tbuckley/cabot-search huggingface dataset:
A Role for Polymerase η in the Cellular Tolerance to Cisplatin-Induced Damage
Authors: Mark R. Albertella, Catherine M. Green, Alan R. Lehmann, Mark J. O'Connor
Journal: Cancer Research (2005)

Mutation of the POLH gene encoding DNA polymerase eta (pol eta) causes the UV-sensitivity syndrome xeroderma pigmentosum-variant (XP-V) which is linked to the ability of pol eta to accurately bypass UV-induced cyclobutane pyrimidine dimers during a process termed translesion synthesis. Pol eta can also bypass other DNA damage adducts in vitro, including cisplatin-induced intrastrand adducts, although the physiological relevance of this is unknown. Here, we show that independent XP-V cell lines are dramatically more sensitive to cisplatin than the same cells complemented with functional pol eta. Similar results were obtained with the chemotherapeutic agents, carboplatin and oxaliplatin, thus revealing a general requirement for pol eta expression in providing tolerance to these platinum-based drugs. The level of sensitization observed was comparable to that of XP-A cells deficient in nucleotide excision repair, a recognized and important mechanism for repair of cisplatin adducts. However, unlike in XP-A cells, the absence of pol eta expression resulted in a reduced ability to overcome cisplatin-induced S phase arrest, suggesting that pol eta is involved in translesion synthesis past these replication-blocking adducts. Subcellular localization studies also highlighted an accumulation of nuclei with pol eta foci that correlated with the formation of monoubiquitinated proliferating cell nuclear antigen following treatment with cisplatin, reminiscent of the response to UV irradiation and further indicating a role for pol eta in dealing with cisplatin-induced damage. Together, these data show that pol eta represents an important determinant of cellular responses to cisplatin, which could have implications for acquired or intrinsic resistance to this key chemotherapeutic agent.
N-acetylcysteine in cystic fibrosis and Pseudomonas aeruginosa infection: clinical score, spirometry and ciliary motility
Authors: G Stafanger, C Koch
Journal: European Respiratory Journal (1989)

The effect of peroral N-acetylcysteine (NAC) in patients with cystic fibrosis (CF) and chronic pulmonary Pseudomonas aeruginosa infection was studied in 52 patients in a double-blind, placebo-controlled, cross-over trial of two, 3 month durations. Active treatment consisted of NAC, 200 mg x 3 daily (patients weighing less than 30 kg) or 400 mg x 2 daily (greater than 30 kg). The effect was evaluated by a subjective clinical score, weight, sputum bacteriology, blood leucocyte count, sedimentation rate, titres of specific antimicrobial antibodies, lung function parameters and measurement of nasal ciliary function in vitro. 31 patients completed the study. No significant differences in lung function or subjective clinical scores were seen between NAC and placebo for the study group as a whole. Patients with peak expiratory flow rate (PEFR) below 70% of predicted normal values showed a satisfactory significant increase in PEFR, forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) during NAC treatment. No effect of NAC on ciliary activity was observed.
The distribution and cell uptake of ApoA1 modified lipid carriers of siRNA in mouse liver in vivo
Authors: Yan Li, Mengjie Rui, Hailing Tang, Yuhong Xu
Journal: Asian Journal of Pharmaceutical Sciences (2013)

Fluorescence labeled small interfering RNAs (siRNAs) were loaded into lipopolyplexes modified with ApoA1 (named as rHDL) and administered by intravenous injection. The biodistribution with time of these lipopolyplexes inside the liver and among various cell types was followed using tissue sections by Confocal fluorescence microscopy. At about 0.5 h after tail vein injection at a dose of 0.408 mg/kg, very few fluorescence signals were found in the liver. But then the signals could be seen to accumulate inside hepatocytes as discrete spots and diffused signals at around 2–4 h after injection. Such a distribution and uptake pattern was significantly different from what were observed using the commercial agent Invivofectamine® 2.0 or DOTAP lipoplexes as the carriers. The differences indicated different mechanisms concerning the in vivo behavior of these carriers. The rHDL carrier system we developed was able to deliver siRNA specifically into hepatocytes while avoiding the uptake by REM cells especially the Kupffer cells. With it's low toxicity and off target effect, it may be suitable to be developed as a hepatocyte targeting delivery system for siRNA.
Exogenous Reinfection with Multidrug-Resistant Mycobacterium tuberculosis in Patients with Advanced HIV Infection
Authors: Peter M. Small, Robert W. Shafer, Philip C. Hopewell, Samir P. Singh, Mary J. Murphy, Ed Desmond, Marcelino F. Sierra, Gary K. Schoolnik
Journal: New England Journal of Medicine (1993)

