tbuckley/cabot-search huggingface dataset:
Abstract 258: Hypoxic and Normoxic Niches Regulate Cardiac Stem Cell Function
Authors: Fumihiro Sanada, Junghyung Kim, Anna Czarna, Noel Y Chan, Sargio Signore, Kazuya Isobe, Andrea Sorrentino, Chiara Mangiaracina, Ewa Wybieralska, Maria Cimini, Giulia Borghetti, Marcello Rota, Toru Hosoda, Jan Kajstura, Piero Anversa, Annarosa Leri
Journal: Circulation Research (2013)

In bone marrow niches, hypoxia favors stem cell quiescence and normoxia is required for stem cell proliferation and commitment. The objectives of this work were to determine whether a) differences in O 2 content regulate the function of cardiac stem cells (CSCs); and b) defects in tissue oxygenation with aging affects niche homeostasis. At 3 and 30 months of age, hypoxic and normoxic CSCs were found in the myocardium, but the senescent mouse heart was characterized by a 1.5-fold increase in hypoxic CSCs. At both ages, hypoxic CSCs were quiescent and lineage negative while cycling and early committed cells were restricted to the normoxic pool. Importantly, telomeres were longer in hypoxic than normoxic CSCs and this difference was more apparent in old mice. Telomere length did not change with age in hypoxic CSCs but decreased 40% in normoxic CSCs. As a consequence, at 3 and 30 months, the fraction of normoxic CSCs expressing the senescence-associated marker p16 INK4a was, respectively, 6-fold and 2.7-fold higher than that of hypoxic CSCs. Collectively, these findings indicate that the old heart contains a larger fraction of CSCs, which are forced in a quiescent state and do not participate in myocyte turnover. To define whether hypoxic CSCs can be activated, senescent mice were kept in an atmosphere of 70% O 2 to increase O 2 content in the hypoxic niches. Hyperoxia decreased significantly the fraction of hypoxic CSCs at 1 day and this response persisted at one week, possibly favoring myocyte formation. These in vivo results suggest that O 2 levels in CSCs may be regulated by the capillary network and the degree of tissue oxygenation. The distance between CSCs and the closest capillary was significantly higher for hypoxic than for normoxic CSCs. The numerical density of capillaries per mm 2 of myocardium computed within a radius of 30 μm from hypoxic CSCs decreased markedly with age. Thus, diffusion distance for O 2 to CSCs appears to constitute a major determinant in the maintenance of the hypoxic state of CSCs. Collectively, our data demonstrate that a balance between hypoxic and normoxic niches is present in the young heart but is disrupted later in life when capillary rarefaction expands the pool of hypoxic quiescent CSCs, which are no longer involved in myocyte replacement.
Challenges in Oncology
Authors: W. Y. Au, C. G.C . Ooi, K. H. Li, T. W. Shek, R. Liang
Journal: Journal of Clinical Oncology (2002)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.3.866 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11821472 Challenges in Oncology Case 1. Oncology Emergencies: A Myeloma Patient with Stridor W. Y. AuxW. Y. AuSearch for articles by this author , C. G.C . OoixC. G.C . OoiSearch for articles by this author , K. H. LixK. H. LiSearch for articles by this author , T. W. ShekxT. W. ShekSearch for articles by this author , R. LiangxR. LiangSearch for articles by this author Show More Queen Mary Hospital, University of Hong Kong, Hong Kong https://doi.org/10.1200/JCO.2002.20.3.866 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
How to: Establish and run a stool bank
Authors: E.M. Terveer, Y.H. van Beurden, A. Goorhuis, J.F.M.L. Seegers, M.P. Bauer, E. van Nood, M.G.W. Dijkgraaf, C.J.J. Mulder, C.M.J.E. Vandenbroucke-Grauls, H.W. Verspaget, J.J. Keller, E.J. Kuijper
Journal: Clinical Microbiology and Infection (2017)
SNIFF AND TWITCH TRANSDIAPHRAGMATIC PRESSURES IN HEALTH AND DISEASE
Authors: W. D-C Man, J. Steier, N. S. Hopkinson, Y-M Luo, C. J. Jolley, N. Mustfa, F. Harraf, D. Nikoletou, Gerrard Rafferty, M. I. Polkey, John Moxham
Journal: Thorax (2008)
The Role of Astrocyte Dysfunction in Parkinson’s Disease Pathogenesis
Authors: Heather D.E. Booth, Warren D. Hirst, Richard Wade-Martins
Journal: Trends in Neurosciences (2017)

