tbuckley/cabot-search huggingface dataset:
Hepatocyte Nuclear Factor 1α Controls the Expression of Terminal Complement Genes
Authors: Marco Pontoglio, Mario Pausa, Antonia Doyen, Benoit Viollet, Moshe Yaniv, Francesco Tedesco
Journal: The Journal of Experimental Medicine (2001)

The terminal components of the complement system contribute to host defense by forming the multiprotein membrane attack complex (MAC) which is responsible for cell lysis and several noncytotoxic effects. Most of the complement proteins are synthesized in the liver, but the mechanisms controlling their tissue-specific expression have not been elucidated. In this study we show that mice lacking the hepatic transcription factor hepatocyte nuclear factor 1alpha (HNF1alpha) fail to transcribe C5 and C8A complement genes. In addition, mRNAs encoding for several other terminal complement components or subunits are expressed at lower levels, including C8beta, C8gamma, and C9. We next used a reconstitution assay involving human sera with selective complement deficiencies to assess mouse complement activity. Sera from HNF1alpha-deficient mice showed negligible hemolytic activity of both C5 and C8alpha-gamma subunits. The activity of C8beta was severely affected despite only a 50% reduction in C8beta mRNA levels in the liver. This is reminiscent of C8alpha-gamma-deficient patients who accumulate extremely low levels of the C8beta subunit. Our results demonstrate that HNF1alpha plays a key role in the expression of C5 and C8A genes, two terminal complement component genes that are essential for the assembly of MAC as a result of complement activation.
Relationship between oxygen uptake kinetics and BODE index at the onset of high-intensity exercise in moderate-to-severe COPD patients
Authors: Audrey Borghi-Silva, Thomas Beltrame, Michel Silva Reis, Luciana Maria Malosa Sampaio Jorge, Ross Arena, Dirceu Costa
Journal: European Respiratory Journal (2012)

Background:  Patients with chronic obstructive pulmonary disease (COPD) present reduced exercise capacity due impaired oxygen uptake delivery-utilization, caused primarily by pulmonary dysfunction and deleterious peripheral adaptations. Assuming that COPD patients present with slower VO 2  and heart rate (HR) kinetics, we hypothesized that this finding is related to degree of severity in according to BODE index.   Aim:  to evaluate the relationship between oxygen consumption (VO 2 ) on-kinetics during high intensity exercise and the BODE index in patients with COPD.   Methods:  Twenty males with moderate to severe stable COPD and thirteen healthy control subjects matched by age and gender were evaluated. Initially, COPD patients were screening by BODE index and then, all volunteers were submitted to an incremental cardiopulmonary exercise testing, and subsequently, a constant speed on a treadmill at 70%, for 6 minutes. The on-transient (first 360 seconds) response of VO 2  and HR was modeled according to a monoexponencial fit.   Results:  VO 2  and HR on-kinetics were slower in the COPD group than controls. Additionally, VO 2  on-kinetic parameters revealed a strong correlation (r=0.77, p   Conclusion:  Our data show that moderate to severe COPD is related to impairment of oxygen delivery and utilization during the onset of intense exercise. In addition, there is a relationship between walking distance as well as BODE index with VO 2  on-kinetic behavior. Thus, the severity of COPD is reflected by progressive slowing of VO 2  on-kinetics.  Financial Support: FAPESP.
Clinical Utility of SMBG: Recommendations on the Use and Reporting of SMBG in Clinical Research
Authors: Oliver Schnell, Katharine Barnard, Richard Bergenstal, Emanuele Bosi, Satish Garg, Bruno Guerci, Thomas Haak, Irl B. Hirsch, Linong Ji, Sashank R. Joshi, Maarten Kamp, Lori Laffel, Chantal Mathieu, William H. Polonsky, Frank Snoek, Philip Home
Journal: Diabetes Care (2015)

