheat bags are therapeutic devices that are heated in microwaves and commonly used to provide relief from muscle and joint pain. The Royal Adelaide Hospital Burns Unit has observed a number of patients with significant burn injuries resulting from their use. Despite their dangers, the products come with limited safety information. Methods: Data were collected from the Burns Unit database for all patients admitted with burns due to hot wheat bags from 2004 to 2009. This was analyzed to determine the severity of the burn injury and identify any predisposing factors. An experimental study was performed to measure the temperature of wheat bags when heated to determine their potential for causing thermal injury. Results: 11 patients were admitted with burns due to hot wheat bags. The median age was 52 years and the mean total body surface area was 1.1%. All burns were either deep dermal (45.5%) or full thickness (54.5%). Ten patients required operative management. Predisposing factors (eg, neuropathy) to thermal injury were identified in 7 patients. The experimental study showed that hot wheat bags reached temperatures of 57.3degreesC (135.1degreesF) when heated according to instructions, 63.3degreesC (145.9degreesF) in a 1000 W microwave and 69.6degreesC (157.3degreesF) on reheating. Conclusions: Hot wheat bags cause serious burn injury. When heated improperly, they can reach temperatures high enough to cause epidermal necrosis in a short period of time. Patients with impaired temperature sensation are particularly at risk. There should be greater public awareness of the dangers of wheat bag use and more specific safety warnings on the products.\n" ], "offsets": [ [ 0, 1734 ] ] } ]

[ { "id": "PMID-21915357_T1", "type": "Organ", "text": [ "muscle" ], "offsets": [ [ 170, 176 ] ], "normalized": [] }, { "id": "PMID-21915357_T2", "type": "Multi-tissue_structure", "text": [ "joint" ], "offsets": [ [ 181, 186 ] ], "normalized": [] }, { "id": "PMID-21915357_T3", "type": "Tissue", "text": [ "dermal" ], "offsets": [ [ 952, 958 ] ], "normalized": [] }, { "id": "PMID-21915357_T5", "type": "Organism_subdivision", "text": [ "body surface area" ], "offsets": [ [ 897, 914 ] ], "normalized": [] }, { "id": "PMID-21915357_T4", "type": "Tissue", "text": [ "epidermal" ], "offsets": [ [ 1493, 1502 ] ], "normalized": [] } ]

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[ { "id": "PMC-2443159-sec-19__text", "type": "sec", "text": [ "Analysis of furAII-katGII region\nThe cDNA from M. fortuitum under the different stresses was analysed by PCR using the primers furAII-Fo and P1.1 (Table 2) to test the presence of furAII and katGII cotranscripts. PCR cycling was performed as follows: a denaturizing step at 95degreesC for 5 minutes; 36 cycles of 95degreesC for 45 seconds, 54degreesC for 45 seconds and 72degreesC for 1 minute; and a final extension at 72degreesC for 10 minutes.\n" ], "offsets": [ [ 0, 447 ] ] } ]

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[ { "id": "PMC-2744784-sec-02__text", "type": "sec", "text": [ "Method\n\n" ], "offsets": [ [ 0, 8 ] ] } ]

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[ { "id": "PMC-2920104-caption-01__text", "type": "caption", "text": [ "Pteris vittata\n" ], "offsets": [ [ 0, 15 ] ] } ]

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[ { "id": "PMID-18043872__text", "type": "abstract", "text": [ "Tumor microenvironment, a dangerous society leading to cancer metastasis. From mechanisms to therapy and prevention.\nCancer is no longer considered by scientists just a jumble of mutated cells. To grow, invade and metastasize, a treacherous society between cancer and host cells must be formed, and this association provides novel and effective clinical targets for cancer control and prevention. This collection of reviews at the front-edge of scientific knowledge focuses on host-tumor cell interactions, the disastrous consequences they can produce and approaches the ways to break up these cellular conspiracies, to leave the tumor cells unattended and vulnerable.\n" ], "offsets": [ [ 0, 669 ] ] } ]

[ { "id": "PMID-18043872_T1", "type": "Cancer", "text": [ "Tumor" ], "offsets": [ [ 0, 5 ] ], "normalized": [] }, { "id": "PMID-18043872_T2", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 55, 61 ] ], "normalized": [] }, { "id": "PMID-18043872_T3", "type": "Cancer", "text": [ "Cancer" ], "offsets": [ [ 117, 123 ] ], "normalized": [] }, { "id": "PMID-18043872_T4", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 187, 192 ] ], "normalized": [] }, { "id": "PMID-18043872_T5", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 257, 263 ] ], "normalized": [] }, { "id": "PMID-18043872_T6", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 273, 278 ] ], "normalized": [] }, { "id": "PMID-18043872_T7", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 366, 372 ] ], "normalized": [] }, { "id": "PMID-18043872_T9", "type": "Cell", "text": [ "tumor cell" ], "offsets": [ [ 482, 492 ] ], "normalized": [] }, { "id": "PMID-18043872_T10", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 594, 602 ] ], "normalized": [] }, { "id": "PMID-18043872_T11", "type": "Cell", "text": [ "tumor cells" ], "offsets": [ [ 630, 641 ] ], "normalized": [] } ]

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[ { "id": "PMID-15160301__text", "type": "abstract", "text": [ "Potent antibacterial activity of Y-754, a novel benzimidazole compound with selective action against Helicobacter pylori.\nY-754, a novel benzimidazole compound, was investigated for in vitro and in vivo antibacterial activity. Unlike amoxicillin, clarithromycin, and metronidazole, the compound had no activity against common aerobic and anaerobic bacteria other than Helicobacter pylori. The minimum inhibitory concentration of Y-754 against H. pylori, at 0.025 microg/ml, was nearly equal to that of amoxicillin and clarithromycin. The respective concentrations of Y-754, amoxicillin, clarithromycin, and metronidazole required to inhibit 90% of 39 isolates of H. pylori were 0.05, 0.39, 6.25, and 25 microg/ml, indicating the potent activity of Y-754, including activity against clarithromycin- and metronidazole-resistant strains. The anti-H. pylori activity of Y-754 was potent even at pH 5.5 and was bactericidal at concentrations of 0.1 microg/ml and above. Exposure of H. pylori to Y-754 did not result in the induction of drug-resistant mutation. Oral administration (10 mg/kg twice a day for 7 days) to Mongolian gerbils infected with strain ATCC 43504 demonstrated that Y-754 was effective in H. pylori eradication and that its eradication efficacy increased in line with the progress of damage to the gastric mucosa caused by H. pylori infection. Y-754 was also efficacious in the treatment of infection by the clarithromycin-resistant strain OIT-36. The results obtained lead to the expectation that the new benzimidazole Y-754 will, in the near future, be used for H. pylori eradication therapy in peptic ulcer patients.\n" ], "offsets": [ [ 0, 1635 ] ] } ]

[ { "id": "PMID-15160301_T1", "type": "Multi-tissue_structure", "text": [ "gastric mucosa" ], "offsets": [ [ 1313, 1327 ] ], "normalized": [] }, { "id": "PMID-15160301_T2", "type": "Pathological_formation", "text": [ "peptic ulcer" ], "offsets": [ [ 1612, 1624 ] ], "normalized": [] }, { "id": "PMID-15160301_T3", "type": "Organism_subdivision", "text": [ "Oral" ], "offsets": [ [ 1056, 1060 ] ], "normalized": [] }, { "id": "PMID-15160301_T4", "type": "Cell", "text": [ "strains" ], "offsets": [ [ 826, 833 ] ], "normalized": [] }, { "id": "PMID-15160301_T5", "type": "Cell", "text": [ "strain" ], "offsets": [ [ 1145, 1151 ] ], "normalized": [] }, { "id": "PMID-15160301_T6", "type": "Cell", "text": [ "strain" ], "offsets": [ [ 1448, 1454 ] ], "normalized": [] } ]

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[ { "id": "PMID-12479523__text", "type": "abstract", "text": [ "Combined tracheal and esophageal stenting for palliation of tracheoesophageal symptoms from mediastinal lymphoma.\nMediastinal lymphoma as a cause of tracheobronchial obstruction is uncommon, and a malignant tracheoesophageal fistula in the setting of mediastinal lymphoma is rare. Malignant tracheoesophageal fistulas are associated with pronounced morbidity and mortality. We describe a patient with mediastinal lymphomatous infiltration resulting in tracheal obstruction, esophageal obstruction, and tracheoesophageal fistula that were successfully palliated with combined airway and esophageal stent placement.\n" ], "offsets": [ [ 0, 614 ] ] } ]

[ { "id": "PMID-12479523_T1", "type": "Multi-tissue_structure", "text": [ "tracheal" ], "offsets": [ [ 9, 17 ] ], "normalized": [] }, { "id": "PMID-12479523_T2", "type": "Multi-tissue_structure", "text": [ "esophageal" ], "offsets": [ [ 22, 32 ] ], "normalized": [] }, { "id": "PMID-12479523_T3", "type": "Multi-tissue_structure", "text": [ "tracheoesophageal" ], "offsets": [ [ 60, 77 ] ], "normalized": [] }, { "id": "PMID-12479523_T4", "type": "Cancer", "text": [ "mediastinal lymphoma" ], "offsets": [ [ 92, 112 ] ], "normalized": [] }, { "id": "PMID-12479523_T5", "type": "Cancer", "text": [ "Mediastinal lymphoma" ], "offsets": [ [ 114, 134 ] ], "normalized": [] }, { "id": "PMID-12479523_T6", "type": "Multi-tissue_structure", "text": [ "tracheobronchial" ], "offsets": [ [ 149, 165 ] ], "normalized": [] }, { "id": "PMID-12479523_T7", "type": "Immaterial_anatomical_entity", "text": [ "malignant tracheoesophageal fistula" ], "offsets": [ [ 197, 232 ] ], "normalized": [] }, { "id": "PMID-12479523_T8", "type": "Cancer", "text": [ "mediastinal lymphoma" ], "offsets": [ [ 251, 271 ] ], "normalized": [] }, { "id": "PMID-12479523_T9", "type": "Immaterial_anatomical_entity", "text": [ "Malignant tracheoesophageal fistulas" ], "offsets": [ [ 281, 317 ] ], "normalized": [] }, { "id": "PMID-12479523_T10", "type": "Cancer", "text": [ "mediastinal lymphomatous" ], "offsets": [ [ 401, 425 ] ], "normalized": [] }, { "id": "PMID-12479523_T11", "type": "Multi-tissue_structure", "text": [ "tracheal" ], "offsets": [ [ 452, 460 ] ], "normalized": [] }, { "id": "PMID-12479523_T12", "type": "Multi-tissue_structure", "text": [ "esophageal" ], "offsets": [ [ 474, 484 ] ], "normalized": [] }, { "id": "PMID-12479523_T13", "type": "Immaterial_anatomical_entity", "text": [ "tracheoesophageal fistula" ], "offsets": [ [ 502, 527 ] ], "normalized": [] }, { "id": "PMID-12479523_T14", "type": "Multi-tissue_structure", "text": [ "airway" ], "offsets": [ [ 575, 581 ] ], "normalized": [] }, { "id": "PMID-12479523_T15", "type": "Multi-tissue_structure", "text": [ "esophageal" ], "offsets": [ [ 586, 596 ] ], "normalized": [] } ]

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[ { "id": "PMID-9199500__text", "type": "abstract", "text": [ "The Wilms tumor suppressor gene WT1 induces G1 arrest and apoptosis in myeloblastic leukemia M1 cells. \nWT1 was isolated as a tumor suppressor gene of Wilms tumor. However, high expression of WT1 correlates with poor prognosis in acute leukemia. In addition suppression of WT1 expression by WT1 anti-sense oligonucleotide inhibits proliferation of leukemia cells, suggesting that WT1 is important for their proliferation. To further elucidate the biological significance of WT1 in leukemic cell growth, we overexpressed exogenous WT1 in murine M1 myeloblastic leukemia cells using the isopropyl-beta-D-thiogalactoside (IPTG)-controlled expression system. We found that induction of one splicing variant of WT1 [WT1-17AA(+)-KTS(-)] in M1 cells induces cell cycle arrest and apoptotic cell death. These results suggest that the role of WT1 is different depending on the type of leukemia cell in which it is expressed.\n" ], "offsets": [ [ 0, 916 ] ] } ]

[ { "id": "PMID-9199500_T1", "type": "Cancer", "text": [ "Wilms tumor" ], "offsets": [ [ 4, 15 ] ], "normalized": [] }, { "id": "PMID-9199500_T3", "type": "Cell", "text": [ "myeloblastic leukemia M1 cells" ], "offsets": [ [ 71, 101 ] ], "normalized": [] }, { "id": "PMID-9199500_T5", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 126, 131 ] ], "normalized": [] }, { "id": "PMID-9199500_T6", "type": "Cancer", "text": [ "Wilms tumor" ], "offsets": [ [ 151, 162 ] ], "normalized": [] }, { "id": "PMID-9199500_T8", "type": "Cancer", "text": [ "acute leukemia" ], "offsets": [ [ 230, 244 ] ], "normalized": [] }, { "id": "PMID-9199500_T11", "type": "Cell", "text": [ "leukemia cells" ], "offsets": [ [ 348, 362 ] ], "normalized": [] }, { "id": "PMID-9199500_T14", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 490, 494 ] ], "normalized": [] }, { "id": "PMID-9199500_T17", "type": "Cell", "text": [ "M1 myeloblastic leukemia cells" ], "offsets": [ [ 544, 574 ] ], "normalized": [] }, { "id": "PMID-9199500_T22", "type": "Cell", "text": [ "M1 cells" ], "offsets": [ [ 734, 742 ] ], "normalized": [] }, { "id": "PMID-9199500_T23", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 751, 755 ] ], "normalized": [] }, { "id": "PMID-9199500_T24", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 783, 787 ] ], "normalized": [] }, { "id": "PMID-9199500_T26", "type": "Cell", "text": [ "leukemia cell" ], "offsets": [ [ 876, 889 ] ], "normalized": [] } ]

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[ { "id": "PMC-1200425-caption-05__text", "type": "caption", "text": [ "Transcripts Upregulated in ST-HSC Compared to LT-HSC\n(181 KB XLS)\n" ], "offsets": [ [ 0, 66 ] ] } ]

[ { "id": "PMC-1200425-caption-05_T1", "type": "Cell", "text": [ "ST-HSC" ], "offsets": [ [ 27, 33 ] ], "normalized": [] }, { "id": "PMC-1200425-caption-05_T2", "type": "Cell", "text": [ "LT-HSC" ], "offsets": [ [ 46, 52 ] ], "normalized": [] } ]

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[ { "id": "PMID-19654314__text", "type": "abstract", "text": [ "Endothelial cell migration and vascular endothelial growth factor expression are the result of loss of breast tissue polarity.\nRecruiting a new blood supply is a rate-limiting step in tumor progression. In a three-dimensional model of breast carcinogenesis, disorganized, proliferative transformed breast epithelial cells express significantly higher expression of angiogenic genes compared with their polarized, growth-arrested nonmalignant counterparts. Elevated vascular endothelial growth factor (VEGF) secretion by malignant cells enhanced recruitment of endothelial cells (EC) in heterotypic cocultures. Significantly, phenotypic reversion of malignant cells via reexpression of HoxD10, which is lost in malignant progression, significantly attenuated VEGF expression in a hypoxia-inducible factor 1alpha-independent fashion and reduced EC migration. This was due primarily to restoring polarity: forced proliferation of polarized, nonmalignant cells did not induce VEGF expression and EC recruitment, whereas disrupting the architecture of growth-arrested, reverted cells did. These data show that disrupting cytostructure activates the angiogenic switch even in the absence of proliferation and/or hypoxia and restoring organization of malignant clusters reduces VEGF expression and EC activation to levels found in quiescent nonmalignant epithelium. These data confirm the importance of tissue architecture and polarity in malignant progression.\n" ], "offsets": [ [ 0, 1455 ] ] } ]

[ { "id": "PMID-19654314_T1", "type": "Cell", "text": [ "Endothelial cell" ], "offsets": [ [ 0, 16 ] ], "normalized": [] }, { "id": "PMID-19654314_T3", "type": "Tissue", "text": [ "breast tissue" ], "offsets": [ [ 103, 116 ] ], "normalized": [] }, { "id": "PMID-19654314_T4", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 144, 149 ] ], "normalized": [] }, { "id": "PMID-19654314_T5", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 184, 189 ] ], "normalized": [] }, { "id": "PMID-19654314_T6", "type": "Organism_subdivision", "text": [ "breast" ], "offsets": [ [ 235, 241 ] ], "normalized": [] }, { "id": "PMID-19654314_T7", "type": "Cell", "text": [ "breast epithelial cells" ], "offsets": [ [ 298, 321 ] ], "normalized": [] }, { "id": "PMID-19654314_T8", "type": "Cell", "text": [ "nonmalignant counterparts" ], "offsets": [ [ 429, 454 ] ], "normalized": [] }, { "id": "PMID-19654314_T11", "type": "Cell", "text": [ "malignant cells" ], "offsets": [ [ 520, 535 ] ], "normalized": [] }, { "id": "PMID-19654314_T12", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 560, 577 ] ], "normalized": [] }, { "id": "PMID-19654314_T13", "type": "Cell", "text": [ "EC" ], "offsets": [ [ 579, 581 ] ], "normalized": [] }, { "id": "PMID-19654314_T14", "type": "Cell", "text": [ "malignant cells" ], "offsets": [ [ 649, 664 ] ], "normalized": [] }, { "id": "PMID-19654314_T18", "type": "Cell", "text": [ "EC" ], "offsets": [ [ 843, 845 ] ], "normalized": [] }, { "id": "PMID-19654314_T19", "type": "Cell", "text": [ "nonmalignant cells" ], "offsets": [ [ 938, 956 ] ], "normalized": [] }, { "id": "PMID-19654314_T21", "type": "Cell", "text": [ "EC" ], "offsets": [ [ 992, 994 ] ], "normalized": [] }, { "id": "PMID-19654314_T22", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1073, 1078 ] ], "normalized": [] }, { "id": "PMID-19654314_T23", "type": "Cellular_component", "text": [ "cytostructure" ], "offsets": [ [ 1116, 1129 ] ], "normalized": [] }, { "id": "PMID-19654314_T24", "type": "Cancer", "text": [ "malignant clusters" ], "offsets": [ [ 1244, 1262 ] ], "normalized": [] }, { "id": "PMID-19654314_T26", "type": "Cell", "text": [ "EC" ], "offsets": [ [ 1291, 1293 ] ], "normalized": [] }, { "id": "PMID-19654314_T27", "type": "Tissue", "text": [ "nonmalignant epithelium" ], "offsets": [ [ 1334, 1357 ] ], "normalized": [] }, { "id": "PMID-19654314_T28", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 1396, 1402 ] ], "normalized": [] } ]

