tbuckley/cabot-search huggingface dataset:
Association of ovarian Malignancy With Expression of Paltelet-Derived Endothelial Cell Growth Factor
Authors: K. Reynolds, F. Farzaneh, W. P. Collins, S. Campbell, T. H. Bourne, F. Lawton, A. Moghaddam, A. L. Harris, R. Bicknell
Journal: JNCI Journal of the National Cancer Institute (1994)

At the present time, the pathogenesis of ovarian cancer remains poorly understood, with invasive diagnosis and ineffective treatment for women with the disease. Despite scientific and medical advances in oncology, the overall 5-year survival rate of 30% for ovarian cancer patients has not changed in 20 years. An understanding of the angiogenic process as it occurs in ovarian cancer would not only increase our knowledge of the pathogenesis of this cancer but also might offer novel opportunities for therapeutic intervention.Our aim was to study the expression of messenger RNA (mRNA) coding for four putative angiogenic factors in normal ovaries and benign and malignant ovarian tumors: platelet-derived endothelial cell growth factor (thymidine phosphorylase), vascular endothelial growth factor, basic fibroblast growth factor, and transforming growth factor-beta 1.Four normal ovaries and 25 tumors (seven benign, one of borderline malignancy, and 17 malignant) were collected from 29 patients during elective oophorectomy. The site of sampling (areas of high-velocity blood flow) was directed by transvaginal color Doppler imaging performed within 24 hours of the surgery. Increased blood flow within the tissues was demonstrated by the presence of color (i.e., the velocity was > 7 cm/s) and, together with a pulsatile index of less than 1.0, constituted a positive scanning result. In scan-positive tissues, the area of maximum blood flow was chosen. In scan-negative tissues, a solid area was chosen in complex lesions, or the cyst wall was chosen in simple lesions. Ovarian RNA was subsequently extracted from areas of high-velocity flow (i.e., tissues with a positive scanning result) or from solid areas or septa in tissues with a negative scanning result. A ribonuclease protection assay was used to assess the expression of mRNA coding for the four angiogenic factors.Two normal ovaries (containing a corpus luteum) and one benign and 17 malignant tumors (plus the borderline) gave a positive scanning result. There was a significant difference between the expression of mRNA for platelet-derived endothelial cell growth factor between scan-positive and scan-negative tissues (P < .001) and between benign and malignant tumors (P < .001).Areas of high blood velocity in ovarian tumors are associated with increased expression of platelet-derived endothelial cell growth factor.Drugs that affect the angiogenic activity of platelet-derived endothelial cell growth factor offer a potential route for therapeutic intervention.
Retroperitoneal sarcomas: patterns of care in advanced stages, prognostic factors and focus on main histological subtypes: a multicenter analysis of the French Sarcoma Group
Authors: M. Toulmonde, S. Bonvalot, I. Ray-Coquard, E. Stoeckle, O. Riou, N. Isambert, E. Bompas, N. Penel, C. Delcambre-Lair, E. Saada, A. Lecesne, C. Le Péchoux, J.Y. Blay, S. Piperno-Neumann, C. Chevreau, J.O. Bay, V. Brouste, P. Terrier, D. Ranchère-Vince, A. Neuville, A. Italiano
Journal: Annals of Oncology (2014)