Free to read Introduction Quality glucose information is a core prerequisite for successful diabetes management. It enables professionals and people with diabetes to make medically relevant decisions on therapy. Details of glucose profile information beyond HbA1c have been largely derived from self-monitoring of blood glucose (SMBG). Given the evidence base demonstrating the benefits of SMBG, its routine use is recommended for diabetes management and therapy by many international and regional guidelines (1–3). Today, SMBG is considered an important aspect of the management of glycemic control (3,4). Glucose information of high quality, considering the products used and the processes conducted, is also needed in clinical research in order to gain new evidence and insights on effective treatment strategies in diabetes. SMBG is widely and routinely applied in large clinical trials, where it is used to understand the glycemic state, to enhance awareness of the effects of lifestyle modification and the adaptation of treatment including insulin titration, and to enable documentation of intraday pre- and postprandial glucose excursions (glycemic variability) and the subsequent statistical analysis of this and the confirmation of hypoglycemic episodes. Examples of recent studies that used SMBG are Outcome Reduction With Initial Glargine Intervention (ORIGIN) trial, Action to Control Cardiovascular Risk in Diabetes (ACCORD), and, from earlier times, the Diabetes Control and Complications Trial (DCCT) (5–8). Indeed, SMBG is now applied in most studies of glucose-lowering agents, including glucagon-like peptide 1 (GLP-1) receptor agonist and sodium–glucose cotransporter 2 (SGLT2) inhibitor studies.
Hepatic expression of scavenger receptor class B type I (SR-BI) is a positive regulator of macrophage reverse cholesterol transport in vivo
Authors: Y. Zhang
Journal: Journal of Clinical Investigation (2005)

Hepatic expression of the scavenger receptor class B type I (SR-BI) promotes selective uptake of HDL cholesterol by the liver and is believed to play a role in the process of reverse cholesterol transport (RCT). We hypothesized that hepatic SR-BI expression is a regulator of the rate of integrated macrophage-to-feces RCT and used an in vivo model to test this hypothesis. Cholesterol-loaded and [3H]cholesterol-labeled J774 macrophages were injected intraperitoneally into mice, after which the appearance of the [3H]cholesterol in the plasma, liver, and feces over 48 hours was quantitated. Mice overexpressing SR-BI in the liver had significantly reduced [3H]cholesterol in the plasma but markedly increased [3H] tracer excretion in the feces over 48 hours. Conversely, mice deficient in SR-BI had significantly increased [3H]cholesterol in the plasma but markedly reduced [3H] tracer excretion in the feces over 48 hours. These studies demonstrate that hepatic SR-BI expression, despite its inverse effects on steady-state plasma HDL cholesterol concentrations, is an important positive regulator of the rate of macrophage RCT.
Advertising campaign on a major internet search engine to promote colorectal cancer screening
Authors: Crystale Purvis Cooper, Kymber N Williams, Kathleen A Carey, Cameron S Fowler, Marcus Frank, Cynthia A Gelb
Journal: BMJ (2004)

To attract internet users to an educational website on colorectal cancer, the US Centers for Disease Control and Prevention (CDC) posted advertisements on Yahoo!, an internet search engine used by 232 million people worldwide. 1 The six week campaign included 12 advertisements in four formats ("east module," "north banner," "large rectangular," and "streaming video large rectangular"-see bmj.com for examples) posted in locations throughout Yahoo!.Exposure to the advertisements was limited to health professionals and selected lay populations.Through a hyperlink, a software function that transfers users from one internet location to another, 2 3 those who selected or "clicked" on an advertisement were transferred to the SFL website (Screen for Life: National Colorectal Cancer Action Campaign) (www.cdc.gov/cancer/screenforlife). 4 5 The first phase of the campaign on Yahoo! lasted five weeks, from 29 April to 2 June 2002, and the advertisement space was paid for by the CDC.In the second phase of the campaign, which lasted one week (17-23 June 2002) the space was donated by Yahoo! as part of the "six weeks for the price of five" incentive deal that the CDC had accepted.This report analyses the traffic to the SFL website generated by the campaign, and the associated costs.
T-cell-mediated concomitant immunity to syngeneic tumors. I. Activated macrophages as the expressors of nonspecific immunity to unrelated tumors and bacterial parasites.
Authors: R J North, D P Kirstein
Journal: The Journal of Experimental Medicine (1977)