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[ { "id": "PMID-2730023__text", "type": "abstract", "text": [ "[Tumor metastasis and the fibrinolytic system]. \nMetastatic spread of malignant tumor appears to correlate with activation of the fibrolytic system. The role of fibrinolysis in growth and metastasis was examined in Lewis lung carcinoma of mice. The inhibition of fibrinolysis or proteases decreased the primary tumor growth and pulmonary metastasis, whereas the activation of fibrinolysis or proteases increased the number of metastatic foci in the lung. Electronmicroscopically, thrombus formation in the primary site prevented tumor invasion and metastasis formation. Plasminogen activator (PA) content of excised tumors was determined by SDS-PAGE, and major PA was found to be urokinase (UK) type. Immunohistochemical study with specific antisera was done. When tumor cells possessed a high level of UK, laminin and type IV collagen, components of the basement membrane, disappeared from tumor tissues. These findings suggest that PA through protease cascade plays a role in tumor invasion and metastasis. Clinically, patients with advanced cancer are usually in a hypercoagulable state with elevated fibrinogen, and fibrin deposition around tumor mass is a serious problem in cancer chemotherapy. UK infusion prior to 5-fluorouracil increased tissue concentration of antitumor agent. However, development of consumption coagulopathy characterized by progression from hypercoagulable state to disseminated intravascular coagulation has also been found in several cases.\n" ], "offsets": [ [ 0, 1473 ] ] } ]

[ { "id": "PMID-2730023_T1", "type": "Cancer", "text": [ "Tumor" ], "offsets": [ [ 1, 6 ] ], "normalized": [] }, { "id": "PMID-2730023_T2", "type": "Cancer", "text": [ "malignant tumor" ], "offsets": [ [ 70, 85 ] ], "normalized": [] }, { "id": "PMID-2730023_T3", "type": "Cancer", "text": [ "Lewis lung carcinoma" ], "offsets": [ [ 215, 235 ] ], "normalized": [] }, { "id": "PMID-2730023_T5", "type": "Cancer", "text": [ "primary tumor" ], "offsets": [ [ 303, 316 ] ], "normalized": [] }, { "id": "PMID-2730023_T6", "type": "Organ", "text": [ "pulmonary" ], "offsets": [ [ 328, 337 ] ], "normalized": [] }, { "id": "PMID-2730023_T7", "type": "Organ", "text": [ "lung" ], "offsets": [ [ 449, 453 ] ], "normalized": [] }, { "id": "PMID-2730023_T8", "type": "Pathological_formation", "text": [ "thrombus" ], "offsets": [ [ 480, 488 ] ], "normalized": [] }, { "id": "PMID-2730023_T9", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 529, 534 ] ], "normalized": [] }, { "id": "PMID-2730023_T12", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 616, 622 ] ], "normalized": [] }, { "id": "PMID-2730023_T16", "type": "Cell", "text": [ "tumor cells" ], "offsets": [ [ 765, 776 ] ], "normalized": [] }, { "id": "PMID-2730023_T20", "type": "Cellular_component", "text": [ "basement membrane" ], "offsets": [ [ 855, 872 ] ], "normalized": [] }, { "id": "PMID-2730023_T21", "type": "Tissue", "text": [ "tumor tissues" ], "offsets": [ [ 891, 904 ] ], "normalized": [] }, { "id": "PMID-2730023_T23", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 978, 983 ] ], "normalized": [] }, { "id": "PMID-2730023_T25", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 1044, 1050 ] ], "normalized": [] }, { "id": "PMID-2730023_T28", "type": "Cancer", "text": [ "tumor mass" ], "offsets": [ [ 1145, 1155 ] ], "normalized": [] }, { "id": "PMID-2730023_T29", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 1180, 1186 ] ], "normalized": [] }, { "id": "PMID-2730023_T32", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 1247, 1253 ] ], "normalized": [] }, { "id": "PMID-2730023_T33", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1275, 1280 ] ], "normalized": [] }, { "id": "PMID-2730023_T34", "type": "Immaterial_anatomical_entity", "text": [ "intravascular" ], "offsets": [ [ 1409, 1422 ] ], "normalized": [] }, { "id": "PMID-2730023_T56", "type": "Cancer", "text": [ "metastatic foci" ], "offsets": [ [ 426, 441 ] ], "normalized": [] }, { "id": "PMID-2730023_T4", "type": "Multi-tissue_structure", "text": [ "site" ], "offsets": [ [ 514, 518 ] ], "normalized": [] } ]

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[ { "id": "PMID-19372461__text", "type": "abstract", "text": [ "Rab GTPase regulation of VEGFR2 trafficking and signaling in endothelial cells.\nOBJECTIVE: Vascular endothelial growth factor receptor 2 (VEGFR2) is a receptor tyrosine kinase that regulates vascular physiology. However, mechanism(s) by which VEGFR2 signaling and trafficking is coordinated are not clear. Here, we have tested endocytic Rab GTPases for regulation of VEGFR2 trafficking and signaling linked to endothelial cell migration. METHODS AND RESULTS: Quiescent VEGFR2 displays endosomal localization and colocalization with the Rab5a GTPase, an early endosome fusion regulator. Expression of GTP or GDP-bound Rab5a mutants block activated VEGFR2 trafficking and degradation. Manipulation of Rab7a GTPase activity associated with late endosomes using overexpression of wild-type or mutant proteins blocks activated VEGFR2 trafficking and degradation. Depletion of Rab7a decreased VEGFR2 Y1175 phosphorylation but increased p42/44 (pERK1/2) MAPK phosphorylation. Endothelial cell migration was increased by Rab5a depletion but decreased by Rab7a depletion. CONCLUSIONS: Rab5a and Rab7a regulate VEGFR2 trafficking toward early and late endosomes. Our data suggest that VEGFR2-mediated regulation of endothelial function is dependent on different but specific Rab-mediated GTP hydrolysis activity required for endosomal trafficking.\n" ], "offsets": [ [ 0, 1338 ] ] } ]

[ { "id": "PMID-19372461_T3", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 61, 78 ] ], "normalized": [] }, { "id": "PMID-19372461_T6", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 191, 199 ] ], "normalized": [] }, { "id": "PMID-19372461_T10", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 410, 426 ] ], "normalized": [] }, { "id": "PMID-19372461_T12", "type": "Cellular_component", "text": [ "endosomal" ], "offsets": [ [ 485, 494 ] ], "normalized": [] }, { "id": "PMID-19372461_T14", "type": "Cellular_component", "text": [ "early endosome" ], "offsets": [ [ 553, 567 ] ], "normalized": [] }, { "id": "PMID-19372461_T20", "type": "Cellular_component", "text": [ "late endosomes" ], "offsets": [ [ 737, 751 ] ], "normalized": [] }, { "id": "PMID-19372461_T27", "type": "Cell", "text": [ "Endothelial cell" ], "offsets": [ [ 969, 985 ] ], "normalized": [] }, { "id": "PMID-19372461_T33", "type": "Cellular_component", "text": [ "early" ], "offsets": [ [ 1127, 1132 ] ], "normalized": [] }, { "id": "PMID-19372461_T34", "type": "Cellular_component", "text": [ "late endosomes" ], "offsets": [ [ 1137, 1151 ] ], "normalized": [] }, { "id": "PMID-19372461_T36", "type": "Cell", "text": [ "endothelial" ], "offsets": [ [ 1205, 1216 ] ], "normalized": [] }, { "id": "PMID-19372461_T39", "type": "Cellular_component", "text": [ "endosomal" ], "offsets": [ [ 1315, 1324 ] ], "normalized": [] } ]

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[ { "id": "PMID-19347270__text", "type": "abstract", "text": [ "Molecular analysis of genetic instability caused by chronic inflammation. \nGenetic instability is a hallmark of human cancers. It is the driving force for tumor development as it facilitates the accumulation of mutations in genes that regulate cell death and proliferation and therefore promotes malignant transformation. Chronic inflammation is a common underlying condition for human tumor development, accounting for approximately 20% of human cancers. TNFalpha is an important inflammation cytokine and is crucial to the development of inflammation-associated cancers. We have shown that TNFalpha can cause DNA damages through reactive oxygen species (ROS). TNFalpha treatment in cultured cells resulted in increased gene mutations, gene amplification, micronuclei formation and chromosomal instability. Antioxidants significantly reduced TNFalpha-induced genetic damage. In addition, TNFalpha treatment alone led to increased malignant transformation of mouse embryo fibroblasts, which could be partially suppressed by antioxidants. Therefore, genetic instability plays an important role in inflammation-associated cancers.\n" ], "offsets": [ [ 0, 1129 ] ] } ]

[ { "id": "PMID-19347270_T2", "type": "Cancer", "text": [ "cancers" ], "offsets": [ [ 118, 125 ] ], "normalized": [] }, { "id": "PMID-19347270_T3", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 155, 160 ] ], "normalized": [] }, { "id": "PMID-19347270_T4", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 244, 248 ] ], "normalized": [] }, { "id": "PMID-19347270_T6", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 386, 391 ] ], "normalized": [] }, { "id": "PMID-19347270_T8", "type": "Cancer", "text": [ "cancers" ], "offsets": [ [ 447, 454 ] ], "normalized": [] }, { "id": "PMID-19347270_T10", "type": "Cancer", "text": [ "cancers" ], "offsets": [ [ 564, 571 ] ], "normalized": [] }, { "id": "PMID-19347270_T16", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 693, 698 ] ], "normalized": [] }, { "id": "PMID-19347270_T17", "type": "Cellular_component", "text": [ "micronuclei" ], "offsets": [ [ 757, 768 ] ], "normalized": [] }, { "id": "PMID-19347270_T18", "type": "Cellular_component", "text": [ "chromosomal" ], "offsets": [ [ 783, 794 ] ], "normalized": [] }, { "id": "PMID-19347270_T22", "type": "Cell", "text": [ "embryo fibroblasts" ], "offsets": [ [ 965, 983 ] ], "normalized": [] }, { "id": "PMID-19347270_T23", "type": "Cancer", "text": [ "cancers" ], "offsets": [ [ 1120, 1127 ] ], "normalized": [] } ]

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[ { "id": "PMC-2939889-sec-15__text", "type": "sec", "text": [ "Animals\nSTOP null mice and their WT littermates were generated on a mixed BALBc/129 SvPas and on a pure 129 SvPas background as previously reported by Andrieux et al. [4]. All animals used in the study underwent immunohistochemistry for the detection of STOP protein, resulting in no staining in STOP null mice, and genotyping by PCR as described by Andrieux et al. [4]. All mice were kept under standard housing conditions with a 12-hour/12-hour dark-light cycle. The experiments were carried out in accordance with the European Communities Council Directive of 24 November 1986 (86/609/EEC), and the French Department of Agriculture (License Ndegrees 67-95). The protocol was approved by the ethical Animal Research Committee of Louis Pasteur University (CREMEAS #AL/01/19/10/07).\nIn a first experiment, we searched for differences in glomerular ultrastructure and peripheral neurogenesis between WT and STOP null mice: a first group of 24 mice, 3- to 6- month-old, was used for ultrastructural study of the OBs; a second group of 13 animals was used to analyse proliferation and apoptosis in the OE and VNE on paraffin sections in 3-month-old mice. In a second experiment we analysed, in WT and STOP null mice, the effect of OE regeneration on glomeruli structure and ultrastructure and on peripheral neurogenesis at two age times (3 and 10 months).\n" ], "offsets": [ [ 0, 1353 ] ] } ]

[ { "id": "PMC-2939889-sec-15_T1", "type": "Multi-tissue_structure", "text": [ "glomerular" ], "offsets": [ [ 837, 847 ] ], "normalized": [] }, { "id": "PMC-2939889-sec-15_T2", "type": "Tissue", "text": [ "paraffin sections" ], "offsets": [ [ 1113, 1130 ] ], "normalized": [] }, { "id": "PMC-2939889-sec-15_T3", "type": "Tissue", "text": [ "OE" ], "offsets": [ [ 1099, 1101 ] ], "normalized": [] }, { "id": "PMC-2939889-sec-15_T4", "type": "Tissue", "text": [ "VNE" ], "offsets": [ [ 1106, 1109 ] ], "normalized": [] }, { "id": "PMC-2939889-sec-15_T5", "type": "Tissue", "text": [ "OE" ], "offsets": [ [ 1228, 1230 ] ], "normalized": [] }, { "id": "PMC-2939889-sec-15_T6", "type": "Multi-tissue_structure", "text": [ "glomeruli" ], "offsets": [ [ 1247, 1256 ] ], "normalized": [] } ]

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[ { "id": "PMC-3248852-sec-15__text", "type": "sec", "text": [ "Cation binding to yolk platelet phosvitin\nIn addition to non-heme iron [23], yolk phosvitin also contains Ca2+, Mg2+, Na+ and K+ [11]. Partially relaxed 23Na Fourier transform NMR spectra revealed the existence of at least two major intracellular compartments of NMR-visible Na+ [35]. A large fraction of the Rana oocyte Na+ was NMR-invisible and could be recovered in the yolk platelets [35]. During the first meiotic division there is a net increase in NMR-visible Na+; by completion of the second meiotic division (following fertilization), about 70% of the total Na+ becomes NMR-visible. Thus, phosvitin not only serves as a site for energy storage, but also as a storage site for iron and other ions essential for embryonic development in ponds and streams that contain little dissolved salts and minerals.\n" ], "offsets": [ [ 0, 812 ] ] } ]

[ { "id": "PMC-3248852-sec-15_T1", "type": "Cell", "text": [ "yolk platelet" ], "offsets": [ [ 18, 31 ] ], "normalized": [] }, { "id": "PMC-3248852-sec-15_T2", "type": "Developing_anatomical_structure", "text": [ "yolk" ], "offsets": [ [ 77, 81 ] ], "normalized": [] }, { "id": "PMC-3248852-sec-15_T3", "type": "Cell", "text": [ "oocyte" ], "offsets": [ [ 314, 320 ] ], "normalized": [] }, { "id": "PMC-3248852-sec-15_T4", "type": "Cell", "text": [ "yolk platelets" ], "offsets": [ [ 373, 387 ] ], "normalized": [] }, { "id": "PMC-3248852-sec-15_T5", "type": "Developing_anatomical_structure", "text": [ "embryonic" ], "offsets": [ [ 719, 728 ] ], "normalized": [] }, { "id": "PMC-3248852-sec-15_T6", "type": "Cellular_component", "text": [ "intracellular compartments" ], "offsets": [ [ 233, 259 ] ], "normalized": [] } ]

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[ { "id": "PMC-2983913-sec-03__text", "type": "sec", "text": [ "Crystal data\nC24H21ClN4O2S\nM r = 464.96\nTriclinic, \na = 8.6798 (18) A\nb = 11.078 (2) A\nc = 11.372 (2) A\nalpha = 78.984 (7)degrees\nbeta = 81.867 (10)degrees\ngamma = 81.718 (11)degrees\nV = 1054.8 (4) A3\nZ = 2\nCu Kalpha radiation\nmu = 2.78 mm-1\nT = 113 K\n0.28 x 0.24 x 0.20 mm\n" ], "offsets": [ [ 0, 274 ] ] } ]

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[ { "id": "PMID-6328275__text", "type": "abstract", "text": [ "DNA methylation and expression of HLA-DR alpha. \nB-cell lines established from two individuals with T-cell acute lymphocytic leukemia (T-ALL) express HLA-DR antigens, whereas the isogenic T-cells do not. The lack of expression correlates with a lack of detectable HLA-DR mRNA. All of the DR alpha DNA sequences detected by a cloned DR alpha cDNA probe are contained in a BglII fragment which varies slightly in size (4.0 to 4.8 kilobases) from one individual to another. In DNA from the T-cells not expressing DR alpha mRNA, all of the potential HpaII sites within the BglII fragment appeared to be methylated. In contrast, at least some of these sites were not methylated in DNA from the B-cells expressing high levels of DR alpha mRNA. Treatment of these T-cells with 5-azacytidine resulted in the induction of DR surface antigen expression, the appearance of DR alpha mRNA, and the partial demethylation of the DR alpha DNA sequences. T-cell lines established from human T-cell leukemia-lymphoma virus associated T-cell neoplasias, in contrast to the T-cell acute lymphocytic leukemia cell lines, expressed both DR antigens and DR alpha mRNA; the HpaII sites within the BglII fragment of DR alpha DNA of these human T-cell leukemia-lymphoma virus-positive T-cell lines were in all cases at least partially unmethylated. Uncultured peripheral blood T-cells from human T-cell leukemia-lymphoma virus-infected individuals expressed DR antigens at a low level, and the DR alpha locus was partially unmethylated. After 48 h in culture, DR antigen expression was substantially increased, but no significant changes were observed in methylation of the DR alpha locus or in the amount of DR mRNA which was present. This suggests that expression of DR antigens also can be modulated post-transcriptionally.\n" ], "offsets": [ [ 0, 1801 ] ] } ]

