tbuckley/cabot-search huggingface dataset:
Polysome profiling reveals translational control of gene expression in the human malaria parasite Plasmodium falciparum
Authors: Evelien M Bunnik, Duk-Won Doug Chung, Michael Hamilton, Nadia Ponts, Anita Saraf, Jacques Prudhomme, Laurence Florens, Karine G Le Roch
Journal: Genome biology (2013)

Abstract Background In eukaryotic organisms, gene expression is regulated at multiple levels during the processes of transcription and translation. The absence of a tight regulatory network for transcription in the human malaria parasite suggests that gene expression may largely be controlled at post-transcriptional and translational levels. Results In this study, we compare steady-state mRNA and polysome-associated mRNA levels of Plasmodium falciparum at different time points during its asexual cell cycle. For more than 30% of its genes, we observe a delay in peak transcript abundance in the polysomal fraction as compared to the steady-state mRNA fraction, suggestive of strong translational control. Our data show that key regulatory mechanisms could include inhibitory activity of upstream open reading frames and translational repression of the major virulence gene family by intronic transcripts. In addition, we observe polysomal mRNA-specific alternative splicing events and widespread transcription of non-coding transcripts. Conclusions These different layers of translational regulation are likely to contribute to a complex network that controls gene expression in this eukaryotic pathogen. Disrupting the mechanisms involved in such translational control could provide novel anti-malarial strategies.
Length and protein kinase A modulations of myocytes in cardiac myosin binding protein C-deficient mice
Authors: O CAZORLA, S SZILAGYI, N VIGNIER, G SALAZAR, E KRAMER, G VASSORT, L CARRIER, A LACAMPAGNE
Journal: Cardiovascular Research (2005)

Journal Article Length and protein kinase A modulations of myocytes in cardiac myosin binding protein C-deficient mice Get access Olivier Cazorla, Olivier Cazorla * aINSERM, U 637, Montpellier, F-34295, FrancebUniversité MONTPELLIER1, UFR de Médecine, Montpellier, F-34295, France *Corresponding author. INSERM U-637, CHU Arnaud de Villeneuve, 34295 Montpellier, France. Tel.: +33 467 41 52 44; fax: +33 467 41 52 42. Email address: [email protected] Search for other works by this author on: Oxford Academic PubMed Google Scholar Szabolcs Szilagyi, Szabolcs Szilagyi aINSERM, U 637, Montpellier, F-34295, FrancebUniversité MONTPELLIER1, UFR de Médecine, Montpellier, F-34295, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Nicolas Vignier, Nicolas Vignier cINSERM, U 582, Paris, F-75013, FrancedUniversité Pierre et Marie Curie, UFR de Médecine, Paris, F-75013, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Guillermo Salazar, Guillermo Salazar aINSERM, U 637, Montpellier, F-34295, FrancebUniversité MONTPELLIER1, UFR de Médecine, Montpellier, F-34295, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Elisabeth Krämer, Elisabeth Krämer eInstitute of Experimental and Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Guy Vassort, Guy Vassort aINSERM, U 637, Montpellier, F-34295, FrancebUniversité MONTPELLIER1, UFR de Médecine, Montpellier, F-34295, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Lucie Carrier, Lucie Carrier cINSERM, U 582, Paris, F-75013, FrancedUniversité Pierre et Marie Curie, UFR de Médecine, Paris, F-75013, FranceeInstitute of Experimental and Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Alain Lacampagne Alain Lacampagne aINSERM, U 637, Montpellier, F-34295, FrancebUniversité MONTPELLIER1, UFR de Médecine, Montpellier, F-34295, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 69, Issue 2, February 2006, Pages 370–380, https://doi.org/10.1016/j.cardiores.2005.11.009 Published: 01 February 2006 Article history Received: 13 September 2005 Revision received: 17 October 2005 Accepted: 04 November 2005 Published: 01 February 2006
The economics of global tobacco control
Authors: P. Jha
Journal: BMJ (2000)

Few people now dispute that smoking is damaging human health on a global scale.1 However, many governments have avoided taking action to control smoking—such as higher taxes—because of concerns that their interventions might have harmful economic consequences, such as permanent job losses.

In 1997 the World Bank, in partnership with the World Health Organization, began a global study on the economics of tobacco control. A team of over 40 economists, epidemiologists, and tobacco control experts critically examined the current state of knowledge about tobacco control. The aim was to provide a sound and comprehensive evidence base for the design of effective tobacco control policies in any country, with an emphasis on the needs of the low income and middle income countries, where most smokers live. A synopsis of this work, including interim results, was published in 1999.2 Final results, including 19 chapters and a statistical appendix, are now available.3 This article presents the key findings from this study.