Progressive growth of the SA1 sarcoma was shown to result in the generation of a state of concomitant resistance to growth of a second implant of the same tumor. The responding lymph nodes of concomitantly immune mice were shown to contain theta-positive T cells that could specifically neutralize the growth of tumor cells in a normal test recipient. Nevertheless, the concomitantly immune host itself was capable to a limited extent of suppressing the growth of unrelated tumors. The generation of immunity, moreover, was associated with the generation of a powerful state of macrophage-mediated, nonspecific resistance to the bacterial parasite, Listeria monocytogenes. It was concluded that systemic macrophage activation was the consequence of the generation of T-cell-mediated immunity to the progressively growing tumor, and that this not only gave the host the capacity to inhibit the growth of unrelated tumors, but also to protect itself against microbial infection. The results gives credence to the view that macrophages play a central role in defense against microbial and neoplastic growth.
Expression of LOX-1, an Oxidized Low-Density Lipoprotein Receptor, in Experimental Hypertensive Glomerulosclerosis
Authors: MIKI NAGASE, SHINYA KANAME, TAKASHI NAGASE, GANG WANG, KATSUYUKI ANDO, TATSUYA SAWAMURA, TOSHIRO FUJITA
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Oxidized low-density lipoprotein (OxLDL) has been implicated in atherosclerosis and glomerulosclerosis. LOX-1 is a recently identified OxLDL receptor that is abundantly expressed in vascular endothelial cells. The aim of the present study was to investigate LOX-1 expression in the kidneys of hypertensive rats. Dahl salt-sensitive (DS) and salt-resistant (DR) rats were fed a 0.3% or 8% NaCl diet. Some DS 8% rats were treated with manidipine or hydralazine. LOX-1 gene expression was markedly elevated in the kidneys and glomeruli of hypertensive DS 8% rats compared with those of normotensive DR and DS 0.3% rats. Prolonged salt loading further increased the renal LOX-1 expression in DS rats. The LOX-1 upregulation in DS 8% rats was accompanied by renal overexpression of transforming growth factor-β1 and type I collagen, impaired renal function, and histologic glomerulosclerotic changes, all of which were ameliorated by antihypertensive treatment. LOX-1 was indeed expressed in the glomeruli in vivo and in cultured glomerular cells in vitro . However, LOX-1 expression was elevated in the aorta but not the kidneys of spontaneously hypertensive rats, which exhibited hypertension but minor glomerulosclerotic changes. In conclusion, the LOX-1 upregulation in the kidney of DS 8% rats was parallel to glomerulosclerotic changes and renal dysfunction, suggesting a possible pathogenetic role for renal LOX-1 in the progression to hypertensive glomerulosclerosis.
The role of dietary polyunsaturated fat in lowering blood cholesterol in man.
Authors: R L Jackson, O D Taunton, J D Morrisett, A M Gotto
Journal: Circulation Research (1978)

IT HAS BEEN nearly a quarter of a century since Keys and coworkers (see Refs. 1-3 and the pertinent references therein) demonstrated a statistically significant relationship between the death rate from coronary heart disease (CHD), plasma cholesterol levels, and the proportion of calories derived from total dietary fat.In these pioneer studies, it was shown that a Cape Town population which consumed foods rich in fat had a higher serum cholesterol level than a Bantu tribe which consumed less fat.Following these observations, there were a number of experimental studies in the mid-1950's in patients 1 " 7 and animals'*"" which showed that the feeding of saturated fat led to an elevation of plasma cholesterol, whereas polyunsaturated fats produced a decrease.The strong correlation between elevated plasma cholesterol levels and CHD led to several clinical trials which attempted to relate the consumption of the type of dietary fat and the course of the disease. 12" 15 Although the overall results of these trials were inconclusive, many of the participants had prior CHD and were less likely to be helped by dietary modification. 1" Nonetheless, based on epidemiological evidence and animal experiments, the American Heart Association, 17 the American Health Foundation, 1 " the Food and Nutrition Board of the National Research Council and the American Medical Association,'" and the Royal College of Physicians of London and the British Cardiac Society 2 " all have recommended changes in the diet which include a reduction of the total consumption of fat and cholesterol and the substitution of polyunsaturated for saturated fat.It is possible that one of the reasons for
RB Family Tumor Suppressor Activity May Not Relate to Active Silencing of E2F Target Genes
Authors: Tinke L. Vormer, Kamila Wojciechowicz, Marleen Dekker, Sandra de Vries, Anja van der Wal, Elly Delzenne-Goette, Sjalin H. Naik, Ji-Ying Song, Jan-Hermen Dannenberg, Jacob B. Hansen, Hein te Riele
Journal: Cancer Research (2014)