[ { "id": "PMID-6328275_T3", "type": "Cell", "text": [ "B-cell lines" ], "offsets": [ [ 49, 61 ] ], "normalized": [] }, { "id": "PMID-6328275_T4", "type": "Cancer", "text": [ "T-cell acute lymphocytic leukemia" ], "offsets": [ [ 100, 133 ] ], "normalized": [] }, { "id": "PMID-6328275_T5", "type": "Cancer", "text": [ "T-ALL" ], "offsets": [ [ 135, 140 ] ], "normalized": [] }, { "id": "PMID-6328275_T7", "type": "Cell", "text": [ "T-cells" ], "offsets": [ [ 188, 195 ] ], "normalized": [] }, { "id": "PMID-6328275_T14", "type": "Cell", "text": [ "T-cells" ], "offsets": [ [ 487, 494 ] ], "normalized": [] }, { "id": "PMID-6328275_T20", "type": "Cell", "text": [ "B-cells" ], "offsets": [ [ 689, 696 ] ], "normalized": [] }, { "id": "PMID-6328275_T22", "type": "Cell", "text": [ "T-cells" ], "offsets": [ [ 757, 764 ] ], "normalized": [] }, { "id": "PMID-6328275_T28", "type": "Cell", "text": [ "T-cell lines" ], "offsets": [ [ 938, 950 ] ], "normalized": [] }, { "id": "PMID-6328275_T30", "type": "Pathological_formation", "text": [ "T-cell neoplasias" ], "offsets": [ [ 1016, 1033 ] ], "normalized": [] }, { "id": "PMID-6328275_T31", "type": "Cell", "text": [ "T-cell acute lymphocytic leukemia cell lines" ], "offsets": [ [ 1054, 1098 ] ], "normalized": [] }, { "id": "PMID-6328275_T40", "type": "Cell", "text": [ "T-cell lines" ], "offsets": [ [ 1259, 1271 ] ], "normalized": [] }, { "id": "PMID-6328275_T41", "type": "Cell", "text": [ "peripheral blood T-cells" ], "offsets": [ [ 1334, 1358 ] ], "normalized": [] }, { "id": "PMID-6328275_T1", "type": "Cellular_component", "text": [ "surface" ], "offsets": [ [ 816, 823 ] ], "normalized": [] } ]

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[ { "id": "PMC-2374702-caption-19__text", "type": "caption", "text": [ "Click here for file\n" ], "offsets": [ [ 0, 20 ] ] } ]

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[ { "id": "PMID-19446450__text", "type": "abstract", "text": [ "AngiomiRs--key regulators of angiogenesis.\nThe formation of new blood vessels through the process of angiogenesis is critical in vascular development and homeostasis. Aberrant angiogenesis leads to a variety of diseases, such as ischemia and cancer. Recent studies have revealed important roles for miRNAs in regulating endothelial cell (EC) function, especially angiogenesis. Mice with EC-specific deletion of Dicer, a key enzyme for generating miRNAs, display defective postnatal angiogenesis. Specific miRNAs (angiomiRs) have recently been shown to regulate angiogenesis in vivo. miRNA-126, an EC-restricted miRNA, regulates vascular integrity and developmental angiogenesis. miR-378, miR-296, and the miR-17-92 cluster contribute to tumor angiogenesis. Manipulating angiomiRs in the settings of pathological vascularization represents a new therapeutic approach.\n" ], "offsets": [ [ 0, 867 ] ] } ]

[ { "id": "PMID-19446450_T2", "type": "Multi-tissue_structure", "text": [ "blood vessels" ], "offsets": [ [ 64, 77 ] ], "normalized": [] }, { "id": "PMID-19446450_T3", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 129, 137 ] ], "normalized": [] }, { "id": "PMID-19446450_T4", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 242, 248 ] ], "normalized": [] }, { "id": "PMID-19446450_T5", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 320, 336 ] ], "normalized": [] }, { "id": "PMID-19446450_T6", "type": "Cell", "text": [ "EC" ], "offsets": [ [ 338, 340 ] ], "normalized": [] }, { "id": "PMID-19446450_T8", "type": "Cell", "text": [ "EC" ], "offsets": [ [ 387, 389 ] ], "normalized": [] }, { "id": "PMID-19446450_T12", "type": "Cell", "text": [ "EC" ], "offsets": [ [ 597, 599 ] ], "normalized": [] }, { "id": "PMID-19446450_T13", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 628, 636 ] ], "normalized": [] }, { "id": "PMID-19446450_T18", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 737, 742 ] ], "normalized": [] } ]

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[ { "id": "PMC-2660356-caption-07__text", "type": "caption", "text": [ "Additional File 2\nFull Model Code. Full model code plus instructions for running in Berkeley Madonna(TM).\n" ], "offsets": [ [ 0, 106 ] ] } ]

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[ { "id": "PMID-19922082__text", "type": "abstract", "text": [ "Effectiveness of different approaches for establishing cisplatin-induced cochlear lesions in mice.\nCONCLUSIONS:\nMouse cochleae are highly resistant to systemically administered cisplatin. However, cochlear lesions can be produced effectively in mice when cisplatin is applied locally through the round window niche or tympanum.\nOBJECTIVE:\nTo explore the optimal approach for creating cisplatin-induced cochlear lesions in mice.\nMATERIALS AND METHODS:\nCisplatin was administered to adult C57BL/6J mice via four approaches: (1) transtympanic injection, (2) round window niche injection, (3) intraperitoneal injection (i.p.) at 4 mg/kg/day for 4 consecutive days, and (4) one 15 mg/kg dose i.p. The hearing was monitored using frequency-specific auditory brainstem responses (ABRs) and distortion-product otoacoustic emissions (DPOAEs). Cochlear pathology was observed in cochleograms with Harris' hematoxylin staining.\nRESULTS:\nCisplatin applied systemically did not cause any significant ABR threshold elevation across the frequencies tested (2-32 kHz), whereas local application of cisplatin through the round window niche or tympanum resulted in significant ABR threshold elevations from high to medium frequencies. The functional changes were consistent with the cochlear pathology across groups.\n" ], "offsets": [ [ 0, 1299 ] ] } ]

[ { "id": "PMID-19922082_T1", "type": "Pathological_formation", "text": [ "cochlear lesions" ], "offsets": [ [ 73, 89 ] ], "normalized": [] }, { "id": "PMID-19922082_T2", "type": "Multi-tissue_structure", "text": [ "cochleae" ], "offsets": [ [ 118, 126 ] ], "normalized": [] }, { "id": "PMID-19922082_T3", "type": "Pathological_formation", "text": [ "cochlear lesions" ], "offsets": [ [ 197, 213 ] ], "normalized": [] }, { "id": "PMID-19922082_T4", "type": "Immaterial_anatomical_entity", "text": [ "round window niche" ], "offsets": [ [ 296, 314 ] ], "normalized": [] }, { "id": "PMID-19922082_T5", "type": "Multi-tissue_structure", "text": [ "tympanum" ], "offsets": [ [ 318, 326 ] ], "normalized": [] }, { "id": "PMID-19922082_T6", "type": "Pathological_formation", "text": [ "cochlear lesions" ], "offsets": [ [ 402, 418 ] ], "normalized": [] }, { "id": "PMID-19922082_T7", "type": "Immaterial_anatomical_entity", "text": [ "round window niche" ], "offsets": [ [ 555, 573 ] ], "normalized": [] }, { "id": "PMID-19922082_T8", "type": "Multi-tissue_structure", "text": [ "brainstem" ], "offsets": [ [ 752, 761 ] ], "normalized": [] }, { "id": "PMID-19922082_T9", "type": "Multi-tissue_structure", "text": [ "Cochlear" ], "offsets": [ [ 834, 842 ] ], "normalized": [] }, { "id": "PMID-19922082_T10", "type": "Immaterial_anatomical_entity", "text": [ "round window niche" ], "offsets": [ [ 1104, 1122 ] ], "normalized": [] }, { "id": "PMID-19922082_T11", "type": "Multi-tissue_structure", "text": [ "tympanum" ], "offsets": [ [ 1126, 1134 ] ], "normalized": [] }, { "id": "PMID-19922082_T12", "type": "Multi-tissue_structure", "text": [ "cochlear" ], "offsets": [ [ 1265, 1273 ] ], "normalized": [] }, { "id": "PMID-19922082_T13", "type": "Immaterial_anatomical_entity", "text": [ "intraperitoneal" ], "offsets": [ [ 589, 604 ] ], "normalized": [] }, { "id": "PMID-19922082_T14", "type": "Immaterial_anatomical_entity", "text": [ "transtympanic" ], "offsets": [ [ 526, 539 ] ], "normalized": [] } ]

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[ { "id": "PMID-18709350__text", "type": "abstract", "text": [ "[TESE and mTESE. Therapeutic options in male infertility due to testicular azoospermia].\nModern techniques of testicular sperm extraction (TESE) make it possible for an infertile man to father a child. The operations are standardized to a large extent and the underlying morphological alterations of spermatogenesis also appear to be sufficiently known. Current research is focused on prognostic factors for the testicular material that determine the sperm retrieval rate and success rates after in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI).TESE and microTESE are accepted standard operations for testicular sperm retrieval for IVF/ICSI. Predictions for effective sperm recovery are addressed.\n" ], "offsets": [ [ 0, 716 ] ] } ]

[ { "id": "PMID-18709350_T1", "type": "Cell", "text": [ "testicular sperm" ], "offsets": [ [ 110, 126 ] ], "normalized": [] }, { "id": "PMID-18709350_T2", "type": "Organ", "text": [ "testicular" ], "offsets": [ [ 412, 422 ] ], "normalized": [] }, { "id": "PMID-18709350_T3", "type": "Organ", "text": [ "testicular" ], "offsets": [ [ 64, 74 ] ], "normalized": [] }, { "id": "PMID-18709350_T4", "type": "Cell", "text": [ "sperm" ], "offsets": [ [ 451, 456 ] ], "normalized": [] }, { "id": "PMID-18709350_T5", "type": "Cell", "text": [ "sperm" ], "offsets": [ [ 536, 541 ] ], "normalized": [] }, { "id": "PMID-18709350_T6", "type": "Cell", "text": [ "testicular sperm" ], "offsets": [ [ 619, 635 ] ], "normalized": [] }, { "id": "PMID-18709350_T7", "type": "Cell", "text": [ "sperm" ], "offsets": [ [ 686, 691 ] ], "normalized": [] } ]

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[ { "id": "PMID-15586242__text", "type": "abstract", "text": [ "Hypoxia-responsive element-mediated soluble Tie2 vector exhibits an anti-angiogenic activity in vitro under hypoxic condition.\nHypoxia-inducible factor-1 (HIF-1) is one of the key mammalian transcription factors and shows increased levels in both protein stability and intrinsic transcriptional activity during low oxygen tension. Hypoxia-activated functional HIF-1 protein binds to hypoxia-responsive elements (HRE) in the enhancers of several genes including VEGF, the major player in angiogenesis, and initiates their mRNA expression. The molecular mechanisms regulating the gene expression under hypoxic conditions could increase the therapeutic window of tumor-specific delivery systems. In this study, to examine hypoxia-specific production of anti-angiogenic therapeutic gene, we constructed 5 copies of HRE (5xHRE) of human VEGF linked to soluble Tie2 (sTie2) driven by minimal SV40 promoter (5xHRE/SV40/sTie2). Our data showed that under hypoxia the secreted sTie2 selectively inhibited tube formation and migration capacities of endothelial cells in vitro. Hence, we propose that the vector system, 5xHRE/SV40/sTie2, might be a useful tool for down-regulating tumor angiogenesis under hypoxic condition.\n" ], "offsets": [ [ 0, 1214 ] ] } ]

[ { "id": "PMID-15586242_T7", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 660, 665 ] ], "normalized": [] }, { "id": "PMID-15586242_T16", "type": "Tissue", "text": [ "tube" ], "offsets": [ [ 996, 1000 ] ], "normalized": [] }, { "id": "PMID-15586242_T17", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 1039, 1056 ] ], "normalized": [] }, { "id": "PMID-15586242_T20", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1170, 1175 ] ], "normalized": [] } ]

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[ { "id": "PMID-15652356__text", "type": "abstract", "text": [ "HIF-2alpha expression in human fetal paraganglia and neuroblastoma: relation to sympathetic differentiation, glucose deficiency, and hypoxia.\nSolid tumors are frequently necrotic and hypoxic due to poor vascularization. Tumor cells adapt to hypoxia by modulating their phenotype. Key players in this process are the hypoxia-inducible factors (HIF-1alpha to 3alpha). HIFs are also expressed during normal development; for example, HIF-2alpha is specifically expressed and appears to be involved in the development of the murine sympathetic nervous system (SNS). Here, we demonstrate that HIF-2alpha protein is selectively present in human fetal week 8.5 SNS paraganglia. Neuroblastoma is derived from SNS precursors. In a subset of neuroblastomas, a spontaneous neuronal to neuroendocrine differentiation occurs in areas adjacent to necrotic zones. As HIF-2alpha activity has been associated not only with hypoxic but also with hypoglycemic conditions, we have investigated putative effects of hypoxia, glucose depletion, and HIF-2alpha on the neuroblastoma phenotype. HIF-2alpha was detected in hypoxic and in well-oxygenized neuroblastoma cells and tissue, presumably reflecting their embryonic features. With regard to differentiation, hypoxic cells lost their neuronal/neuroendocrine features and gained marker gene expression associated with an immature, neural crest-like phenotype. Low glucose potentiated the effect of hypoxia. These findings suggest that poorly vascularized neuroblastomas become immature and maintain a more aggressive phenotype, which possibly could involve a sustained stabilization and activation of HIF-2alpha.\n" ], "offsets": [ [ 0, 1641 ] ] } ]

[ { "id": "PMID-15652356_T3", "type": "Cell", "text": [ "fetal paraganglia" ], "offsets": [ [ 31, 48 ] ], "normalized": [] }, { "id": "PMID-15652356_T4", "type": "Cancer", "text": [ "neuroblastoma" ], "offsets": [ [ 53, 66 ] ], "normalized": [] }, { "id": "PMID-15652356_T6", "type": "Cancer", "text": [ "Solid tumors" ], "offsets": [ [ 142, 154 ] ], "normalized": [] }, { "id": "PMID-15652356_T7", "type": "Cell", "text": [ "Tumor cells" ], "offsets": [ [ 220, 231 ] ], "normalized": [] }, { "id": "PMID-15652356_T14", "type": "Anatomical_system", "text": [ "sympathetic nervous system" ], "offsets": [ [ 527, 553 ] ], "normalized": [] }, { "id": "PMID-15652356_T15", "type": "Anatomical_system", "text": [ "SNS" ], "offsets": [ [ 555, 558 ] ], "normalized": [] }, { "id": "PMID-15652356_T18", "type": "Developing_anatomical_structure", "text": [ "fetal" ], "offsets": [ [ 638, 643 ] ], "normalized": [] }, { "id": "PMID-15652356_T19", "type": "Cell", "text": [ "SNS paraganglia" ], "offsets": [ [ 653, 668 ] ], "normalized": [] }, { "id": "PMID-15652356_T20", "type": "Cancer", "text": [ "Neuroblastoma" ], "offsets": [ [ 670, 683 ] ], "normalized": [] }, { "id": "PMID-15652356_T21", "type": "Developing_anatomical_structure", "text": [ "SNS precursors" ], "offsets": [ [ 700, 714 ] ], "normalized": [] }, { "id": "PMID-15652356_T22", "type": "Cancer", "text": [ "neuroblastomas" ], "offsets": [ [ 731, 745 ] ], "normalized": [] }, { "id": "PMID-15652356_T23", "type": "Cell", "text": [ "neuronal" ], "offsets": [ [ 761, 769 ] ], "normalized": [] }, { "id": "PMID-15652356_T24", "type": "Cell", "text": [ "neuroendocrine" ], "offsets": [ [ 773, 787 ] ], "normalized": [] }, { "id": "PMID-15652356_T25", "type": "Tissue", "text": [ "necrotic zones" ], "offsets": [ [ 832, 846 ] ], "normalized": [] }, { "id": "PMID-15652356_T29", "type": "Cancer", "text": [ "neuroblastoma" ], "offsets": [ [ 1043, 1056 ] ], "normalized": [] }, { "id": "PMID-15652356_T31", "type": "Cell", "text": [ "neuroblastoma cells" ], "offsets": [ [ 1126, 1145 ] ], "normalized": [] }, { "id": "PMID-15652356_T32", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 1150, 1156 ] ], "normalized": [] }, { "id": "PMID-15652356_T33", "type": "Developing_anatomical_structure", "text": [ "embryonic" ], "offsets": [ [ 1186, 1195 ] ], "normalized": [] }, { "id": "PMID-15652356_T34", "type": "Cell", "text": [ "hypoxic cells" ], "offsets": [ [ 1238, 1251 ] ], "normalized": [] }, { "id": "PMID-15652356_T35", "type": "Cell", "text": [ "neuronal" ], "offsets": [ [ 1263, 1271 ] ], "normalized": [] }, { "id": "PMID-15652356_T36", "type": "Cell", "text": [ "neuroendocrine" ], "offsets": [ [ 1272, 1286 ] ], "normalized": [] }, { "id": "PMID-15652356_T38", "type": "Cancer", "text": [ "neuroblastomas" ], "offsets": [ [ 1483, 1497 ] ], "normalized": [] }, { "id": "PMID-15652356_T58", "type": "Cell", "text": [ "neural crest" ], "offsets": [ [ 1359, 1371 ] ], "normalized": [] } ]