BackgroundRetroperitoneal sarcomas (RPS) are heterogeneous. Advanced stages include unresectable locoregional (LR) disease, abdominal sarcomatosis and distant metastasis. There is no available report assessing palliative chemotherapy in advanced RPS. This study analyzes management and outcome in a large cohort of patients with advanced RPS, considering main histological subtypes separately.Patients and methodsWe conducted a retrospective analysis of adult patients diagnosed with a RPS between 1 January 1988 and 31 December 2008 across 12 centers of the French Sarcoma Group. All cases were centrally reviewed by an expert pathologist.ResultsFive-hundred eighty-six patients were included, 299 patients received palliative chemotherapy, with a median of two lines (range 0–8). Fifty patients underwent palliative surgery. Two hundred fifty-five patients (85%) were assessable for response after first line of chemotherapy. Among them, 69 patients (27%) had progressive disease, 145 (57%) had stable disease, 37 (14.5%) had partial response and 4 (1.5%) complete response. Median time from first line of palliative chemotherapy to progression was 5.9 months [4.9–7.3] and median overall survival (OS), 15.8 months [13–18]. In multivariate analysis, prognosis factors independently associated with poor OS were male gender, performance status (PS) >1 and grade >1. There was no difference according to stage of disease. Palliative surgery did not appear to add any survival benefit.ConclusionThese results emphasize the scarcity of available options for RPS in the advanced setting and the urgent need to develop new strategies. Patients with good PS should be included in clinical trials and best supportive care should be considered in those with poor PS.
Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk
Authors: Malcolm G Dunlop, Sara E Dobbins, Susan Mary Farrington, Angela M Jones, Claire Palles, Nicola Whiffin, Albert Tenesa, Sarah Spain, Peter Broderick, Li-Yin Ooi, Enric Domingo, Claire Smillie, Marc Henrion, Matthew Frampton, Lynn Martin, Graeme Grimes, Maggie Gorman, Colin Semple, Yusanne P Ma, Ella Barclay, James Prendergast, Jean-Baptiste Cazier, Bianca Olver, Steven Penegar, Steven Lubbe, Ian Chander, Luis G Carvajal-Carmona, Stephane Ballereau, Amy Lloyd, Jayaram Vijayakrishnan, Lina Zgaga, Igor Rudan, Evropi Theodoratou, John M Starr, Ian Deary, Iva Kirac, Dujo Kovacević, Lauri A Aaltonen, Laura Renkonen-Sinisalo, Jukka-Pekka Mecklin, Koichi Matsuda, Yusuke Nakamura, Yukinori Okada, Steven Gallinger, David J Duggan, David Conti, Polly Newcomb, John Hopper, Mark A Jenkins, Fredrick Schumacher, Graham Casey, Douglas Easton, Mitul Shah, Paul Pharoah, Annika Lindblom, Tao Liu, Christopher G Smith, Hannah West, Jeremy P Cheadle, Rachel Midgley, David J Kerr, Harry Campbell, Ian P Tomlinson, Richard S Houlston
Journal: Nature Genetics (2012)
Diet Shapes the Evolution of the Vertebrate Bitter Taste Receptor Gene Repertoire
Authors: Diyan Li, Jianzhi Zhang
Journal: Molecular Biology and Evolution (2013)

Vertebrate Tas2r taste receptors bind to bitter compounds, which are typically poisonous, to elicit bitter sensation to prevent the ingestion of toxins. Previous studies noted a marked variation in the number of Tas2r genes among species, but the underlying cause is unclear. To address this question, we compile the Tas2r gene repertoires from 41 mammals, 4 birds, 2 reptiles, 1 amphibian, and 6 fishes. The number of intact Tas2r genes varies from 0 in the bottlenose dolphin to 51 in the Western clawed frog, with numerous expansions and contractions of the gene family throughout vertebrates, especially among tetrapods. The Tas2r gene number in a species correlates with the fraction of plants in its diet. Because plant tissues contain more toxic compounds than animal tissues do, our observation supports the hypothesis that dietary toxins are a major selective force shaping the diversity of the Tas2r repertoire.
Human CD68 promoter GFP transgenic mice allow analysis of monocyte to macrophage differentiation in vivo
Authors: Asif J. Iqbal, Eileen McNeill, Theodore S. Kapellos, Daniel Regan-Komito, Sophie Norman, Sarah Burd, Nicola Smart, Daniel E. W. Machemer, Elena Stylianou, Helen McShane, Keith M. Channon, Ajay Chawla, David R. Greaves
Journal: Blood (2014)
Phylogeography and Population Dynamics of Dengue Viruses in the Americas
Authors: O. M. Allicock, P. Lemey, A. J. Tatem, O. G. Pybus, S. N. Bennett, B. A. Mueller, M. A. Suchard, J. E. Foster, A. Rambaut, C. V. F. Carrington
Journal: Molecular Biology and Evolution (2012)