Astrocytes are the most populous glial subtype and are critical for brain function. Despite this, historically there have been few studies into the role that they may have in neurodegenerative diseases, such as Parkinson's disease (PD). Recently, however, several studies have determined that genes known to have a causative role in the development of PD are expressed in astrocytes and have important roles in astrocyte function. Here, we review these recent developments and discuss their impact on our understanding of the pathophysiology of PD, and the implications that this might have for its treatment.
Randomized Comparison of Enoxaparin, a Low-Molecular-Weight Heparin, With Unfractionated Heparin Adjunctive to Recombinant Tissue Plasminogen Activator Thrombolysis and Aspirin
Authors: Allan M. Ross, Peter Molhoek, Conor Lundergan, Merrill Knudtson, Yasmine Draoui, Lorna Regalado, Veronique Le Louer, Frederique Bigonzi, Whitney Schwartz, Egbert de Jong, Karin Coyne
Journal: Circulation (2001)

Adjunctive unfractionated heparin (UFH) during thrombolytic therapy for acute myocardial infarction (AMI) promotes the speed and magnitude of coronary artery recanalization and reduces reocclusion. Low-molecular-weight heparins offer practical and potential pharmacological advantages over UFH in multiple applications but have not been systematically studied as adjuncts to fibrinolysis in AMI.Four hundred patients undergoing reperfusion therapy with an accelerated recombinant tissue plasminogen activator regimen and aspirin for AMI were randomly assigned to receive adjunctive therapy for at least 3 days with either enoxaparin or UFH. The study was designed to show noninferiority of enoxaparin versus UFH with regard to infarct-related artery patency. Ninety minutes after starting therapy, patency rates (thrombolysis in myocardial infarction [TIMI] flow grade 2 or 3) were 80.1% and 75.1% in the enoxaparin and UFH groups, respectively. Reocclusion at 5 to 7 days from TIMI grade 2 or 3 to TIMI 0 or 1 flow and TIMI grade 3 to TIMI 0 or 1 flow, respectively, occurred in 5.9% and 3.1% of the enoxaparin group versus 9.8% and 9.1% in the UFH group. Adverse events occurred with similar frequency in both treatment groups.Enoxaparin was at least as effective as UFH as an adjunct to thrombolysis, with a trend toward higher recanalization rates and less reocclusion at 5 to 7 days.
PWE-064 Increased mucosa-associated diffusely adherentE coliin Crohn's and colon cancer: possible role in pathogenesis
Authors: M K Friswell, C L Roberts, C Winstanley, J Marchesi, J M Rhodes, B J Campbell
Journal: Gut (2010)