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[ { "id": "PMC-1550851-caption-02__text", "type": "caption", "text": [ "Inflammation-modulating effect of antithrombin on the endothelium. Ligation of heparan sulfate proteoglycans (HSPGs) of endothelium with antithrombin (AT) induces cellular signalling events that alter the cell's biochemical and functional responses to inflammatory stimuli (e.g. bacterial lipopolysaccharide [LPS]). Changes include reduced release of inflammatory and procoagulatory mediators (e.g. interleukin [IL]-1, IL-6, tumour necrosis factor-alpha[TNF]), tissue factor (TF), adenosine diphosphate (ADP) and cellular adhesion molecules (not shown), as well as increased release of anticoagulatory prostacyclin (prostaglandin [PG]I) or CD39/ATPDase. In neuronal tissue, protective mechanisms may by mediated via the release of calcitonin gene-related peptide and nitric oxide with the potential to affect prostacyclin release [55].\n" ], "offsets": [ [ 0, 836 ] ] } ]

[ { "id": "PMC-1550851-caption-02_T1", "type": "Tissue", "text": [ "endothelium" ], "offsets": [ [ 54, 65 ] ], "normalized": [] }, { "id": "PMC-1550851-caption-02_T2", "type": "Tissue", "text": [ "endothelium" ], "offsets": [ [ 120, 131 ] ], "normalized": [] }, { "id": "PMC-1550851-caption-02_T3", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 163, 171 ] ], "normalized": [] }, { "id": "PMC-1550851-caption-02_T4", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 205, 209 ] ], "normalized": [] }, { "id": "PMC-1550851-caption-02_T6", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 513, 521 ] ], "normalized": [] }, { "id": "PMC-1550851-caption-02_T7", "type": "Tissue", "text": [ "neuronal tissue" ], "offsets": [ [ 657, 672 ] ], "normalized": [] } ]

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[ { "id": "PMID-15225208__text", "type": "abstract", "text": [ "Matrix metalloproteinase activity and immunohistochemical profile of matrix metalloproteinase-2 and -9 and tissue inhibitor of metalloproteinase-1 during human dermal wound healing.\nProteolytic activity is required for the turnover of the extracellular matrix during wound healing. Matrix metalloproteinases can collectively cleave all components of the extracellular matrix, with the endogenous tissue inhibitor of metalloproteinase-1 regulating their activity. Breast tissue taken at varying postoperative times (n= 92) or during surgery (controls, n= 17), was used to investigate the temporal and spatial activity of matrix metalloproteinase-2 and -9 and tissue inhibitor of metalloproteinase-1 during human wound healing. Matrix metalloproteinase activity, determined using a quenched fluorescence substrate assay, increased during early healing (3-8 weeks) compared to controls, and then decreased between 24 and 36 weeks after surgery (p less than 0.05 until 24 weeks, Mann-Whitney U-test). Immunohistochemistry scores for matrix metalloproteinase-9 expression were significantly elevated compared to controls in scar endothelial cells and fibroblasts from 2 until 12 and 20 weeks, respectively. Matrix metalloproteinase-2 staining was observed exclusively in fibroblasts, reaching maximum levels 8-12 weeks after surgery, decreasing by 1.5 years but remaining significantly increased. Tissue inhibitor of metalloproteinase-1 staining was relatively sparse but was significantly increased until 8 weeks after surgery. These results show that matrix metalloproteinases are present at elevated levels during early wound healing, when angiogenesis occurs, and suggest that matrix metalloproteinase-9 may play a significant role. The later expression of matrix metalloproteinase-2 and -9 in fibroblasts suggests a role in extracellular matrix remodeling.\n" ], "offsets": [ [ 0, 1859 ] ] } ]

[ { "id": "PMID-15225208_T6", "type": "Pathological_formation", "text": [ "dermal wound" ], "offsets": [ [ 160, 172 ] ], "normalized": [] }, { "id": "PMID-15225208_T7", "type": "Cellular_component", "text": [ "extracellular matrix" ], "offsets": [ [ 239, 259 ] ], "normalized": [] }, { "id": "PMID-15225208_T8", "type": "Pathological_formation", "text": [ "wound" ], "offsets": [ [ 267, 272 ] ], "normalized": [] }, { "id": "PMID-15225208_T10", "type": "Cellular_component", "text": [ "extracellular matrix" ], "offsets": [ [ 354, 374 ] ], "normalized": [] }, { "id": "PMID-15225208_T12", "type": "Tissue", "text": [ "Breast tissue" ], "offsets": [ [ 463, 476 ] ], "normalized": [] }, { "id": "PMID-15225208_T17", "type": "Pathological_formation", "text": [ "wound" ], "offsets": [ [ 711, 716 ] ], "normalized": [] }, { "id": "PMID-15225208_T20", "type": "Cell", "text": [ "scar endothelial cells" ], "offsets": [ [ 1121, 1143 ] ], "normalized": [] }, { "id": "PMID-15225208_T21", "type": "Cell", "text": [ "fibroblasts" ], "offsets": [ [ 1148, 1159 ] ], "normalized": [] }, { "id": "PMID-15225208_T23", "type": "Cell", "text": [ "fibroblasts" ], "offsets": [ [ 1268, 1279 ] ], "normalized": [] }, { "id": "PMID-15225208_T26", "type": "Pathological_formation", "text": [ "wound" ], "offsets": [ [ 1620, 1625 ] ], "normalized": [] }, { "id": "PMID-15225208_T30", "type": "Cell", "text": [ "fibroblasts" ], "offsets": [ [ 1795, 1806 ] ], "normalized": [] }, { "id": "PMID-15225208_T31", "type": "Cellular_component", "text": [ "extracellular matrix" ], "offsets": [ [ 1826, 1846 ] ], "normalized": [] }, { "id": "PMID-15225208_T50", "type": "Cell", "text": [ "controls" ], "offsets": [ [ 1109, 1117 ] ], "normalized": [] } ]

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[ { "id": "PMC-3052097-caption-01__text", "type": "caption", "text": [ "The asymmetric unit of the title compound with the atomic labelling scheme.Displacement are drawn at the 50% probability level. H atoms are represented as small spheres of arbitrary radii. Hydrogen bonds are shown as dashed lines.\n" ], "offsets": [ [ 0, 231 ] ] } ]

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[ { "id": "PMC-3135183-sec-06__text", "type": "sec", "text": [ "4.2. Histological Findings\nMicroscopy revealed features of a diffusely growing discohesive carcinoma, exclusively growing in the alveolar interstitium, thus expanding it, while leaving the original alveolar architecture intact (Figure 2). There was local ulceration of the pleura, while, beyond this ulcer, the tumor formed a thick cake of discohesive tumor cells lining the pleural membrane (Figure 2(c)), with only focal, microscopic invasion into the fatty tissue of the parietal pleura.\nThe tumor consisted of atypical, moderately polymorphous, and irregularly shaped tumor cells with marked discohesiveness. They featured scant eosinophilic cytoplasm and irregularly contoured and hyperchromatic nuclei, often containing one or more prominent nucleoli (Figure 2(b)). There were many mitoses and apoptoses present, but necrosis was not observed. No squamous or glandular differentiation was observed, and mucin stains (PAS-D and alcian blue) were negative. Within the tumor, there were multiple small blood-filled clefts and blood lakes. Angioinvasion in medium-sized vessels, including an artery, was demonstrated (Figure 2(d)).\nOf note, the broadened alveolar septa were lined by markedly atypical epithelial cells, yet less atypical than the interstitial carcinoma (Figures 2(a) and 2(b)). The atypia of the lining cells extended beyond the tumor front, showing a sharp demarcation with normal type I pneumocytes (Figure 2(a)), a feature characteristic to nonmucinous adenocarcinoma in situ with lepidic growth pattern (former bronchioloalveolar carcinoma, BAC) [3].\n" ], "offsets": [ [ 0, 1574 ] ] } ]

[ { "id": "PMC-3135183-sec-06_T1", "type": "Cancer", "text": [ "discohesive carcinoma" ], "offsets": [ [ 79, 100 ] ], "normalized": [] }, { "id": "PMC-3135183-sec-06_T2", "type": "Multi-tissue_structure", "text": [ "alveolar interstitium" ], "offsets": [ [ 129, 150 ] ], "normalized": [] }, { "id": "PMC-3135183-sec-06_T3", "type": "Multi-tissue_structure", "text": [ "alveolar" ], "offsets": [ [ 198, 206 ] ], "normalized": [] }, { "id": "PMC-3135183-sec-06_T4", "type": "Multi-tissue_structure", "text": [ "pleura" ], "offsets": [ [ 273, 279 ] ], "normalized": [] }, { "id": "PMC-3135183-sec-06_T5", "type": "Pathological_formation", "text": [ "ulcer" ], "offsets": [ [ 300, 305 ] ], "normalized": [] }, { "id": "PMC-3135183-sec-06_T6", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 311, 316 ] ], "normalized": [] }, { "id": "PMC-3135183-sec-06_T7", "type": "Cell", "text": [ "discohesive tumor cells" ], "offsets": [ [ 340, 363 ] ], "normalized": [] }, { "id": "PMC-3135183-sec-06_T8", "type": "Multi-tissue_structure", "text": [ "pleural membrane" ], "offsets": [ [ 375, 391 ] ], "normalized": [] }, { "id": "PMC-3135183-sec-06_T9", "type": "Tissue", "text": [ "fatty tissue" ], "offsets": [ [ 454, 466 ] ], "normalized": [] }, { "id": "PMC-3135183-sec-06_T10", "type": "Multi-tissue_structure", "text": [ "parietal pleura" ], "offsets": [ [ 474, 489 ] ], "normalized": [] }, { "id": "PMC-3135183-sec-06_T11", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 495, 500 ] ], "normalized": [] }, { "id": "PMC-3135183-sec-06_T12", "type": "Cell", "text": [ "tumor cells" ], "offsets": [ [ 572, 583 ] ], "normalized": [] }, { "id": "PMC-3135183-sec-06_T13", "type": "Organism_substance", "text": [ "eosinophilic cytoplasm" ], "offsets": [ [ 633, 655 ] ], "normalized": [] }, { "id": "PMC-3135183-sec-06_T14", "type": "Cellular_component", "text": [ "nuclei" ], "offsets": [ [ 701, 707 ] ], "normalized": [] }, { "id": "PMC-3135183-sec-06_T15", "type": "Cellular_component", "text": [ "nucleoli" ], "offsets": [ [ 748, 756 ] ], "normalized": [] }, { "id": "PMC-3135183-sec-06_T16", "type": "Cell", "text": [ "squamous" ], "offsets": [ [ 853, 861 ] ], "normalized": [] }, { "id": "PMC-3135183-sec-06_T17", "type": "Cell", "text": [ "glandular" ], "offsets": [ [ 865, 874 ] ], "normalized": [] }, { "id": "PMC-3135183-sec-06_T18", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 972, 977 ] ], "normalized": [] }, { "id": "PMC-3135183-sec-06_T19", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 1005, 1010 ] ], "normalized": [] }, { "id": "PMC-3135183-sec-06_T20", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 1029, 1034 ] ], "normalized": [] }, { "id": "PMC-3135183-sec-06_T21", "type": "Multi-tissue_structure", "text": [ "vessels" ], "offsets": [ [ 1072, 1079 ] ], "normalized": [] }, { "id": "PMC-3135183-sec-06_T22", "type": "Multi-tissue_structure", "text": [ "artery" ], "offsets": [ [ 1094, 1100 ] ], "normalized": [] }, { "id": "PMC-3135183-sec-06_T23", "type": "Multi-tissue_structure", "text": [ "alveolar septa" ], "offsets": [ [ 1157, 1171 ] ], "normalized": [] }, { "id": "PMC-3135183-sec-06_T24", "type": "Cell", "text": [ "epithelial cells" ], "offsets": [ [ 1204, 1220 ] ], "normalized": [] }, { "id": "PMC-3135183-sec-06_T25", "type": "Cancer", "text": [ "interstitial carcinoma" ], "offsets": [ [ 1249, 1271 ] ], "normalized": [] }, { "id": "PMC-3135183-sec-06_T26", "type": "Cell", "text": [ "lining cells" ], "offsets": [ [ 1315, 1327 ] ], "normalized": [] }, { "id": "PMC-3135183-sec-06_T27", "type": "Cancer", "text": [ "tumor front" ], "offsets": [ [ 1348, 1359 ] ], "normalized": [] }, { "id": "PMC-3135183-sec-06_T28", "type": "Cell", "text": [ "type I pneumocytes" ], "offsets": [ [ 1401, 1419 ] ], "normalized": [] }, { "id": "PMC-3135183-sec-06_T29", "type": "Cancer", "text": [ "nonmucinous adenocarcinoma in situ" ], "offsets": [ [ 1463, 1497 ] ], "normalized": [] }, { "id": "PMC-3135183-sec-06_T30", "type": "Cancer", "text": [ "bronchioloalveolar carcinoma" ], "offsets": [ [ 1534, 1562 ] ], "normalized": [] }, { "id": "PMC-3135183-sec-06_T31", "type": "Cancer", "text": [ "BAC" ], "offsets": [ [ 1564, 1567 ] ], "normalized": [] } ]

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[ { "id": "PMID-2153347__text", "type": "abstract", "text": [ "Vimentin is preferentially expressed in human breast carcinomas with low estrogen receptor and high Ki-67 growth fraction. \nVimentin expression, growth fractions (GF), and estrogen receptor (ER) levels were determined for 90 untreated primary breast carcinomas. Coexpression of keratin and vimentin was found in approximately 20% of the tumors regardless of menopausal status. Vimentin was expressed preferentially in tumor cells of high-grade ductal breast carcinomas (15 of 28 histologic grade 3 vs. 0 of 40 grades 1 and 2). Vimentin expression was found preferentially in tumors with high GF (greater than 15% Ki-67 positive by immunoperoxidase staining) and low ER levels (less than 60 fmols/mg protein by a monoclonal enzyme immunoassay). Sixty-eight percent of tumors in this group were vimentin positive and 88% of all vimentin-positive tumors fell into this category. More than 50% of the tumor cells coexpressed vimentin and keratin. Thus, vimentin expression may be helpful in identifying a substantial subset of ER-independent breast carcinomas with poor prognostic indicators.\n" ], "offsets": [ [ 0, 1089 ] ] } ]

[ { "id": "PMID-2153347_T3", "type": "Cancer", "text": [ "breast carcinomas" ], "offsets": [ [ 46, 63 ] ], "normalized": [] }, { "id": "PMID-2153347_T9", "type": "Cancer", "text": [ "primary breast carcinomas" ], "offsets": [ [ 235, 260 ] ], "normalized": [] }, { "id": "PMID-2153347_T12", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 337, 343 ] ], "normalized": [] }, { "id": "PMID-2153347_T14", "type": "Cell", "text": [ "tumor cells" ], "offsets": [ [ 418, 429 ] ], "normalized": [] }, { "id": "PMID-2153347_T15", "type": "Cancer", "text": [ "high-grade ductal breast carcinomas" ], "offsets": [ [ 433, 468 ] ], "normalized": [] }, { "id": "PMID-2153347_T17", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 575, 581 ] ], "normalized": [] }, { "id": "PMID-2153347_T21", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 767, 773 ] ], "normalized": [] }, { "id": "PMID-2153347_T24", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 844, 850 ] ], "normalized": [] }, { "id": "PMID-2153347_T25", "type": "Cell", "text": [ "tumor cells" ], "offsets": [ [ 897, 908 ] ], "normalized": [] }, { "id": "PMID-2153347_T30", "type": "Cancer", "text": [ "breast carcinomas" ], "offsets": [ [ 1038, 1055 ] ], "normalized": [] } ]