#### Summary points

Tax increases are the single most effective intervention to reduce demand for tobacco (tax increases that raise the real price of cigarettes by 10% would reduce smoking by about 4% in high income countries and by about 8% in low income or middle income countries)

Tax comprises about two thirds of retail price of cigarettes in most high income countries but is less than half of the total price on average in lower income countries

Improvements in the quality and extent of information, comprehensive bans on tobacco advertising and promotion, prominent warning labels, restrictions on smoking in public places, and increased access to nicotine replacement treatments are effective in reducing smoking

Reducing the supply of tobacco is not effective in reducing tobacco consumption

Comprehensive tobacco control policies are unlikely to harm economies

Each chapter of the study relied on …
Lymphocyte and Plasma Vitamin C Levels in Type 2 Diabetic Patients With and Without Diabetes Complications
Authors: Hiroshi Yamada, Kaoru Yamada, Masako Waki, Keizo Umegaki
Journal: Diabetes Care (2004)

men and 8 women, 137 45 mg/dl, and 7.2 1.0% for diabetic patients with complications compared with 64 7.5 years, 7 men and 8 women, 137 42 mg/dl, and 6.8 0.8% for diabetic patients without complications, respectively). The duration of illness was longer in the diabetic patients with complications than in diabetic patients without complications (13 9.1 vs. 7.7 5.2 years, respectively, P 0.051). For the normal control subjects, 50 age- and sexmatched healthy volunteers (63 5.7 years, 31 men and 19 women) were recruited. The participants taking vitamin supplements were excluded from the study. All participants gave informed consent before entering the study. The study was conducted in accordance with the Declaration of Helsinki and was approved by the ethics committee at the hospital. Blood samples were obtained by vein puncture in the morning while the patients were in the fasting state. Lymphocytes and plasma were prepared by centrifugation and the Ficoll gradients method, then immediately treated with metaphosphoric acid (final 5% wt/wt) to stabilize vitamin C (9,10). These processes were performed within 2 h under cooled conditions on ice to obtain reliable data. The vitamin C samples were stored at 80°C until analyzed, and the vitamin C (ascorbic acid, reduced form) levels were measured by high-performance liquid chromatography with the electrochemical detector method (11). All samples were handled and stored similarly in both diabetic patients and control subjects. The lymphocyte and plasma vitamin C levels in type 2 diabetic patients were compared with those of the control subjects. The differences between the vitamin C levels in type 2 diabetic patients with and without diabetes complications were also studied. Statistical analysis was performed with the unpaired Student’s t test to compare the data between diabetic patients and control subjects and between type 2 diabetic patients with and without diabetes complications. A P value 0.05 was considered significant. RESULTS — The lymphocyte vitamin C level in diabetic patients was significantly lower than in control subjects (18 4.5 vs. 28 7.9 nmol/mg protein,
Pericyte TIMP3 and ADAMTS1 Modulate Vascular Stability after Kidney Injury
Authors: Claudia Schrimpf, Cuiyan Xin, Gabriella Campanholle, Sean E. Gill, William Stallcup, Shuei-Liong Lin, George E. Davis, Sina A. Gharib, Benjamin D. Humphreys, Jeremy S. Duffield
Journal: Journal of the American Society of Nephrology (2012)

Kidney pericytes are progenitors of scar-forming interstitial myofibroblasts that appear after injury. The function of kidney pericytes as microvascular cells and how these cells detach from peritubular capillaries and migrate to the interstitial space, however, are poorly understood. Here, we used an unbiased approach to identify genes in kidney pericytes relevant to detachment and differentiation in response to injury in vivo, with a particular focus on genes regulating proteolytic activity and angiogenesis. Kidney pericytes rapidly activated expression of a disintegrin and metalloprotease with thrombospondin motifs-1 (ADAMTS1) and downregulated its inhibitor, tissue inhibitor of metalloproteinase 3 (TIMP3) in response to injury. Similarly to brain pericytes, kidney pericytes bound to and stabilized capillary tube networks in three-dimensional gels and inhibited metalloproteolytic activity and angiogenic signaling in endothelial cells. In contrast, myofibroblasts did not have these vascular stabilizing functions despite their derivation from kidney pericytes. Pericyte-derived TIMP3 stabilized and ADAMTS1 destabilized the capillary tubular networks. Furthermore, mice deficient in Timp3 had a spontaneous microvascular phenotype in the kidney resulting from overactivated pericytes and were more susceptible to injury-stimulated microvascular rarefaction with an exuberant fibrotic response. Taken together, these data support functions for kidney pericytes in microvascular stability, highlight central roles for regulators of extracellular proteolytic activity in capillary homoeostasis, and identify ADAMTS1 as a marker of activation of kidney pericytes.
Prevention of diabetes: Lifestyle and metformin are the way forward
Authors: John S Ashcroft
Journal: BMJ (2006)