Changes in Dengue virus (DENV) disease patterns in the Americas over recent decades have been attributed, at least in part, to repeated introduction of DENV strains from other regions, resulting in a shift from hypoendemicity to hyperendemicity. Using newly sequenced DENV-1 and DENV-3 envelope (E) gene isolates from 11 Caribbean countries, along with sequences available on GenBank, we sought to document the population genetic and spatiotemporal transmission histories of the four main invading DENV genotypes within the Americas and investigate factors that influence the rate and intensity of DENV transmission. For all genotypes, there was an initial invasion phase characterized by rapid increases in genetic diversity, which coincided with the first confirmed cases of each genotype in the region. Rapid geographic dispersal occurred upon each genotype's introduction, after which individual lineages were locally maintained, and gene flow was primarily observed among neighboring and nearby countries. There were, however, centers of viral diversity (Barbados, Puerto Rico, Colombia, Suriname, Venezuela, and Brazil) that were repeatedly involved in gene flow with more distant locations. For DENV-1 and DENV-2, we found that a "distance-informed" model, which posits that the intensity of virus movement between locations is inversely proportional to the distance between them, provided a better fit than a model assuming equal rates of movement between all pairs of countries. However, for DENV-3 and DENV-4, the more stochastic "equal rates" model was preferred.
Short-Term Psychotherapy with the Compulsive Personality and the Obsessive-Compulsive Neurotic
Authors: JAMES F. SUESS
Journal: American Journal of Psychiatry (1972)

The psychotherapist often bypasses short-term treatment of compulsive neuroses and character disorders because of the tenacity with which these patients cling to their defenses and the defense mechanisms they use to deny affect and behavior. Therapeutic attention is better focused on current feeling levels rather than on genetic content. Validation and recognition of the patient's feelings in the interviews and in his current life help relieve his guilt, self-doubt, and fear. The author discusses patients' defensive manipulations and proposes possible interventions.
<i>CREB3L2-PPARγ</i> Fusion Mutation Identifies a Thyroid Signaling Pathway Regulated by Intramembrane Proteolysis
Authors: Weng-Onn Lui, Lingchun Zeng, Victoria Rehrmann, Seema Deshpande, Maria Tretiakova, Edwin L. Kaplan, Ingo Leibiger, Barbara Leibiger, Ulla Enberg, Anders Höög, Catharina Larsson, Todd G. Kroll
Journal: Cancer Research (2008)

Abstract The discovery of gene fusion mutations, particularly in leukemia, has consistently identified new cancer pathways and led to molecular diagnostic assays and molecular-targeted chemotherapies for cancer patients. Here, we report our discovery of a novel CREB3L2-PPARγ fusion mutation in thyroid carcinoma with t(3;7)(p25;q34), showing that a family of somatic PPARγ fusion mutations exist in thyroid cancer. The CREB3L2-PPARγ fusion encodes a CREB3L2-PPARγ fusion protein that is composed of the transactivation domain of CREB3L2 and all functional domains of PPARγ1. CREB3L2-PPARγ was detected in &amp;lt;3% of thyroid follicular carcinomas. Engineered overexpression of CREB3L2-PPARγ induced proliferation by 40% to 45% in primary human thyroid cells, consistent with a dominant oncogenic mechanism. Wild-type CREB3L2 was expressed in the thyroid as a bZIP transcription factor with a transmembrane domain that has flanking S1P and S2P proteolytic cleavage sites. Native CREB3L2 was cleaved to nuclear CREB3L2 by regulated intramembrane proteolysis in normal thyroid cells that expressed the S1P and S2P proteases. Nuclear CREB3L2 stimulated transcription 8-fold from the EVX1 cyclic AMP (cAMP) response element in the absence of cAMP, whereas CREB3L2-PPARγ inhibited transcription 6-fold from EVX1 in the same experiments. CREB3L2-PPARγ also inhibited 4-fold the expression of thyroglobulin, a native cAMP-responsive gene, in primary thyroid cells treated with thyroid-stimulating hormone. Our findings identify a novel CREB3L2-PPARγ gene fusion mutation in thyroid carcinoma and reveal a thyroid signaling pathway that is regulated by intramembrane proteolysis and disrupted in cancer. [Cancer Res 2008;68(17):7156–64]
Does changing policy to disallow body checking reduce the risk of concussion in 11 and 12-year-old ice hockey players?
Authors: C A Emery, A Macpherson, J Kang, B Hagel, A Black, M Romiti, W H Meeuwisse
Journal: British Journal of Sports Medicine (2013)