<h3>Introduction</h3> Mucosa-associated adherent invasive <i>Escherichia coli</i> (AIEC) are found in colorectal cancer (CRC) and Crohn9s disease (IBD).1 They invade intestinal epithelial cells, replicate in macrophages and interact with epithelial cells in vitro to promote proinflammatory cytokine release and NFkB activation.2 The adherent-invasive phenotype strongly correlates with the ability to agglutinate red blood cells (RBCs). We suspect that mucosa-associated <i>E coli</i> may also play a role in CRC pathogenesis by activation of key cellular pathways. Our aim here was to identify and characterise adherence mechanisms for our colonic AIEC isolates. <h3>Methods</h3> A fosmid library was constructed containing 30–60 kb DNA fragments from <i>E coli</i> HM358, a CRC mucosa-associated isolate. Clones were screened for the ability to haemagglutinate RBCs. Agglutinating positive (HA+) clones were further assessed for their ability to adhere to epithelial Hep2 cells, to replicate within macrophages and for their ability to translocate across M-cells. They were then subjected to 454 DNA sequencing. Subsequently, 280 <i>E coli</i> isolates from IBD, CRC and healthy control patients were assessed for the presence of a gene cluster identified from sequence analysis. <h3>Results</h3> Of the 964 fosmid clones constructed, 8 displayed a strong HA+ phenotype. Sequence data demonstrated all possessed a diffuse adherence gene cluster (<i>afaA-E</i>). HA+ positive clones were diffusely adherent to Hep2 cells and showed marked ability to replicate within macrophages when compared to HA- clones (p&lt;0.01; ANOVA). In vitro data also suggest that the presence of <i>afa/dr</i> in <i>E coli</i> promotes translocation across M cells, a key portal of mucosal entry. <i>E coli</i> containing <i>afa/dr</i> were more commonly isolated from IBD and CRC patients (57% <i>afa</i> positive) than from healthy controls (28% <i>afa</i> positive, p&lt;0.001 χ<sup>2</sup> test). <h3>Conclusion</h3> <i>Afa/dr E coli</i> are more commonly isolated from IBD and CRC patients than from healthy controls and have properties, including epithelial invasion and replication in macrophages, that overlap with AIEC. Other studies have shown that adherent <i>afa/dr E coli</i> play a key role in the upregulation of angiogenic vascular endothelial growth factor (VEGF) in the intestinal epithelium3 and they may thus have a role in pathogenesis of CRC as well as IBD.
RASA1 regulates the function of lymphatic vessel valves in mice
Authors: Philip E. Lapinski, Beth A. Lubeck, Di Chen, Abbas Doosti, Scott D. Zawieja, Michael J. Davis, Philip D. King
Journal: Journal of Clinical Investigation (2017)

Capillary malformation-arteriovenous malformation (CM-AVM) is a blood and lymphatic vessel (LV) disorder that is caused by inherited inactivating mutations of the RASA1 gene, which encodes p120 RasGAP (RASA1), a negative regulator of the Ras small GTP-binding protein. How RASA1 mutations lead to the LV leakage defects that occur in CM-AVM is not understood. Here, we report that disruption of the Rasa1 gene in adult mice resulted in loss of LV endothelial cells (LECs) specifically from the leaflets of intraluminal valves in collecting LVs. As a result, valves were unable to prevent fluid backflow and the vessels were ineffective pumps. Furthermore, disruption of Rasa1 in midgestation resulted in LEC apoptosis in developing LV valves and consequently failed LV valvulogenesis. Similar phenotypes were observed in induced RASA1-deficient adult mice and embryos expressing a catalytically inactive RASA1R780Q mutation. Thus, RASA1 catalytic activity is essential for the function and development of LV valves. These data provide a partial explanation for LV leakage defects and potentially other LV abnormalities observed in CM-AVM.
Potential psychological accounts for the relation between food insecurity and body overweight
Authors: Eyal Ert, Amir Heiman
Journal: Behavioral and Brain Sciences (2017)

Abstract We suggest two psychological mechanisms, temporal discounting and feeling of resource scarcity, for explaining the relation between food insecurity and body overweight. We demonstrate how Nettle et al.’s findings could be explained, post hoc, by each of these accounts, suggesting that their data are not rich enough to allow identification of mechanisms that underlie food insecurity and overweight relationship.
Reproductive Factors and Incidence of Heart Failure Hospitalization in the Women’s Health Initiative
Authors: Philip S. Hall, Gregory Nah, Barbara V. Howard, Cora E. Lewis, Matthew A. Allison, Gloria E. Sarto, Molly E. Waring, Lisette T. Jacobson, JoAnn E. Manson, Liviu Klein, Nisha I. Parikh
Journal: Journal of the American College of Cardiology (2017)
Angiotensin II formation in the intact human heart. Predominance of the angiotensin-converting enzyme pathway.
Authors: L S Zisman, W T Abraham, G E Meixell, B N Vamvakias, R A Quaife, B D Lowes, R L Roden, S J Peacock, B M Groves, M V Raynolds
Journal: Journal of Clinical Investigation (1995)