EDITOR—The concern expressed by Heneghan et al1 that drug treatment to prevent diabetes may not be as attractive as it first seems, may be justified for rosiglitazone but is not for metformin, which is effective, safe, and cheap.

While the 31% reduction in new cases of diabetes with metformin in the Diabetes Prevention Program (DPP)2 seems unimpressive compared with the lifestyle groups' 58%, in …
Inflammasome pathway activation in patients with non-small cell lung cancer (NSCLC): A bronchoalveolar lavage fluid study
Authors: Katerina Samara, Katerina Antoniou, Ioannis Giannarakis, Ismini Lasithiotaki, Anna Psaraki, Gianna Soufla, Prodromos Sidiropoulos, Nikolaos Siafakas
Journal: European Respiratory Journal (2013)

Introduction: Inflammasome activation is mediated by NLR proteins. Among NLRs, NLRP3-inflammasome is a multiprotein molecular platform activated by infection or host-derived  signals that trigger an innate immune response via maturation of pro-inflammatory cytokines such as interleukin-1 β (IL-1 β), in a caspase-1-dependent way.  Aim of the study: Our aim was to investigate the NLRP3 pathway activation in human BALF and peripheral blood samples from NSCLC patients and healthy controls.  Methods: We prospectively studied BALF and peripheral blood leukocyte samples from 19 NSCLC and 12 healthy controls.  All samples were treated with LPS (250 pg/ml, 2hrs) to induce TLR4 stimulation, followed by NLRP3-inflammasome activation with pulse ATP (5mM, 20min). Secreted TNFa, IL-1β and IL-6 were measured using commercial ELISA kits.  Results: The main result is that LPS treatment resulted in increased levels of IL-1b production in NSCLC patients. Moreover, LPS treatment, pulse ATP and inhibition of the NLRP3-inflammasome activation using caspase-1 inhibitor resulted in increased IL-6 levels in NSCLC in comparison with controls. On the contrary, the same treatments resulted in a significant decrease in TNF-a secretion in NSCLC in comparison with controls.  Conclusion: NLRP3-inflammasome is activated in NSCLC patients in the presence of infectious stimuli thus exhibiting a possible role as a proinflammatory danger receptor.
THE RÔLE OF THE THYROID IN THE REGULATION OF THE BLOOD CHOLESTEROL OF RABBITS
Authors: Kenneth B. Turner, Clara H. Present, Emily H. Bidwell
Journal: The Journal of Experimental Medicine (1938)

1. The blood cholesterol of rabbits on a normal diet without added cholesterol is increased only slightly (19 per cent) by thyroidectomy. 2. In rabbits with a hypercholesterolemia due to long continued cholesterol feeding, thyroidectomy causes a marked rise (137 per cent) in the blood cholesterol. This rise is usually maintained. 3. When long continued cholesterol feeding has failed to cause a rise in the blood cholesterol of rabbits, thyroidectomy abolishes this resistance and a hypercholesterolemia is promptly produced. 4. A single injection of thyroxin causes a significant drop in the blood cholesterol of rabbits with hypercholesterolemia. This reaction is not influenced by thyroidectomy. 5. Potassium iodide causes an increase in the blood cholesterol of rabbits with hypercholesterolemia. This reaction is not influenced by thyroidectomy in contrast to the effect of KI in preventing a rise in blood cholesterol when given concurrently from the beginning of cholesterol feeding, an effect which is abolished by thyroidectomy. It is suggested that two different mechanisms are involved. 6. A single injection of insulin produces a fall in the blood cholesterol of rabbits with hypercholesterolemia. If anything, thyroidectomy increases the magnitude of this effect.
Ultrafiltration after cardiopulmonary bypass in children: effects on hemodynamics, cytokines and complement
Authors: K. Saatvedt, H. Lindberg, O.R. Geiran, S. Michelsen, T. Pedersen, E. Seem, T.E. Mollnes
Journal: Cardiovascular Research (1996)