In the United States there have been recent outbreaks of multidrug-resistant tuberculosis. These outbreaks have primarily involved persons infected with the human immunodeficiency virus (HIV).
Current Progress in Nanotechnology Applications for Diagnosis and Treatment of Kidney Diseases
Authors: Sue Hyun Lee, Jung Bok Lee, Min Soo Bae, Daniel A. Balikov, Amy Hwang, Timothy C. Boire, Il Keun Kwon, Hak‐Joon Sung, Jae Won Yang
Journal: Advanced Healthcare Materials (2015)

Significant progress has been made in nanomedicine, primarily in the form of nanoparticles, for theranostic applications to various diseases. A variety of materials, both organic and inorganic, have been used to develop nanoparticles with promise to achieve improved efficacy in medical applications as well as reduced systemic side effects compared to current standard of care medical practices. In particular, this article highlights the recent development and application of nanoparticles for diagnosing and treating nephropathologies.
Year in review 2013: basic science and epidemiology
Authors: Paul Cullinan, Clare M Lloyd
Journal: Thorax (2014)

In the second of our reviews of 2013 we reveal our prize winners in the fields of basic science and epidemiology. As before, manuscripts arising from Imperial, Leicester and Oxford are disallowed, not because we would like to level the playing field (nice as this would be) but because of editors’ conflict of interest. If you read to the end we reveal our overall winners in the traditional gold, silver and bronze positions.

The Basic Science for the Chest Physician section has proved popular with our readers according to our most recent survey. Although many of these pieces are commissioned to accompany particular articles, we also welcome uncommissioned articles and suggestions for potential subjects from readers. So, if there is an area of basic science that you would like to highlight for the respiratory community, please let us know.

Manuscripts within the basic science sphere incorporated those seeking to understand the molecular mechanism underlying lung diseases as well as those aimed at discovering novel biomarkers and preclinical testing of novel therapeutic pathways. We continue to publish models and systems designed to reflect the broad range of lung diseases that are of interest to the readers of Thorax , including chronic obstructive pulmonary disease (COPD), asthma, idiopathic pulmonary fibrosis (IPF) and cystic fibrosis as well as respiratory infections.

Pulmonary inflammation may occur either as a result of excessive activation of inflammatory pathways or a failure in immune regulation. Several studies this year indicated that inflammation during COPD may occur as a general failure of pulmonary immune regulation, leading to reduced regulatory T cell populations but increased proportions of effector Th cells such as those defined by interleukin 17 (IL-17) secretion.1 ,2 Similarly, aberrant epidermal growth factor receptor activity was shown to be behind the decreased expression of FoxO3A—a negative …
Prevention of severe Candida infections in nonneutropenic, high-risk, critically ill patients: a randomized, double-blind, placebo-controlled trial in patients treated by selective digestive decontamination
Authors: Jorge Garbino, Daniel P. Lew, Jacques-A. Romand, Stéphane Hugonnet, Raymond Auckenthaler, Didier Pittet
Journal: Intensive Care Medicine (2002)
Efficacy and Tolerability of Budesonide/Formoterol Added to Tiotropium in Patients with Chronic Obstructive Pulmonary Disease
Authors: Tobias Welte, Marc Miravitlles, Paul Hernandez, Göran Eriksson, Stefan Peterson, Tomasz Polanowski, Romain Kessler
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Rationale: Budesonide/formoterol and tiotropium are commonly used maintenance treatments for patients with chronic obstructive pulmonary disease. Combining these medications may provide additional benefits.Objectives: To assess the efficacy and tolerability of budesonide/formoterol added to tiotropium in patients eligible for inhaled corticosteroid/long-acting β2-agonist combination therapy.Methods: In this 12-week, randomized, double-blind, parallel-group, multicenter study, after a 2-week run-in, 660 subjects (75% male; mean age, 62 yr; FEV1, 1.1 L; 38% predicted normal), 40 years of age or older, received tiotropium (18 μg once daily) plus either budesonide/formoterol (320/9 μg) (n = 329) or placebo (n = 331) twice daily.Measurements and Main Results: Clinic predose (primary outcome) and postdose FEV1, predose and postdose forced vital capacity and inspiratory capacity, and health status were measured. Other outcomes included daily measurements taken at home (pre- and postdose morning FEV1 and peak expiratory flow, morning symptoms and activities, and morning reliever use), severe exacerbations, and tolerability. Over the treatment period, budesonide/formoterol plus tiotropium significantly increased predose FEV1 by 6% (65 ml) and postdose by 11% (123 and 131 ml at 5 and 60 min postdose, respectively) versus tiotropium alone (both P < 0.001). Other outcomes all significantly improved with budesonide/formoterol plus tiotropium versus tiotropium alone. The number of severe exacerbations decreased by 62% (rate ratio, 0.38; 95% confidence interval, 0.25–0.57; P < 0.001). Both treatments were well tolerated.Conclusions: In patients with chronic obstructive pulmonary disease, budesonide/formoterol added to tiotropium versus tiotropium alone provides rapid and sustained improvements in lung function, health status, morning symptoms and activities, and reduces severe exacerbations.Clinical trial registered with www.clinicaltrials.gov (NCT00496470).
Sulfatase modifying factor 1–mediated fibroblast growth factor signaling primes hematopoietic multilineage development
Authors: Mario Buono, Ilaria Visigalli, Roberta Bergamasco, Alessandra Biffi, Maria Pia Cosma
Journal: The Journal of Experimental Medicine (2010)