It has been proposed that the contribution of myocardial tissue angiotensin converting enzyme (ACE) to angiotensin II (Ang II) formation in the human heart is low compared with non-ACE pathways. However, little is known about the actual in vivo contribution of these pathways to Ang II formation in the human heart. To examine angiotensin II formation in the intact human heart, we administered intracoronary 123I-labeled angiotensin I (Ang I) with and without intracoronary enalaprilat to orthotopic heart transplant recipients. The fractional conversion of Ang I to Ang II, calculated after separation of angiotensin peptides by HPLC, was 0.415 +/- 0.104 (n = 5, mean +/- SD). Enalaprilat reduced fractional conversion by 89%, to a value of 0.044 +/- 0.053 (n = 4, P = 0.002). In a separate study of explanted hearts, a newly developed in vitro Ang II-forming assay was used to examine cardiac tissue ACE activity independent of circulating components. ACE activity in solubilized left ventricular membrane preparations from failing hearts was 49.6 +/- 5.3 fmol 125I-Ang II formed per minute per milligram of protein (n = 8, +/- SE), and 35.9 +/- 4.8 fmol/min/mg from nonfailing human hearts (n = 7, P = 0.08). In the presence of 1 microM enalaprilat, ACE activity was reduced by 85%, to 7.3 +/- 1.4 fmol/min/mg in the failing group and to 4.6 +/- 1.3 fmol/min/mg in the nonfailing group (P < 0.001). We conclude that the predominant pathway for angiotensin II formation in the human heart is through ACE.
Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders
Authors: Daniel J Weiner, Emilie M Wigdor, Stephan Ripke, Raymond K Walters, Jack A Kosmicki, Jakob Grove, Kaitlin E Samocha, Jacqueline I Goldstein, Aysu Okbay, Jonas Bybjerg-Grauholm, Thomas Werge, David M Hougaard, Jacob Taylor, David Skuse, Bernie Devlin, Richard Anney, Stephan J Sanders, Somer Bishop, Preben Bo Mortensen, Anders D Børglum, George Davey Smith, Mark J Daly, Elise B Robinson
Journal: Nature Genetics (2017)
The relationship between fractional lymphocyte counts and survival in malignant melanoma.
Authors: Michael Thomas McCarthy, David James Gallagher
Journal: Journal of Clinical Oncology (2015)

e20116 Background: While strong evidence supports a relationship between acquired immune deficiency states and virus-associated malignancy, the relationship between immune function and epithelial malignancy in the setting of immunocompetence is less clear. In malignant melanoma, the success of lymphocyte-targeted immunotherapies suggest that lymphocyte immunity may play a role disease outcomes. Separate evidence suggests that immunosenescence in old age is associated with impaired lymphocyte immunity. We hypothesized that fractional lymphocyte counts are associated with survival in melanoma, and that this relationship is likely to be stronger in younger as compared to older individuals. Methods: We retrospectively examined the relationship between peripheral blood immune indices and survival in malignant melanoma. We identified individuals who had died from malignant melanoma in our unit over the past 2 years. We recorded pre-treatment neutrophil, lymphocyte, and total white cell counts. Survival time from diagnosis of metastatic melanomawas calculated. The principal endpoint was the assessment of correlation between lymphocyte-neutrophil ratio or fractional lymphocyte count and survival in individuals younger or older than 65 years of age. The Pearson product-moment correlation coefficient was used to assess the degree of linear dependence between these variables. Results: In total, 21 patients were identified; 11 patients aged less than 65, and 10 patients older than 65. In those aged under 65, the fractional lymphocyte count correlated positively with survival (r = 0.703; p < 0.02), and a negative correlation was observed between the fractional neutrophil count and survival (r = 0.705, p < 0.02). Approximately 70% of the variation in survival is explained by the baseline fractional lymphocyte count. In contrast to previous studies, the neutrophil-lymphocyte ratio did not correlate with survival. In the over 65 group, no significant correlations were identified. Conclusions: Pre-treatment fractional lymphocyte counts correlate positively with survival in individuals with malignant melanoma aged under 65. These results suggest further prospective studies in larger populations are warranted.
Successful autologous stem cell transplantation in aggressive prolymphocytic leukemia
Authors: Lev Shvidel, Mordechai Shtalrid, Abraham Klepfish, Michal Haran, Alain Berrebi
Journal: American Journal of Hematology (2000)