Objective The objective of this study was to determine if the risk of concussion differed for non-elite Pee Wee ice hockey players (ages 11–12) in leagues where Body Checking (BC) is permitted (Alberta, Canada) versus leagues where policy no longer permits BC (Ontario, Canada). Design Cohort study. Setting Community ice rinks and sport medicine clinics during the 2011/12 season. Participants Forty-four teams from Alberta (n=658) and 32 from Ontario (n=258) participated. Players were from non-elite Pee Wee teams (lower 70% of divisions of play). Assessment of Risk Factors Non-elite Pee Wee ice hockey leagues where BC is permitted (Alberta) compared to leagues where policy no longer permits BC (Ontario). Main Outcome Measurements Players with a suspected concussion were identified by a team therapist or safety designate and referred to a sport medicine physician. Results There were 83 concussions (Incidence Proportion (IP)=12.61 (95% CI; 10.17 to 15.4)) in Alberta and 11 concussions (IP=4.26 (95% CI; 2.15 to 7.5)) in Ontario. The Concussion Risk Ratio was 2.96 (95% CI; 1.6 to 5.46). Overall, 76% of players identified with a concussion were assessed by a physician. Conclusions There was a 3-fold increased risk of concussion in non-elite Pee Wee ice hockey players in leagues where BC is permitted compared to a cohort where BC is no longer permitted. These findings have important implications for further BC policy change to reduce the public health burden of injury and concussion in youth ice hockey. Acknowledgements The University of Calgary Sport Injury Prevention Research Centre is one of the International Research Centres for Prevention of Injury and Protection of Athlete Health supported by the International Olympic Committee. We also acknowledge the support of Max Bell Foundation, Alberta Innovates Health Solutions and the Alberta Children's Hospital Institute for Child and Maternal Health (Alberta Children's Hospital Foundation).
Association between birth weight and adult blood pressure in twins: historical cohort study
Authors: N R Poulter, C L Chang, A J MacGregor, H Snieder, T D Spector
Journal: BMJ (1999)