Self-renewal and differentiation of hematopoietic stem cells (HSCs) are balanced by the concerted activities of the fibroblast growth factor (FGF), Wnt, and Notch pathways, which are tuned by enzyme-mediated remodeling of heparan sulfate proteoglycans (HSPGs). Sulfatase modifying factor 1 (SUMF1) activates the Sulf1 and Sulf2 sulfatases that remodel the HSPGs, and is mutated in patients with multiple sulfatase deficiency. Here, we show that the FGF signaling pathway is constitutively activated in Sumf1−/− HSCs and hematopoietic stem progenitor cells (HSPCs). These cells show increased p-extracellular signal-regulated kinase levels, which in turn promote β-catenin accumulation. Constitutive activation of FGF signaling results in a block in erythroid differentiation at the chromatophilic erythroblast stage, and of B lymphocyte differentiation at the pro–B cell stage. A reduction in mature myeloid cells and an aberrant development of T lymphocytes are also seen. These defects are rescued in vivo by blocking the FGF pathway in Sumf1−/− mice. Transplantation of Sumf1−/− HSPCs into wild-type mice reconstituted the phenotype of the donors, suggesting a cell autonomous defect. These data indicate that Sumf1 controls HSPC differentiation and hematopoietic lineage development through FGF and Wnt signaling.
Cardiac-Specific Expression and Hypertrophic Upregulation of the Feline Na <sup>+</sup> -Ca <sup>2+</sup> Exchanger Gene H1-Promoter in a Transgenic Mouse Model
Authors: Joachim G. Müller, Yukihisa Isomatsu, Srinagesh V. Koushik, Michael O’Quinn, Lin Xu, Christiana S. Kappler, Elizabeth Hapke, Michael R. Zile, Simon J. Conway, Donald R. Menick
Journal: Circulation Research (2002)

The NCX1 gene contains three promoters (H1, K1, and Br1), and as a result of alternative promoter usage and alternative splicing, there are multiple tissue-specific variants of the Na + -Ca 2+ exchanger. We have proposed that for NCX1, the H1 promoter regulates expression in the heart, the K1 promoter regulates expression in the kidney, and the Br1 promoter regulates expression in the brain as well as low-level ubiquitous expression. Here, using a transgenic mouse model, we test the role of the DNA region including −1831 to 67 bp of intron 1, encompassing exon H1 of the feline NCX1 gene (NCX1H1). The NCX1H1 promoter was sufficient for driving the normal spatiotemporal pattern of NCX1 expression in cardiac development. The luciferase reporter gene was expressed in a heart-restricted pattern both in early embryos (embryonic days 8 to 14) and in later embryos (after embryonic day 14), when NCX1 is also expressed in other tissues. In the adult, no luciferase activity was detected in the kidney, liver, spleen, uterus, or skeletal muscle; minimal activity was detected in the brain; and very high levels of luciferase expression were detected in the heart. Transverse aortic constriction–operated mice showed significantly increased left ventricular mass after 7 days. In addition, there was a 2-fold upregulation of NCX1H1 promoter activity in the left ventricle in animals after 7 days of pressure overload compared with both control and sham-operated animals. This work demonstrates that the NCX1H1 promoter directs cardiac-specific expression of the exchanger in both the embryo and adult and is also sufficient for the upregulation of NCX1 in response to pressure overload.
Microengineering of Cellular Interactions
Authors: Albert Folch, Mehmet Toner
Journal: Annual Review of Biomedical Engineering (2000)