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[ { "id": "PMC-2979164-sec-17__text", "type": "sec", "text": [ "Atomic displacement parameters (A2)\nU11 U22 U33 U12 U13 U23\nBr 0.03555 (15) 0.05091 (17) 0.03161 (14) -0.01198 (11) 0.01077 (10) -0.00502 (11)\nS 0.0273 (3) 0.0176 (2) 0.0338 (3) 0.0016 (2) -0.0020 (2) 0.0026 (2)\nF 0.0514 (10) 0.0486 (9) 0.0464 (9) 0.0068 (8) 0.0279 (8) -0.0001 (7)\nO1 0.0293 (8) 0.0186 (7) 0.0251 (7) -0.0030 (6) 0.0028 (6) 0.0004 (6)\nO2A 0.0417 (12) 0.0238 (9) 0.0326 (10) -0.0001 (8) -0.0051 (8) 0.0102 (7)\nO2B 0.036 (11) 0.010 (7) 0.025 (9) -0.003 (7) 0.003 (7) 0.007 (6)\nC1 0.0228 (11) 0.0192 (9) 0.0233 (10) 0.0001 (8) -0.0023 (8) 0.0019 (8)\nC2 0.0258 (11) 0.0199 (10) 0.0193 (9) 0.0000 (8) -0.0033 (8) 0.0016 (7)\nC3 0.0263 (11) 0.0229 (10) 0.0177 (9) -0.0020 (8) -0.0031 (8) 0.0008 (8)\nC4 0.0294 (12) 0.0228 (10) 0.0277 (11) -0.0014 (9) -0.0008 (9) 0.0027 (8)\nC5 0.0323 (13) 0.0297 (11) 0.0285 (11) -0.0081 (10) -0.0003 (9) 0.0042 (9)\nC6 0.0257 (12) 0.0389 (13) 0.0207 (10) -0.0049 (10) 0.0013 (8) 0.0001 (9)\nC7 0.0320 (13) 0.0304 (11) 0.0218 (10) 0.0015 (9) 0.0009 (9) -0.0005 (9)\nC8 0.0298 (12) 0.0257 (10) 0.0178 (9) 0.0006 (9) -0.0012 (8) 0.0001 (8)\nC9 0.0392 (14) 0.0205 (10) 0.0219 (10) 0.0034 (9) 0.0031 (9) -0.0010 (8)\nC10 0.0378 (13) 0.0184 (10) 0.0234 (10) -0.0017 (9) 0.0014 (9) 0.0006 (8)\nC11 0.0254 (11) 0.0227 (10) 0.0198 (10) -0.0024 (8) 0.0004 (8) 0.0006 (8)\nC12 0.0254 (11) 0.0187 (10) 0.0222 (10) -0.0003 (8) -0.0032 (8) -0.0007 (7)\nC13 0.0237 (11) 0.0220 (10) 0.0222 (10) 0.0012 (8) -0.0008 (8) 0.0030 (8)\nC14 0.0298 (12) 0.0241 (10) 0.0286 (11) -0.0009 (9) -0.0007 (9) -0.0006 (9)\nC15 0.0408 (14) 0.0267 (11) 0.0269 (11) 0.0049 (10) 0.0028 (10) -0.0031 (9)\nC16 0.0353 (14) 0.0326 (12) 0.0294 (12) 0.0094 (10) 0.0094 (10) 0.0058 (9)\nC17 0.0255 (12) 0.0281 (11) 0.0349 (12) -0.0001 (9) 0.0015 (9) 0.0082 (9)\nC18 0.0271 (12) 0.0231 (10) 0.0250 (11) 0.0002 (9) -0.0032 (9) 0.0011 (8)\nC19 0.0353 (14) 0.0251 (11) 0.0375 (13) -0.0045 (10) -0.0070 (10) -0.0012 (9)\n" ], "offsets": [ [ 0, 1901 ] ] } ]

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[ { "id": "PMID-12796817__text", "type": "abstract", "text": [ "[Screening and identification of novel genes involved in biosynthesis of ginsenoside in Panax ginseng plant].\nThe root of Panax ginseng plant undergoes a specific developmental process to become a biosynthesis and accumulation organ for ginsenosides. To identify and analyze genes involved in the biosynthesis of ginsenoside, suppression subtractive hybridization (SSH) between mRNAs of 4- and 1-year-old root tissues was performed, and a subtracted cDNA library specific to 4-year-old roots was constructed. Forty cDNA clones selected randomly from the subtracted cDNA library were sequenced. Sequence information of all clones was evaluated by Nucleotide Blast analysis in GenBank/DDBJ/EMBL. The results showed that six subtracted cDNA clones represented the novel genes (ESTs), because no sequence homology with any known sequences was found in the database. Expression in 4-year-old P. ginseng root tissues was verified by reverse Northern dot hybridization for the six clones. These six novel genes were named GBR1, GBR2, GBR3, GBR4, GBR5, and GBR6, and their Accession numbers of GenBank are AF485334, AF485335, AF485336, AF485337, AF485332, and AF485333, respectively. Finally, Northern blot analysis and semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) confirmed that these six novel genes were differentially expressed in the defined development stage of P. ginseng plant roots. It is possible that their overexpression may play an important role in the ginsenoside biosynthesis. In addition, most of transcripts of all genes could also be detected in other P. ginseng plant tissues such as stem, leaf and seed. Our results provided a basis for obtaining the full-length cDNA sequences of such six novel genes, and for identifying their function involved in the biosynthesis of ginsenoside.\n" ], "offsets": [ [ 0, 1826 ] ] } ]

[ { "id": "PMID-12796817_T1", "type": "Organ", "text": [ "root" ], "offsets": [ [ 114, 118 ] ], "normalized": [] }, { "id": "PMID-12796817_T2", "type": "Organ", "text": [ "organ" ], "offsets": [ [ 227, 232 ] ], "normalized": [] }, { "id": "PMID-12796817_T3", "type": "Tissue", "text": [ "root tissues" ], "offsets": [ [ 405, 417 ] ], "normalized": [] }, { "id": "PMID-12796817_T4", "type": "Organ", "text": [ "roots" ], "offsets": [ [ 486, 491 ] ], "normalized": [] }, { "id": "PMID-12796817_T5", "type": "Tissue", "text": [ "root tissues" ], "offsets": [ [ 898, 910 ] ], "normalized": [] }, { "id": "PMID-12796817_T6", "type": "Organ", "text": [ "roots" ], "offsets": [ [ 1407, 1412 ] ], "normalized": [] }, { "id": "PMID-12796817_T7", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 1610, 1617 ] ], "normalized": [] }, { "id": "PMID-12796817_T8", "type": "Tissue", "text": [ "stem" ], "offsets": [ [ 1626, 1630 ] ], "normalized": [] }, { "id": "PMID-12796817_T9", "type": "Tissue", "text": [ "leaf" ], "offsets": [ [ 1632, 1636 ] ], "normalized": [] }, { "id": "PMID-12796817_T10", "type": "Tissue", "text": [ "seed" ], "offsets": [ [ 1641, 1645 ] ], "normalized": [] } ]

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[ { "id": "PMID-7226107__text", "type": "abstract", "text": [ "Metabolic alterations in a noncachectic animal tumor system. \nThe increased energy expended by the host to synthesize substrate, which is utilized by the tumor, is a potential cause of cancer cachexia. In vivo glucose and alanine kinetics were examined by tracer methodology in a sarcoma-bearing rat model. The effects of 3-mercaptopicolinic acid, a potent inhibitor of gluconeogenesis, was also examined on this model. Both tumor-bearing (TB) and nontumor bearing (NTB) animals were gaining weight prior to study and the tumors were relatively small. The TB animals had significantly lower plasma glucose and higher blood lactic acid levels compared with NTB animals. After inhibition of gluconeogenesis, the plasma glucose decreased and the blood lactate increased significantly more in TB than NTB animals. The glucose turnover rate was significantly greater in TB compared with NTB animals, as was the rate of glucose recycling and the rate of gluconeogenesis (alanine leads to glucose), both energy demanding processes. These results suggest that the tumor-bearing animal, even prior to significant cachexia, has an excess demand for energy, the provision of which may be a significant factor in malignant cachexia.\n" ], "offsets": [ [ 0, 1221 ] ] } ]

[ { "id": "PMID-7226107_T1", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 47, 52 ] ], "normalized": [] }, { "id": "PMID-7226107_T2", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 154, 159 ] ], "normalized": [] }, { "id": "PMID-7226107_T3", "type": "Organism_substance", "text": [ "cancer cachexia" ], "offsets": [ [ 185, 200 ] ], "normalized": [] }, { "id": "PMID-7226107_T6", "type": "Cancer", "text": [ "sarcoma" ], "offsets": [ [ 280, 287 ] ], "normalized": [] }, { "id": "PMID-7226107_T9", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 425, 430 ] ], "normalized": [] }, { "id": "PMID-7226107_T10", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 451, 456 ] ], "normalized": [] }, { "id": "PMID-7226107_T12", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 522, 528 ] ], "normalized": [] }, { "id": "PMID-7226107_T14", "type": "Organism_substance", "text": [ "plasma" ], "offsets": [ [ 591, 597 ] ], "normalized": [] }, { "id": "PMID-7226107_T16", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 617, 622 ] ], "normalized": [] }, { "id": "PMID-7226107_T18", "type": "Organism_substance", "text": [ "plasma" ], "offsets": [ [ 710, 716 ] ], "normalized": [] }, { "id": "PMID-7226107_T20", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 743, 748 ] ], "normalized": [] }, { "id": "PMID-7226107_T26", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1056, 1061 ] ], "normalized": [] }, { "id": "PMID-7226107_T27", "type": "Cancer", "text": [ "cachexia" ], "offsets": [ [ 1104, 1112 ] ], "normalized": [] }, { "id": "PMID-7226107_T28", "type": "Cancer", "text": [ "malignant cachexia" ], "offsets": [ [ 1201, 1219 ] ], "normalized": [] } ]

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[ { "id": "PMC-2638008-sec-12__text", "type": "sec", "text": [ "Whole-Body gamma-Irradiation\nTo evaluate differential sensitivity to irradiation, mice were exposed to gamma-irradiation (4-10 Gy, single dose) and closely monitored throughout the experimentation period. Animals were killed at the first appearance of signs of poor health. Recipients of bone marrow transplants were pre-irradiated with a total dose of 10.2 Gy (two doses of 5.1 Gy, 3 h apart). For in vivo DNA damage experiments, mice were irradiated with a single dose of 5Gy and killed after 1, 3 or 6 hours. All irradiations were carried out in a Cesium Mark1 irradiator (Shepherd Associates).\n" ], "offsets": [ [ 0, 598 ] ] } ]

[ { "id": "PMC-2638008-sec-12_T1", "type": "Multi-tissue_structure", "text": [ "bone marrow" ], "offsets": [ [ 288, 299 ] ], "normalized": [] } ]

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[ { "id": "PMID-18995207__text", "type": "abstract", "text": [ "Atypical mycobacteriosis of the larynx: an unusual clinical presentation secondary to steroids inhalation.\nVocal cords stiffness can be associated with a variety of etiologic agents, but it is rarely seen with atypical mycobacteria, for example, Mycobacterium avium complex. We report a case of a 35-year-old white woman who is and was maintained on inhaled steroids. She presented with hoarseness and low-grade fever, but her medical history was otherwise unremarkable. Laryngoscopy revealed bilateral scarring of the vocal cords. Vocal cord biopsies were performed. Histologic examination revealed unremarkable laryngeal mucosa, except for abundant subepithelial non-necrotizing granulomata. The differential diagnosis included sarcoid, Klebsiella scleroma, and tuberculosis. Special stains reviewed abundant acid-fast bacilli, later confirmed by a DNA assay on induced deep sputum, consistent with M avium complex. Subsequently, steroids were withdrawn, and the patient was treated with a multiple-drug antituberculous regimen and had a full recovery. This unusual clinical presentation of the atypical mycobacteriosis may be encountered by otolaryngologists and pathologists, and it is critical to recognize it in patients immunocompromised because of steroids.\n" ], "offsets": [ [ 0, 1266 ] ] } ]

[ { "id": "PMID-18995207_T1", "type": "Multi-tissue_structure", "text": [ "larynx" ], "offsets": [ [ 32, 38 ] ], "normalized": [] }, { "id": "PMID-18995207_T2", "type": "Multi-tissue_structure", "text": [ "vocal cords" ], "offsets": [ [ 519, 530 ] ], "normalized": [] }, { "id": "PMID-18995207_T3", "type": "Multi-tissue_structure", "text": [ "Vocal cord" ], "offsets": [ [ 532, 542 ] ], "normalized": [] }, { "id": "PMID-18995207_T4", "type": "Multi-tissue_structure", "text": [ "laryngeal mucosa" ], "offsets": [ [ 613, 629 ] ], "normalized": [] }, { "id": "PMID-18995207_T5", "type": "Pathological_formation", "text": [ "subepithelial non-necrotizing granulomata" ], "offsets": [ [ 651, 692 ] ], "normalized": [] }, { "id": "PMID-18995207_T6", "type": "Pathological_formation", "text": [ "sarcoid" ], "offsets": [ [ 730, 737 ] ], "normalized": [] }, { "id": "PMID-18995207_T7", "type": "Pathological_formation", "text": [ "Klebsiella scleroma" ], "offsets": [ [ 739, 758 ] ], "normalized": [] }, { "id": "PMID-18995207_T8", "type": "Organism_substance", "text": [ "sputum" ], "offsets": [ [ 877, 883 ] ], "normalized": [] }, { "id": "PMID-18995207_T9", "type": "Multi-tissue_structure", "text": [ "Vocal cords" ], "offsets": [ [ 107, 118 ] ], "normalized": [] } ]

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[ { "id": "PMID-10229326__text", "type": "abstract", "text": [ "N-glycosylation of glucose transporter-1 (Glut-1) is associated with increased transporter affinity for glucose in human leukemic cells.\nTo elucidate the role of N-glycosylation in the functional activity of the universal glucose transporter, Glut-1, we investigated effects of the N-glycosylation inhibitor, tunicamycin, on glucose transport by human leukemic cell lines K562, U937 and HL60. Treatment with tunicamycin produced a 40-50% inhibition of 2-deoxyglucose uptake and this was associated with a 2-2.5-fold decrease in transporter affinity for glucose (Km) without a change in Vmax. Leukemic K562, U937 and HL60 cells expressed Glut-1 transporter protein. With K562 cells Glut-1 appeared as a broad band of 50-60 kDa, whereas with U937 and HL60 cells a diffuse band was observed at approximately 55 kDa. Treatment of K562 cells with tunicamycin for 18 h, resulted in extensive loss of the 50-60 kDa glycoprotein, appearance of a 30-40 kDa band and increased staining of a 45 kDa band. With U937 cells, tunicamycin treatment resulted in the appearance of a 30-40 kDa band and increased staining of a 45 kDa band. With HL60 cells loss of the 55 kDa Glut-1 band was observed and a band of 45 kDa appeared. Tunicamycin-treatment resulted in 75-90% inhibition in [3H]mannose incorporation but only 20-25% inhibition in [3H]thymidine and [3H]leucine incorporation. In contrast, tunicamycin had little effect on the viability and MTT responses of the cells used. These results suggest that in leukemic cells N-glycosylation of Glut-1 plays an important role in maintaining its structure and functional integration.\n" ], "offsets": [ [ 0, 1617 ] ] } ]

[ { "id": "PMID-10229326_T5", "type": "Cell", "text": [ "leukemic cells" ], "offsets": [ [ 121, 135 ] ], "normalized": [] }, { "id": "PMID-10229326_T11", "type": "Cell", "text": [ "leukemic cell lines K562" ], "offsets": [ [ 352, 376 ] ], "normalized": [] }, { "id": "PMID-10229326_T12", "type": "Cell", "text": [ "U937" ], "offsets": [ [ 378, 382 ] ], "normalized": [] }, { "id": "PMID-10229326_T13", "type": "Cell", "text": [ "HL60" ], "offsets": [ [ 387, 391 ] ], "normalized": [] }, { "id": "PMID-10229326_T17", "type": "Cell", "text": [ "Leukemic K562" ], "offsets": [ [ 592, 605 ] ], "normalized": [] }, { "id": "PMID-10229326_T18", "type": "Cell", "text": [ "U937" ], "offsets": [ [ 607, 611 ] ], "normalized": [] }, { "id": "PMID-10229326_T19", "type": "Cell", "text": [ "HL60 cells" ], "offsets": [ [ 616, 626 ] ], "normalized": [] }, { "id": "PMID-10229326_T21", "type": "Cell", "text": [ "K562 cells" ], "offsets": [ [ 670, 680 ] ], "normalized": [] }, { "id": "PMID-10229326_T23", "type": "Cell", "text": [ "U937" ], "offsets": [ [ 740, 744 ] ], "normalized": [] }, { "id": "PMID-10229326_T24", "type": "Cell", "text": [ "HL60 cells" ], "offsets": [ [ 749, 759 ] ], "normalized": [] }, { "id": "PMID-10229326_T25", "type": "Cell", "text": [ "K562 cells" ], "offsets": [ [ 826, 836 ] ], "normalized": [] }, { "id": "PMID-10229326_T28", "type": "Cell", "text": [ "U937 cells" ], "offsets": [ [ 999, 1009 ] ], "normalized": [] }, { "id": "PMID-10229326_T30", "type": "Cell", "text": [ "HL60 cells" ], "offsets": [ [ 1126, 1136 ] ], "normalized": [] }, { "id": "PMID-10229326_T38", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1453, 1458 ] ], "normalized": [] }, { "id": "PMID-10229326_T39", "type": "Cell", "text": [ "leukemic cells" ], "offsets": [ [ 1495, 1509 ] ], "normalized": [] } ]

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[ { "id": "PMC-3100324-sec-10__text", "type": "sec", "text": [ "Statistics\nThe survival of mice was analyzed using Kaplan-Meier survival analysis. All other data were analyzed by one-way ANOVA, followed by the Student-Newman-Keuls test for all pairwise comparisons. Prior to ANOVA, Levene's Test for Equality of Variances was performed. All statistical analyses were performed using MedCalc software, version 11.2.1.0.\n" ], "offsets": [ [ 0, 355 ] ] } ]

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[ { "id": "PMID-11712346__text", "type": "abstract", "text": [ "[Anesthetic management of a patient with Dyggve-Melchior-Clausen syndrome].\nThe Dyggve-Melchior-Clausen syndrome (DMCS) is a rare autosomal recessive skeletal dysplasia characterized by short-trunk dwarfism and mental retardation. A 49-year-old male with DMCS underwent resection arthroplasty for contracture of the right hip joint under general anesthesia using thiamylal, nitrous oxide, sevoflurane, and vecuronium. Although he was assumed to have difficult airway due to short neck, macroglossia, and disturbance of neck flexion, tracheal intubation was not difficult. No complications including malignant hyperthermia were observed during the 95 min of the operation.\n" ], "offsets": [ [ 0, 672 ] ] } ]