<h3>Abstract</h3> <b>Objectives:</b> To evaluate the associations in twins between within pair differences in birth weight and subsequent blood pressures as adults thereby removing the impact of potential parental confounding variables. <b>Design:</b> Historical cohort study. <b>Setting:</b> St Thomas9s UK adult twin register, June 1992 to September 1995. <b>Participants:</b> 492 pairs of female twins (mean age 54 years). <b>Main outcome measures:</b> Mean within pair differences in adult blood pressure in each of four strata of within pair differences in birth weight (0, 1-500 g, 501-1000 g, &gt;1000 g). Differences in blood pressure were analysed before and after adjustment for potential confounders between adult twins, after exclusion of those twin pairs including at least one twin taking antihypertensive drugs, and by zygosity. <b>Results:</b> Reported mean birth weights of heavier and lighter twins were 2.51 (SD 0.61)<i>v</i> 2.12 (0.59) kg respectively. A graded inverse relation between strata of within pair differences in birth weight and differences in adult blood pressure was apparent, with an adjusted blood pressure range of 8.7/5.1 mm Hg across the four strata (test for trend: systolic, P=0.05; diastolic, P=0.09). After excluding those women taking antihypertensive drugs the significance of the association was similar (systolic, P=0.04; diastolic, P=0.10). When differences in blood pressure were stratified for zygosity similar but non-significant trends were apparent. <b>Conclusion:</b> It would seem that birth weight is inversely associated with adult blood pressure and that this association is independent of parental confounding variables probably including, in view of the findings in monozygotic twins, genetic factors. The observed blood pressure differences are likely to result from retarded intrauterine growth due to placental dysfunction rather than inadequate maternal nutrition. <h3>Key messages</h3> Among adult twins, blood pressures tend to be lower among those twins who were heavier at birth Strata of within pair birthweight differences of twins show a graded inverse relation with adult blood pressure differences Monozygotic and dizygotic twins show a similar inverse association between birthweight differences and adult blood pressure differences The inverse association between birth weight and adult blood pressure is independent of parental confounding variables
Prognostic Value of T-Wave Alternans in Patients With Heart Failure Due to Nonischemic Cardiomyopathy
Authors: Jorge A. Salerno-Uriarte, Gaetano M. De Ferrari, Catherine Klersy, Roberto F.E. Pedretti, Massimo Tritto, Luciano Sallusti, Luigi Libero, Giacinto Pettinati, Giulio Molon, Antonio Curnis, Eraldo Occhetta, Fabrizio Morandi, Paolo Ferrero, Francesco Accardi
Journal: Journal of the American College of Cardiology (2007)
Off-Label Use of Approved Drugs
Authors: William M. Bennett
Journal: Journal of the American Society of Nephrology (2004)

In this issue of the JASN , Booth et al. ([1][1]) report a well-designed study using TNF-α blockade with infliximab (Remicade) to treat ANCA-associated systemic vasculitis. The use of infliximab, already approved by the US Food and Drug Administration (FDA) for treatment of inflammatory bowel
FTY720: A Promising Agent for Treatment of Metastatic Hepatocellular Carcinoma
Authors: Terence K. Lee, Kwan Man, Joanna W. Ho, Xiang Hong Wang, Ronnie T.P. Poon, Yang Xu, Kevin T. Ng, Alan C. Chu, Chris K. Sun, Irene O. Ng, Hui Chuan Sun, Zao You Tang, Ray Xu, Sheung Tat Fan
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Recurrence after resection and metastasis are common in hepatocellular carcinoma and are associated with poor prognosis. Therefore, effective treatment is urgently needed for improvement of patients' survival. Previously, we reported that FTY720 has an antimetastatic effect on hepatocellular carcinoma cell line through down-regulation of Rac signaling pathway. This study aims to investigate the in vivo antimetastatic potential of FTY720 in an orthotopic nude mice model using metastatic human hepatocellular carcinoma cell lines MHCC-97L (lower metastatic potential) and MHCC-97H (higher metastatic potential). Experimental Design: The nude mice bearing liver tumors were randomized into a treatment group and a control group, each with 12 mice. FTY720 was administered at a dosage of 5 or 10 mg/kg via i.p. injection after 7 days of tumor inoculation. Thirty-five days later, the mice were sacrificed for record of intrahepatic and pulmonary metastases. Results: After 35 days of FTY720 treatment at the dosages of 5 and 10 mg/kg, all 12 mice in the treatment group were alive and well. FTY720 at the dosages of 5 and 10 mg/kg significantly suppressed the tumor volume and intrahepatic and pulmonary metastases in the metastatic nude mice model. FTY720 suppressed intrahepatic and pulmonary metastases by inhibition of Rac expression, which at least in part down-regulated the vascular endothelial growth factor expression and CD34 staining in a dose-dependent manner. Conclusion: FTY720 is a promising novel therapeutic drug for treatment of hepatocellular carcinoma metastasis.
Renal Primary Cilia Lengthen after Acute Tubular Necrosis
Authors: Elizabeth Verghese, Sharon D. Ricardo, Raphael Weidenfeld, Junli Zhuang, Prudence A. Hill, Robyn G. Langham, James A. Deane
Journal: Journal of the American Society of Nephrology (2009)