▪ Abstract Tissue function is modulated by an intricate architecture of cells and biomolecules on a micrometer scale. Until now, in vitro cellular interactions were mainly studied by random seeding over homogeneous substrates. Although this strategy has led to important discoveries, it is clearly a nonoptimal analog of the in vivo scenario. With the incorporation—and adaptation—of microfabrication technology into biology, it is now possible to design surfaces that reproduce some of the aspects of that architecture. This article reviews past research on the engineering of cell-substrate, cell-cell, and cell-medium interactions on the micrometer scale.
Frontline Treatment of Combat Stress Reaction: A 20-Year Longitudinal Evaluation Study
Authors: Zahava Solomon, Rami Shklar, Mario Mikulincer
Journal: American Journal of Psychiatry (2005)

The purpose of the study was to evaluate the long-term (20-year) effectiveness of frontline treatment provided to combat stress reaction casualties.A longitudinal quasi-experimental design was employed. Participants were combat stress reaction casualties of the 1982 Lebanon War who received frontline treatment (N=79), comparable combat stress reaction casualties who did not receive frontline treatment (N=156), and matched soldiers who did not experience combat stress reaction (N=194). Subjects were asked which of the frontline treatment principles (proximity, immediacy, expectancy) were applied in their treatment, whether or not they returned to their unit after frontline treatment, and if so, whether they returned before or after they felt completely recovered. Outcome assessments included measures of posttraumatic and psychiatric symptoms and of social functioning.Twenty years after the war, traumatized soldiers who received frontline treatment had lower rates of posttraumatic and psychiatric symptoms, experienced less loneliness, and reported better social functioning than similarly traumatized soldiers who did not receive frontline treatment. In addition, a cumulative effect of application of frontline treatment principles was documented: the more principles applied, the stronger the effect on psychiatric outcomes.Frontline treatment is associated with improved outcomes even two decades after its application. This treatment may also be effective for nonmilitary precursors of posttraumatic stress disorder.
Injury current modulates afterdepolarizations in single human ventricular cells
Authors: A Verkerk
Journal: Cardiovascular Research (2000)

Objective: Injury current (Iinjury) and afterdepolarizations are thought to play an important role in arrhythmias that occur during acute ischemia. However, little is known about the effects of Iinjury on afterdepolarizations. The present study was designed to study the effect of Iinjury on afterdepolarizations and action potentials in single human ventricular cells. Methods: The patch-clamp technique was used to record action potentials and to apply Iinjury to human ventricular cells. In these cells, early and delayed afterdepolarizations (EADs and DADs) were induced by 1 μM norepinephrine. Iinjury was simulated by coupling cells via a variable coupling resistance to a passive resistance circuit with a potential of 0, −20, or −40 mV, mimicking a depolarized ischemic region. Results: At all potentials, Iinjury induced depolarization of the resting membrane potential and action potential shortening. Flowing from 0 mV, Iinjury induced EADs by itself and aggravated the EADs and DADs that were induced by norepinephrine. Flowing from −40 mV, Iinjury abolished the noradrenaline-induced EADs and DADs. Conclusions: Our results demonstrate that Iinjury may either prevent or promote the occurrence of afterdepolarizations in human ventricle. The latter holds if conduction is slowed to such an extent that it permits flow of current from depolarized ischemic cells at plateau level to cells in phase 3 or phase 4.
STUDIES OF CALCIUM METABOLISM IN CERTAIN DISEASES OF THE SKIN*
Authors: NORMAN BURGESS
Journal: British Journal of Dermatology (1928)

Journal Article STUDIES OF CALCIUM METABOLISM IN CERTAIN DISEASES OF THE SKIN Get access NORMAN BURGESS, M.A., M.B., M.R.C.P. NORMAN BURGESS, M.A., M.B., M.R.C.P. Clinical Assistant, Skin Department, Bristol General Hospital; formerly Physician, Skin‐Department, Queen's Hospital for Children. From the Dermatological Department, Guy's Hospital Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 40, Issue 7, 1 July 1928, Pages 279–294, https://doi.org/10.1111/j.1365-2133.1928.tb12119.x Published: 01 July 1928
Acute and Chronic Cardiovascular Effects of Pentolinium in Hypertensive Patients
Authors: JOSEF R. SMITH, S. W. HOOBLER
Journal: Circulation (1956)