With the C282Y Mutation in the HFE GeneTo the Editor: The association between hereditary hemochromatosis and thalassemia syndrome might lead to a severe iron overload [1,2], but the results are still controversial.By PCR and restriction enzyme digestion [3], we analyzed the C282Y and H63D mutations in the HFE gene in one family whose propositus carried the ␤-thalassemia trait.The patient was a female, 38 years old, presenting weakness and arthralgia.She had 4 children and received transfusion (1 unit of red cell) during her last gestation.She did not present diabetes or cardiac disease and her hepatic enzymes were normal.Her mother and 2 sons also carried the ␤-thalassemia trait.
Superior survival of breast cancer BRCA1 /2 mutation carriers harboringG/G at the -309 position at the MDM2 promoter compared to those harboring T/T or G/T at this SNP
Authors: H. Nechushtan, T. Hamburger, S. Mendelson, L. Kadouri, N. Sharon, E. Pikarsky, T. Peretz
Journal: Journal of Clinical Oncology (2007)

10600 Background: A germ line single polymorphism in the promoter of the gene encoding the important modulator of P53, MDM2 has been described. The findings of G/G nucleotides at this position in contrast to G/Tor T/T were demonstrated to increase MDM2 transcriptional levels and were correlated with younger onset of cancers in patients with the Li-Fraumeni syndrome. Furhtermore gastric cancer patients harboring T/T at this position and treated with chemotherapy were found to have decresed survival compared to the other SNP carriers. P53 mutations appear in high frequency in tumors associated with BRCA1/2 mutations. Indeed it has been suggested that mutations in the p53 gene are a necessary step in tumorigenesis in BRCA tumors. Methods: Here we investigate the effect of the MDM2 SNP309 on overall survival and age of onset in breast cancer patients. MDM2 SNP309 was evaluated in Breast cancer Ashkenazy patients analyzed for the three common mutations in BRCA1/2- 180 patients who are positive for either of these mutation and 272 negative ones. 194 negative, Disease onset age and survival were analyzed for the different subgroups Results: Around a quarter of the whole population analyzed were identified as carriers of G/G at the -309 MDM2. There was no correlation between age of disease onset in either BRCA1/2mutation carriers and the specific genotype. In the BRCA1/2 mutation carriers we found a survival advantage in patients harboring the SNP309 G/G genotype(p-0.001 log rank test). Such an effect was not demonstrated in patients tested negative for the known Ashkenazy mutations Conclusions: In specific subgroups of breast cancer patients SNP309 G/G is associated with improved patient survival. A possible explanation for this finding could be the presence of a P53 which can be reactivated in the MDM2 SNP309 G/G carriers. No significant financial relationships to disclose.
Prognostic value of baseline 18F-FDG-PET (PET) in anal cancer (AC) patients (pts): A Bologna Multidisciplinary Rectal Cancer Group analysis (BMRCG-AC01).
Authors: Sara Pini, Francesca Di Fabio, Bruno Iacopino, Alessandra Guido, Paolo Castellucci, Dajana Cuicchi, Stefano Fanti, Ferdinando Lecce, Fabiola Lorena Rojas Llimpe, Stefania Giaquinta, Daniela Adua, Renzo Mazzarotto, Carmine Pinto
Journal: Journal of Clinical Oncology (2013)