[ { "id": "PMID-11712346_T1", "type": "Pathological_formation", "text": [ "skeletal dysplasia" ], "offsets": [ [ 150, 168 ] ], "normalized": [] }, { "id": "PMID-11712346_T2", "type": "Organism_subdivision", "text": [ "trunk" ], "offsets": [ [ 192, 197 ] ], "normalized": [] }, { "id": "PMID-11712346_T3", "type": "Multi-tissue_structure", "text": [ "airway" ], "offsets": [ [ 460, 466 ] ], "normalized": [] }, { "id": "PMID-11712346_T4", "type": "Organism_subdivision", "text": [ "neck" ], "offsets": [ [ 480, 484 ] ], "normalized": [] }, { "id": "PMID-11712346_T5", "type": "Organism_subdivision", "text": [ "neck" ], "offsets": [ [ 519, 523 ] ], "normalized": [] }, { "id": "PMID-11712346_T6", "type": "Multi-tissue_structure", "text": [ "right hip joint" ], "offsets": [ [ 316, 331 ] ], "normalized": [] }, { "id": "PMID-11712346_T7", "type": "Multi-tissue_structure", "text": [ "tracheal" ], "offsets": [ [ 533, 541 ] ], "normalized": [] } ]

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[ { "id": "PMID-19622311__text", "type": "abstract", "text": [ "[The prediction of the level of depression by cognitive, behavioral, and temperamental variables in a six-month time interval].\nSeveral models have been proposed to explain the depressive phenomenon, such as the theory of dysfunctional attitudes, the hopelessness theory, the behavioral model of activity level, or temperamental models. This article presents data about the role of those models in the prediction of the level of depression in a sample of 414 college students, assessed over a temporal interval of six months. Dysfunctional attitudes, attributional styles, the level of activity, and the five-factors of personality were assessed. The BDI-II was the depression level measure. The results showed that these variables predict depression levels, but with low coefficients. The dimensions of Need of Achievement (a dysfunctional attitude) and Neuroticism had particularly greater weight in the prediction, but only Neuroticism seems to behave like a vulnerability element. Attributional styles did not contribute significantly to the prediction of depression. Activity level lost its predictive role during the 6-month interval. These results are discussed according to the role of the proposed models and the need for a deeper explanation of the variance of depression scores.\n" ], "offsets": [ [ 0, 1290 ] ] } ]

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[ { "id": "PMID-1802941__text", "type": "abstract", "text": [ "M. leprae- and BCG-induced chemiluminescence response of monocytes from leprosy patients and healthy subjects: effects of gamma-interferon and GM-CSF.\nMycobacterium leprae, in contrast to BCG, failed to trigger any chemiluminescence (CL) response in mononuclear cells from either leprosy patients or healthy subjects, a deficit not reversed by either interferon-gamma or GM-CSF. Chemiluminescence responses induced without mycobacteria or with BCG were found to be lower in leprosy patients than in controls. M. leprae were also less well phagocytosed than BCG. However, there was a significant difference in phagocytosis between healthy and tuberculoid leprosy subjects. Phagocytosis was not altered by the addition of either lymphokine, and no major differences between healthy subjects and patients were observed. Preincubating mononuclear cells with anti-mycobacteria antibodies (lepromatous patients' sera) did not increase the CL response nor the phagocytosis of M. leprae or BCG.\n" ], "offsets": [ [ 0, 987 ] ] } ]

[ { "id": "PMID-1802941_T1", "type": "Cell", "text": [ "monocytes" ], "offsets": [ [ 57, 66 ] ], "normalized": [] }, { "id": "PMID-1802941_T2", "type": "Cell", "text": [ "mononuclear cells" ], "offsets": [ [ 250, 267 ] ], "normalized": [] }, { "id": "PMID-1802941_T3", "type": "Cell", "text": [ "mononuclear cells" ], "offsets": [ [ 831, 848 ] ], "normalized": [] }, { "id": "PMID-1802941_T4", "type": "Organism_substance", "text": [ "sera" ], "offsets": [ [ 906, 910 ] ], "normalized": [] } ]

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[ { "id": "PMC-3143519-caption-01__text", "type": "caption", "text": [ "Paederus dermatitis involving the neck\n" ], "offsets": [ [ 0, 39 ] ] } ]

[ { "id": "PMC-3143519-caption-01_T1", "type": "Organism_subdivision", "text": [ "neck" ], "offsets": [ [ 34, 38 ] ], "normalized": [] } ]

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[ { "id": "PMID-15217720__text", "type": "abstract", "text": [ "Multicriteria evaluation of simulated logging scenarios in a tropical rain forest.\nForest growth models are useful tools for investigating the long-term impacts of logging. In this paper, the results of the rain forest growth model FORMIND were assessed by a multicriteria decision analysis. The main processes covered by FORMIND include tree growth, mortality, regeneration and competition. Tree growth is calculated based on a carbon balance approach. Trees compete for light and space; dying large trees fall down and create gaps in the forest. Sixty-four different logging scenarios for an initially undisturbed forest stand at Deramakot (Malaysia) were simulated. The scenarios differ regarding the logging cycle, logging method, cutting limit and logging intensity. We characterise the impacts with four criteria describing the yield, canopy opening and changes in species composition. Multicriteria decision analysis was used for the first time to evaluate the scenarios and identify the efficient ones. Our results plainly show that reduced-impact logging scenarios are more 'efficient' than the others, since in these scenarios forest damage is minimised without significantly reducing yield. Nevertheless, there is a trade-off between yield and achieving a desired ecological state of logged forest; the ecological state of the logged forests can only be improved by reducing yields and enlarging the logging cycles. Our study also demonstrates that high cutting limits or low logging intensities cannot compensate for the high level of damage caused by conventional logging techniques.\n" ], "offsets": [ [ 0, 1597 ] ] } ]

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[ { "id": "PMC-2960999-sec-02__text", "type": "sec", "text": [ "Experimental\n\n" ], "offsets": [ [ 0, 14 ] ] } ]

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[ { "id": "PMID-10841092__text", "type": "abstract", "text": [ "Specific subgroup B adenovirus diagnosis by PCR of the fibre gene.\nOBJECTIVE:\nA highly sensitive and specific PCR assay targeting regions of the fibre gene was developed for the identification of subgroup B adenovirus strains. This is critical, since these adenovirus strains are frequently associated with severe respiratory infections in infants and new-borns.\nMETHODS:\nClinical samples from nasopharyngeal aspirates were analysed by PCR using several sets of primers corresponding to sequences of the gene coding for the fibre protein.\nRESULTS:\nThe assay allowed the detection and identification of all the genotypes of adenovirus subgroup B, based on the size of the amplified product when analysed on polyacrilamide gel electrophoresis. Specifically, one set of primers was able to amplify DNA of subgroup B but not subgroup C and E viruses.\nCONCLUSION:\nThe detection of adenovirus and the genotyping can be done on a routine basis by a PCR assay using the fibre gene as a target. The assay allows the identification of ADV subgroup B, including genotype 7h, which is the single most important viral pathogen associated with respiratory diseases in infants and young children in the southern part of South America.\n" ], "offsets": [ [ 0, 1220 ] ] } ]

[ { "id": "PMID-10841092_T1", "type": "Anatomical_system", "text": [ "respiratory" ], "offsets": [ [ 314, 325 ] ], "normalized": [] }, { "id": "PMID-10841092_T2", "type": "Organism_substance", "text": [ "nasopharyngeal aspirates" ], "offsets": [ [ 394, 418 ] ], "normalized": [] }, { "id": "PMID-10841092_T3", "type": "Anatomical_system", "text": [ "respiratory" ], "offsets": [ [ 1130, 1141 ] ], "normalized": [] }, { "id": "PMID-10841092_T4", "type": "Organism_substance", "text": [ "samples" ], "offsets": [ [ 381, 388 ] ], "normalized": [] } ]

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[ { "id": "PMC-3212806-sec-17__text", "type": "sec", "text": [ "Authors' contributions\nEEKN was responsible for data collection, statistical analysis and drafting the manuscript. SAGN and YW involved in data collection and helped with the data analysis. AS helped in data analysis. EST and JL directed the study and helped in revising the manuscript. RMVD helped in data analysis, interpretation of the results and led writing of the manuscript. All authors read and approved the final manuscript.\n" ], "offsets": [ [ 0, 434 ] ] } ]

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[ { "id": "PMID-19489226__text", "type": "abstract", "text": [ "[Activation of sterol regulatory element binding protein and its involvement in endothelial cell migration]\nOBJECTIVE: To study the activation of sterol regulatory element binding protein (SREBP) and its critical role in endothelial cell migration. METHODS: Bovine aortic endothelial cells (ECs) were cultured. The expression of SREBP and Cdc42 were determined by Western blot and quantitative real-time PCR. Moreover, outward growth migration model and transwell chamber assay were used to detect ECs migration. RESULTS: (1) SREBP was activated during ECs migration. Western blot analysis demonstrated increased active form SREBP in migrating as compared to non-migrating ECs population. SREBP activation decreased as ECs migration slowed;(2) Coincidental with SREBP activation, mRNA expression of its target genes such as low density lipoprotein receptor, HMG-CoA reductase, and fatty acid synthase also increased in migrating ECs population as detected by real-time PCR; (3) Migration induced SREBP activation in ECs was inhibited by SREBP-acting protein RNAi and pharmacologically by 25-hydroxycholesterol; (4) Inhibition of SREBP led to decreased ECs migration in various models; (5) Cells genetically deficient in SREBP-acting protein, S1P, or S2P, phenotypically exhibited impaired migration; (6) SREBP inhibition in ECs suppressed the activity of small GTPase Cdc42, a key molecule for ECs motility. CONCLUSIONS: SREBP is activated during and plays a critical role in ECs migration. Targeting SREBP could become a novel approach in fighting diseases involving abnormal ECs migration.\n" ], "offsets": [ [ 0, 1592 ] ] } ]

[ { "id": "PMID-19489226_T2", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 80, 96 ] ], "normalized": [] }, { "id": "PMID-19489226_T5", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 221, 237 ] ], "normalized": [] }, { "id": "PMID-19489226_T7", "type": "Cell", "text": [ "aortic endothelial cells" ], "offsets": [ [ 265, 289 ] ], "normalized": [] }, { "id": "PMID-19489226_T8", "type": "Cell", "text": [ "ECs" ], "offsets": [ [ 291, 294 ] ], "normalized": [] }, { "id": "PMID-19489226_T11", "type": "Cell", "text": [ "ECs" ], "offsets": [ [ 498, 501 ] ], "normalized": [] }, { "id": "PMID-19489226_T13", "type": "Cell", "text": [ "ECs" ], "offsets": [ [ 553, 556 ] ], "normalized": [] }, { "id": "PMID-19489226_T15", "type": "Cell", "text": [ "ECs" ], "offsets": [ [ 673, 676 ] ], "normalized": [] }, { "id": "PMID-19489226_T17", "type": "Cell", "text": [ "ECs" ], "offsets": [ [ 719, 722 ] ], "normalized": [] }, { "id": "PMID-19489226_T22", "type": "Cell", "text": [ "ECs" ], "offsets": [ [ 929, 932 ] ], "normalized": [] }, { "id": "PMID-19489226_T24", "type": "Cell", "text": [ "ECs" ], "offsets": [ [ 1016, 1019 ] ], "normalized": [] }, { "id": "PMID-19489226_T28", "type": "Cell", "text": [ "ECs" ], "offsets": [ [ 1152, 1155 ] ], "normalized": [] }, { "id": "PMID-19489226_T29", "type": "Cell", "text": [ "Cells" ], "offsets": [ [ 1189, 1194 ] ], "normalized": [] }, { "id": "PMID-19489226_T34", "type": "Cell", "text": [ "ECs" ], "offsets": [ [ 1324, 1327 ] ], "normalized": [] }, { "id": "PMID-19489226_T36", "type": "Cell", "text": [ "ECs" ], "offsets": [ [ 1394, 1397 ] ], "normalized": [] }, { "id": "PMID-19489226_T38", "type": "Cell", "text": [ "ECs" ], "offsets": [ [ 1476, 1479 ] ], "normalized": [] }, { "id": "PMID-19489226_T40", "type": "Cell", "text": [ "ECs" ], "offsets": [ [ 1577, 1580 ] ], "normalized": [] } ]

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[ { "id": "PMID-11912515__text", "type": "abstract", "text": [ "Upregulation of vascular endothelial growth factor receptors is associated with advanced neuroblastoma.\nBACKGROUND: Angiogenesis is essential for tumor growth and relies on the production of angiogenic factors. Vascular endothelial growth factor (VEGF) is a major regulator of angiogenesis that binds to tyrosine kinase receptors Flt-1 and KDR. The interaction of VEGF and its receptors at gene and protein levels in neuroblastoma remains widely unknown. METHODS: Tumor biopsy specimens and serum were obtained from 37 neuroblastoma patients; adrenal biopsy sections and sera of 7 normal children served as controls. Biopsy specimens were examined by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blotting; serum was analyzed by enzyme-linked immunosorbent assay (ELISA). VEGF-A(165), B, C, Flt-1, and KDR were analyzed. RESULTS: VEGF isoforms and its receptors' mRNA were expressed in neuroblastoma and control tissues. Whereas the ligands were increased in stages III and IV, the receptors were upregulated in stage III only. At protein level, VEGF-B and C, Flt-1, and KDR were not detectable in tissue lysates, whereas VEGF-A was increased in stages III and IV. Serum VEGF protein levels were upregulated in stage III. CONCLUSIONS: VEGF-A(165) is one of the major angiogenesis regulators among the ligands' family of VEGF, whereas its receptors KDR, and most probably Flt-1, may contribute to a poor prognosis (angiogenic) phenotype, as indicated by their upregulated MRNA levels in stage III neuroblastoma. VEGF-A(165) mainly contributes to increased serum VEGF levels and may serve as a diagnostic tool in advanced-stage neuroblastoma.\n" ], "offsets": [ [ 0, 1674 ] ] } ]

[ { "id": "PMID-11912515_T2", "type": "Cancer", "text": [ "neuroblastoma" ], "offsets": [ [ 89, 102 ] ], "normalized": [] }, { "id": "PMID-11912515_T3", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 146, 151 ] ], "normalized": [] }, { "id": "PMID-11912515_T9", "type": "Cancer", "text": [ "neuroblastoma" ], "offsets": [ [ 417, 430 ] ], "normalized": [] }, { "id": "PMID-11912515_T10", "type": "Cancer", "text": [ "Tumor biopsy specimens" ], "offsets": [ [ 464, 486 ] ], "normalized": [] }, { "id": "PMID-11912515_T11", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 491, 496 ] ], "normalized": [] }, { "id": "PMID-11912515_T12", "type": "Cancer", "text": [ "neuroblastoma" ], "offsets": [ [ 519, 532 ] ], "normalized": [] }, { "id": "PMID-11912515_T14", "type": "Multi-tissue_structure", "text": [ "adrenal biopsy sections" ], "offsets": [ [ 543, 566 ] ], "normalized": [] }, { "id": "PMID-11912515_T15", "type": "Organism_substance", "text": [ "sera" ], "offsets": [ [ 571, 575 ] ], "normalized": [] }, { "id": "PMID-11912515_T17", "type": "Cancer", "text": [ "Biopsy specimens" ], "offsets": [ [ 617, 633 ] ], "normalized": [] }, { "id": "PMID-11912515_T18", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 740, 745 ] ], "normalized": [] }, { "id": "PMID-11912515_T25", "type": "Cancer", "text": [ "neuroblastoma" ], "offsets": [ [ 919, 932 ] ], "normalized": [] }, { "id": "PMID-11912515_T26", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 945, 952 ] ], "normalized": [] }, { "id": "PMID-11912515_T31", "type": "Organism_substance", "text": [ "tissue lysates" ], "offsets": [ [ 1131, 1145 ] ], "normalized": [] }, { "id": "PMID-11912515_T33", "type": "Organism_substance", "text": [ "Serum" ], "offsets": [ [ 1198, 1203 ] ], "normalized": [] }, { "id": "PMID-11912515_T39", "type": "Cancer", "text": [ "stage III neuroblastoma" ], "offsets": [ [ 1519, 1542 ] ], "normalized": [] }, { "id": "PMID-11912515_T41", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 1588, 1593 ] ], "normalized": [] }, { "id": "PMID-11912515_T43", "type": "Cancer", "text": [ "neuroblastoma" ], "offsets": [ [ 1659, 1672 ] ], "normalized": [] } ]

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[ { "id": "PMID-18313522__text", "type": "abstract", "text": [ "Radiation retinopathy is treatable with anti-vascular endothelial growth factor bevacizumab (Avastin).\nPURPOSE: To report on bevacizumab treatment for radiation retinopathy affecting the macula. PATIENTS AND METHODS: Twenty-one patients with radiation retinopathy (edema, hemorrhages, capillary dropout, and neovascularization) and a subjective or objective loss of vision were treated. Treatment involved intravitreal injection of bevacizumab (1.25 mg in 0.05 mL) every 6-12 weeks. Treatment was discontinued at patient request or if there was no measurable response to therapy. Main outcome measures included best corrected visual acuity, ophthalmic examination, retinal photography, and angiography. RESULTS: Bevacizumab treatment was followed by reductions in retinal hemorrhage, exudation, and edema. Visual acuities were stable or improved in 86% (n=18). Three patients discontinued therapy. Each was legally blind before treatment (n=1), experienced little to no subjective improvement (n=2), or was poorly compliant (n=2). Three patients (14%) regained 2 or more lines of visual acuity. No ocular or systemic bevacizumab-related side effects were observed. CONCLUSIONS: Intravitreal bevacizumab can be used to treat radiation retinopathy. In most cases treatment was associated with decreased vascular leakage, stabilization, or improved vision. An anti-vascular endothelial growth factor strategy may reduce tissue damage associated with radiation vasculopathy and neuropathy.\n" ], "offsets": [ [ 0, 1486 ] ] } ]