Renal primary cilia are sensory antennas required for the maintenance of normal epithelial differentiation and proliferation in the kidney, but they also have a potential role in epithelial differentiation during renal injury and repair. In mice, tubular damage causes an increase in the length of renal cilia, which may modify their sensory sensitivity during repair. Here, we investigated whether the alteration of renal cilium length during renal injury is clinically relevant. Using biopsies of human renal transplants that suffered acute tubular necrosis during transplantation, we compared the length of renal primary cilia with renal function. Serial biopsies showed that acute tubular necrosis resulted in more than a doubling of cilium length throughout the nephron and collecting duct approximately 1 wk after injury. Allografts displayed a trend toward normalization of cilium length in later biopsies, and this correlated with functional recovery. A mouse model of renal ischemia-reperfusion confirmed the increase and subsequent regression of cilium length during renal repair, displaying complete normalization of cilium length within 6 wk of injury. These findings demonstrate that the length of renal cilia is a clinically relevant indicator of renal injury and repair.
General practitioners with special interests–not a cheap option
Authors: Martin Roland
Journal: BMJ (2005)

General practitioners with a special interest are general practitioners with special experience or training that enables them to take referrals which would normally be seen by specialists. The training of a new cadre of general practitioners with special interest was a key part of the UK government's 2000 NHS Plan.

Are general practitioners with special interests likely to be an effective and cost effective way of providing care? A randomised controlled trial by Salisbury et al and an economic evaluation by Coast et al provide some answers.1 2 The results show that in dermatology a general practitioner with special interest service was effective: patients were seen more quickly, were more satisfied, and had similar clinical …
Comparative analysis of processed ribosomal protein pseudogenes in four mammalian genomes
Authors: Suganthi Balasubramanian, Deyou Zheng, Yuen-Jong Liu, Gang Fang, Adam Frankish, Nicholas Carriero, Rebecca Robilotto, Philip Cayting, Mark Gerstein
Journal: Genome biology (2009)

The availability of genome sequences of numerous organisms allows comparative study of pseudogenes in syntenic regions. Conservation of pseudogenes suggests that they might have a functional role in some instances. We report the first large-scale comparative analysis of ribosomal protein pseudogenes in four mammalian genomes (human, chimpanzee, mouse and rat). To this end, we have assigned these pseudogenes in the four organisms using an automated pipeline and make the results available online. Each organism has a large number of ribosomal protein pseudogenes (approximately 1,400 to 2,800). The majority of them are processed (generated by retrotransposition). However, we do not see a correlation between the number of pseudogenes associated with a ribosomal protein gene and its mRNA abundance. Analysis of pseudogenes in syntenic regions between species shows that most are conserved between human and chimpanzee, but very few are conserved between primates and rodents. Interestingly, syntenic pseudogenes have a lower rate of nucleotide substitution than their surrounding intergenic DNA. Moreover, evidence from expressed sequence tags indicates that two pseudogenes conserved between human and mouse are transcribed. Detailed analysis shows that one of them, the pseudogene of RPS27, is likely to be a protein-coding gene. This is significant as previous reports indicated there are exactly 80 ribosomal protein genes encoded by the human genome. Our analysis indicates that processed ribosomal protein pseudogenes abound in mammalian genomes, but few of these are conserved between primates and rodents. This highlights the large amount of recent retrotranspositional activity in mammals and a relatively larger amount of it in the rodent lineage.