e15154 Background: The incidence of AC has increased. In locally advanced disease treatment is curative radio-chemotherapy (RCT) followed by brachytherapy boost (BRT) or external beam radiotherapy (EBR). The aim of this analysis is to evaluate prognostic factors in predicting disease recurrence. Methods: We retrospectively evaluated pts with diagnosis of T2-3-4, N-/+ AC. External RT was delivered up to a dose of 4,500 cGy in 25 fr and CT consisted in 5-fluorouracil CI day 1-4 and Mitomicin-C bolus day 1 in the first and fifth weeks of radiotherapy as per Nigroregimen. BRT or EBR were performed at the end of RCT. A PET scan was performed at diagnosis before starting treatment. The standard uptake value (SUV) was determined from the most active tumor site. Results: Between March 2006 and August 2012, 50 pts with AC accessed the BMRCG. In this analysis we considered 29 pts evaluated by PET. The pt characteristics were: 8(27.6%) men, 21(72.4%) women; median age 63 (42-89) years; 17(58.6%) squamous cell carcinoma (scc), 12(41.4%) basaloid carcinoma (bc); 6(20.7%) cT2N0, 5(17.2%) cT3N0, 7(24.1%) cT3N+, 2(6.9%) cT4N0, 9(31.1%) cT4N+. Twenty-six (90%) pts received full-dose standard protocol RCT and subsequent radiotherapy boost. After a median follow-up of 25 months we observed 4 (13.8%) recurrences: 3 local and 1 lung metastasis. No disease-related death occurred. Stage at diagnosis (T2-3N0 vs T3N+T4N+/-) and tumor histotype (scc vs bc) did not relate to DFS (p=0.67 and p=0.86 respectively). ROC analysis identified a SUV cut-off of 12.5 at the baseline PET related to recurrence. In 15(51.7%) pts the baseline SUV was ≤12.5 (low SUV) and in 14 (48.3%) it was &gt;12.5 (high SUV). Pts with high SUV had significantly worse DFS than those with low SUV (p=0.02). Multivariate Cox regression did not confirm any SUV prognostic value (p=0.95). Conclusions: These results suggest that high SUV could predict relapse in AC pts treated with curative RCT. The small number of pts rules out any definitive conclusion; a controlled trial should be conducted to explore the prognostic role of SUV to define good prognosis pts for “tailored” treatment and reduce therapy-related toxicities.
Diagnostic Challenges in Patients With Tumors
Authors: Raffaele Longo, Scolastica Amici, Guido Carillio, Giampietro Gasparini
Journal: Journal of Clinical Oncology (2003)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.02.991 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 14512404 Diagnostic Challenges in Patients With Tumors CASE 2. STAPHYLOCOCCAL SCALDED-SKIN SYNDROME IN A PATIENT WITH EXTENDED SMALL-CELL LUNG CANCER Raffaele LongoxRaffaele LongoSearch for articles by this author , Scolastica AmicixScolastica AmiciSearch for articles by this author , Guido CarillioxGuido CarillioSearch for articles by this author , Giampietro GasparinixGiampietro GaspariniSearch for articles by this author Show More Azienda Ospedaliera S. Filippo Neri, Rome, Italy https://doi.org/10.1200/JCO.2003.02.991 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology
A Clinical, Epidemiologic and Laboratory Investigation of Aseptic Meningitis during the Four-Year Period, 1955–1958
Authors: Martha L. Lepow, Nadine Coyne, Letitia B. Thompson, David H. Carver, Frederick C. Robbins
Journal: New England Journal of Medicine (1962)

IN a previous report1 the results of virologic investigations of specimens obtained from 407 patients with the syndrome of aseptic meningitis were presented. Enteroviruses or mumps virus were implicated as the probable etiologic agents of the illnesses in 50 per cent of the patients by the technics employed. In recent years it has become more clearly recognized that a specific agent may cause illnesses ranging in severity and clinical manifestations from benign aseptic meningitis to a severe disease of the central nervous system that may result in varying degrees of disability and even death.2 3 4 5 6 The clinical features of the Central-nervous-system . . .