[ { "id": "PMID-18313522_T5", "type": "Tissue", "text": [ "macula" ], "offsets": [ [ 187, 193 ] ], "normalized": [] }, { "id": "PMID-18313522_T7", "type": "Pathological_formation", "text": [ "edema" ], "offsets": [ [ 265, 270 ] ], "normalized": [] }, { "id": "PMID-18313522_T8", "type": "Tissue", "text": [ "capillary" ], "offsets": [ [ 285, 294 ] ], "normalized": [] }, { "id": "PMID-18313522_T11", "type": "Multi-tissue_structure", "text": [ "retinal" ], "offsets": [ [ 665, 672 ] ], "normalized": [] }, { "id": "PMID-18313522_T13", "type": "Multi-tissue_structure", "text": [ "retinal" ], "offsets": [ [ 764, 771 ] ], "normalized": [] }, { "id": "PMID-18313522_T14", "type": "Pathological_formation", "text": [ "edema" ], "offsets": [ [ 799, 804 ] ], "normalized": [] }, { "id": "PMID-18313522_T19", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 1301, 1309 ] ], "normalized": [] }, { "id": "PMID-18313522_T21", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 1417, 1423 ] ], "normalized": [] }, { "id": "PMID-18313522_T29", "type": "Organ", "text": [ "ocular" ], "offsets": [ [ 1098, 1104 ] ], "normalized": [] } ]

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[ { "id": "PMID-12869564__text", "type": "abstract", "text": [ "The role of organ vascularization and lipoplex-serum initial contact in intravenous murine lipofection.\nFollowing intravenous administration of cationic lipid-DNA complexes (lipoplexes) into mice, transfection (lipofection) occurs predominantly in the lungs. This was attributed to high entrapment of lipoplexes in the extended lung vascular tree. To determine whether lipofection in other organs could be enhanced by increasing the degree of vascularization, we used a transgenic mouse model with tissue-specific angiogenesis in liver. Tail vein injection of N-(1-(2,3-dioleoyloxy)propyl)-N,N,N-trimethylammonium chloride (DOTAP)/cholesterol lipoplexes resulted in increased lipoplex entrapment in hypervascularized liver but did not boost luciferase expression, suggesting that lipoplex delivery is not a sufficient condition for efficient organ lipofection. Because the intravenously injected lipoplexes migrated within seconds to lungs, we checked whether the effects of immediate contact with serum correlate with lung lipofection efficiency of different DOTAP-based formulations. Under conditions mimicking the injection environment, the lipoplex-serum interaction was strongly dependent on helper lipid and ionic strength: lipoplexes prepared in 150 mM NaCl or lipoplexes with high ( greater than 33 mol%) cholesterol were found to aggregate immediately. This aggregation process was irreversible and was inversely correlated with the percentage of lung cells that took up lipoplexes and with the efficiency of lipofection. No other structural changes in serum were observed for cholesterol-based lipoplexes. Dioleoyl phosphatidylethanolamine-based lipoplexes were found to give low expression, apparently because of an immediate loss of integrity in serum, without lipid-DNA dissociation. Our study suggests that efficient in vivo lipofection is the result of cross-talk between lipoplex composition, interaction with serum, hemodynamics, and target tissue \"susceptibility\" to transfection.\n" ], "offsets": [ [ 0, 1999 ] ] } ]

[ { "id": "PMID-12869564_T1", "type": "Organ", "text": [ "organ" ], "offsets": [ [ 12, 17 ] ], "normalized": [] }, { "id": "PMID-12869564_T3", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 47, 52 ] ], "normalized": [] }, { "id": "PMID-12869564_T4", "type": "Immaterial_anatomical_entity", "text": [ "intravenous" ], "offsets": [ [ 72, 83 ] ], "normalized": [] }, { "id": "PMID-12869564_T6", "type": "Immaterial_anatomical_entity", "text": [ "intravenous" ], "offsets": [ [ 114, 125 ] ], "normalized": [] }, { "id": "PMID-12869564_T10", "type": "Organ", "text": [ "lungs" ], "offsets": [ [ 252, 257 ] ], "normalized": [] }, { "id": "PMID-12869564_T12", "type": "Multi-tissue_structure", "text": [ "lung vascular tree" ], "offsets": [ [ 328, 346 ] ], "normalized": [] }, { "id": "PMID-12869564_T13", "type": "Organ", "text": [ "organs" ], "offsets": [ [ 390, 396 ] ], "normalized": [] }, { "id": "PMID-12869564_T15", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 498, 504 ] ], "normalized": [] }, { "id": "PMID-12869564_T16", "type": "Organ", "text": [ "liver" ], "offsets": [ [ 530, 535 ] ], "normalized": [] }, { "id": "PMID-12869564_T17", "type": "Multi-tissue_structure", "text": [ "Tail vein" ], "offsets": [ [ 537, 546 ] ], "normalized": [] }, { "id": "PMID-12869564_T20", "type": "Organ", "text": [ "liver" ], "offsets": [ [ 717, 722 ] ], "normalized": [] }, { "id": "PMID-12869564_T23", "type": "Organ", "text": [ "organ" ], "offsets": [ [ 842, 847 ] ], "normalized": [] }, { "id": "PMID-12869564_T24", "type": "Immaterial_anatomical_entity", "text": [ "intravenously" ], "offsets": [ [ 873, 886 ] ], "normalized": [] }, { "id": "PMID-12869564_T26", "type": "Organ", "text": [ "lungs" ], "offsets": [ [ 934, 939 ] ], "normalized": [] }, { "id": "PMID-12869564_T27", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 998, 1003 ] ], "normalized": [] }, { "id": "PMID-12869564_T28", "type": "Organ", "text": [ "lung" ], "offsets": [ [ 1019, 1023 ] ], "normalized": [] }, { "id": "PMID-12869564_T31", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 1153, 1158 ] ], "normalized": [] }, { "id": "PMID-12869564_T36", "type": "Cell", "text": [ "lung cells" ], "offsets": [ [ 1456, 1466 ] ], "normalized": [] }, { "id": "PMID-12869564_T38", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 1562, 1567 ] ], "normalized": [] }, { "id": "PMID-12869564_T41", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 1758, 1763 ] ], "normalized": [] }, { "id": "PMID-12869564_T44", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 1926, 1931 ] ], "normalized": [] }, { "id": "PMID-12869564_T45", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 1958, 1964 ] ], "normalized": [] } ]

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[ { "id": "PMID-19406993__text", "type": "abstract", "text": [ "Erbb2 suppresses DNA damage-induced checkpoint activation and UV-induced mouse skin tumorigenesis. \nThe Erbb2 receptor is activated by UV irradiation, the primary cause of non-melanoma skin cancer. We hypothesized that Erbb2 activation contributes to UV-induced skin tumorigenesis by suppressing cell cycle arrest. Consistent with this hypothesis, inhibition of Erbb2 in v-ras(Ha) transgenic mice before UV exposure resulted in both 56% fewer skin tumors and tumors that were 70% smaller. Inhibition of the UV-induced activation of Erbb2 also resulted in milder epidermal hyperplasia, S-phase accumulation, and decreased levels of the cell cycle regulator Cdc25a, suggesting altered cell cycle regulation on inhibition of Erbb2. Further investigation using inhibition or genetic deletion of Erbb2 in vitro revealed reduced Cdc25a levels and increased S-phase arrest in UV-irradiated cells lacking Erbb2 activity. Ectopic expression of Cdc25a prevented UV-induced S-phase arrest in keratinocytes lacking Erbb2 activity, demonstrating that maintenance of Cdc25a by Erbb2 suppresses cell cycle arrest. Examination of checkpoint pathway activation upstream of Cdc25a revealed Erbb2 activation did not alter Ataxia Telangiectasia and Rad3-related/Ataxia Telangiectasia Mutated activity but increased inhibitory phosphorylation of Chk1-Ser(280). Since Akt phosphorylates Chk1-Ser(280), the effect of Erbb2 on phosphatidyl inositol-3-kinase (PI3K)/Akt signaling during UV-induced cell cycle arrest was determined. Erbb2 ablation reduced the UV-induced activation of PI3K while inhibition of PI3K/Akt increased UV-induced S-phase arrest. Thus, UV-induced Erbb2 activation increases skin tumorigenesis through inhibitory phosphorylation of Chk1, Cdc25a maintenance, and suppression of S-phase arrest via a PI3K/Akt-dependent mechanism.\n" ], "offsets": [ [ 0, 1827 ] ] } ]

[ { "id": "PMID-19406993_T4", "type": "Organ", "text": [ "skin" ], "offsets": [ [ 79, 83 ] ], "normalized": [] }, { "id": "PMID-19406993_T6", "type": "Cancer", "text": [ "non-melanoma skin cancer" ], "offsets": [ [ 172, 196 ] ], "normalized": [] }, { "id": "PMID-19406993_T8", "type": "Organ", "text": [ "skin" ], "offsets": [ [ 262, 266 ] ], "normalized": [] }, { "id": "PMID-19406993_T9", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 296, 300 ] ], "normalized": [] }, { "id": "PMID-19406993_T14", "type": "Cancer", "text": [ "skin tumors" ], "offsets": [ [ 443, 454 ] ], "normalized": [] }, { "id": "PMID-19406993_T15", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 459, 465 ] ], "normalized": [] }, { "id": "PMID-19406993_T17", "type": "Pathological_formation", "text": [ "epidermal hyperplasia" ], "offsets": [ [ 562, 583 ] ], "normalized": [] }, { "id": "PMID-19406993_T18", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 635, 639 ] ], "normalized": [] }, { "id": "PMID-19406993_T20", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 683, 687 ] ], "normalized": [] }, { "id": "PMID-19406993_T24", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 883, 888 ] ], "normalized": [] }, { "id": "PMID-19406993_T27", "type": "Cell", "text": [ "keratinocytes" ], "offsets": [ [ 981, 994 ] ], "normalized": [] }, { "id": "PMID-19406993_T31", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1080, 1084 ] ], "normalized": [] }, { "id": "PMID-19406993_T44", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1473, 1477 ] ], "normalized": [] }, { "id": "PMID-19406993_T50", "type": "Organ", "text": [ "skin" ], "offsets": [ [ 1674, 1678 ] ], "normalized": [] } ]

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[ { "id": "PMID-14500555__text", "type": "abstract", "text": [ "Transcriptional and post-translation regulation of the Tie1 receptor by fluid shear stress changes in vascular endothelial cells.\nThe interaction between the vascular endothelium and hemodynamic forces (and more specifically, fluid shear stress), induced by the flow of blood, plays a major role in vascular remodeling and in new blood vessels formation via a process termed arteriogenesis. Tie1 is an orphan tyrosine kinase receptor expressed almost exclusively in endothelial cells and is required for normal vascular development and maintenance. The present study demonstrates that Tie1 expression is rapidly down-regulated in endothelial cells exposed to shear stress, and more so to shear stress changes. This down-regulation is accompanied by a rapid cleavage of Tie1 and binding of the cleaved Tie1 45 kDa endodomain to Tie2. The rapid cleavage of Tie1 is followed by a transcriptional down-regulation in response to shear stress. The activity of the Tie1 promoter is suppressed by shear stress and by tumor necrosis factor alpha. Shear stress-induced transcriptional suppression of Tie1 is mediated by a negative shear stress response element, localized in a region of 250 bp within the promoter. The rapid down-regulation of Tie1 by shear stress changes and its rapid binding to Tie2 may be required for destabilization of endothelial cells in order to initiate the process of vascular restructuring.\n" ], "offsets": [ [ 0, 1410 ] ] } ]

[ { "id": "PMID-14500555_T2", "type": "Cell", "text": [ "vascular endothelial cells" ], "offsets": [ [ 102, 128 ] ], "normalized": [] }, { "id": "PMID-14500555_T3", "type": "Tissue", "text": [ "vascular endothelium" ], "offsets": [ [ 158, 178 ] ], "normalized": [] }, { "id": "PMID-14500555_T4", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 270, 275 ] ], "normalized": [] }, { "id": "PMID-14500555_T5", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 299, 307 ] ], "normalized": [] }, { "id": "PMID-14500555_T6", "type": "Multi-tissue_structure", "text": [ "blood vessels" ], "offsets": [ [ 330, 343 ] ], "normalized": [] }, { "id": "PMID-14500555_T8", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 466, 483 ] ], "normalized": [] }, { "id": "PMID-14500555_T9", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 511, 519 ] ], "normalized": [] }, { "id": "PMID-14500555_T11", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 630, 647 ] ], "normalized": [] }, { "id": "PMID-14500555_T21", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 1332, 1349 ] ], "normalized": [] }, { "id": "PMID-14500555_T22", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 1386, 1394 ] ], "normalized": [] } ]

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[ { "id": "PMID-21416173__text", "type": "abstract", "text": [ "Predictive value of serum carbohydrate antigen 19-9 in malignant intraductal papillary mucinous neoplasms.\nBACKGROUND:\nThe goal of the present study was to evaluate the predictive value of serum carbohydrate antigen 19-9 (CA 19-9) in the diagnosis of malignant intraductal papillary mucinous neoplasms of pancreas (IPMNs).\nMETHODS:\nEighty-six patients with pathological diagnosis of IPMNs in Zhongshan Hospital between March 1999 and November 2008 were retrospectively reviewed. Data reflecting clinical characteristics, tumor marker level, and prognosis were collected. The potential predictive value of CA 19-9 was analyzed by receiver operating characteristic (ROC) curve.\nRESULTS:\nEighty-six consecutive patients with IPMNs all underwent surgical intervention. A high level of CA 19-9 or carcinoembryonic antigen (CEA) was associated with more advanced stage of malignant IPMNs. Carbohydrate antigen 19-9 was significant for judging malignant IPMNs in the binary logistic regression model (p=0.047). The hazard ratio was 1.014, whose 95.0% confidence interval was 0.91-1.028. Receiver operating characteristic analysis showed that the serum CA 19-9 level had good predictive value for malignant or invasive IPMNs, postoperative survival, and disease-specific recurrence. The area under the curve (AUC) was 0.856, 0.893, 0.815, and 0.857 (p<0.05), respectively. According to the follow-up, mean survival time for groups with CA 19-9>63.60 U/ml was dramatically shorter than that for groups with CA 19-9<=63.60 U/ml (57.38+/-2.85 versus 29.24+/-5.82 [months]; p<0.01).\nCONCLUSIONS:\nSerum CA 19-9 level has good predictive value for malignant or invasive IPMNs. Patients with CA 19-9 > 63.60 U/ml had poor postoperative prognosis in IPMNs. Preoperative abnormal serum CA 19-9 might be predictive for an aggressive surgical intervention in IPMNs.\n" ], "offsets": [ [ 0, 1847 ] ] } ]

[ { "id": "PMID-21416173_T1", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 20, 25 ] ], "normalized": [] }, { "id": "PMID-21416173_T2", "type": "Cancer", "text": [ "malignant intraductal papillary mucinous neoplasms" ], "offsets": [ [ 55, 105 ] ], "normalized": [] }, { "id": "PMID-21416173_T3", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 189, 194 ] ], "normalized": [] }, { "id": "PMID-21416173_T4", "type": "Cancer", "text": [ "malignant intraductal papillary mucinous neoplasms" ], "offsets": [ [ 251, 301 ] ], "normalized": [] }, { "id": "PMID-21416173_T5", "type": "Organ", "text": [ "pancreas" ], "offsets": [ [ 305, 313 ] ], "normalized": [] }, { "id": "PMID-21416173_T6", "type": "Cancer", "text": [ "IPMNs" ], "offsets": [ [ 315, 320 ] ], "normalized": [] }, { "id": "PMID-21416173_T7", "type": "Cancer", "text": [ "IPMNs" ], "offsets": [ [ 383, 388 ] ], "normalized": [] }, { "id": "PMID-21416173_T8", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 521, 526 ] ], "normalized": [] }, { "id": "PMID-21416173_T9", "type": "Cancer", "text": [ "malignant IPMNs" ], "offsets": [ [ 866, 881 ] ], "normalized": [] }, { "id": "PMID-21416173_T10", "type": "Cancer", "text": [ "malignant IPMNs" ], "offsets": [ [ 937, 952 ] ], "normalized": [] }, { "id": "PMID-21416173_T11", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 1139, 1144 ] ], "normalized": [] }, { "id": "PMID-21416173_T12", "type": "Cancer", "text": [ "invasive IPMNs" ], "offsets": [ [ 1202, 1216 ] ], "normalized": [] }, { "id": "PMID-21416173_T18", "type": "Cancer", "text": [ "IPMNs" ], "offsets": [ [ 722, 727 ] ], "normalized": [] }, { "id": "PMID-21416173_T13", "type": "Organism_substance", "text": [ "Serum" ], "offsets": [ [ 1584, 1589 ] ], "normalized": [] }, { "id": "PMID-21416173_T14", "type": "Cancer", "text": [ "invasive IPMNs" ], "offsets": [ [ 1647, 1661 ] ], "normalized": [] }, { "id": "PMID-21416173_T15", "type": "Cancer", "text": [ "IPMNs" ], "offsets": [ [ 1734, 1739 ] ], "normalized": [] }, { "id": "PMID-21416173_T16", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 1763, 1768 ] ], "normalized": [] }, { "id": "PMID-21416173_T17", "type": "Cancer", "text": [ "IPMNs" ], "offsets": [ [ 1840, 1845 ] ], "normalized": [] }, { "id": "PMID-21416173_T20", "type": "Cancer", "text": [ "malignant" ], "offsets": [ [ 1189, 1198 ] ], "normalized": [] }, { "id": "PMID-21416173_T21", "type": "Cancer", "text": [ "malignant" ], "offsets": [ [ 1634, 1643 ] ], "normalized": [] } ]