Using a tracer injection technic, modified to provide accurate and repeated determinations of cardiac output in the ambulatory patient, the authors have shown that chronic pentolinium therapy for hypertension lowers blood pressure by reducing cardiac output in the seated position. From these observations and the work of others, they believe that the effect of ganglionic blockade on venoconstrictor tone deserves greater emphasis.
Hypofrontality in Attention Deficit Hyperactivity Disorder During Higher-Order Motor Control: A Study With Functional MRI
Authors: Katya Rubia, Stephan Overmeyer, Eric Taylor, Michael Brammer, Steve C.R. Williams, Andrew Simmons, Edward T. Bullmore
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: Functional magnetic resonance imaging (MRI) was used to investigate the hypothesis that attention deficit hyperactivity disorder (ADHD) is associated with a dysfunction of prefrontal brain regions during motor response inhibition and motor timing. METHOD: Generic brain activation of seven adolescent boys with ADHD was compared to that of nine comparison subjects equivalent in sex, age, and IQ while they were performing a stop task, requiring inhibition of a planned motor response, and a motor timing task, requiring timing of a motor response to a sensory cue. RESULTS: The hyperactive adolescents showed lower power of response in the right mesial prefrontal cortex during both tasks and in the right inferior prefrontal cortex and left caudate during the stop task. CONCLUSIONS: ADHD is associated with subnormal activation of the prefrontal systems responsible for higher-order motor control. Functional MRI is a feasible technique for investigation of neural correlates of ADHD.
Effects of Obesity on Transcriptomic Changes and Cancer Hallmarks in Estrogen Receptor–Positive Breast Cancer
Authors: Enrique Fuentes-Mattei, Guermarie Velazquez-Torres, Liem Phan, Fanmao Zhang, Ping-Chieh Chou, Ji-Hyun Shin, Hyun Ho Choi, Jiun-Sheng Chen, Ruiying Zhao, Jian Chen, Chris Gully, Colin Carlock, Yuan Qi, Ya Zhang, Yun Wu, Francisco J. Esteva, Yongde Luo, Wallace L. McKeehan, Joe Ensor, Gabriel N. Hortobagyi, Lajos Pusztai, W. Fraser Symmans, Mong-Hong Lee, Sai-Ching Jim Yeung
Journal: JNCI Journal of the National Cancer Institute (2014)

BackgroundObesity increases the risk of cancer death among postmenopausal women with estrogen receptor–positive (ER+) breast cancer, but the direct evidence for the mechanisms is lacking. The purpose of this study is to demonstrate direct evidence for the mechanisms mediating this epidemiologic phenomenon.
P-glycoprotein expression and function in patients with temporal lobe epilepsy: a case-control study
Authors: Maria Feldmann, Marie-Claude Asselin, Joan Liu, Shaonan Wang, Adam McMahon, José Anton-Rodriguez, Matthew Walker, Mark Symms, Gavin Brown, Rainer Hinz, Julian Matthews, Martin Bauer, Oliver Langer, Maria Thom, Terry Jones, Christian Vollmar, John S Duncan, Sanjay M Sisodiya, Matthias J Koepp
Journal: The Lancet Neurology (2013)
The Mutational Profile of the Yeast Genome Is Shaped by Replication
Authors: N. Agier, G. Fischer
Journal: Molecular Biology and Evolution (2011)

Despite the scrutiny that has been directed for years at the yeast genome, relatively little is known about the impact of replication on the substitution dynamics in Saccharomyces cerevisiae. Here, we show that the mutation rate increases with the replication timing by more than 30% between the earliest and the latest replicating regions. In addition, we found a mutational asymmetry associated with the polarity of replication resulting in higher rates of substitutions toward C and A than toward G and T in leading strands (reciprocally more substitutions toward G and T in lagging strands). Such mutational asymmetries applied over long evolutionary periods should generate compositional skews between the two DNA strands. Thus, we show that the leading replicating strands present an excess of C over G and of A over T in the genome of S. cerevisiae (reciprocally an excess of G + T over C + A in lagging strands). We also show that the nucleotide frequencies at mutational equilibrium predict a compositional skew at equilibrium very close to the observed skew between leading and lagging strands, suggesting that compositional equilibrium has been nearly attained in the present day genome of S. cerevisiae. Surprisingly, the direction of this skew is inverted compared with the one in the human genome.