Abstract The retinoblastoma protein pRB and its two homologs p130 and p107 form the family of pocket proteins and play a major role in cell-cycle regulation and suppression of human and mouse tumorigenesis. Pocket proteins regulate the activity of E2F transcription factors during G1–S transition. Two mechanisms have been described: (i) pocket protein binding blocks the transactivation domain of activator E2Fs, inhibiting E2F-dependent transcription and (ii) E2F-bound pocket proteins can recruit chromatin remodeling proteins containing an LxCxE motif (x encoding any amino acid), resulting in active repression of E2F target genes. To investigate the importance of pRB's LxCxE-interacting motif in cell-cycle control and tumor suppression, we generated mouse embryonic fibroblasts and mice expressing a mutant pRB protein carrying an asparagine for phenylalanine substitution at position 750, abrogating LxCxE binding. Because p130 may compensate for loss of pRB, we studied pRBN750F activity in the presence and absence of p130. The pRB–LxCxE interaction was not required for cell-cycle arrest upon mitogen deprivation and cell-cell contact, but did contribute to RASV12- and radiation-induced cell-cycle arrest. Remarkably, the pRB–LxCxE interaction was not required for suppression of in vitro and in vivo transformation, even in the absence of p130. These results indicate that pRB's tumor suppressor activity is not effectuated by active silencing of E2F target genes, but rather by regulation of activator E2Fs or another unidentified mechanism. Furthermore, the in vitro response of pocket protein–perturbed cells to mitogen deprivation and cell–cell contact seems a better predictor of tumor development than the response to ectopic RASV12 expression. Cancer Res; 74(18); 5266–76. ©2014 AACR.
Origin of nascent lineages and the mechanisms used to prime second-strand DNA synthesis in the R1 and R2 retrotransposons of Drosophila
Authors: Deborah E Stage, Thomas H Eickbush
Journal: Genome biology (2009)

Abstract Background Most arthropods contain R1 and R2 retrotransposons that specifically insert into the 28S rRNA genes. Here, the sequencing reads from 12 Drosophila genomes have been used to address two questions concerning these elements. First, to what extent is the evolution of these elements subject to the concerted evolution process that is responsible for sequence homogeneity among the different copies of rRNA genes? Second, how precise are the target DNA cleavages and priming of DNA synthesis used by these elements? Results Most copies of R1 and R2 in each species were found to exhibit less than 0.2% sequence divergence. However, in many species evidence was obtained for the formation of distinct sublineages of elements, particularly in the case of R1. Analysis of the hundreds of R1 and R2 junctions with the 28S gene revealed that cleavage of the first DNA strand was precise both in location and the priming of reverse transcription. Cleavage of the second DNA strand was less precise within a species, differed between species, and gave rise to variable priming mechanisms for second strand synthesis. Conclusions These findings suggest that the high sequence identity amongst R1 and R2 copies is because all copies are relatively new. However, each active element generates its own independent lineage that can eventually populate the locus. Independent lineages occur more often with R1, possibly because these elements contain their own promoter. Finally, both R1 and R2 use imprecise, rapidly evolving mechanisms to cleave the second strand and prime second strand synthesis.
CSPG4-Specific Immunity and Survival Prolongation in Dogs with Oral Malignant Melanoma Immunized with Human CSPG4 DNA
Authors: Federica Riccardo, Selina Iussich, Lorella Maniscalco, Saray Lorda Mayayo, Giuseppe La Rosa, Maddalena Arigoni, Raffaella De Maria, Francesca Gattino, Stefania Lanzardo, Elena Lardone, Marina Martano, Emanuela Morello, Simone Prestigio, Alessandra Fiore, Elena Quaglino, Sara Zabarino, Soldano Ferrone, Paolo Buracco, Federica Cavallo
Journal: Clinical Cancer Research (2014)