The purpose of the study was to evaluate the clinical and hemodynamic effect of intraoperative extracorporeal ultrafiltration (UF) and its potential in reducing the plasma concentration of circulating cytokines and complement activation products following open heart surgery in children.Eighteen children with congenital heart disease were prospectively randomized into a control group (n = 9) and a group who underwent UF (n = 9). Serial plasma samples for measurements of circulating cytokines (interleukin 6 (IL-6), tumor necrosis factor alpha (TNF), and its soluble receptor (sTNF receptor)), and complement factors (C3 activation products (C3a and C3bc) and terminal complement complex (TCC)) were obtained before, during and up to 48 h after cardiopulmonary bypass (CPB). A pulmonary artery thermodilution catheter was introduced preoperatively for hemodynamic monitoring.Postoperative hemodynamics were similar in both groups. Plasma levels of IL-6, sTNF receptors, C3a, C3bc and TCC increased significantly perioperatively (P < 0.01) in both groups. TNF was detected transiently in 16 patients perioperatively and in 4 of the 9 ultrafiltrate samples in concentrations similar to the plasma levels. Complement activating products were not detected in the ultrafiltration samples except for small amounts of C3a in two cases. Compared to the control group the plasma levels of C3a, C3bc and TCC were unaffected by the ultrafiltration procedure. The level of IL-6 and sTNF receptors increased significantly after 15 min of UF but there was no significant difference between the two groups postoperatively.In this study no clinical or hemodynamic effect was registered after UF. TNF and C3a were occasionally detected in the ultrafiltrate but we were unable to demonstrate reduction of these or any of the other markers tested in the group subjected to ultrafiltration.
Partial Inhibition of Sodium/Calcium Exchange Restores Cellular Calcium Handling in Canine Heart Failure
Authors: Ion A. Hobai, Christoph Maack, Brian O’Rourke
Journal: Circulation Research (2004)

Sodium/calcium (Na + /Ca 2+ ) exchange (NCX) overexpression is common to human heart failure and heart failure in many animal models, but its specific contribution to the cellular Ca 2+ ([Ca 2+ ] i ) handling deficit is unclear. Here, we investigate the effects of exchange inhibitory peptide (XIP) on Ca 2+ handling in myocytes isolated from canine tachycardic pacing-induced failing hearts. Whole-cell patch-clamped left ventricular myocytes from failing hearts (F) showed a 52% decrease in steady-state sarcoplasmic reticulum (SR) Ca 2+ load and a 44% reduction in the amplitude of the [Ca 2+ ] i transient, as compared with myocytes from normal hearts (N). Intracellular application of XIP (30 μmol/L) normalized the [Ca 2+ ] i transient amplitude in F (3.86-fold increase), concomitant with a similar increase in SR Ca 2+ load. The degree of NCX inhibition at this concentration of XIP was ≈27% and was selective for NCX: L-type Ca 2+ currents and plasmalemmal Ca 2+ pumps were not affected. XIP also indirectly improved the rate of [Ca 2+ ] i removal at steady-state, secondary to Ca 2+ -dependent activation of SR Ca 2+ uptake. The findings indicate that in the failing heart cell, NCX inhibition can improve SR Ca 2+ load by shifting the balance of Ca 2+ fluxes away from trans-sarcolemmal efflux toward SR accumulation. Hence, inhibition of the Ca 2+ efflux mode of the exchanger could potentially be an effective therapeutic strategy for improving contractility in congestive heart failure.
Angioimmunoblastic lymphadenopathy with dysproteinaemia (AILD) and sicca syndrome.
Authors: Y J Bignon, A Janin-Mercier, J J Dubost, J M Ristori, Y Fonck, J C Alphonse, B J Sauvezie
Journal: Annals of the Rheumatic Diseases (1986)

We report a case of AILD and sicca syndrome. The patient had presented with renal insufficiency, lymphadenopathy, hepatosplenomegaly, polyclonal hypergammaglobulinaemia, dryness of the eyes and mouth. Lip biopsy specimens showed an unusual cellular infiltrate similar to his kidney lesions. Data from the eight previously reported cases support the hypothesis that the association is a distinct pathological entity differing from pseudolymphoma and malignant lymphoma, which occur in the course of Sjögren9s syndrome. The recognition of AILD is important because lymphoproliferation may lead to death after a few months.
Phase I Trial of Continuous Infusion Anti-Mesothelin Recombinant Immunotoxin SS1P
Authors: Robert J. Kreitman, Raffit Hassan, David J. FitzGerald, Ira Pastan
Journal: Clinical Cancer Research (2009)