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[ { "id": "PMC-2924302-sec-08__text", "type": "sec", "text": [ "Intervention\nPatients' initial introduction to the Wrist Extension Dynasplint (WED) system, [Dynasplint Systems, Inc., Severna Park, MD, USA] included customized fitting (wrist length, width, and girth so that the force and counter force straps could be properly aligned) and training on donning and doffing of the device. (See figure 1.) Verbal and written instructions were provided throughout the duration of treatment for safety, general wear and care, and tension setting goals based on patient tolerance.\nFigure 1\nWrist Extension Dynasplint.\nEach patient initially wore the WED for 4-6 continuous hours at an initial tension setting of #2 (0.1 foot pounds of torque). This duration was for acclimatization to the system; then patients were instructed to wear the WED system at night while sleeping for 6-8 hours of continuous wear. After each patient was comfortable wearing the unit for one week at tension level #2, they were instructed to increase the tension level to #3 (0.3 ft lbs.) and make continual increases every two weeks. If prolonged soreness followed a session (soreness for more than 15 minutes) the patient was instructed to decrease the tension one half a setting for two days until they were comfortable wearing it for 6-8 hours at the new tension setting. The majority of all patients reached level #5 (0.8 foot pounds of torque) by the end of two months. All range of motion measurements were recorded by the prescribing clinician.\n" ], "offsets": [ [ 0, 1459 ] ] } ]

[ { "id": "PMC-2924302-sec-08_T1", "type": "Organism_subdivision", "text": [ "Wrist" ], "offsets": [ [ 51, 56 ] ], "normalized": [] }, { "id": "PMC-2924302-sec-08_T2", "type": "Organism_subdivision", "text": [ "wrist" ], "offsets": [ [ 171, 176 ] ], "normalized": [] }, { "id": "PMC-2924302-sec-08_T3", "type": "Organism_subdivision", "text": [ "Wrist" ], "offsets": [ [ 520, 525 ] ], "normalized": [] } ]

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[ { "id": "PMC-1681490-sec-01__text", "type": "sec", "text": [ "Figures and Tables\nFigure 1\nModular crosstalking in synthetic gene networks. A promoter with binding sites for lambda cI dimers (OR1 and OR2) and for the lac repressor (Olac) controls the production of the lac repressor (encoded by lacI) in module 1 and lambda cI (encoded by cI) in module 2. The lac repressor and lambda cI dimers are represented by blue ellipsoids and red circles, respectively. When the two modules are put together, two pairs of lambda cI dimers bound at different operators can loop DNA and octamerize, forming a tetramer of dimers.\n" ], "offsets": [ [ 0, 555 ] ] } ]

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[ { "id": "PMID-18202228__text", "type": "abstract", "text": [ "RUNX1 DNA-binding mutations and RUNX1-PRDM16 cryptic fusions in BCR-ABL+ leukemias are frequently associated with secondary trisomy 21 and may contribute to clonal evolution and imatinib resistance. \nAcquired molecular abnormalities (mutations or chromosomal translocations) of the RUNX1 transcription factor gene are frequent in acute myeloblastic leukemias (AMLs) and in therapy-related myelodysplastic syndromes, but rarely in acute lymphoblastic leukemias (ALLs) and chronic myelogenous leukemias (CMLs). Among 18 BCR-ABL+ leukemias presenting acquired trisomy of chromosome 21, we report a high frequency (33%) of recurrent point mutations (4 in myeloid blast crisis [BC] CML and one in chronic phase CML) within the DNA-binding region of RUNX1. We did not found any mutation in de novo BCR-ABL+ ALLs or lymphoid BC CML. Emergence of the RUNX1 mutations was detected at diagnosis or before the acquisition of trisomy 21 during disease progression. In addition, we also report a high frequency of cryptic chromosomal RUNX1 translocation to a novel recently described gene partner, PRDM16 on chromosome 1p36, for 3 (21.4%) of 14 investigated patients: 2 myeloid BC CMLs and, for the first time, 1 therapy-related BCR-ABL+ ALL. Two patients presented both RUNX1 mutations and RUNX1-PRDM16 fusion. These events are associated with a short survival and support the concept of a cooperative effect of BCR-ABL with molecular RUNX1 abnormalities on the differentiation arrest phenotype observed during progression of CML and in BCR-ABL+ ALL.\n" ], "offsets": [ [ 0, 1539 ] ] } ]

[ { "id": "PMID-18202228_T5", "type": "Cancer", "text": [ "BCR-ABL+ leukemias" ], "offsets": [ [ 64, 82 ] ], "normalized": [] }, { "id": "PMID-18202228_T8", "type": "Cellular_component", "text": [ "21" ], "offsets": [ [ 132, 134 ] ], "normalized": [] }, { "id": "PMID-18202228_T9", "type": "Cell", "text": [ "clonal" ], "offsets": [ [ 157, 163 ] ], "normalized": [] }, { "id": "PMID-18202228_T11", "type": "Cellular_component", "text": [ "chromosomal" ], "offsets": [ [ 247, 258 ] ], "normalized": [] }, { "id": "PMID-18202228_T13", "type": "Cancer", "text": [ "acute myeloblastic leukemias" ], "offsets": [ [ 330, 358 ] ], "normalized": [] }, { "id": "PMID-18202228_T14", "type": "Cancer", "text": [ "AMLs" ], "offsets": [ [ 360, 364 ] ], "normalized": [] }, { "id": "PMID-18202228_T15", "type": "Cancer", "text": [ "acute lymphoblastic leukemias" ], "offsets": [ [ 430, 459 ] ], "normalized": [] }, { "id": "PMID-18202228_T16", "type": "Cancer", "text": [ "ALLs" ], "offsets": [ [ 461, 465 ] ], "normalized": [] }, { "id": "PMID-18202228_T17", "type": "Cancer", "text": [ "chronic myelogenous leukemias" ], "offsets": [ [ 471, 500 ] ], "normalized": [] }, { "id": "PMID-18202228_T18", "type": "Cancer", "text": [ "CMLs" ], "offsets": [ [ 502, 506 ] ], "normalized": [] }, { "id": "PMID-18202228_T19", "type": "Cancer", "text": [ "BCR-ABL+ leukemias" ], "offsets": [ [ 518, 536 ] ], "normalized": [] }, { "id": "PMID-18202228_T22", "type": "Cellular_component", "text": [ "chromosome 21" ], "offsets": [ [ 568, 581 ] ], "normalized": [] }, { "id": "PMID-18202228_T23", "type": "Cancer", "text": [ "myeloid blast crisis [BC] CML" ], "offsets": [ [ 651, 680 ] ], "normalized": [] }, { "id": "PMID-18202228_T24", "type": "Cancer", "text": [ "chronic phase CML" ], "offsets": [ [ 692, 709 ] ], "normalized": [] }, { "id": "PMID-18202228_T27", "type": "Cancer", "text": [ "BCR-ABL+ ALLs" ], "offsets": [ [ 792, 805 ] ], "normalized": [] }, { "id": "PMID-18202228_T30", "type": "Cancer", "text": [ "lymphoid BC CML" ], "offsets": [ [ 809, 824 ] ], "normalized": [] }, { "id": "PMID-18202228_T32", "type": "Cellular_component", "text": [ "21" ], "offsets": [ [ 922, 924 ] ], "normalized": [] }, { "id": "PMID-18202228_T33", "type": "Cellular_component", "text": [ "chromosomal" ], "offsets": [ [ 1009, 1020 ] ], "normalized": [] }, { "id": "PMID-18202228_T36", "type": "Cellular_component", "text": [ "chromosome 1p36" ], "offsets": [ [ 1095, 1110 ] ], "normalized": [] }, { "id": "PMID-18202228_T38", "type": "Cancer", "text": [ "myeloid BC CMLs" ], "offsets": [ [ 1157, 1172 ] ], "normalized": [] }, { "id": "PMID-18202228_T39", "type": "Cancer", "text": [ "BCR-ABL+ ALL" ], "offsets": [ [ 1216, 1228 ] ], "normalized": [] }, { "id": "PMID-18202228_T49", "type": "Cancer", "text": [ "CML" ], "offsets": [ [ 1514, 1517 ] ], "normalized": [] }, { "id": "PMID-18202228_T50", "type": "Cancer", "text": [ "BCR-ABL+ ALL" ], "offsets": [ [ 1525, 1537 ] ], "normalized": [] } ]

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[ { "id": "PMC-2374931-sec-01__text", "type": "sec", "text": [ "Aim\nThis study reports the results of a large prospective single-blinded clinical trial of 3 SSRI (paroxetine, fluoxetine and escitalopram) in PE using a validated questionnaire.\n" ], "offsets": [ [ 0, 179 ] ] } ]

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[ { "id": "PMC-2811192-caption-03__text", "type": "caption", "text": [ "Electrostatic interaction energies between the SNARE complex and fusing membranes.\n(A) Schematic diagram and definitions of intermolecular interaction energies presented in (B) and (C). In (A) through (C), only the SNARE core complex is considered. Interaction free energies are calculated for (B) a series of SNARE/membrane distances and (C) different membrane lipid compositions. Arrow in (B) indicates the most physiologically relevant distance when the closest points between SNARE and membranes are 3 A, the thickness of a layer of water.[19] In (D) through (F), TMDs of VAMP and syntaxin are present and embedded in membranes. Furthermore, the C-terminus of the SNARE motif is partially unraveled into individual alpha-helices by molecular dynamics simulations to represent trans-SNARE complex. Interaction free energies are then calculated for (E) a series of SNARE motif C-terminus separation distances and (F) different lipid compositions of the membranes. Conclusions drawn from both groups of studies are essentially the same. V (circles): Interaction energies between the SNARE complex and the v-membrane. T (squares): Interaction energies between SNARE and the t-membrane. VT (triangles): Interaction energies between the v- and the t-membranes if the SNARE complex were extracted.\n" ], "offsets": [ [ 0, 1295 ] ] } ]

[ { "id": "PMC-2811192-caption-03_T1", "type": "Cellular_component", "text": [ "membranes" ], "offsets": [ [ 72, 81 ] ], "normalized": [] }, { "id": "PMC-2811192-caption-03_T2", "type": "Cellular_component", "text": [ "membrane" ], "offsets": [ [ 316, 324 ] ], "normalized": [] }, { "id": "PMC-2811192-caption-03_T3", "type": "Cellular_component", "text": [ "membrane" ], "offsets": [ [ 353, 361 ] ], "normalized": [] }, { "id": "PMC-2811192-caption-03_T4", "type": "Cellular_component", "text": [ "membranes" ], "offsets": [ [ 490, 499 ] ], "normalized": [] }, { "id": "PMC-2811192-caption-03_T5", "type": "Cellular_component", "text": [ "membranes" ], "offsets": [ [ 622, 631 ] ], "normalized": [] }, { "id": "PMC-2811192-caption-03_T6", "type": "Cellular_component", "text": [ "membranes" ], "offsets": [ [ 955, 964 ] ], "normalized": [] }, { "id": "PMC-2811192-caption-03_T7", "type": "Cellular_component", "text": [ "v-membrane" ], "offsets": [ [ 1106, 1116 ] ], "normalized": [] }, { "id": "PMC-2811192-caption-03_T8", "type": "Cellular_component", "text": [ "t-membrane" ], "offsets": [ [ 1174, 1184 ] ], "normalized": [] }, { "id": "PMC-2811192-caption-03_T9", "type": "Cellular_component", "text": [ "v-" ], "offsets": [ [ 1235, 1237 ] ], "normalized": [] }, { "id": "PMC-2811192-caption-03_T10", "type": "Cellular_component", "text": [ "t-membranes" ], "offsets": [ [ 1246, 1257 ] ], "normalized": [] } ]

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[ { "id": "PMC-2074286-sec-01__text", "type": "sec", "text": [ "Images\nFigure 1\n" ], "offsets": [ [ 0, 16 ] ] } ]

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[ { "id": "PMC-3194540-sec-04__text", "type": "sec", "text": [ "Conclusions\nThis is the first prospective evaluation of parents' preferences in newly diagnosed juvenile idiopathic arthritis patients participating in the BeSt for Kids trial. Within the limitations of the small amounts, patients clearly preferred initial combination therapy with etanercept and disliked taking prednisone. After actual exposure and follow up, this questionnaire will be repeated to see if preferences remain the same.\n" ], "offsets": [ [ 0, 437 ] ] } ]

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[ { "id": "PMID-20525074__text", "type": "abstract", "text": [ "Acoustic trauma evokes hyperactivity and changes in gene expression in guinea-pig auditory brainstem.\nHearing loss from acoustic trauma is a risk factor for tinnitus. Animal models using acoustic trauma have demonstrated hyperactivity in central auditory pathways, which has been suggested as a substrate for tinnitus. We used a guinea-pig model of unilateral acoustic trauma. Within the same animals, measurements of peripheral hearing loss, spontaneous activity of single neurons in the inferior colliculus and gene expression in cochlear nucleus and inferior colliculus were combined, acutely and after recovery from acoustic trauma. Genes investigated related to inhibitory (GABA-A receptor subunit alpha 1; glycine receptor subunit alpha 1) and excitatory neurotransmission (glutamate decarboxylase 1; glutamate receptor AMPA subunit alpha 2; glutamate receptor NMDA subunit 1), regulation of transmitter release (member of RAB family of small GTPase; RAB3 GTPase activating protein subunit 1) and neuronal excitability (potassium channel subfamily K member 15). Acoustic trauma resulted in unilateral hearing loss and hyperactivity bilaterally in inferior colliculus. Changes in expression of different mRNAs were observed in ipsilateral cochlear nucleus and in ipsi- and contralateral inferior colliculus, immediately after acoustic trauma, and after 2 and 4 weeks' recovery. Gene expression was generally reduced immediately after trauma, followed by a return to near normal levels or over-expression as recovery time increased. Different mechanisms appear to underlie the spontaneous hyperactivity observed. There is evidence of down-regulation of genes associated with neuronal inhibition in the contralateral inferior colliculus, whereas in ipsilateral cochlear nucleus, competing actions of inhibitory and excitatory systems seem to play a major role in determining overall excitability.\n" ], "offsets": [ [ 0, 1900 ] ] } ]

[ { "id": "PMID-20525074_T1", "type": "Multi-tissue_structure", "text": [ "brainstem" ], "offsets": [ [ 91, 100 ] ], "normalized": [] }, { "id": "PMID-20525074_T2", "type": "Cell", "text": [ "neurons" ], "offsets": [ [ 474, 481 ] ], "normalized": [] }, { "id": "PMID-20525074_T3", "type": "Multi-tissue_structure", "text": [ "cochlear nucleus" ], "offsets": [ [ 532, 548 ] ], "normalized": [] }, { "id": "PMID-20525074_T4", "type": "Multi-tissue_structure", "text": [ "inferior colliculus" ], "offsets": [ [ 489, 508 ] ], "normalized": [] }, { "id": "PMID-20525074_T5", "type": "Multi-tissue_structure", "text": [ "inferior colliculus" ], "offsets": [ [ 553, 572 ] ], "normalized": [] }, { "id": "PMID-20525074_T6", "type": "Cell", "text": [ "neuronal" ], "offsets": [ [ 1003, 1011 ] ], "normalized": [] }, { "id": "PMID-20525074_T7", "type": "Multi-tissue_structure", "text": [ "inferior colliculus" ], "offsets": [ [ 1153, 1172 ] ], "normalized": [] }, { "id": "PMID-20525074_T8", "type": "Multi-tissue_structure", "text": [ "cochlear nucleus" ], "offsets": [ [ 1244, 1260 ] ], "normalized": [] }, { "id": "PMID-20525074_T9", "type": "Multi-tissue_structure", "text": [ "inferior colliculus" ], "offsets": [ [ 1292, 1311 ] ], "normalized": [] }, { "id": "PMID-20525074_T10", "type": "Cell", "text": [ "neuronal" ], "offsets": [ [ 1679, 1687 ] ], "normalized": [] }, { "id": "PMID-20525074_T11", "type": "Multi-tissue_structure", "text": [ "inferior colliculus" ], "offsets": [ [ 1720, 1739 ] ], "normalized": [] }, { "id": "PMID-20525074_T12", "type": "Multi-tissue_structure", "text": [ "cochlear nucleus" ], "offsets": [ [ 1764, 1780 ] ], "normalized": [] } ]

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[ { "id": "PMC-2259298-sec-18__text", "type": "sec", "text": [ "Authors' contributions\nAll authors contributed to the development of the methodology. CY and NZ led method conceptualization and prepared the original draft, which was revised by JR. CY and VD performed most implementations. All authors read and approved the final manuscript.\n" ], "offsets": [ [ 0, 277 ] ] } ]

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