Due to the many similarities with its human counterpart, canine malignant melanoma (cMM) is a valuable model in which to assess the efficacy of novel therapeutic strategies. The model is herein used to evaluate the immunogenicity, safety, and therapeutic efficacy of a human chondroitin sulfate proteoglycan-4 (hCSPG4) DNA-based vaccine. The fact that homology between hCSPG4 and cCSPG4 amino-acidic sequences stands at more than 80% provides the rationale for using an hCSPG4 DNA vaccine in the cMM model.Dogs with stage II-III surgically resected CSPG4-positive oral MM were subjected to monthly intramuscular plasmid administration, which was followed immediately by electroporation (electrovaccination) for at least 6, and up to 20, months. The immunogenicity, safety, and therapeutic efficacy of the vaccine have been evaluated.hCSPG4 electrovaccination caused no clinically relevant local or systemic side effects and resulted in significantly longer overall and disease-free survival times in 14 vaccinated dogs as compared with 13 nonvaccinated controls. All vaccinated dogs developed antibodies against both hCSPG4 and cCSPG4. Seven vaccinated dogs were also tested for a cCSPG4-specific T-cell response and only two gave a detectable interferon (IFN)γ response.Xenogeneic electrovaccination against CSPG4 is able to overcome host unresponsiveness to the "self" antigen and seems to be effective in treating cMM, laying the foundation for its translation to a human clinical setting.
Bevacizumab with or without erlotinib as maintenance therapy in patients with metastatic colorectal cancer (GERCOR DREAM; OPTIMOX3): a randomised, open-label, phase 3 trial
Authors: Christophe Tournigand, Benoist Chibaudel, Benoit Samson, Werner Scheithauer, Dewi Vernerey, Paul Mésange, Gérard Lledo, Frédéric Viret, Jean-François Ramée, Nicole Tubiana-Mathieu, Jérôme Dauba, Olivier Dupuis, Yves Rinaldi, May Mabro, Nathalie Aucoin, Jean Latreille, Franck Bonnetain, Christophe Louvet, Annette K Larsen, Thierry André, Aimery de Gramont
Journal: The Lancet Oncology (2015)
Allergic Skin Prick Test Results in Thai Children with Respiratory Allergy in 2011-2013
Authors: Wanwipa Chaimongkol, Jittima Veskitkul, Punchama Pacharn, Orathai Jirapongsananuruk, Pakit Vichyanond, Nualanong Visitsunthorn
Journal: Journal of Allergy and Clinical Immunology (2015)
Effect of castration and sex hormone treatment on survival, anti-nucleic acid antibodies, and glomerulonephritis in NZB/NZW F1 mice.
Authors: J R Roubinian, N Talal, J S Greenspan, J R Goodman, P K Siiteri
Journal: The Journal of Experimental Medicine (1978)

NZB/NZW F1 mice of both sexes were castrated at 2 wk of age and implanted subcutaneously with silastic tubes containing either 5-alpha-dihydrotestosterone or estradiol-17-beta. Mice receiving androgen showed improved survival, reduced anti-nucleic acid antibodies, or less evidence of glomerulonephritis as determined by light, immunofluorescent, and electron microscopy. By contrast, opposite effects were observed in castrated mice receiving estrogen. Intact male NZB/NZW F1 mice received androgen implants at 8 mo, an age when they develop an accelerated autoimmune disease associated with a decline in serum testosterone concentration. Such treated mice had improved survival and reduced concentrations of antibodies to DNA and to polyadenylic acid (Poly A). Prepubertal castration of male NZB/NZW F1 mice results in an earlier appearance of IgG antibodies to Poly A. This effect of castration was prevented if neonatal thymectomy was also performed.
DNA Damage and Repair Capacity in Patients With Lung Cancer: Prediction of Multiple Primary Tumors
Authors: Irene Orlow, Bernard J. Park, Urvi Mujumdar, Himali Patel, Puiki Siu-Lau, Brian A. Clas, Robert Downey, Raja Flores, Manjit Bains, Nabil Rizk, Gemma Dominguez, Jen Jani, Marianne Berwick, Colin B. Begg, Mark G. Kris, Valerie W. Rusch
Journal: Journal of Clinical Oncology (2008)

Purpose Patients who survive one occurrence of non–small-cell lung cancer (NSCLC) are at higher risk of a second malignancy. Capacity to repair damaged DNA may modulate individual susceptibility to develop lung cancer. Therefore, we evaluated constitutive and induced DNA damage, and repair capacity, in patients with multiple NSCLCs (cases) and compared the results to those obtained in patients with a single NSCLC (controls). Patients and Methods One hundred eight cases and 99 controls matched by age, sex, and time since diagnosis were studied. DNA damage was assessed on peripheral blood lymphocytes by the comet assay before and after exposing cells to a tobacco-derived carcinogen, using the tail moment and the tail intensity as measures to assess baseline damage, induced damage and repair capacity. Results Constitutive DNA damage, benzo(a)pyrene diol epoxide–induced damage, and repair after BPDE-induced damage were all significantly higher in cases than in controls. These results were confirmed in regression analyses adjusted for potential confounders. Conclusion DNA damage as measured by the comet assay is associated with the development of multiple primary tumors in individuals with NSCLC.
Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial
Authors: François-Xavier Mahon, Delphine Réa, Joëlle Guilhot, François Guilhot, Françoise Huguet, Franck Nicolini, Laurence Legros, Aude Charbonnier, Agnès Guerci, Bruno Varet, Gabriel Etienne, Josy Reiffers, Philippe Rousselot
Journal: The Lancet Oncology (2010)