Abstract Purpose: To conduct a phase I trial of recombinant immunotoxin SS1P given by continuous infusion in chemoresistant solid tumors expressing mesothelin. Experimental Design: Eligible patients had mesothelioma, ovarian, or pancreatic cancer, which was recurrent or unresectable despite standard therapy, and were mesothelin positive by immunohistochemistry. SS1P was given by continuous infusion for 10 days, and cycles could be repeated at 4-week intervals in the absence of neutralizing antibodies or progressive disease. Results: Twenty-four patients, five with peritoneal mesothelioma, nine with pleural mesothelioma, two with pleural-peritoneal mesothelioma, seven with ovarian carcinoma, and one with pancreatic carcinoma, received 4, 8, 12, 18, and 25 μg/kg/d ×10. The maximum tolerated dose was 25 μg/kg/d ×10, where one of six patients had dose-limiting toxicity due to reversible vascular leak syndrome. Immunogenicity was observed in 18 (75%) of 24 patients, and five (21%) received a second cycle. Constant plasma levels of SS1P were maintained for most of the 10-day infusion time, with median peak levels of up to 153 ng/mL. One patient had a partial response. Nonmajor responses included cessation of ascites and independence from paracentesis, resolution of masses by positron emission tomography, and improved pain and range of motion. Conclusions: As a single agent by continuous infusion, recombinant immunotoxin SS1P was well tolerated up to 25 μg/kg/d ×10 and showed evidence of modest clinical activity. Continuous infusion showed no significant advantage over bolus dosing, and further clinical development of SS1P is proceeding by bolus dosing in combination with chemotherapy. (Clin Cancer Res 2009;15(16):5274–9)
Peripheral Vascular Disease Risk Factors among Patients Undergoing Hemodialysis
Authors: Ann M. O’Hare, Chi-yuan Hsu, Peter Bacchetti, Kirsten L. Johansen
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Peripheral vascular disease (PVD) is common among patients undergoing hemodialysis, but little is known regarding the risk factors for PVD in this population. Data from waves 1, 3, and 4 of the United States Renal Data System Dialysis Morbidity and Mortality Study were used to examine cross-sectional associations of a range of conventional cardiovascular risk factors and uremia- or dialysis-related variables with PVD. Univariate and multivariate logistic regression models were developed using wave 3 and 4 data. Odds ratios for the multivariate model derived using wave 3 and 4 data were then compared with those obtained with the wave 1 data set. For both data sets, PVD was positively associated with the duration of dialysis (vintage) and malnourished status and was negatively associated with serum albumin and parathyroid hormone levels and predialysis diastolic BP. Kt/V was negatively associated with PVD in waves 3 and 4 but not in wave 1. PVD was associated with increasing age, white (versus non-white) race, male gender, diabetes mellitus, coronary artery disease, cerebrovascular disease, smoking, and left ventricular hypertrophy, as for the general population, but not with hypertension or hyperlipidemia. In conclusion, PVD among hemodialysis patients is associated with both dialysis-specific variables and most conventional cardiovascular risk factors other than hypertension and hyperlipidemia. Future studies should prospectively examine the association of these variables identified in cross-sectional analyses with the de novo development of PVD in this population.
Factors Contributing to the Lower Mortality With Ticagrelor Compared With Clopidogrel in Patients Undergoing Coronary Artery Bypass Surgery
Authors: Christoph Varenhorst, Ulrica Alström, Benjamin M. Scirica, Charles W. Hogue, Nils Åsenblad, Robert F. Storey, Ph. Gabriel Steg, Jay Horrow, Kenneth W. Mahaffey, Richard C. Becker, Stefan James, Christopher P. Cannon, Gunnar Brandrup-Wognsen, Lars Wallentin, Claes Held
Journal: Journal of the American College of Cardiology (2012)
Multiple anterograde atrioventricular node pathways in patients with atrioventricular node reentrant tachycardia
Authors: Ching-Tai Tai, Shih-Ann Chen, Chern-En Chiang, Shih-Huang Lee, Chuen-Wang Chiou, Kwo-Chang Ueng, Zu-Chi Wen, Yi-Jen Chen, Mau-Song Chang
Journal: Journal of the American College of Cardiology (1996)